October 27, 2020
Without reliable information, we rely on fear or luck.
“This virus is going to have a heyday. We are looking at some pretty sobering and difficult months ahead.”David Relman, a microbiologist at Stanford University in California
“Even if a vaccine was available by the spring, it would not wipe out the virus, which would, in fact, become endemic in Britain. We will simply have to live with this disease, he said, and learn to manage it in the best possible way.”Sir Patrick Vallance, UK Chief Scientific Officer
“I feel like there is this perception that once we have a coronavirus vaccine life will go back to normal. Life will not be like it was pre-COVID. Even after we have a #vaccine you will still need to use good hand hygiene, maintain physical distance, avoid crowds and wear masks.”Dr. Krutika Kuppalli, an expert witness for the U.S. Congress
1. Cases & Tests
3. Top 5 States in Cases, Deaths, Hospitalizations & Positivity
4. The Spread of C19 — Spring, Summer and Fall
O. Linked Stories
- Massive Analysis Reveals New C19 Related Genes – Helpful and Harmful
- People Who Have Recovered From C19 Could Hold the Key to Understanding Immunity to the Disease
- Molecular processes in kidney cells may ‘prime’ diabetics for C19 infection
- Mini-lungs’ reveal early stages of C19
- Dexamethasone discovery carries treatment implications
- Cardiac Ultrasounds Show Damaging Impact of C19 on the Heart
- CRISPR screen identifies genes, drug targets to protect against the coronavirus infection
- Healthcare’s Earthquake: Lessons From the C19 Pandemic
- Scientist develops new way to test for C19 antibodies
- Simulated Sunlight Rapidly Inactivates Coronavirus on Surfaces
- Home tests could help in the fight against the coronavirus. So where are they?
- Why False Positives Merit Concern, Too
- Residents of U.S. counties with more connections to China or Italy were more likely to follow early pandemic restrictions
- Anti-COVID products to be developed in new partnership
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A. The Pandemic As Seen Through Headlines
(In no particular order)
- Eli Lilly said its antibody treatment does not work on patients hospitalized with Covid-19
- ‘Enormous impact’ of COVID-19 translates to 2.5 million years of potential life lost
- Drop in flu deaths may indicate that most at risk died from COVID-19
- Trump to make COVID-19 vaccine free for Medicare, Medicaid recipients
- Surgeon General issues Thanksgiving warning
- Johnson & Johnson, AstraZeneca coronavirus vaccine trials set to resume
- AstraZeneca trial data shows vaccine effective on elderly
- Dr. Fauci says if people won’t wear masks, maybe it should be mandated
- Dr. Fauci says even with a vaccine, masks and social distancing will continue until 2022
- Nearly 130,000 lives could be saved if everyone wears masks: study
- Kansas counties with mask mandates had half the rate of new infections, a study finds
- White House Chief of Staff says ‘we’re not going to control’ COVID-19 pandemic
- CDC Reaffirms Warning Against Nonessential Travel, Including Cruises
- Health Expert: Mask Wearing Will Remain Mandatory Even After A COVID Vaccine
- US and Europe hit record high daily COVID-19 Cases Last Friday
- Second Wave of COVID-19 Batters Europe
- Europe’s daily coronavirus cases more than double in 10 days
- US sees 7-day average for cases hit new record
- Ex-FDA chief warns of ‘dangerous tipping point’ in COVID-19 pandemic
- The COVID-19 surge is global — stop politicizing it to bash Trump
- Dr. Fauci says US still in first wave of virus
- Fauci: COVID-19 taskforce only meets weekly despite US case surge
- C.D.C. study says nurses are at high risk among health care workers
- Hospitals across US near capacity
- Idaho refusing mask rules despite hospitals reaching full capacity
- Rate of positive tests for coronavirus creeps up in New York
- Texas county issues COVID-19 curfew amid ‘crisis stage’
- California’s dire coronavirus prediction was wrong, hospitalizations went down instead
- Twitter disputes veracity of Trump tweet on testing
- Newark’s mayor says nonessential businesses must close by 8 p.m. daily, starting Tuesday
- Chinese Authorities Scramble To Suppress Biggest COVID-19 Outbreak In Months
- ‘Shove Your New World Order Up Your *ss!’ — London Erupts in Protest Against Lockdown
- Multiple journals reject major mask study amid hints that it shows masks don’t stop COVID
- Netherlands tops 300,000 new cases
- Czech Republic, Belgium and Denmark weigh new measures
- NYC Mayor de Blasio allows students to opt into hybrid learning
- Utah hospitals ask Governor to approve new triage plan
- French official warns France seeing 100,000 new cases per day
- Infectious disease expert warns France has ‘lost control’ of coronavirus
- France’s President Macron predicts nine more months of COVID-19 agony
- Spain, Italy impose tougher lockdown measures as COVID-19 cases surge
- Malaysia extends lockdown
- In hard-hit Peru, worry mounts over both COVID-19 and dengue
- ‘Eating rats’: Myanmar’s second lockdown drives hunger in city slums
- Hong Kong focuses COVID efforts on public transit
- UK approves new rapid test
- Sweden Refuses To Impose New Lockdown Measures, Saying People Have Suffered Enough
- Czech Republic Sets Daily Record of 15,000 Coronavirus Cases
- Major Italian Cities Risk Lockdown ‘Red Zone’ Status as Coronavirus Cases Surge
- Italians Rise Up Against “Health Dictatorship” As Country Moves Toward New Lockdown
- German Chancellor Merkel sees increased urgency in fight against the pandemic
- Ethiopia jailing people for up to 2 years for not wearing masks in public
- Wary of angering public, Iran has few ways to contain coronavirus
- Welsh People Blocked From Buying “Non-Essential” Items Due To Lockdown
- German police probe arson attack on infectious disease institute leading country’s COVID-19 response
- Illinois restaurants, bars remain open to defy governor’s closure orders
- UK doctors demand free meals for kids as COVID fuels hunger
- Largest food bank in US has more than doubled distribution during COVID-19
- Colleges testing students’ wastewater for COVID-19
- Just more than a quarter of N.Y.C. public school students have attended in-person classes, the mayor says
- NYC Hotel Occupancy Rate Crashes Toward 10% As Permanent Closures Loom
- Manhattan rents hit record lows, report finds
- Recent College Grads Face Worst Employment Prospects In Decades Thanks To C19
- Puerto Rico Shuts Down 911 Call-Centers after employees become infected
- 76% of US CEOs Will Slash Office Space As Remote Work Dominates
- Big landlords move to evict thousands of tenants despite COVID ban
- NFL punishes team for COVID-19 violations — and another team is in trouble
- 460 passengers put on ‘no-fly list’ by airline for refusing to wear masks
- WSJ Reporter Documents How The Pandemic Turned Her Once-Frugal Parents Into Daytraders
- Caesars Entertainment is resuming live entertainment on Las Vegas Strip
B. Numbers & Trends
Note: Unless otherwise noted, (i) all cases/deaths are confirmed cases/deaths that have been reported, (ii) all numbers reported in this update are as of the end of the most recent reporting period, and (iii) all changes reflect changes since the preceding day.
1. Cases & Tests
- Total Cases = 43,770,537
- New Cases = 411,372
- New Cases (7 day average) = 442,722 (+10,042) (+2.3%)
- New record high number of new cases (490,806) occurred on 10/23
- 7 day average of new cases at a new record high
- 7 day average of new cases is increasing at a rapid rate
- 1,000,000 new cases every 2.4 days (based on 7 day average)
US Cases & Testing:
- Total Cases = 8,962,783
- New Cases = 69,841
- New Cases (7 day average) = 70,987 (+1,552) (+2.2%)
- Percentage of New Global Cases (7 day average) = 16%
- Total Number of Tests = 134,376,092
- Percentage of positive tests (7 day average) = 7.2%
- A new record high number of new cases (81,421) occurred on 10/23
- 7 day average of new cases is a new record high
- 7 day average of new cases is increasing at a rapid rate
- 7 day average percentage of positive tests is increasing at a rapid rate
- Total Cases = 8,891,984 (slightly larger number of total cases than total US cases)
- New Cases = 224,000 on 10/23 (approx. 3x the number of new cases in US)
- Total Deaths = 1,164,236
- New Deaths = 5,110
- New Deaths (7 day average) = 5,922 (+100) (+1.7%)
- 7 day average of new deaths has been rapidly increasing since 10/15
- Since 10/15, the 7 day average has increased from 5,149 to 5,922, an increase of 15%
- 7 day average of new deaths is approaching the 2nd peak of 5,992, which occurred on 8/13
- Total Deaths = 231,045
- New Deaths = 529
- New Deaths (7 day average) = 828 (+10) (+1.2%)
- Percentage of Global New Deaths (7 day average) = 14%
- 7 day average of new deaths has been steadily increasing since 10/17
- Since 10/17, the 7 day average has increased from 704 to 828, an increase of 14.4%
- Total deaths = 262,766 (approx. 30,000 more than US)
- New deaths = 5,363 on 10/23 (almost 6x more than number of new deaths in the US)
3. Top 5 States in Cases, Deaths, Hospitalizations & Positivity (10/26)
- The positivity rate continues to rise across the country
- Nationally, the average 7-day positivity rate was 7.2% — up from 5.5% as of 10/12.
- More than 40% of all tests are now positive in ND and SD.
- Nine states (ID WI, IA, NE, MT, AL, IN, KS) had 7-day positivity rates greater than 20%.
- In total, 37 states have 7-day positivity rates greater than 5% (+3 states since 10/12)
- Hospitalizations in the US increased to 42,917, up 13.5% over the past week.
- TX hospitalizations have reached their highest level since 8/21
- CA, AK, HI and OR – only states with a drop in hospitalizations since 10/12
4. The Spread of C19 — Spring, Summer and Fall
- Spring Surge – Initial surge in the northeast
- Summer Surge — spreads into the deep south and sunbelt states
- Fall Surge — spreads into the midwest, plains and mountain states
5. U.S. average daily cases hits an all-time high as experts warn of difficult winter
- The 7 day average number of new daily cases of coronavirus in the United States is at a record.
- “We are likely to see a very dense epidemic,” former Food and Drug Administration Commissioner Dr. Scott Gottlieb told CNBC on Monday.
- As daily new cases skyrocket, hospitalizations are rising, too, and deaths, which lag furthest behind those other indicators, are beginning to tick up.
- The average number of new daily cases of coronavirus in the United States is at a record — stressing local hospital systems and forcing new curfews and other restrictions in some parts of the country.
- With fall holidays such as Halloween and Thanksgiving approaching, the U.S. has now established its third peak of daily new cases with no signs of letting up.
- Over the past seven days, the country reported an average of about 68,767 new cases every day, the highest seven-day average recorded yet, according to a CNBC analysis of Johns Hopkins University data. The seven-day average is up more than 22% compared with a week ago, according to CNBC’s analysis.
- “We are likely to see a very dense epidemic,” former Food and Drug Administration Commissioner Dr. Scott Gottlieb told CNBC on Monday. “I think we are right now at the cusp of what is going to be exponential spread in parts of the country.”
- The U.S. is also testing more people than ever, according to data compiled by the Covid Tracking Project. However, more testing cannot account for the rise in cases, health officials say, because the percent of tests coming back positive has increased as well. About 6.2% of tests were positive on Sunday based on a seven-day average, according to Hopkins, up from 5.2% a week earlier.
- The U.S. reported an all-time high single-day spike in cases on Friday, when the country reported 83,757 new cases, according to Hopkins data. Health officials have warned for months that cases would likely rise as parts of the country entered the fall and winter. That’s largely because people are spending more time indoors, where the virus can spread more easily. Epidemiologists also say the virus may be able to spread more easily in colder, drier air.
- More than 20 states reported record-high numbers of average daily new cases, and cases are rising by 5% or more in 40 states, according to CNBC’s analysis. Many of the states with the fastest growing outbreaks are those in the Midwest and West, which did not report many cases of the virus earlier in the pandemic. Adjusted for population, the Dakotas, Wisconsin, Montana and Idaho are reporting more average daily new cases than anywhere else in the country.
- “We have one more cycle to get through with this. I know people are exhausted. It’s been very hard on families and on individuals, on businesses especially, but we really have two or three months of the acute phase of this pandemic to get through,” Gottlieb said Monday. “This is going to be the hardest phase probably.”
- As daily new cases skyrocket, hospitalizations are rising, too. Deaths, which lag furthest behind those other indicators, are beginning to tick up as well. With advances in clinical care for C19 patients and new treatments such as the antiviral remdesivir and steroids like dexamethasone, health officials say they are able to save more Covid patients than ever. But with deaths on the rise, it remains to be seen how substantially the death rate has dropped in the roughly 11 months since the virus emerged.
- Hospital systems in some parts of the country are scrambling to shore up resources amid the new surge in infections and hospitalized patients. In Texas, El Paso County Judge Ricardo Samaniego issued a curfew on Sunday, saying that hospitals and health workers are now “overwhelmed and exhausted.” The Salt Lake Tribune reported over the weekend that the Utah Hospital Association is asking the governor to authorize criteria for rationing care.
- And in Illinois, tighter business restrictions were implemented last week in response to the rising case count. The governor ordered the closure of restaurants and bars in four counties and Chicago.
- Chicago Mayor Lori Lightfoot announced a curfew for residents last week, saying the city is at a “critical moment.”
- Newark Mayor Ras Baraka announced on Monday a series of new restrictions on businesses as the New Jersey city faces a rapidly growing outbreak. All stores except supermarkets, pharmacies and gas stations will close at 8 p.m. every day under the new restrictions. Restaurants and bars must end indoor service at 8 p.m. and outdoor service at 11 p.m., according to the restrictions. The restrictions say that gyms will have to close for a 30-minute cleaning every hour.
- Andy Slavitt, former acting administrator at the Centers for Medicare and Medicaid Services, said the rise in cases in the northern parts of the country is a preview of what’s to come as other parts of the country hit colder weather. He said family gatherings during the holidays could prove especially dangerous.
- “As families consider getting together for Thanksgiving, they really need to think twice about bringing their elderly parents and their younger kids and college kids in contact with one another,” he told CNBC’s “Squawk Box Asia” on Monday. “Because I think we’re about to go through our most dangerous time here in the U.S.”
- The worrying rise in new cases come after White House chief of staff Mark Meadows acknowledged on Sunday that the U.S. is not going to control the pandemic.
- “We’re not going to control the pandemic,” Meadows told CNN. “We are going to control the fact that we get vaccines, therapeutics and other mitigations.”
- Pressed on why the U.S. can’t make efforts to control the pandemic, Meadows said: “Because it is a contagious virus just like the flu.”
- Assistant Secretary for Health Adm. Brett Giroir, who leads the U.S. testing effort, said Monday, however, that “I think we can control the pandemic.”
- He cited efforts in Arizona, Florida and Texas earlier this year to bring outbreaks there under control as evidence that a coordinated effort to implement public health measures can bring the virus under control. He urged people to frequently wash their hands, wear a mask and to practice social distancing.
- “The data are pretty clear that we can, not 100% defeat, but we can control it,” he said.
6. ‘At Capacity’: C19 Patients Push US Hospitals to Brink
- A hospital in Idaho is 99% full and warning that it may have to transfer coronavirus patients to hospitals in Seattle and Portland, Ore. Medical centers in Kansas City, Mo., turned away ambulances on a recent day because they had no room for more patients. And in West Allis, just outside Milwaukee, an emergency field hospital erected on the grounds of the Wisconsin State Fair admitted its first virus patient this week.
- More than 41,000 people are currently hospitalized with the coronavirus in the United States, a 40% rise in the past month, and cooler weather that pushes more people indoors is threatening to expand the outbreak still more. At least 14 states saw more people hospitalized for the virus on a day in the past week than on any other day in the pandemic, according to the Covid Tracking Project. Seven more states are nearing their peaks.
- The nation has seen more people hospitalized at earlier points — during an onslaught of cases in New York City in April and in the Sun Belt in July — but the sharply rising numbers now are deeply worrisome, in part, because they are testing the limits of smaller hospital systems.
- Patients are now spread more broadly across the country, with troubling hot spots from North Dakota to Kentucky. More people than ever are falling critically ill in rural areas, particularly in the Midwest and the Mountain West, where they must rely on hospitals that may have only a handful of beds. And experts worry that the growing numbers in need of hospital care will only get worse if cases continue to mount.
- “I don’t really see any signs that things are slowing down and that concerns me a lot,” Caitlin M. Rivers, an epidemiologist at Johns Hopkins University, said. “It has to be our starting premise that it’s not going to slow down unless we force it to slow down.”
- Even as hospitalizations and known cases of the virus have grown, daily deaths across the country have remained fairly steady at around 760 in recent days. But some experts fear that the rate of deaths is beginning to rise again. Upticks in deaths usually lag behind rises in cases and hospitalizations because of the time it takes for the virus to progress.
- For families around the country, the mounting hospitalizations were frightening — and personal. Among the thousands of patients, there was a retired Air Force lieutenant colonel who had trouble catching her breath in Missouri, grandparents being treated in separate hospitals in Utah and a beloved uncle whose niece said he had been on a ventilator for five weeks in Wisconsin.
- Amy Stadler, the niece, sat in a black minivan outside of the Milwaukee Brewers’ stadium this week as she waited for a nurse to swab her nose. She said relatives had collected messages for her uncle — who is gravely ill — to be shared if his condition were to grow even more dire. Ms. Stadler, 49, said she sent hers: “That I love him, and that it’s OK to go.”
- In recent days, Ms. Stadler, who works as a teaching assistant, began coughing and registered a fever. “I’m careful, but there’s a lot of people that aren’t,” she said softly from behind her face mask as she waited for her test.
- The signs of a crunch for hospital space were painfully clear across several states.
- “Make no mistake about this, this is an urgent crisis,” Gov. Tony Evers of Wisconsin said on Thursday of the state’s outbreak.
- In months past, field hospitals have opened in several cities, including Seattle and New York. Some closed after seeing only small numbers of patients, or none at all. But in Wisconsin, the health secretary-designee, Andrea Palm, said hospital officials had sounded an “urgent call” as more and more patients arrived at their doors.
- The 530-bed field hospital in West Allis, she said, is the state’s “ultimate insurance policy.” The hospital was built inside the Exposition Center, a brick building the size of three football fields where the fair, in most years, is a widely attended event. Inside the hospital, hundreds of white cubicles are lined up one after the next, each with little more than a bed, a waste bin and a curtain for privacy.
- In Utah, officials sounded frustrated on Thursday as they issued urgent pleas.
- “Our health care system is at capacity, our health care providers are overwhelmed and exhausted, our public health system is stressed,” Dr. Angela Dunn, the state epidemiologist, said.
- “I don’t know what to do anymore,” Dr. Dunn added. “I’m really not trying to scare anyone, I’m just trying to inform you of what’s going on.”
- Gov. Gary Herbert said the state was preparing to open a field hospital of its own at an exposition center south of Salt Lake City. One out of five patients in intensive care units across the state are C19 patients, he said.
- In separate hospitals in Utah — about 20 miles apart — Rebecca Hannett’s grandmother, a 79-year-old retired bus driver, is feeling better, but her grandfather, who is 85, is not, Ms. Hannett said. The isolation and separation of being hospitalized with C19 has added to their struggle with the illness.
- “My grandma called us yesterday because she’s worried about our grandpa,” Ms. Hannett, 22, said. “He’s kind of decided that if this is the end, this is the end. And my grandmother is just worried that they won’t be able to say their goodbyes to each other.”
- In some rural parts of the nation, hospital officials are having to act “almost like air traffic control,” moving around patients to open up beds, said Dr. David Basel, a vice president at the Avera Medical Group, which is based in South Dakota and runs about three dozen hospitals in the Midwest.
- “Our regional hospitals are all running at or near capacity on a daily basis,” Dr. Basel said.
- One in four of the patients now being admitted to the group’s hospitals are C19 patients, Dr. Basel said, a proportion that could rise if the infection rate remains high. As more patients arrive from rural parts of the region, he said, he feared that hospitals might have to cancel cancer screenings, back operations and other nonemergency procedures to make room.
- As the pandemic wears on, hospital officials said they were most worried about a shortage in workers, rather than physical supplies. Unlike when the virus was largely concentrated in New York and the Northeast, when medical workers arrived to assist from across the country, the virus is now more widespread, meaning there are few nurses or doctors arriving to help.
- “It feels more like a slog that we’re getting through, rather than something we can rally together and defeat rapidly,” said Nancy Foster, a vice president at the American Hospital Association. “There are not as many folks who can leave their community to help out in another one because they’re struggling to keep up in their own community.”
- Karina Brown, a nurse, has been helping to treat virus patients at the Aurora Sinai Medical Center in Milwaukee since the pandemic began. Even though she felt prepared for the influx of patients, it was still a shock when they came.
- “We had a plan, but once you really saw it and it was go time, that’s kind of different,” Ms. Brown said.
- Now she is assigned to more patients and they are, on average, much sicker, meaning she has to monitor and care for them more often. She and other nurses have also become, in many cases, one of the few connections between patients and relatives who are not allowed to visit. It has brought her closer to her patients, but also makes it more painful if they succumb to the illness.
- “We’re their person while they’re here,” Ms. Brown said. “Because they’re all alone.”
- She added: “You get to know people, and you have to sit at the bedside with them and hold their hand because their family might not be able to come.”
C. New Scientific Findings & Research
1. New Research Helps Explain Dramatic Declines in C19 Death Rates
- Fewer New Yorkers are dying from the coronavirus than health experts had anticipated, a new study shows. Regional death rates have dropped from the highs seen at the start of the outbreak, partially due to a shift in the population contracting the disease toward those who are more resilient.
- After New York became the epicenter for the pandemic in early March, with tens of thousands dying from C19, experts had expected that the infection would remain as deadly in the following months.
- Instead, a new investigation showed that by mid-August the death rate in those hospitalized with coronavirus-related illness had dropped from 27% to about 3 percentage points. Led by researchers at NYU Grossman School of Medicine, the study showed that a younger, healthier group of people were getting infected and were arriving at the hospital with less-severe symptoms than those infected in the spring.
- However, the researchers’ analysis showed that these factors accounted for only part of the improvement in survival. The rest, they suspect, resulted from health care providers’ growing experience with the coronavirus. For example, physicians learned that resting C19 patients on their stomachs rather than their backs and delaying the use of ventilators as long as possible were more effective practices, say the study authors. Drugs likely helped as well. In addition, other factors such as decreasing hospital volumes, less exposure to infection, and earlier testing and treatment, may have played a role.
- “Our findings suggest that while C19 remains a terrible disease, our efforts to improve treatment are probably working,” says study lead author Leora Horwitz, MD, an associate professor in the Department of Population Health at NYU Langone Health. “Even in the absence of a silver-bullet treatment or vaccine, we are protecting more of our patients through a host of small changes,” says Horwitz, who is also director of the Center for Healthcare Innovation and Delivery Science at NYU Langone.
- New York was among the first states to grapple with a severe outbreak of C19. By contrast, death rates in more recent waves in southern and western regions of the country, which also had younger, healthier coronavirus patients, have been lower, says Horwitz. However, it had remained unclear whether the virus was less deadly due to the different patient demographics or improved care.
- Horwitz says the new study, publishing online next week in the Journal of Hospital Medicine, is the most detailed analysis to date of coronavirus death rates over time. By accounting for age, obesity, and other key factors, the researchers were able to eliminate some explanations from the analysis.
- For the investigation, the research team analyzed 5,263 patient records of people treated for C19 at NYU Langone hospitals in New York City and Long Island between March 1 and August 8. Using a range of risk factors for the disease as well as indicators of the severity of the illness upon hospitalization, the study authors developed a model that predicted likelihood of death for each patient.
- According to the findings, the likelihood of death was on average 22% lower in August than in March for most critically ill patients.
- The average age of hospitalized C19 patients also dropped from 63 to 47. In March, while 73% had chronic conditions like lung disease and diabetes, by mid-June only about 65% had such risk factors.
- “Other pandemic hotspots should take hope from the lessons learned here in New York,” says study senior author Christopher Petrilli, MD, an assistant professor in the Department of Medicine at NYU Langone. “If we can do better at managing the disease, they can too.”
- Still, he adds that the research team next plans to expand the investigation to hospitals outside of New York.
- Petrilli also cautions that while death rates are improving, C19 still causes symptoms in some people that continue long after hospital patients are sent home, including fatigue, blood clots, and lung damage.
2. Long-Lived Antibodies Detected in Both Blood and Saliva of Patients With C19
- Two separate studies have documented the persistence of antibodies that target the coronavirus (SARS-CoV-2) in hundreds of patients with C19 at least 3 months after symptom onset. Both studies point to the IgG class of antibodies as the longest-lasting antibodies detectable in the blood and saliva of patients during this timeframe, suggesting that SARS-CoV-2-specific IgG antibodies may serve as promising targets to detect and evaluate immune responses against the virus. That these antibodies could be detected at similar levels in both blood and saliva suggests that saliva could be used as an alternative biofluid for antibody testing.
- In the first study, Anita Iyer and colleagues measured antibody responses in the blood of 343 patients with C19 for up to 122 days after symptom onset — and compared these responses to those of 1,548 control individuals sampled before the pandemic. The researchers focused only on antibodies specific to the SARS-CoV-2 spike protein’s receptor binding domain. To provide a baseline, the researchers estimated sensitivities of IgG, IgA, and IgM antibody types at 95%, 90%, and 81%, respectively, for detecting infected individuals between 15 to 28 weeks after symptom onset. Among these antibodies, spike protein-specific IgM and IgA were short-lived, dropping beneath detection levels at around 49 and 71 days, respectively, after the appearance of symptoms. In contrast, spike protein-targeted IgG responses decayed slowly over a period of 90 days, with only 3 individuals losing them within this timeframe. Levels of spike protein-specific IgG strongly correlated with levels of neutralizing antibodies in the patients. The researchers also did not observe cross-reactivity of any SARS-CoV-2-targeting antibodies with other “common cold” coronaviruses.
- Similar to Iyer et al., Baweleta Isho and colleagues found that while IgA and IgM antibodies targeting the spike protein’s receptor binding domain rapidly decayed, IgG antibodies remained relatively stable for up to 105 days after symptom onset in 402 patients with C19. The researchers detected spike protein-specific antibodies in the saliva, as well as the blood, of these patients. They charted the patients’ antibody responses from 3 to 115 days after symptom onset, and compared their profiles with 339 pre-pandemic controls. Patients with C19 showed peak IgG levels at 16 to 30 days after the appearance of symptoms. Levels of all spike protein-specific IgG, IgM, and IgA antibodies in the blood positively correlated with levels observed in matched saliva samples. “Given that the virus can also be measured in saliva by PCR, using saliva as a biofluid for both virus and antibody measurements may have some diagnostic value,” the authors say.
3. Scientists Find That Age Does NOT Contribute to C19 Susceptibility
- Scientists have estimated that the age of an individual does not indicate how likely they are to be infected by the coronavirus (SARS-CoV-2). However, development of symptoms, progression of the disease, and mortality are age-dependent.
- There have been a large number of deaths due to the ongoing C19 pandemic, and it has been shown that elderly individuals disproportionately develop severe symptoms and show higher mortality.
- A team of scientists, including Associate Professor Ryosuke Omori from the Research Center for Zoonoses Control at Hokkaido University, have modeled available data from Japan, Spain and Italy to show that susceptibility to C19 is independent of age, while occurrence of symptomatic COVID-19, severity and mortality is likely dependent on age. Their results were published in the journal Scientific Reports earlier this month.
The age distribution of mortality by C19 was similar in Italy (reported on 13th May 2020), Japan (reported on 7th May 2020), and Spain (reported on 12th May 2020).
- Causes of mortality in elderly individuals may be due to two factors: how likely they are to be infected due to their advanced age (age-dependent susceptibility), which is reflected in the number of cases; and, how likely they will be affected by a severe form of the disease due to their advanced age (age-dependent severity), which is reflected in the mortality rate. These factors are not fully understood for C19.
- The scientists chose to analyze data from Italy, Spain, and Japan to determine if any relationship between age, susceptibility, and severity. These three countries were chosen as they have well recorded, publicly available data. As of May 2020, the mortality rate (number of deaths per 100,000) was 382.3 for Italy, 507.2 for Spain and 13.2 for Japan. However, despite the wide disparity in mortality rates, the age distribution of mortality (the proportional number of deaths per age group) was similar for these countries.
- The scientists developed a mathematical model to calculate susceptibility in each age group under different conditions. They also factored in the estimated human-to-human contact level in each age group, as well as varying restriction levels for outside-home activities in the three countries.
- The model showed that the susceptibility has to be unrealistically different between age groups if they assume age does not influence severity and mortality. On the other hand, the model indicated the age should not influence susceptibility but should negatively influence severity and mortality, to explain the fact that the age distribution of mortality is similar between the three countries.
4. Mathematical modeling suggests optimal timing for antiviral therapies against C19
- A new mathematical modeling study by Ashish Goyal and colleagues, informed by data collected from 25 patients hospitalized with C19 in 4 different countries, offers some important new insights into the optimal timing of 4 different antiviral therapies to combat the disease.
- The results indicate that treatment with either of two small molecule drugs (remdesivir and selinexor), broadly neutralizing antibodies, or cellular immunotherapy may reduce the duration of viral shedding and the intensity of immune responses when administered after peak viral load, at the typical onset of symptoms. However, this timing may not have an appreciable impact on viral “area under the curve” (AUC), a measure of total viral load as a function of time over the entire duration of infection.
- Instead, administration of a strongly potent antiviral therapy before peak viral load, during the pre-symptomatic phase of infection, will likely provide the greatest suppression of viral AUC, Goyal et al. suggest. The authors warn, however, that administering a moderately potent antiviral agent on this same timeframe could result in drug resistance.
- Absent a vaccine or widespread herd immunity, antiviral therapies may be able to lessen the severity of the C19 pandemic. However, most information regarding the efficacy of various antivirals to combat COVID-19 has come from empirical evidence – which to date has proven scarce, the authors say.
- Seeking to close this knowledge gap, Goyal et al. developed a mathematical model based on four datasets of SARS-CoV-2 viral shedding and viral load from 25 infected people: 11 from Singapore, 9 from Germany, 1 from South Korea, and 4 from France. They then applied the model individually to four separate antiviral therapies: the small molecule drugs remdesivir and selinexor, broadly neutralizing antibodies, and cellular immunotherapy.
- The authors conclude that their model “provides a broad platform for assessment of all major types of therapies,” even as they note some important limitations. “Most critically, [our model] cannot be used to predict trial outcomes but rather establishes important principles to consider when designing and interpreting trials,” they say.
- A key question when deciding when and how to deploy various therapies, they note, will be to determine whether duration of viral shedding or viral AUC is more relevant for assessing C19 severity. “If AUC is most predictive of poor outcomes, then all forms of antiviral therapy outside of potent [post-exposure prophylaxis] are unlikely to provide clinical benefit,” Goyal et al. write.
- “However, if shedding duration is the best surrogate, then an early test and treat approach is highly promising for limiting the likelihood of severe disease.”
5. Asymptomatic kids carry less virus that symptomatic kids
- A study published in the Journal of Clinical Microbiology from nine children’s hospitals found that most asymptomatic children who tested positive for C19 had relatively low levels of the virus compared to symptomatic children. The authors caution that the reason for this finding is unclear and more questions need to be answered. Were the asymptomatic children generally tested later in their disease, and were their viral loads potentially higher closer to the beginning of their infections? If tested early in disease, would asymptomatic children have viral loads as high as symptomatic children? Or do asymptomatic children typically not carry as much virus as children with symptoms? If so, how would lower viral loads impact the risk of transmission? These questions are essential to further clarify the public health impact of pediatric C19.
- “While these findings provide some reassurance about the safety of asymptomatically infected children attending school, these unanswered questions suggest that risk mitigation measures in daycares, schools and the community remain critical to reduce the spread of C19. Children must continue to wear masks, maintain social distance and wash their hands frequently,” said first author Larry Kociolek, MD, pediatric infectious diseases expert at Ann & Robert H. Lurie Children’s Hospital of Chicago and Assistant Professor of Pediatrics at Northwestern University Feinberg School of Medicine. “At this stage, we can’t predict which children are likely to carry more or less virus, because in every age group we tested, there were some asymptomatic kids with a higher viral load. However, even the groups of asymptomatic kids with highest viral load in our study still had lower viral loads than the children with symptoms.”
- The study included 339 asymptomatic and 478 symptomatic children (ages 0-17 years) matched by age groups. All children in the study screened positive for C19 using PCR tests at nine children’s hospitals across the United States and Canada. To be able to combine PCR data from the different assays used at the nine institutions, the team adjusted cycle threshold (Ct) values by centering each value around the institutional median Ct value from symptomatic children tested with that assay, and also converted them to estimated viral loads (copies/mL). It is the first large and comprehensive investigation into viral loads of the coronavirus (SARS-CoV-2) in asymptomatic children.
- The analysis demonstrated that asymptomatic children with diabetes and/or recent contact with a C19 case, as well as those tested for surveillance purposes (rather than for pre-procedure or pre-admission purposes), had significantly higher estimated risk of being in the quartile with the highest viral burden. The authors note that the finding that patients more likely to have recent infections (contact/surveillance) were more likely to have higher viral loads suggests that timing of infection relative to diagnostic testing impacted the viral loads in the asymptomatic kids in the study. However, they also note that even in the asymptomatic surveillance sub-cohort with highest viral loads, median viral loads were still significantly lower than in the symptomatic cohort.
- “We now need to know what the peak viral loads are in asymptomatic kids with C19,” said principal investigator and senior author Nira Pollock, MD, PhD, Associate Medical Director of the Infectious Diseases Diagnostic Laboratory at Boston Children’s Hospital and Associate Professor of Pathology and Medicine at Harvard Medical School. “Did the timing of testing just miss the peak in many of the asymptomatic kids in this study, or do asymptomatic kids actually have lower peak viral loads than symptomatic kids?”
- The authors also point out that the levels of the virus they found in the asymptomatic children were mostly lower than the levels that the available rapid antigen tests are able to detect.
- “It is important to recognize that rapid antigen tests are less sensitive than the PCR tests used in hospitals, and that many of the asymptomatic kids in our study likely would have tested negative using the rapid tests based on our understanding of the limits of detection of those tests,” said Dr. Pollock. “Our findings should raise caution about using low sensitivity tests for asymptomatic screening programs in pediatric populations. Overall, we want to encourage more studies to better understand the viral loads in asymptomatic kids–particularly peak viral loads early in infection.”
6. Risk score predicts prognosis of outpatients with C19
- A new artificial intelligence-based score considers multiple factors to predict the prognosis of individual patients with C19 seen at urgent care clinics or emergency departments. The tool, which was created by investigators at Massachusetts General Hospital (MGH), can be used to rapidly and automatically determine which patients are most likely to develop complications and need to be hospitalized.
- The impetus for the study began early during the U.S. epidemic when Massachusetts experienced frequent urgent care visits and hospital admissions. While working as an infectious diseases physician and as part of the MGH Biothreats team, Gregory Robbins, MD, recognized the need for a more sophisticated method to identify outpatients at greatest risk for experiencing negative outcomes.
- As described in The Journal of Infectious Diseases, a team of experts in neurology, infectious disease, critical care, radiology, pathology, emergency medicine and machine learning designed the C19 Acuity Score (CoVA) based on input from information on 9,381 adult outpatients seen in MGH’s respiratory illness clinics and emergency department between March 7 and May 2, 2020. “The large sample size helped ensure that the machine learning model was able to learn which of the many different pieces of data available allow reliable predictions about the course of C19 infection,” said M. Brandon Westover, MD, PhD, an investigator in the Department of Neurology and director of Data Science at the MGH McCance Center for Brain Health. Westover is one of three co-senior authors of the study, along with Robbins and Shibani Mukerji, MD, PhD, associate director of MGH’s Neuro-Infectious Diseases Unit.
- CoVA was then tested in another 2,205 patients seen between May 3 and May 14. “Testing the model prospectively helped us to verify that the CoVA score actually works when it sees ‘new’ patients, in the real world,” said first author Haoqi Sun, PhD, an investigator in the Department of Neurology and a research faculty member in the MGH Clinical Data Animation Center (CDAC). In this prospective validation group, 26.1%, 6.3% and 0.5% of patients experienced hospitalization, critical illness or death, respectively, within seven days. CoVA demonstrated excellent performance in predicting which patients would fall into these categories.
- Among 30 predictors–which included demographics like age and gender, C19 testing status, vital signs, medical history and chest X-ray results (when available)–the top five were age, diastolic blood pressure, blood oxygen saturation, C19 testing status and respiratory rate.
- “While several other groups have developed risk scores for complications of C19, ours is unique in being based on such a large patient sample, being prospectively validated, and in being specifically designed for use in the outpatient setting, rather than for patients who are already hospitalized,” Mukerji said. “CoVA is designed so that automated scoring could be incorporated into electronic medical record systems. We hope that it will be useful in case of future C19 surges, when rapid clinical assessments may be critical.”
7. Researchers Discover a Second ‘Key’ That Makes The New Coronavirus So Infectious
- It’s been 17 years since the first coronavirus (SARS-CoV) threatened to erupt into a global pandemic.
- This time we weren’t so fortunate. Just what makes the coronavirus (SARS-CoV-2) so much more infectious than its predecessor is a question we’re now a little closer to solving, with researchers uncovering yet another way the virus gains entry into our cells.
- Researchers from the Technical University of Munich in Germany and the University of Helsinki in Finland led a study that discovered a receptor called neuropilin-1 gives the novel coronavirus a leg-up in infecting our tissues.
- This particular protein is relatively abundant on cells lining the nasal cavity, making it a piece of cake for the virus to establish a home inside our bodies, raise a virus family, and then spread to a new host.
- Earlier this year it was discovered that a receptor called angiotensin-converting enzyme 2 (ACE2) helps the coronavirus bind to the surface of cells, while an enzyme called Type II transmembrane serine protease (TMPRSS2) is crucial for it gaining entry.
- This kind of molecular lock-picking does a good job of explaining why both SARS coronaviruses wreak havoc throughout a range of tissues in our bodies, from the lining of our lungs to our digestive tract.
- But it doesn’t say why one of the viruses does a better job of spreading than the other.
- “The starting point of our study was the question why SARS-CoV, a coronavirus that led to a much smaller outbreak in 2003, and SARS-CoV-2, spread in such a different way even if they use the same main receptor ACE2”, says University of Helsinki virologist Ravi Ojha.
- A crucial piece of the puzzle appeared on comparing the two viral genomes; SARS-CoV-2 had picked up sequences responsible for producing a prickly array of ‘hooks’, not unlike those used by other nasty pathogens to grip onto host tissues.
- “Compared to its older relative, the new coronavirus had acquired an ‘extra piece’ on its surface proteins, which is also found in the spikes of many devastating human viruses, including Ebola, HIV, and highly pathogenic strains of avian influenza, among others,” says Olli Vapalahti, also a virologist from the University of Helsinki.
- “We thought this could lead us to the answer. But how?”
- Consulting with colleagues around the world, the researchers zeroed in on neuropilin-1 as a common factor.
- Typically, this receptor plays a role in responding to growth factors important in tissue development, especially among nerves. But to many viruses, it’s a convenient handle for holding onto host cells long enough to break in.
- Electron microscopy of the surface spikes coating SARS-CoV-2 particles certainly hinted at the potential for a relationship with the receptor.
- To help confirm it, the researchers made use of monoclonal antibodies specifically selected to block access to garden variety neuropilin-1, but not to mutant varieties tweaked to have a slightly different structure.
- Sure enough, ‘pseudoviruses’ sporting SARS-CoV-2 proteins (great for watching viruses enter cells without worrying about the whole messy replication business that follows) had a much harder time getting inside when neuropilin-1 was locked up.
- “If you think of ACE2 as a door lock to enter the cell, then neuropilin-1 could be a factor that directs the virus to the door,” says Balistreri.
- “ACE2 is expressed at very low levels in most cells. Thus, it is not easy for the virus to find doors to enter. Other factors such as neuropilin-1 might help the virus finding its door.”
- With neuropilin-1 expressed in large amounts in nerve tissues within the nasal cavity, we might imagine SARS-CoV-2 has a convenient red carpet rolled out for it the moment we sniff an infected droplet.
- A close look at tissue samples expressing neuropilin-1 taken from deceased C19 patients added to suspicions, while an experiment involving mice helped confirm the receptor’s role in assisting the virus’s entry into our nervous system.
- Whether this might help explain why SARS-CoV-2 infections can have such a traumatic impact on the brain’s function is a question for future research.
- “We could determine that neuropilin-1, at least under the conditions of our experiments, promotes transport into the brain, but we cannot make any conclusion whether this is also true for SARS-CoV-2. It is very likely that this pathway is suppressed by the immune system in most patients,” says neurologist Mika Simons from the Technical University of Munich.
- It’s tempting to picture new forms of antiviral medication on the horizon. Though as rapidly as SARS-CoV-2 reveals its criminal talents, simply blocking off cell receptors is likely to be bad news for our health.
- That’s not to say the discovery isn’t without opportunity.
- “Currently our laboratory is testing the effect of new molecules that we have specifically designed to interrupt the connection between the virus and neuropilin,” says Balistreri.
- “Preliminary results are very promising and we hope to obtain validations in vivo in the near future.”
D. Vaccines & Testing
1. Why decoding the immune response to C19 matters for vaccines
- The race is on to develop a vaccine to protect people against the new coronavirus (SARS-CoV-2). Less than a year after the virus was identified, almost 200 vaccines are in development and more than 40 are in clinical trials — thanks, in part, to an unprecedented collaborative effort by researchers around the world. The vaccine quest makes it necessary for researchers to answer questions about how the body’s immune system responds to the virus, and why some people experience severe symptoms, whereas others recover quickly.
The immunity challenge
- At the start of the coronavirus pandemic, researchers lacked an understanding of how natural immunity to SARS-CoV-2 might develop. But that quickly changed. Within months, studies had shown that infected people can make antibodies that neutralize the virus1, as well as T cells that can recognize and kill SARS-CoV-2-infected cells.
- Further research has revealed that even people who have not been infected with the virus can have antibodies and T cells2 that recognize SARS-CoV-2. This might be the result of people having previously been infected with related coronaviruses that cause the common cold. However, it isn’t yet known whether these pre-existing responses provide any protection against infection with SARS-CoV-2.
- The presence of these antibodies and T-cell responses was promising news for vaccine development; if natural infection can elicit these sorts of responses, then vaccination might be able to elicit similar or more potent protective responses.
Immunity has implications for therapies, too
- In August, the FDA gave emergency authorization to a treatment called convalescent plasma. This treatment involves giving people with C19 blood plasma from individuals recovering from the disease, the rationale being that the plasma contains many antibodies that recognize SARS-CoV-2. However, the consensus among clinicians and researchers is that the FDA’s decision was premature, because not all these antibodies will be protective.
- There is not yet definitive evidence that this treatment is effective, although trials are ongoing to explore whether convalescent plasma from people with high levels of neutralizing antibodies against the virus might be beneficial in the treatment of severe C19.
- A more promising approach than convalescent plasma would be to isolate specific and potent neutralizing antibodies from infected patients, and to develop antibody treatments based on these. This approach has been successful for other viral diseases: just last week, the FDA approved one such treatment for Ebola virus. And trials are under way to test the effectiveness of such monoclonal antibodies against C19.
How likely is reinfection?
- Another urgent question is whether a person who has recovered from C19 is protected from future infection. August saw the first confirmed report of a person being reinfected after they had recovered from C19; this was determined by sequencing of the viral strains responsible for the original and the second infection. There have since been a handful of other confirmed cases of coronavirus reinfection, although against a background of more than 40 million infections globally.
- People who recover from other types of coronavirus infection can be reinfected, because the antibody responses in those cases are relatively short-lived. In the case of C19, it is not yet known how long any potential protection might last; how common reinfection is; or to what extent reinfected individuals are going undetected. In at least two of the documented cases of reinfection, the disease was more severe the second time around, although mild cases of reinfection might go undetected.
- Autopsy studies indicate that the germinal centres — structures in the lymph nodes and spleen where antibody-producing B cells mature and differentiate — can be absent in people with severe C19, causing a loss of antibody-producing B cells. This might mean that the antibody response to natural infection is not long-lasting.
- But other studies on infected people have shown evidence of more durable responses: antibodies peak soon after infection and then wane after the infection has been cleared, remaining at lower levels thereafter, at least for the time frame studied.
How does the immune response affect disease severity?
- One notable feature of severe C19 is that the health of affected people often seems to deteriorate rapidly during the second week of infection, in many cases after initially relatively mild symptoms. Early studies of these patients hinted at an imbalanced immune response, with an overactive inflammatory response failing to control the virus and instead driving the disease.
- The drug dexamethasone, which dampens the inflammatory response and is widely used to treat many inflammatory conditions, has been one of the few therapies that has so far been proven11 to reduce mortality from severe C19.
- Work published last month showed that at least 10% of men and a smaller percentage of women with severe disease have auto-antibodies. These interfere with the function of a group of proteins known as interferons — a crucial component of the anti-viral immune response.
Vaccines: the questions that need answers
- As the effort to develop vaccines gathers pace, key questions will need to be answered to ensure that they are safe and effective.
- On the plus side, the virus doesn’t seem to be mutating fast — unlike, for example, the influenza virus. This means that SARS-CoV-2 probably won’t quickly mutate to evade a vaccine-induced response. At the same time, it is not yet known whether vaccine-induced immunity will be short- or long-lived, nor how effective a vaccine will be in older people, whose immune systems often respond less well to vaccination. If immunity is short-lived, then vaccinated populations will need regular boosters.
- A host of logistical and supply-chain questions will take time to resolve, too. The administration of vaccines requires equipment such as vials and needles. In some countries, stocks might need to be kept in cold storage, and in many places, extra health workers will need to be recruited and trained. Then there is the question of which countries — and which groups within countries — should get priority access. Several organizations are working to resolve these questions.
Trust and verify
- C19 vaccines will be considered for approval by the World Health Organization (WHO) under its emergency-use listing — in which a vaccine is approved for use while trials are still taking place. The WHO and national regulators are working under tremendous pressure from governments and the pharmaceutical industry, but all sides must realize that there can be no short cuts to regulatory approval. Public trust in vaccines is essential, which is why regulators must be allowed to complete their work without interference.
- Vaccine hesitancy presents further challenges. Any new vaccine must be carefully monitored for adverse effects, especially in vulnerable populations. As we have written before, overcoming vaccine hesitancy will also require radical transparency from drug companies and their academic partners.
- Much of the coronavirus vaccine effort is an example of just what can be achieved when researchers, clinicians, funders, regulators, corporations — in short, people — come together to act in the common good. A working vaccine is essential, but it must be safe and effective, and it needs to be distributed equitably and to those who need it most. Until it arrives, and probably for a long time afterwards, people must stick to solutions that work — rigorous testing, tracing and isolating — and change their behaviour to help curb the virus’s spread.
2. Oxford C19 Vaccine Prompts Immune Response in Young & Elderly
- A C19 vaccine being developed by Oxford University that is considered a front-runner in the race for an inoculation against the deadly bug produces a similar immune response among older and younger adults, UK drugmaker AstraZeneca said Monday.
- The vaccine’s adverse reactions also were lower among the elderly, the company said, according to Reuters.
- “It is encouraging to see immunogenicity responses were similar between older and younger adults and that reactogenicity was lower in older adults, where the C19 disease severity is higher,” an AstraZeneca spokesman told the news outlet.
- “The results further build the body of evidence for the safety and immunogenicity of AZD1222,” the rep added, using the scientific name of the vaccine.
- News that older adults get an immune response is encouraging because the immune system weakens with age and older people are those who are most at risk of dying from the disease.
- The Financial Times has reported that the vaccine — being developed by Oxford and AstraZeneca — triggers protective antibodies and T-cells among older people, according to Reuters.
- Immunogenicity blood tests performed on older subjects back data released in July that showed the inoculation generated “robust immune responses” in a group of healthy adults between the ages of 18 and 55, the Financial Times reported.
- British Health Secretary Matt Hancock said a vaccine is not ready yet, but added that he was preparing logistics for a possible rollout.
- “I would expect the bulk of the rollout to be in the first half of next year,” he told the BBC, adding that he was not ruling out the possibility that some people could receive a shot this year.
- “We want to be ready in case everything goes perfectly but it’s not my central expectation that we’ll be doing that this year, but the program is progressing well, we’re not there yet,” he said.
- Meanwhile, London health officials said staff at a hospital in the capital are on standby to receive the first batches of the vaccine as early as the week beginning Nov. 2, the Sun reported Monday.
- Other clinical trials at the unidentified hospital have been paused as all resources have been allocated to preparing to vaccinate thousands of doctors, nurses and other front-line workers, according to the newspaper.
3. How Tobacco Plants Could Help Accelerate a C19 Vaccine
- For the past 80 years, eggs have been a main ingredient in vaccines for measles, mumps, rubella, chicken pox, the flu, and others. Typically, modified genetic material from a virus is inserted into an egg’s proteins, and those proteins are then introduced into the human body to “teach” it an immune response. But since each egg must be modified individually, the lag time for egg-based vaccines can literally be a killer.
- In the U.S., for example, the CDC must predict in January what strains of the flu will erupt nearly a year later, to give drugmakers time to manufacture enough inoculations. A handful of companies, however, are pioneering vaccines developed in plants, which can be grown and treated in bulk. Using a cousin of the tobacco plant (nicotiana benthamiana), biomedical companies Kentucky Bioprocessing (KBP) and Medicago have been pursuing plant-based flu vaccines for years, and are currently working on C19 immunizations. The companies also both began human trials of vaccines over the summer. Here’s how they turn plants into lifesaving weapons against illness.
Preparing the virus
- The companies’ scientists identify an antigen—a version of the virus that will elicit an immune response without triggering symptoms in a patient. These must be specifically formulated to work in plant carriers.
Infecting the plants
- Once a safe and effective antigen is determined, the companies submerge the nicotiana benthamiana plants into an antigen-infused solution and force the viral particles into the leaves via a vacuum.
Incubation and growth
- The antigens rapidly replicate inside the plant, taking one to two weeks to fully infiltrate the host cells and transform them into antigen-carrying proteins. Because plants can be grown quickly and affordably, KBP estimates that it could make 3 million doses of a vaccine in five weeks, compared to three to six months for traditional vaccines.
Harvest and transformation
- Plants are harvested and go through a purification process that turns them into a medical-grade solution that, combined with other ingredients, can be injected directly into the human body.
- Medicago medical officer Brian Ward says that because they’re cheaper to grow and incubate, plant vaccines have the potential to “democratize vaccine production.” Medicago estimates that its large-scale facility opening in 2023 could produce 1 billion vaccine doses per year.
E. Improved & Potential Treatments
1. CBD Helps Reduce C19 Lung Damage by Increasing Levels of Protective Peptide
- One way CBD appears to reduce the “cytokine storm” that damages the lungs and kills many patients with C19 is by enabling an increase in levels of a natural peptide called apelin, which is known to reduce inflammation and whose levels are dramatically reduced in the face of this storm.
- Dental College of Georgia and Medical College of Georgia researchers reported this summer CBD’s ability to improve oxygen levels and reduce inflammation as well as physical lung damage in their laboratory model of deadly adult respiratory distress syndrome, or ARDS.
- Now they have shown that apelin levels go way down with the viral infection and that CBD quickly helps normalize those levels along with lung function.
- “It was dramatic in both directions,” says Dr. Babak Baban, DCG immunologist and associate dean for research, of shifting apelin levels in both circulating blood and lung tissue.
- Blood levels of the peptide dropped close to zero in their ARDS model and increased 20 times with CBD, they report in the Journal of Cellular and Molecular Medicine.
- “CBD almost brought it back to a normal level,” Dr. Jack Yu, physician scientist and chief of pediatric plastic surgery at MCG, says of the apparent first connection between CBD and apelin.
- Apelin is a pervasive peptide made by cells in the heart, lung, brain, fat tissue and blood, and is an important regulator in bringing both blood pressure and inflammation down, says Baban, the study’s corresponding author.
- When our blood pressure gets high, for example, apelin levels should go up in the right place, like endothelial cells that line blood vessels, to help bring it down. Apelin should do the same to help normalize the significant increases in inflammation in the lungs and related breathing difficulties associated with ARDS.
- “Ideally with ARDS it would increase in areas of the lungs where it’s needed to improve blood and oxygen flow to compensate and to protect,” Baban says. But when they looked at their ARDS model, apelin didn’t do either, and instead decreased in both the lung tissue itself and the general circulation. Until they gave CBD.
- They reported this summer in the journal Cannabis and Cannabinoid Research that treatment with CBD reduced excessive lung inflammation, enabling improvements in lung function, heathier oxygen levels, and repair of some of the structural damage to the lungs that are classic with ARDS. The investigators said then more work was needed, including finding how CBD produced the significant changes as well as human trials, before it should be included as part of a treatment regimen for C19.
- Now they have correlated those improvements with regulation of apelin. While they don’t attribute all CBD’s benefits to apelin, they say the peptide clearly has an important role in this scenario. They also don’t yet know whether the novel coronavirus, or CBD for that matter, have a direct effect on apelin, or if these are downstream consequences, but they are already pursuing answers to those unknowns.
- “It is an association; we don’t know yet about causative, but it is a very good indicator of the disease,” Baban says of the bottom line impact of the viral infection on apelin levels.
- The now familiar spiked virus enters human cells via the also pervasive angiotensin-converting enzyme 2, or ACE2, receptor. “The spike proteins have just the right docking mechanism,” says coauthor Yu. And there is plenty of common ground between ACE2 and apelin, including the fact that many cell types and tissues have both, including the lungs.
- Apelin and ACE2 also normally work together to control blood pressure, and upregulation of both may be helpful in cardiovascular disease, including heart failure, by decreasing blood pressure while increasing the heart’s ability to pump. In fact, apelin and ACE2 work together to regulate a healthy cardiovascular system and they are factors in pretty much any condition, like obesity or hypertension, that hurt the cardiovascular system, Baban says.
- Like other disease, the novel coronavirus appears to upset their positive partnership. The virus’ binding to the receptor for ACE2 has been shown to decrease ACE2 levels and increase levels of the powerful blood vessel constrictor angiotensin II, because less angiotensin II gets degraded and fewer vasodilators get produced, which worsens the patient’s prognosis.
- “Instead of ACE2 helping blood vessels relax, it helps the virus get into the host where it makes more virus instead of helping the lungs relax and do their job,” says Yu.
- While the researchers are still putting the pieces together, reduced levels of ACE2 appear to enable less apelin and less protection.
- However it happens, their finding of dramatic reductions in apelin in the face of ARDS, makes levels of the protective peptide a potential early biomarker for ARDS and response to treatment efforts, they say.
- The new finding was their first in learning more about how CBD produces the beneficial effects they saw in their model of ARDS. Next steps include better understanding the interaction between CBD, apelin and the novel coronavirus including why apelin goes down in the face of the virus and why CBD brings it up. That includes exploring how eliminating apelin affects ARDS and if CBD produces the same lung benefit without apelin.
- Likely the virus suppresses something that suppresses apelin, they say and CBD interferes. But they doubt the apelin-CBD interaction is the only way the compound, the second most prevalent found in the marijuana plant, works in this and other scenarios.
- The studies were enabled by the investigators’ development of a safe, relatively inexpensive model of ARDS by giving a synthetic analog of double-stranded RNA called POLY (I:C). The novel coronavirus also has double-stranded RNA, while ours is single-stranded, so this analog produced a response similar to the virus, including the extreme lung damage that has led to the need for ventilator and other extreme support measures for patients, and is a major cause of death. Much as with the SARS-CoV-2 infection, the result is the “cytokine storm” that reflects an over-the-top immune response in the lungs, which results in an attack rather than protection.
- For these studies, a control group received intranasal saline for three consecutive days while the C19 model received POLY (I:C) intranasally for three days. A third group, the treatment group, received POLY ((I:C) and CBD over the same timeframe.
- This time they looked and also found significantly reduced apelin levels in the mice that developed COVID-like symptoms compared to controls. Treatment with CBD normalized the immune response and apelin levels, along with oxygen levels and swelling and scarring in the lungs characteristic of the deadly ARDS.
- “The apelinergic system is a very, very ubiquitous signaling system,” Yu says. While it has diverse jobs in different places, and levels may rise and fall depending on what is needed, its levels are consistently measurable in the lungs, one of the reasons it should be a good biomarker, and it’s also generally considered protective, they say.
- Apelin’s important, diverse roles include helping ensure the placenta is well supplied with blood and the oxygen and nutrients it carries during a pregnancy. In fact, DCG and MCG investigators decided to look at apelin because of the work of Dr. Évila Lopes Salles, a postdoctoral fellow with Baban in the DCG Department of Oral Biology and the study’s first author, who was looking at the peptide’s significant impact in gestation and clear anti-inflammatory role, Baban says.
- Synthetic agonists that increase apelin levels exist and are showing promise in the laboratory for cardiovascular disease, including slowing the growth rate of weak points in blood vessels called aneurysms. CBD appears to be a natural apelin agonist, the researchers say.
3. T-Cells from recovered C19 patients show promise to protect vulnerable patients from infection
- T-cells taken from the blood of people who recovered from a C19 infection can be successfully multiplied in the lab and maintain the ability to effectively target proteins that are key to the virus’s function, according to a new study published Oct. 26 in Blood.
- “We found that many people who recover from C19 have T-cells that recognize and target viral proteins of the coronavirus (SARS-CoV-2), giving them immunity from the virus because those T-cells are primed to fight it,” says Michael Keller, M.D., a pediatric immunology specialist at Children’s National Hospital, who led the study. “This suggests that adoptive immunotherapy using convalescent T-cells to target these regions of the virus may be an effective way to protect vulnerable people, especially those with compromised immune systems due to cancer therapy or transplantation.”
- Based on evidence from previous phase 1 clinical trials using virus-targeting T-cells “trained” to target viruses such as Epstein-Barr virus, the researchers in the Cellular Therapy Program at Children’s National hypothesized that the expanded group of C19 virus-targeting T-cells could be infused into immunocompromised patients, helping them build an immune response before exposure to the virus and therefore protecting the patient from a serious or life-threatening infection.
- “We know that patients who have immune deficiencies as a result of pre-existing conditions or following bone marrow or solid organ transplant are extremely vulnerable to viruses like SARS-CoV-2,” says Catherine Bollard, M.D., M.B.Ch.B., senior author of the study and director of the novel cell therapies program and the Center for Cancer and Immunology Research at Children’s National. “We’ve seen that these patients are unable to easily clear the virus on their own, and that can prevent or delay needed treatments to fight cancer or other diseases. This approach could serve as a viable option to protect or treat them, especially since their underlying conditions may make vaccines for SARS-CoV-2 unsafe or ineffective.”
- The T-cells were predominantly grown from the peripheral blood of donors who were seropositive for SARS-CoV-2. The study also identified that SARS-CoV-2 directed T-cells have adapted to predominantly target specific parts of the viral proteins found on the cell membrane, revealing new ways that the immune system responds to C19 infection.
- Current vaccine research focuses on specific proteins found mainly on the “spikes” of the coronavirus SARS-CoV-2. The finding that T-cells are successfully targeting a membrane protein instead may add another avenue for vaccine developers to explore when creating new therapeutics to protect against the virus.
4. Study finds no C19 benefit for convalescent plasma
- A study, which is published in the British Medical Journal (BMJ) on Friday, suggests “convalescent plasma” has only limited effectiveness and fails to reduce deaths or stop the progression to severe disease.
- Plasma is the clear, yellowish liquid part of the blood which carries red and white blood cells and platelets around the body. After an infection, plasma is often packed with antibodies generated by the immune system. As such, it is sometimes harvested from people who have recovered from a disease and transfused into patients who are fighting it. This convalescent plasma therapy was used during the 1918 flu pandemic, as well as during more recent global health emergencies, treating patients with Sars or Ebola.
- Various trials around the world are exploring whether convalescent plasma could help reduce deaths and serious complications from C19, with the largest randomised controlled trial taking place in the UK.
- Despite the findings of the latest published study, convalescent plasma may yet prove to be effective against C19.
- The research involved 464 adults with moderate C19 who were admitted to hospitals in India between April and July. Approximately half received two transfusions of convalescent plasma, 24 hours apart, alongside standard care, while the control group received standard care only.
- One month later, 19% of those who received the plasma had progressed to severe disease or had died of any cause, compared with 18% in the control group. Plasma therapy did, however, seem to reduce symptoms, such as shortness of breath and fatigue, after seven days.
- A spokesperson for NHS Blood and Transplant, which is collecting plasma from people who have recovered from C19, emphasised that UK-based studies are only infusing plasma that contains high levels of coronavirus antibodies. He said the Indian study used plasma with antibody levels around six to 10 times lower than that.
- The Indian researchers agreed that further studies using high antibody levels may find it to be more effective. An interim analysis of 136 C19 patients in a trial at Houston Methodist hospital in Texas suggested a significant reduction in deaths among patients who received plasma with high levels of antibodies early in the course of their disease.
- Followup data from all 351 patients in the Texas study has been published as a preprint and supports this conclusion, although plasma transfusion later in the course of the disease had no significant effect on death rates regardless of antibody levels. “With respect to altering mortality, our analysis identified an optimal window of 44 hours post-hospitalisation for transfusing C19 patients with high titre convalescent plasma,” they wrote.
- Prof Paul Morgan, the director of the Systems Immunity Research Institute at Cardiff University and a member of the British Society for Immunology’s expert taskforce on immunology and C19, said there were other reasons for optimism. For one thing, he said, the study suggested plasma therapy was associated with a reduction in viral load, “so, there does seem to be an antiviral effect of the therapy, even if it isn’t reflected in the final outcomes”.
- The study also hinted that infusing patients with large amounts of donated plasma could lead to a small but significant increase in deaths. “It might be worth considering, rather than giving just convalescent plasma, taking the antibodies out of the plasma and using those,” Morgan said. Such purified antibodies are already used to treat patients with antibody deficiencies.
5. The race to make C19 antibody therapies cheaper and more potent
- Antibodies are a key component of the body’s natural immune response to the coronavirus (SARS-CoV-2), and researchers have been racing to develop therapies that harness their ability to directly bind to viral proteins and prevent the virus from replicating.
- One way to do this is by using blood plasma from people who are recovering from C19 to transfer the antibodies that they have produced to someone else.
- Another is to manufacture and mass-produce specific antibodies against the virus that could supplement the body’s immune response. This approach has proven successful against other diseases: on 14 October, the FDA approved a cocktail of three specific antibodies, also produced by Regeneron, as a treatment against the Ebola virus, after it was shown to reduce deaths from the virus in the Democratic Republic of Congo.
Early trial success
- Regeneron and Eli Lilly in Indianapolis, Indiana, now lead the race in developing antibody treatments against C19. Each is testing its own proprietary antibodies and has applied for an Emergency Use Authorization from the FDA on the back of promising early studies. Eli Lilly’s first antibody therapy reduced visits to the hospital, from 6% in the placebo group to 1.7% in those who received the drug; Regeneron’s combination of 2 antibodies reduced symptoms and viral loads.
- The main hope is that antibody therapies could stop mild C19 from becoming severe. There is less optimism that the treatments will be game-changing for severe C19 cases — when damage is caused by not only the virus, but also the body’s immune response to it. “I can’t imagine how excited I would be if these drugs were available and proved reliable,” says infectious-disease physician Myron Cohen of the University of North Carolina at Chapel Hill.
- At least ten C19 antibodies are being tested in clinical trials; many more are under development. Considering how well these antibodies bind to SARS-CoV-2 proteins, many of these candidates are likely to offer some benefit to people with C19, says chemist Zhiaqiang An at the University of Texas Health Science Center in Houston. “There might be differences in degree,” he says, “but most of these antibodies could have some kind of efficacy.”
- And researchers are finding ways to minimize the chances of the virus becoming resistant to these treatments. When only one antibody is used, it might be possible for the virus to develop mutations — to the binding site, for example — that allow it to evade the antibody. Treatments that combine multiple antibodies, such as the Regeneron therapy that Trump received, can lessen the chance of this happening by targeting the virus with multiple antibodies that bind to different sites.
- Still, there are drawbacks. Antibodies are expensive and difficult to make, and they are administered at relatively high doses. Several researchers who spoke to Nature highlighted the 8 grams of antibodies — the highest dosage tested in clinical trials — that Trump received. “It’s an enormous dose,” says virologist Gerald McInerney of the Karolinska Institute in Stockholm. “Even if it did work, at a dose of 8 grams, it would be incredibly expensive.” Even the lower doses being tested — Regeneron’s lowest is 2.4 grams — would be too high for widespread use as a preventative treatment, says Björkman.
Antibodies from alpacas
- McInerney and others are working to develop small antibody-like molecules called nanobodies, based on a kind of antibody naturally produced by some camelids, including llamas and alpacas. Nanobodies are easier to make, and often can be produced in bacterial cells that are much cheaper to grow and maintain than are the mammalian cells required for normal antibody production. Last year, the FDA approved the first therapeutic nanobody, called caplacizumab, a treatment for a rare clotting disease.
- But the technology is still relatively new, and C19 nanobody treatments trail conventional antibodies in the clinic. McInerney’s team has isolated a nanobody against a crucial SARS-CoV-2 protein called Spike from an alpaca named Tyson. They engineered the antibody to improve its activity, stability and likelihood of working in people, but have not yet tested it in animals.
- Some researchers are hoping to develop nanobodies that can be aerosolized and inhaled, to directly protect the key sites of coronavirus infection: the nose and the lungs. In Shanghai, China, Novamab Biopharmaceuticals was originally developing inhaled nanobodies to treat asthma, but switched to developing C19 nanobodies. The company is now looking for international partners — particularly in regions where C19 is prevalent — to help it to move into clinical trials, says Yakun Wan, founder and chief executive of the company.
- Biochemist Peter Walter at the University of California, San Francisco, hopes that the inhalable approach will allow such nanobodies to be effective at far lower doses than are required for standard antibodies, which are injected and must travel through the blood to the site where they are needed. “We anticipate it being used as a prophylactic spray before you get on an airplane or go to a party,” says Walter, who is working on one such nanobody.
- “We’re a long way off,” from moving such nanobodies into the clinic, says biophysicist Raymond Owens at the University of Oxford, UK. “But I’m cautiously optimistic.”
F. Concerns & Unknowns
1. Does C19 increase the risk of developing Parkinson’s disease?
- “Evidence is mounting that the side effects of C19 infection, such as inflammation and damage to the vascular system, could lay the foundation for development of Parkinson’s disease. C19 is clearly a major and ongoing public health threat, but the consequences of infection may end up being with us for years and decades to come,” said Patrik Brundin, M.D., Ph.D., of Van Andel Institute, Avindra Nath, M.D., of the National Institute of Neurological Disorders and Stroke of the National Institutes of Health.
- Parkinson’s disease is a multi-system disorder that begins years or even decades before its hallmark movement-related symptoms appear. Growing evidence suggests Parkinson’s arises from a complex mix of factors that vary from person to person, including age, genetic predisposition, history of infections and exposure to certain environmental factors such as pollution or pesticides.
- Viral infections in particular may play a role in triggering the earliest stages of Parkinson’s by setting off a cascade that results in the death of brain cells that produce dopamine, a vital chemical messenger whose absence leads to movement issues such as freezing and tremor.
- The three cases referenced in the commentary occurred in people without a family history of Parkinson’s and without any known early Parkinson’s symptoms. Two saw an improvement in their Parkinson’s-like symptoms following treatment with traditional Parkinson’s medications that replenish dopamine; the third recovered spontaneously. Although these medications treat symptoms, they often have challenging side effects and do not slow or stop Parkinson’s progression.
- “The coronavirus (SARS-CoV-2) is considered a respiratory virus, however, its virulence and pathogenic potential particularly for neurological complications continues to surprise us,” Nath said. “Some patients can develop severe neurological manifestations despite mild respiratory symptoms.”
- Based on evidence from the case studies and what is known about the mechanisms underpinning Parkinson’s, Brundin, Nath and Beckham suggest three possible ways that C19 infection could contribute to Parkinson’s onset:
- C19 is linked to blood clots and other problems with the vascular system, including in the brain. These vascular insults could cause damage to the area of the brain that produces dopamine, which subsequently could result in a loss of dopamine that mirrors Parkinson’s.
- There is a demonstrated link between chronic inflammation and Parkinson’s. It is possible that severe inflammation resulting from C19 could trigger brain inflammation and cell death associated with Parkinson’s.
- SARS-CoV-2 may be a neurotropic virus, meaning that it attacks the nervous system. Because of this, C19 and Parkinson’s share some early symptoms such as loss of sense of smell and issues with the gut. Additionally, infection with SARS-CoV-2 could lead to an increase in alpha-synuclein, a protein associated with Parkinson’s (this has been seen in other viral infections).
- Although these cases do not prove that C19 infection causes Parkinson’s, they do suggest a troubling possible relationship between the virus and subsequent neurodegenerative disorders.
- “The large number of respiratory cases due to SARS-CoV2 has allowed us to understand and analyze important neurologic complications of severe respiratory virus infections,” Beckham said. “It is important that we continue our scientific investigations into this new virus so we understand all of the short and long-term complications of the C19 pandemic.”
- Going forward, the authors call for long-term studies that follow people who were infected with C19 to monitor them for Parkinson’s development.
2. Immune response the probable underlying cause of neural damage in C19
- It is probably the immune response to, rather than the virus in itself, that causes sudden confusion and other symptoms from the nervous system in some patients with C19. This is shown by a study of cases involving six Swedish patients, now published in the journal Neurology.
- With accumulated experience of the disease, it has become evident that symptoms and signs from the nervous system is common in patients suffering from C19.
- Symptoms reported in the acute phase of the disease have included, for example, delirium, personality changes, and memory problems, all of which are signs of brain impairment or failure. These signs occur more frequently in more severe cases, and are usually temporary.
- To date, it remains unclear whether the coronavirus (SARS-CoV-2) has the capacity to infect the brain and central nervous system directly. The current study from the University of Gothenburg indicates that, more likely, the patient’s immune response is what may underlie the effects on the nervous system.
- In the study, cerebrospinal fluid (CSF) samples were taken from six hospitalized patients at Sahlgrenska University Hospital in Gothenburg with moderate or severe C19 and signs of brain impairment. The samples were analyzed for biomarkers that reflect how the brain is reacting to infections.
- Every patient exhibited markedly elevated levels of the inflammation (immune activation) markers neopterin and beta-2-microglobulin, suggesting substantial activation of the brain’s immune cells. In two cases, an increase in the protein neurofilament light (NfL), a marker that is sensitive to nerve-cell damage, was also seen.
- On the other hand, no impact was observed on markers for damage to the blood-brain barrier, local antibody production or a raised white blood-cell count, which are otherwise common in virus infections in the central nervous system.
- As for proof of actual SARS-CoV-2 invasion, the results from the analysis were uncertain, but most indications are that no virus was present in the cerebrospinal fluid, at least not to any significant degree.
- Magnus Gisslén, Professor of Infectious Diseases at Sahlgrenska Academy, University of Gothenburg, and Chief Physician at the Department of Infectious Diseases, Sahlgrenska University Hospital, heads the Academy’s clinical research on C19.
- “Overall, we see an unusual picture with marked inflammation and sometimes nerve-cell injury, but without a recruitment of immune-system cells from the bloodstream, detectable virus or damage to the blood-brain barrier, which are usually found in viral infections in the brain,” he says.
- The researchers emphasize that the mechanisms behind the symptoms seem to diverge from those of other viral infections. The first author of the study is Arvid Edén, PhD in Infectious Diseases at Sahlgrenska Academy, University of Gothenburg, and senior consultant at the Department of Infectious Diseases, Sahlgrenska University Hospital.
- “It’s an urgent priority for us to learn more about how C19 affects the nervous system, not least so that we can determine which types of treatment may be suitable to counteract or mitigate the effects of infection with SARS-CoV-2 on the brain, both in the acute phase and in the longer term,” Edén says.
3. C19 a double blow for chronic disease patients
- There has never been a more dangerous time than the C19 pandemic for people with non-communicable diseases (NCDs) such as diabetes, cancer, respiratory problems or cardiovascular conditions, new UNSW Sydney research has found.
- Among the adverse impacts of the pandemic for people with NCDs, the study found they are more vulnerable to catching and dying from C19, while their exposure to NCD risk factors – such as substance abuse, social isolation and unhealthy diets – has increased during the pandemic.
- The researchers also found C19 disrupted essential public health services which people with NCDs rely on to manage their conditions.
- The study, published in Frontiers in Public Health recently, reviewed the literature on the synergistic impact of C19 on people with NCDs in low and middle-income countries such as Brazil, India, Bangladesh, Nepal, Pakistan and Nigeria.
- “This illustrates the negative effect of the C19 ‘syndemic’ – also known as a ‘synergistic epidemic’ – a term coined by medical anthropologist Merrill Singer in the 1990s to describe the relationship between HIV/AIDS, substance abuse and violence,” Mr Yadav said.
- “We applied this term to describe the interrelationship between C19 and the various biological and socio-ecological factors behind NCDs.
- “So, people are familiar with C19 as a pandemic, but we analyzed it through a syndemic lens in order to determine the impact of both C19 and future pandemics on people with NCDs.”
- Mr Yadav said the C19 syndemic would persist, just as NCDs affected people in the long-term.
- “NCDs are the result of a combination of genetic, physiological, environmental and behavioural factors and there is no quick fix, such as a vaccine or cure,” he said.
- “So, it’s no surprise we found that NCD patients’ exposure to NCD risk factors has increased amid the pandemic, and they are more vulnerable to catching C19 because of the syndemic interaction between biological and socio-ecological factors.
- “The evidence we analyzed also showed there was poor self-management of NCDs at a community level and C19 has disrupted essential public health services which people with NCDs rely on.”
Tackling NCDs in the C19 era
- Mr Yadav said the researchers’ findings led them to recommend a series of strategies for healthcare stakeholders – such as decision-makers, policymakers and frontline health workers – to better manage people with NCDs in light of the C19 syndemic.
- “Healthcare systems – such as Australia’s – do have some of these strategies in place, but they need improvement,” he said.
- Highlights from the recommended strategies include:
- Develop plans for how to best provide health services to people with NCDs, from the moment they are assessed through to their treatment and palliation.
- Develop digital campaigns to disseminate information on how to make positive behavior changes and better self-manage NCDs and C19.
- Decentralize healthcare delivery for people with NCDs: involving local health districts and investing in community health worker programs could help to mitigate future outbreaks. In addition, tailor self-management interventions for people with NCDs.
- Ensure effective social and economic support for people with NCDs who are vulnerable to catching C19, particularly Indigenous, rural, Culturally and Linguistically Diverse (CALD) and refugee communities, as well as people with severe mental illness.
- Evaluate technology-assisted medical interventions to improve healthcare services, because complex case management, assessment and support is increasingly being done via telehealth appointments or other technology.
Why healthcare must focus on prevention
- Mr Yadav said high-income countries could also learn from the researchers’ findings.
- “C19 has been a major threat to people with NCDs in developed countries – for example, new statistics from Britain show that in 2020, high numbers of people in England and Wales died from NCDs at home after shunning the healthcare system because of the pandemic,” he said.
- “In Australia, C19 will increase inequality and poses a risk to some high and middle-income earners, but it’s a double threat to others such as Indigenous, rural, CALD and refugee communities, as well as people with severe mental illness – as reflected in our paper.”
- Mr Yadav said in Australia in 2018, the most recent data available, 89% of deaths were associated with 10 chronic diseases.
- “The Australian healthcare system needs a bigger focus on preventive healthcare, to improve outcomes for patients with NCDs and prevent more people from developing these diseases amid the C19 pandemic,” he said.
- Mr Yadav said putting serious preventive healthcare investment on the backburner could lead to individual, societal and economic upheaval in the long-term.
- “If this trend continues, Australia will struggle to achieve Sustainable Development Goal (SDG) target 3.4, which is to reduce premature mortality from NCDs by a third by 2030 – relative to 2015 levels and to promote mental health and wellbeing,” he said.
- “Investment in prevention today will help save healthcare costs in the long-term, help reduce the incidence of NCDs and enhance our resilience against future pandemics.”
2. Aspirin use reduces risk of death in hospitalized patients by 47%
- Hospitalized C19 patients who were taking a daily low-dose aspirin to protect against cardiovascular disease had a significantly lower risk of complications and death compared to those who were not taking aspirin, according to a new study led by researchers at the University of Maryland School of Medicine (UMSOM). Aspirin takers were less likely to be placed in the intensive care unit (ICU) or hooked up to a mechanical ventilator, and they were more likely to survive the infection compared to hospitalized patients who were not taking aspirin, The study, published today in the journal Anesthesia and Analgesia, provides “cautious optimism,” the researchers say, for an inexpensive, accessible medication with a well-known safety profile that could help prevent severe complications.
- “This is a critical finding that needs to be confirmed through a randomized clinical trial,” said study leader Jonathan Chow, MD, Assistant Professor of Anesthesiology at UMSOM. “If our finding is confirmed, it would make aspirin the first widely available, over-the-counter medication to reduce mortality in C19 patients.”
- To conduct the study, Dr. Chow and his colleagues culled through the medical records of 412 C19 patients, age of 55 on average, who were hospitalized over the past few months due to complications of their infection. They were treated at the University of Maryland Medical Center in Baltimore and three other hospitals along the East Coast. About a quarter of the patients were taking a daily low-dose aspirin (usually 81 milligrams) before they were admitted or right after admission to manage their cardiovascular disease.
- The researchers found aspirin use was associated with a 44% reduction in the risk of being put on a mechanical ventilator, a 43% decrease in the risk of ICU admission and – most importantly – a 47% decrease in the risk of dying in the hospital compared to those who were not taking aspirin. The patients in the aspirin group did not experience a significant increase in adverse events such as major bleeding while hospitalized.
- The researchers controlled for several factors that may have played a role in a patient’s prognosis including age, gender, body mass index, race, hypertension and diabetes. They also accounted for heart disease, kidney disease, liver disease and the use of beta blockers to control blood pressure.
- C19 infections increase the risk of dangerous blood clots that can form in the heart, lungs, blood vessels and other organs. Complications from blood clots can, in rare cases, cause heart attacks, strokes and multiple organ failure as well as death.
- Doctors often recommend a daily low-dose aspirin for patients who have previously had a heart attack or stroke caused by a blood clot to prevent future blood clots. Daily use, however, can increase the risk of major bleeding or peptic ulcer disease.
- “We believe that the blood thinning effects of aspirin provides benefits for C19 patients by preventing microclot formation,” said study co-author Michael A. Mazzeffi, MD, Associate Professor of Anesthesiology at UMSOM. “Patients diagnosed with C19 may want to consider taking a daily aspirin as long as they check with their doctor first.” Those at increased bleeding risk due to chronic kidney disease, for example, or because they regularly use certain medications, like steroids or blood thinners, may not be able to safely take aspirin, he added.
- Researchers from Wake Forest School of Medicine, George Washington University School of Medicine, Northeast Georgia Health System, and Walter Reed National Military Medical Center also participated in this study.
- “This study adds to the tremendous work our researchers are doing in the School of Medicine to help find new treatments against C19 and save patients’ lives,” said E. Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs, UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine. “While confirmatory studies are needed to prove that aspirin use leads to better outcomes in C19, the evidence thus far suggests that patients may want to discuss with their doctor whether it is safe for them to take aspirin to manage potentially prevent serious complications.”
G. Innovation & Technology
1. Early Detection of Coronavirus With New Photonic Sensor System
- Detecting the coronavirus (SARS-CoV-2) and related antibodies is essential to control the C19 pandemic. A multidisciplinary team of scientists from the University of Malaga, led by Robert Halir, researcher of the Department of Communications Engineering of the Higher Technical School of Telecommunications Engineering, aware of the limitations of current techniques, are developing a point-of-care detection system based on photonic sensors.
- “PCR techniques currently applied to detect the virus are reliable, but also slow and expensive, while serological assays, though simpler, lack precision and cannot provide quantitative results,” says Robert Halir, who explains that their sensing system will precisely add functionality and, in the future, could offer real-time results at a lower cost. To this end, it has been funded with €95,000 under the C19 Fund of the Government of Andalusia to work, for one year, towards demonstrating the viability of their system.
- The project was proposed by the Andalusian Centre for Nanomedicine and Biotechnology (BIONAND), and it is based on the collaboration of two R&D&I groups of the UMA: the “Biomimetic Dendrimers and Photonics Laboratory” and the “Photonics and Radiofrequency Laboratory,” led by professors Ezequiel Pérez-Inestrosa and Íñigo Molina-Fernández, respectively, both members of the Biomedical Research Institute of Malaga (IBIMA).
- The research team already has a real prototype of a sensing system based on photonic chips, and a measuring device, which is capable of detecting proteins in very low concentrations — inflammation and antibody biomarkers present in patients that are allergic to antibiotics. The prototype has been developed over the past four years and offers quantitative results in a matter of minutes. In fact, such is the sensitivity of the system that is capable of detecting changes in the refraction index of a one-hundred-millionth.
- This multidisciplinary project aims to adapt the system for the detection of SARS-CoV-2 and its antibodies, as well as optimize and reduce the price of the measuring device. To this end, they are going to work on two lines: keep improving the optical sensitivity of the sensor and develop chemical protocols so that only a specific protein that expresses SARS-CoV-2, or the antibodies to such protein, as appropriate, adhere to the surface of the waveguides. “If results are satisfactory, in the future we will be able to develop a completely functional point-of-care equipment to be deployed in primary healthcare centers,” says Halir. According to the researcher, cost reduction would be significant compared to PCR testing, because these tests could be performed directly by family doctors, thus saving the costs of being processed in specialized laboratories and, also, the time frame for results, which would be obtained in a fraction of an hour.
- On the other hand, regarding serological assays, the advantage would be the possibility of detecting lower concentrations of antibodies and, also, determining the exact number of antibodies a tested person has. “If we succeed, we believe that a commercial prototype could be developed in the near future,” says the researcher of the UMA.
2. MIT Designs a Heated COVID Face Mask to Filter and Inactivate Coronaviruses
- Face masks have been shown to be effective at filtering out viruses such as the coronavirus (SARS-CoV-2), thereby reducing the risk of infection. A team of researchers from MIT now hopes to go one step further and create a mask that inactivates viruses using heat.
- The researchers aim to build masks that incorporate a heated copper mesh. As the person wearing the mask breathes in and out, air flows repeatedly across the mesh, and any viral particles in the air are slowed and inactivated by the mesh and high temperatures. Such a mask could be useful for health care professionals, the researchers say, as well as members of the public in situations where social distancing would be difficult to achieve, such as a crowded bus.
- “This is a completely new mask concept in that it doesn’t primarily block the virus. It actually lets the virus go through the mask, but slows and inactivates it,” says Michael Strano, the Carbon P. Dubbs Professor of Chemical Engineering at MIT.
- The researchers have begun building prototypes and hope to begin testing them soon. They described the new concept and design in a paper that they posted to bioRxiv, an online preprint server, and they have also submitted the paper to a peer-reviewed journal.
- Strano is the senior author of the paper, and MIT graduate student Samuel Faucher is the lead author. Other authors include MIT graduate students Daniel Lundberg, Xinyao Liang, and Xiaojia Jin; undergraduate Rosalie Phillips; postdoc Dorsa Parviz; and Jacopo Buongiorno, the TEPCO Professor of Nuclear Science and Engineering at MIT.
- Strano and Buongiorno started exploring concepts for new types of face masks in March, shortly after MIT ramped down on-campus research operations. They began by digging through existing scientific reports on different types of masks, and found no masks that are designed primarily to kill viruses by heating.
- “The masks that we wear now are designed to capture some of the virus. They do offer protection, but there’s no one really thinking about inactivating the virus and sterilizing the air. That surprised me,” Strano says.
- The team set out to design a mask that would kill viruses using heat. They decided to use copper mesh as the heating and capture element, and performed some mathematical modeling to determine the optimal temperature range they would need to achieve to kill coronaviruses flowing inward or outward from natural breathing.
- “The vast majority of masks today function by filtration, filtering particles by size or electric charge,” Faucher says. “This mask relies on a different mechanism and works predominantly by thermal inactivation.”
- The researchers calculated how rapidly coronaviruses degrade at different temperatures and trapping conditions, and found that a temperature of about 90 degrees Celsius could achieve between a thousandfold and millionfold reduction in viral particles, depending on the final mask size. They also showed that that temperature can be achieved by running an electrical current across a 0.1-millimeter thick copper mesh or thermoelectric heater, powered by a small battery. The current prototypes include a 9-volt battery, which would provide enough power to heat the mask for a few hours and would cool the air before it is inhaled.
- “Of course, we need to be mindful of the safety and comfort of mask users,” Faucher says. “The air will be cooled after viral inactivation to make the mask comfortable and safe to use.”
- The researchers were able to enhance the efficiency of virus deactivation by taking advantage of the breath to create a type of reactor known as a reverse-flow reactor. As the person wearing the mask breathes in and out, the air flow continually reverses, allowing any viruses in the mask to pass over the mesh many times and making it more likely that they will be deactivated. Purified air flows out of vents on both sides of the mask.
- “This design means you can wear a small mask, something that will fit on your face, but the virus can spend much more time getting deactivated than it would without the reverse flow reactor design,” Strano says.
- The copper mesh is surrounded by neoprene, an insulating material that prevents the outside of the mask from becoming too hot to wear.
- “Achieving the temperature for virus inactivation while thermally insulating the person’s face and ensuring acceptably cool air inhalation made for an interesting heat transfer challenge, which we resolved with neoprene insulation and regenerative heating,” Buongiorno says.
- N95 respirators, surgical masks, and cloth masks are effective and should be used during the pandemic as directed, Strano says, but one potential advantage of heated masks is that because they kill the virus, they don’t need to be decontaminated or thrown away after use. Additionally, they may offer extra protection by eliminating the virus rather than only filtering it.
- “What we show is that it’s possible to wear something on your face that’s not too cumbersome, that can actually allow you to breathe medically sterile air,” Strano says. “The prospect of being able to breathe in medically sterile air and breathe out medically sterile air, protecting the people around you and protecting yourself, is just the next step. It’s better technology.”
- Heated masks would be more expensive than cloth masks or surgical masks, but they may be useful in situations where exposure risk is high and cost is less of a concern, the researchers say. They have filed for a patent on their mask design, and they plan to begin testing prototypes at MIT with collaborators.
H. The Road Back?
1. Study provides estimates of the effect of introducing and lifting physical distancing measures on C19 reproduction (R) number
- Analysis suggests that individual measures (including school closure, workplace closure, public events ban, ban on gatherings of more than ten people, requirements to stay at home, and internal movement limits) are associated with a reduction in transmission of the coronavirus (SARS-CoV-2) but combined measures are more effective at reducing transmission, according to a modelling study published in The Lancet Infectious Diseases journal.
- The study estimates the effect individual measures and four combinations of measures (ranging from a ban on events and gatherings of more than ten people to a more restrictive combination of measures resembling a lockdown) has on the R number up to 28 days after being introduced or lifted.
- The R number – or reproduction number – is a key measure of virus transmission. An R value above 1 indicates a growing outbreak, whereas an R value below 1 indicates a shrinking outbreak.
- Using data from 131 countries, the study provides a high-level overview of the effects of population-level intervention measures, but does not account for other potentially influential factors that have an impact on R- including, among other things, compliance with the interventions, changes in population behavior (e.g., wearing of face masks), sub-national differences in R, or the effects of contact tracing and isolation – all of which vary by context. Using the R number as a proxy for transmission also has limitations, as it is difficult to estimate accurately, particularly when prevalence is low.
- Professor Harish Nair, University of Edinburgh, UK, says, “We found that combining different measures showed the greatest effect on reducing the transmission of C19. As we experience a resurgence of the virus, policymakers will need to consider combinations of measures to reduce the R number. Our study can inform decisions on which measures to introduce or lift, and when to expect to see their effects, but this will also depend on the local context – the R number at any given time, the local healthcare capacity, and the social and economic impact of measures.”
- When looking at the measures individually, a ban on public events was associated with the greatest reduction in R (24% reduction after 28 days), which the authors suggest may be because they are likely to prevent super spreader events and it was often the first measure to be introduced in countries.
- The measures most strongly associated with an increase in R were lifting bans on gatherings of more than ten people and re-opening of schools (25% and 24% after 28 days). Although reopening schools was associated with a 24% increase in the R by day 28, the authors caution that they were unable to account for different precautions some countries implemented for reopening schools (e.g., limiting class sizes, distancing measure, routine deep cleaning, personal handwashing, face masks, and thermal temperature checks on arrival), which are essential for safer school reopening and should be taken into account when interpreting this finding.
- On school reopening, Professor Nair adds, “We found an increase in R after reopening schools but is not clear whether the increase is attributable to specific age groups, where there may be substantial differences in adherence to social distancing measures within and outside classrooms. Furthermore, more data are needed to understand the specific role of schools in increased SARS-CoV-2 transmission through robust contact tracing.”
- Studies have found that measures, including school closure, social distancing, and lockdown (a combination of all measures), could reduce R substantially to near or below 1, but this is the first study to look at the effects on R following the relaxation of these measures.
- In this modelling study, data on daily country-level estimates of R were linked with data on what measures those countries had in place from January 1, 2020 to July 20, 2020. The timeline of each country was divided into individual phases when all measures remained the same in that country. The analysis included 790 phases from 131 countries and the authors used a model to measure the association between which measures were in place and changes in the R. They used this to estimate the effect up to 28 days on the R of introducing or lifting measures. In addition, they modelled four combinations of measures that could be introduced to tackle the resurgence of SARS-CoV-2.
- A decreasing trend over time in the R was found following the introduction of five individual measures, with a reduction in R 28 days after banning public events (24%), school closures (15%), workplace closure (13%), internal movement limits (7%), and requirements to stay at home (3%). However, when each of these measures were introduced individually, the only one to have a statistically significant effect on the R number was a public events ban.
- Modelling the effect of imposing four combinations of measures was linked to greater reductions in the R number after 28 days. The least comprehensive package of measures (bans on public events and gatherings of more than ten people) reduced R by 29% on day 28. The second package (workplace closure plus ban on public events and gatherings of more than ten people) reduced R by 38% on day 28. The third package (workplace closure, ban on public events and gatherings of more than ten people, and internal movement limits) reduced R by 42% on day 28. The most comprehensive package (school and workplace closure, ban on public events and gatherings of more than ten people, internal movement limits and a stay at home requirement) reduced it by 52%.
- The effect of introducing measures was not immediate; it took an average of 8 days after introducing a measure to see 60% of its effect on reducing the R number.
- The authors also looked at the impact of lifting measures. An increasing trend in R was found following the relaxation of five measures, with an increase after 28 days for the lifting of bans on public gatherings of more than ten people (25%), school closures (24%), public events ban (21%), and internal movement limits (13%), and requirements to stay at home (11%). However, the increase was significant only for reopening school and lifting bans on public gatherings of more than ten people.
- Similarly, the effect of lifting measures was not immediate; it took an average of 17 days to see 60% of its effect on increasing the R number.
- In addition, the authors did a secondary analysis which modelled the total visits to workplaces and the total time spent in residential areas using Google mobility data among 101 countries. Google Mobility data suggests that people took a similar time to adapt their behavior to comply with workplace closures and stay at home requirements as the delay between the measures and the effects seen on R. Therefore, they suggest that delays could be explained by the population taking time to modify their behavior to adhere to measures.
- The authors note that some of the greatest effects on R were seen for measures that are more easily implementable by law, like school reopening and introduction of a public events ban. They suggest that the effect of these measures may be because their effects are more immediate, and compliance is easier to ensure. For example, when schools reopen, the majority of children return, and change is immediate, compared with say lifting of internal movement limits or requirements to stay at home, as there is a need for change in population behavior, which takes time and cannot be measured in the datasets they used.
- Likewise, the authors suggest that low compliance with bans on gatherings of more than ten or more than 100 people may be a possible reason why they did not find a substantial reduction in transmission after this measure being introduced. In addition, they note that they were unable to distinguish between indoor versus outdoor gatherings in this measure due to lack of data.
- Writing in a linked Comment, Professor Chris T Bauch from University of Waterloo, Canada, says, “Despite R’s imperfections, the findings of Li and colleagues tell us that NPIs [non-pharmaceutical interventions] work and which ones work best. This information is crucial, given that some NPIs have massive socioeconomic effects. In a similar vein, transmission models that project C19 cases and deaths under different NPI scenarios could be highly valuable for optimizing a country’s portfolio of NPIs. Moreover, I think R provides a social utility that epidemiologists can easily overlook. The success of large-scale NPIs requires population adherence. R can stimulate populations to act and gives them useful feedback on the fruits of their labor. Perhaps this is one reason that R has entered our vernacular in 2020.”
2. Flexibility Paradox: The Hidden Threat of Working From Home
- It may seem a bit contradictory at first glance, but increased flexibility in our workday may have given us less flexibility in the work itself.
- The daily press and the nascent research literature on C19 speculate on the long-term consequences of the coronavirus situation. These could change the way we think about the methods we employ in our working life, especially with regard to home offices and digital collaboration.
- Several large companies, both internationally and nationally, have announced that they plan to continue the option of working from home for anyone who also wishes after the pandemic. The arguments for this include:
- Greater flexibility in organizing work and family life situations seems to significantly reduce stress for many people.
- Time that was previously used for commuting or traveling between meetings can now be used for other things, which in turn may lead to higher productivity.
- One argument we hear is that a home office situation provides fewer distractions and can make us more efficient.
- Employers, for their part, see an opportunity for reduced travel costs and less need for office space.
- Working from home is also happening in academia, and several universities have said that the home office option will continue.
- On the other hand, it has been pointed out that people cannot work exclusively in physically separate environments. We need opportunities to meet with colleagues and experience the social cohesion and replenishment this provides.
Practices are changing
- The consequences of this kind of distributed work situation for workplace practices constitute an important aspect that has received less attention so far. How does working from home affect collaborative efforts and the quality of work, both in smaller teams and in larger work communities?
- In the article “Learning of academics in the time of the Coronavirus pandemic,” we describe how one academic’s practices changed, quite significantly, under the conditions we have worked under since March.
- While working from a home office, or as a distributed team, provides significantly increased flexibility for the work situation, it could provide less flexibility in carrying out the work, both in terms of meeting colleagues, collaborating, and teaching.
- One of our conclusions is that we cannot expect work practices to remain the same when we move them. As conditions change around practices, so do the practices themselves.
Not everyone becomes more efficient
- In two parallel projects, we collected data from students and academic staff. We focused on their work and study situations during the corona pandemic.
- The data includes 1600 students and 16 lecturers in a course called Experts in Teamwork. Students provided feedback through questionnaires, written exam reports and in-depth interviews. The lecturers represented different faculties and departments and were also interviewed in depth.
- The preliminary findings show great variations in the consequences that the new work and study situations have had for individuals and for groups.
- Some groups became more effective, others less.
- Some people became more efficient in their new work setting, for example, because they had fewer distractions and work became easier to prioritize. But others became less efficient, for example, due to lower motivation and lack of daily structure.
- Some individuals thought it was beneficial to have more peace and flexibility in their daily life, while others felt lonelier and less motivated due to the lack of social and physical contact with fellow students and colleagues.
- A number of the academic staff also had a much busier schedule due to home schooling their children. This factor is less relevant in a situation without a pandemic.
- In our study, we also found many of the positive elements of distributed teamwork and working digitally that are mentioned at the beginning of our article.
The paradox: increased flexibilty and less freedom
- However, one finding stands out as a paradox.
- While working from a home office, or as a distributed team, provides significantly increased flexibility for the work situation, it could provide less flexibility in carrying out the work, both in terms of meeting colleagues, collaborating and teaching.
- This flexibility issue, or paradox, is largely related to a much greater need for structure, planning and clear communication in the digital modality. Meetings and teaching need to be planned in much more detail, and the digital form makes it difficult to deviate from the plan.
- We lose the ability to pick up cues from the room, like we do when we are in a physical space together. Several communication-related aspects of working digitally also make it difficult to achieve a good flow, as well as to make spontaneous and necessary changes.
Higher threshold makes teamwork less flexible
- We also find that the threshold for making small and necessary clarifications with collaborators is significantly higher in the digital realm. The flexibility to complete a task is therefore reduced and can affect the quality of what we do.
- For example, we risk working alone with a task for too long, assuming rather than clarifying along the way. We don’t want to disturb people, and we don’t know what they are doing right now. We found this to be the case both for students who worked synchronously, and for academics who mostly worked asynchronously.
- Home offices may offer benefits for many, but it is hardly advantageous for everyone. More people will probably choose to work from home more than they did before, even when the pandemic has subsided. But having the opportunity to convene physically is still important, not only for each of us to meet our social needs, but also for the employer and for the quality of the work.
3. United Airlines Digital Health Pass Could Reopen Borders
- United Airlines is set on Wednesday to test a digital health pass under a global pilot program seeking to establish a common international standard for C19 test results and eventually vaccine records that could help reopen borders.
- The nonprofit initiative, called CommonPass, is backed by the World Economic Forum and Swiss-based foundation The Commons Project. If successful, it could persuade governments to ease the restrictions and quarantines that have slammed air travel since the coronavirus starting spreading across the globe.
- “The goal of these trials is to demonstrate to governments that they can rely on someone getting tested in one country and present their credentials in another country,” Paul Meyer, chief executive of The Commons Project, told Reuters.
- Broad deployment is targeted for January, he said.
- Volunteers on the United flight, which will be observed by the U.S Centers for Disease Control and Prevention, will upload C19 test results from a certified lab to their smartphones and complete any required health screening questions to generate a verified QR (quick response) code that airline staff and border officials can scan.
- They will present the code, which can be printed for passengers without mobile devices, before departing and on arrival.
- The project aims to build a network of trusted labs and would rely on those results and vaccination records to be certified across borders, replacing the current method of sharing paper-based and easily falsified test results from unknown labs.
- The labs would verify a person’s identity for the app, which is designed to protect personal data and privacy, said Meyer, who is in a dialogue with airlines and countries across the globe for the project.
- “The model only works if countries agree to trust health data from other countries,” he said.
I. Back to School!?
1. The Latest Science on How to Keep C19 Out of School Classrooms
- As the C19 virus continues to spread around the globe, studying aerosol and droplet transport within different environments can help establish effective, physics-informed measures for virus mitigation. One of the most important environments to gain a rapid understanding about C19’s spread is inside the school classroom.
- Flow velocity distribution and particle size are key in aerosol transport, which is one of the main ways C19 spreads, when aerosol particles are released during exhalation, talking, coughing, or sneezing.
- In Physics of Fluids, from AIP Publishing, University of New Mexico researchers used computational fluid-particle dynamics to explore aerosol transport within an air-conditioned classroom model. They discovered opening windows increases the fraction of particles that exit the system by nearly 40%, while also reducing aerosol transmission between people within.
- “Nearly 70% of exhaled 1-micron particles exit the system when windows are open,” said Khaled Talaat, one of the authors. “And air conditioning removes up to 50% of particles released during exhalation and talking, but the rest get deposited onto surfaces within the room and may reenter the air.”
- Particles are transmitted in significant quantities (up to 1% of exhaled particles) between students — even at 2.4 meters (7.8 feet) of separation distance because of airflow.
- “The aerosol distribution within the room isn’t uniform, because of air conditioning and source location,” said Talaat. “Student position within the room affects the likelihood of transmitting particles to others and of receiving particles.”
- The researchers were surprised to find that glass droplet screens placed in front of desks significantly reduced the transmission of 1-micron particles from one student to another, according to Talaat.
- “Screens don’t stop 1-micron particles directly, but they affect the local air flow field near the source, which changes the particle trajectories,” he said. “Their effectiveness depends on the position of the source with respect to the air conditioning diffusers.”
- For school reopenings, the group recommends keeping windows open when possible and installing glass screens in front of desks. Students at higher risk of C19 complications can be seated where they are exposed to fewer particles, which will depend on the air conditioning layout within the room.
- “In our model, the back corners are the safest spots,” Talaat said.
- The group stresses the importance of sanitizing hands — even without contact with other people’s belongings — because “particles can be transmitted from one student to other students’ desks or clothes, etc., even when keeping separated by a distance of 2.4 meters,” he said.
- Their work also highlights the importance of effective filtration and sterilization systems within air conditioners.
- “Given the significance of air conditioning, there is potential for optimization of HVAC systems within classrooms to maximize particle removal, while providing adequate ventilation,” Talaat said.
2. Schoolchildren Seem Unlikely to Fuel Coronavirus Surges
- Months into the school year, school reopenings across the United States remain a patchwork of plans: in-person, remote and hybrid; masked and not; socially distanced and not. But amid this jumble, one clear pattern is emerging.
- So far, schools do not seem to be stoking community transmission of the coronavirus, according to data emerging from random testing in the United States and Britain. Elementary schools especially seem to seed remarkably few infections.
- The evidence is far from conclusive, and much of the research has been tarnished by flaws in data collection and analysis. School reopenings are very much a work in progress. Still, many experts are encouraged by the results to date.
- “The more and more data that I see, the more comfortable I am that children are not, in fact, driving transmission, especially in school settings,” said Brooke Nichols, an infectious disease modeler at the Boston University School of Public Health.
- That is not to say that younger children do not become infected — they do. On Wednesday, Dr. Michael Beach, a senior scientist at the Centers for Disease Control and Prevention, acknowledged that the agency’s guidance on school reopenings does not reflect the latest research showing that children can become infected with the coronavirus and transmit it to others.
- “It does appear that children can become infected” and that children “clearly can transmit,” Dr. Beach, the agency’s deputy incident manager for C19 response, told the House Select Subcommittee on the Coronavirus Crisis.
- But the more pressing question for scientists and policymakers has been how often transmission from children happens. The bulk of evidence now suggests only limited transmission from young children to adults.
- The risk among older children in middle and high schools is less clear, but many experts believe that these schools may be able to contain the coronavirus, provided the community prevalence is low and the schools take abundant precautions.
- Weighed against the substantial harms to children and parents from keeping schools closed, elementary schools should at least offer in-person learning, said Dr. David Rubin, a pediatrician and infectious disease expert at the University of Pennsylvania.
- “I think there’s a pretty good base of evidence now that schools can open safely in the presence of strong safety plans, and even at higher levels of case incidence than we had suspected,” he said.
- Dr. Rubin and his colleagues have devised new guidelines for when to close and reopen schools as the virus continues to march through much of the United States. The decisions should depend not on absolute numbers — for example, 5 percent of tests turning up positive — but on the trend in case numbers, he said.
- “If you’re really trying to keep kids in school, you have to do this in a much different way,” he said — with an expectation not of zero risk, but of risk managed by safety measures.
- Rather than closing schools where community transmission is high, businesses like restaurants, bars or other indoor spaces where adults congregate should be shuttered, Dr. Rubin said.
- Facing an immense second wave, some countries in Europe, like the Netherlands, have instituted restrictions on indoor dining, private gatherings and public transportation. “And they said none of this applies to schools, because education is too important,” Dr. Nichols said. “It’s just such a different priority.”
- While a vast majority of studies suggest that children are not superspreaders, the data is far from perfect. Few schools are routinely testing students or staff and, even when they identify cases, it’s difficult to trace the infection’s origins. Random testing in schools can provide a glimpse of trends within a school or a city, but may miss early signs of a cluster.
- Perhaps the biggest issue in studies of children has been a failure to consistently account for age. Many studies classify anyone under 18 as a child, said Helen Jenkins, an infectious disease expert at Boston University.
- Still, transmission by young children to adults seems to be negligible as long as safety measures are in place. Several studies have suggested that children under 10 are mostly unaffected by the coronavirus and spread it to others less efficiently compared with older children and adults.
- One study published in the journal Pediatrics surveyed more than 57,000 child care providers in the United States and found that they were no more likely to become infected with the coronavirus than other adults in the community.
- “Every study, unfortunately, has sort of different age cutoffs and brackets, which makes the data a bit more difficult to interpret,” Dr. Nichols said. “But certainly, I think grade five seems to be when it changes.”
- As districts planned for reopenings, some schools were unable or unwilling to put in place precautions such as masks for students and teachers, physically distanced desks and improved ventilation.
- New York City mandated precautions for its 1,800 schools, and the virus’s prevalence in the city has remained low since its deadly surge in the spring. Random testing of more than 16,000 staff members and students has turned up only 28 positives and no big outbreaks, apart from localized clusters in two communities.
- But Britain and the Netherlands have kept schools open with few restrictions on class sizes or requirements for mask-wearing. Yet they, too, have shown limited transmission among younger children or from children to their parents, Dr. Nichols noted.
- “We see a similar pattern in places where they’re doing nothing at schools, so I find that fascinating,” she said.
- The trends for older children are much harder to discern. But over all, they suggest a greater chance for infections to spread without careful measures in place.
- Sweden, often cited as a model for having schools operate throughout the pandemic, kept schools open for children under 16, but with small class sizes and physical distancing. According to one recent study, opening elementary schools had limited impact on parents, but teachers in schools with older children had double the rate of infections compared with those who taught remotely.
- In Israel, crowded high school classrooms seeded outbreaks, prompting the health ministry to release a report this week calling children superspreaders. And in the United States, some high school reopenings have been disastrous, like those of a Georgia school shamed for unmasked students in its hallways and a high school in Utah where infections flared to 90 cases within two weeks.
- A significant proportion of cases seem to come from activities outside school, Dr. Rubin said. “Most of the transmission, when we see it, is occurring in carpools, during travel leagues, maybe in a locker room, or parties and gatherings that people have on the weekend,” he said.
- “You’ve assumed that by closing schools, that’s going to negate the problem,” but informal settings that are less regulated may sow more infections, Dr. Rubin said.
- The data from Britain suggests, however, that clusters even among older children may not always lead to infections at home. Random testing in schools there showed sharp increases in infections among children older than 11, but the spikes did not seem to translate to a rise in adult cases.
- “I find this fascinating and something that we need to understand more,” Dr. Nichols said.
- Despite the gathering research, Boston on Wednesday decided to close schools even as restaurants, casinos and gyms remain open. Dr. Jenkins, who has two children, said she was particularly frustrated by the news.
- “Children are not being prioritized, and they’re missing out on all the positive things about going to school,” Dr. Jenkins said. “I don’t understand why we’re not as a community getting together and deciding that schools need to be a priority and making them as safe as we can.”
J. Projections & Our (Possible) Future
1. Why COVID outbreaks look set to worsen this winter
- Winter is fast approaching in the Northern Hemisphere, and researchers warn that C19 outbreaks are likely to get worse, especially in regions that don’t have the virus’s spread under control.
- “This virus is going to have a heyday,” says David Relman, a microbiologist at Stanford University in California. “We are looking at some pretty sobering and difficult months ahead.”
- Infections caused by many respiratory viruses, including influenza and some coronaviruses, swell in winter and drop in summer. Researchers say it’s too early in the C19 pandemic to say whether the coronavirus (SARS-CoV-2) will become a seasonal virus. But growing evidence suggests that a small seasonal effect will probably contribute to bigger outbreaks in winter, on the basis of what is known about how the virus spreads and how people behave in colder months.
- People will be interacting more often indoors in places with poor ventilation, which will increase the risk of transmission, says Mauricio Santillana, a mathematician at Harvard Medical School in Boston, Massachusetts, who models disease spread.
- But even if there is a small seasonal effect, the main driver of increased spread will be the vast number of people who are still susceptible to infection, says Rachel Baker, an epidemiologist at Princeton University in New Jersey. That means people in places that are going into summer shouldn’t be complacent either, say researchers.
- “By far the biggest factor that will affect the size of an outbreak will be control measures such as social distancing and mask wearing,” says Baker.
Evidence so far
- Seasonal trends in viral infection are driven by multiple factors, including people’s behavior and the properties of the virus — some don’t like hot, humid conditions.
- Laboratory experiments reveal that SARS-CoV-2 favors cold, dry conditions, particularly out of direct sunlight. For instance, artificial ultraviolet radiation can inactivate SARS-CoV-2 particles on surfaces and in aerosols, especially in temperatures of around 40 °C. Infectious virus also degrades faster on surfaces in warmer and more humid environments. In winter, people tend to heat their houses to around 20 °C, and the air is dry and not well ventilated, says Dylan Morris, a mathematical biologist at Princeton. “Indoor conditions in the winter are pretty favorable to viral stability.”
- To assess whether infections with a particular virus rise and fall with the seasons, researchers typically study its spread in a specific location, multiple times a year, over many years. But without the benefit of time, they have tried to study the seasonal contribution to SARS-CoV-2 transmission by looking at infection rates in various places worldwide.
- A study published on 13 October looked at the growth in SARS-CoV-2 infections in the first four months of the pandemic, before most countries introduced controls. It found that infections rose fastest in places with less UV light, and predicted that, without any interventions, cases would dip in summer and peak in winter. In winter, “the risk goes up, but you can still dramatically reduce your risk by good personal behavior”, says Cory Merow, an ecologist at the University of Connecticut in Storrs, and a co-author of the study. “The weather is a small drop in the pan.”
- But Francois Cohen, an environmental economist at the University of Barcelona in Spain, says that testing was also quite limited early in the pandemic, and continues to be unreliable, so it is impossible to determine the effect of weather on the spread of the virus so far.
- Baker has tried to tease apart the effect of climate on the seasonal pattern of cases during the course of a pandemic, using data about the humidity sensitivity of another coronavirus. She and her colleagues modelled the rise and fall in infection rates over several years for New York City with and without a climate effect, and with different levels of control measures. They found that a small climate effect can result in substantial outbreaks when the seasons change if control measures are only just managing to contain the virus. “That could be a location where climate might nudge you over,” Baker says. The team posted its results on the preprint server medRxiv on 10 September; the authors suggest that stricter control measures might be needed during winter to reduce the risk of outbreaks.
In the future
- If SARS-CoV-2 can survive better in cold conditions, it’s still difficult to disentangle that contribution from the effect of people’s behavior, says Kathleen O’Reilly, a mathematical epidemiologist at the London School of Hygiene and Tropical Medicine. “Flu has been around for hundreds of years and the specific mechanism as to why you have peaks of flu in the winter is still poorly understood,” says O’Reilly.
- And even if researchers had more reliable data for SARS-CoV-2, they would see only small or negligible seasonal effects so early in the pandemic, when much of the population is still susceptible, says Relman.
- Over time, however, seasonal effects could play a more important part in driving infection trends, as more people build up immunity to the virus. This could take up to five years through natural infection, or less if people are vaccinated, says Baker.
- But whether a seasonal pattern emerges at all, and what it will look like, will depend on many factors that are yet to be understood, including how long immunity lasts, how long recovery takes and how likely it is that people can be reinfected, says Colin Carlson, a biologist who studies emerging diseases at Georgetown University in Washington DC.
2. Morgan Stanley Models The Number Of Covid Infections In 2021: Here Are The Bull, Bear And Base Cases
- At a time when the US just reported record numbers of new cases, some traders – and the general population – are starting to ask if the US economy faces a new round of lockdowns, especially under a Joe Biden administration (who frequently likes to remind his fans “listens to the scientists” which supposedly also includes such “experts” as Minneapolis Fed president who has been demanding a 6-week hard lockdown of the economy).
- As Bank of America summarizes, US cases have now eclipsed the July peak as with the 7-day average of new daily cases topping 68,000 for the first time. The spread of the virus has been broad-based but there have been notable outbreaks in the Midwest. Compared to a week ago 35 states have recorded double digit growth in new cases. Deaths have also started to climb, increasing to just under 800 as of Sunday.
- One should note at this point that as JPMorgan shows in the next two charts, over 70% of the increase in number of US cases has been due to increased testing:
- Meanwhile, in the Euro area (where virtually everyone wears a mask so that excuse can’t be used), the second wave has continued unabated. The 7-day average of new daily cases has risen by 58% from a week ago to over 99k in the big 5 Euro Area economies, as of yesterday. Globally, the 7-day average of new daily cases has risen by over 21% from a week ago to 432,400 (there has been marked improvement in India, which has seen its 7-day average of new daily cases fall by 16% from a week ago and 43% from its peak to 52.9k).
- Of course, there is a distinct possibility that with covid having long ago become a critical political issue in the upcoming election, a Biden win would mean that the pandemic promptly fades away from public attention on Nov 4 should Biden win. Whether that happens or not remains to be seen, but for now two key questions have emerged: will the surge in cases lead to new lockdowns, and what is the most likely trajectory of covid cases in 2021.
- Addressing the first question, Bloomberg’s Ye Xie writes that “lower mortality and less stringent lockdowns than what we experienced in the spring suggest the resurgence of coronavirus in the U.S. and Europe may cause far less damage to the economy and markets than what happened in the early months of the pandemic” even if such an outcome would require more fiscal stimulus from the U.S., which implies more government debt and curve steepening.
- The University of Oxford’s stringency index shows only marginal tightening of government restrictions in France, U.K., Germany and the U.S. recently. While the number of deaths has increased, the mortality rate is far lower than before.
- The bottom line, and as the U.S. showed in the summer, “the economic recovery can continue amid a wave of new infections as people learn to social distance, wear masks and live with the virus.” His conclusion is that while the markets could have fared better than otherwise, “the resurgence of the coronavirus isn’t necessarily a game-changer.”
- As for the second question, which involves a timeline of projected case counts, we go to Morgan Stanley which back in April built an epidemiological model to simulate the dynamics of the infection rate in the US.
- According to the bank’s updated model R will exhibit an upward trend throughout the rest of 2020 both in the base and bear scenario, only to reach a mean value of between 1.3 and 1.5 in the base/bear case by YE20. Such an R value would lead to approximately ~130,000 – 200,000 new daily cases by the end of the year in the bank’s base/bear cases.
- Here, a key assumption is that traditionally the spread of viruses is elevated in the fall compared to the summer principally due to more people being in enclosed spaces; the bank also caveats that its model does not account for any pharmacological intervention (such as vaccines) or strict lockdown measures that could potentially suppress the spread.
- Finally, in the chart below, Morgan Stanley provides an updated Return to Work chart, which includes key events by date, along with bull, bear, and base case scenarios that detail the possible case count trajectory (the base and bear case come from the simulations in Exhibit 1, while the bull case is based on empirical model in Exhibit 2, which assumes similar trajectory as China and major EU countries during February to May with adequate interventions in place.)
- Needless to say, a “bear” case which results in an exponential surge in new cases would almost certainly lead to another economic shutdown, especially under a Biden presidency.
3. Scientists Predict Birthrates, Marriage, Gender Roles Will Change Dramatically in Post-Pandemic World
- C19 and America’s response to it are likely to profoundly affect our families, work lives, relationships and gender roles for years, say 12 prominent scientists and authors who analyzed 90 research studies and used their expertise to evaluate our reaction to the pandemic and predict its aftermath.
- The group, which included several UCLA researchers, foresees enduring psychological fallout from the crisis, even among those who haven’t been infected. Their predictions and insights, published on October 22, 2020, in the journal Proceedings of the National Academy of Sciences, include:
- Planned pregnancies will decrease in a disease-ridden world, birthrates will drop, and many couples will postpone marriage, said senior author and UCLA professor of psychology and communication studies Martie Haselton.
- People who are single are less likely to start new relationships. Women who can afford to be on their own are likely to stay single longer, Haselton said.
- With children home due to the pandemic, women are spending more time providing care and schooling, are less available for paying work and may come to rely more on male partners as breadwinners, Haselton said. This will push us toward socially conservative gender norms and potentially result in a backslide in gender equality.
- Unlike many past crises, this pandemic is not bringing people closer together and, despite some exceptions, it is not producing an increase in kindness, empathy or compassion, especially in the U.S., said lead author Benjamin Seitz, a UCLA psychology doctoral student with expertise in behavioral neuroscience.
- “Our species is not wired for seeking a precise understanding of the world as it actually is,” the authors write, and our tribal predispositions toward groupthink are resulting in the large-scale spread of misinformation We tend to seek out data that supports our opinions, and we too often distrust health experts, they say.
- “The psychological, social and societal consequences of C19 will be very long-lasting,” Haselton said. “The longer C19 continues, the more entrenched these changes are likely to be.”
C19: A worldwide social experiment
- As marriage rates plummet and people postpone reproduction in a virus-plagued world, some nations’ populations will shrink and fall precipitously below “replacement level,” the authors write. These birthrate drops, in turn, can have cascading social and economic consequences, affecting job opportunities, straining the ability of countries to provide a safety net for their aging populations and potentially leading to global economic contraction.
- Research has shown that even before the pandemic, women were more stressed than men by family and job responsibilities. Now they are managing more household responsibilities related to child care and education. In medicine and other sciences, women scholars are already publishing substantially less research than they did a year ago, while men are showing increased productivity, Haselton said.
- She and her co-authors foresee a shift toward social conservatism. A consequence of the pandemic could be less tolerance for legal abortion and the rights for sexual minorities who don’t align with traditional gender roles. In addition, in a time of economic inequality, many women will sexualize themselves more to compete with one another for desirable men, Haselton said.
- People who meet online will often be disappointed when they meet in person. “Does a couple have chemistry? You can’t tell that over Zoom,” Haselton said. In new relationships, people will miss cues, especially online, and the disappointing result will often be overidealization of a potential partner — seeing the person the way you want the person to be rather than the way the person actually is.
- The pandemic has become a worldwide social experiment, say the authors, whose areas of expertise include psychology, neuroscience, behavioral science, evolutionary biology, medicine, evolutionary social science, and economics.
An evolutionary struggle
- For the study, the authors used an evolutionary perspective to highlight the strategies the virus has evolved to use against us, the strategies we possess to combat it and the strategies we need to acquire.
- Humans today are the products of social and genetic evolution in environments that look very little like our current world. These “evolutionary mismatches” are likely responsible for our frequent lack of alarm in response to the pandemic, the scientists write.
- Americans in particular value individuality and the ability to challenge authority. “This combination does not work especially well in a pandemic,” Seitz said. “This virus is exposing us and our weaknesses.”
- Haselton agreed, calling the virus “wily” for its ability to infect us through contact with people we love who seem to be healthy. “Our social features that define much of what it is to be human make us a prime target for viral exploitation,” she said. “Policies asking us to isolate and distance profoundly affect our families, work lives, relationships and gender roles.”
- All infectious agents, including viruses, are under evolutionary pressure to manipulate the physiology and behavior of their hosts — in this case, us — in ways that enhance their survival and transmission. The coronavirus (SARS-CoV-2) may be altering human neural tissue to change our behavior, the authors say. It may be suppressing feelings of sickness, and perhaps even enhancing our social impulses, during times of peak transmissibility before symptoms appear. People who are infected but do not feel sick are more likely to go about their usual activities and come in contact with others whom they might infect.
- Disgust is useful and motivates us to avoid people who display clear signs of disease — such as blood, pale skin, lesions, yellow eyes or a runny nose. But with C19 infections, this is not what most people see. Family, friends, co-workers and strangers can look perfectly healthy and be asymptomatic for days without knowing they are infected, the authors note.
- It may sound counterintuitive, but normal brain development requires exposure to a diverse set of microbes to help prepare younger animals for a range of pathogenic dangers they may encounter in adulthood. But safer-at-home and quarantine health measures have temporarily halted social activities that would otherwise bring millions of adolescents into contact with new microbes. As a result, children and adolescents whose immune systems and brains would, in normal times, be actively shaped by microbial exposures may be adversely impacted by this change, the scientists say.
- By understanding how SARS-CoV-2 is evolving and having behavioral and psychological effects on us that enhance its transmission, we will be better able to combat it so it becomes less harmful and less lethal, the authors write.
4. Pandemic Fatigue Is Real—And It’s Spreading
- From the corridors of Washington to the cobblestones of Paris, the coronavirus is roaring back and authorities are ramping up restrictions again. This time around, however, everyone is tired.
- Hospital staff world-wide are demoralized after seven months of virus-fighting triage. The wartime rhetoric that world leaders initially used to rally support is gone. Family members who willingly sealed themselves off during spring lockdowns are suddenly finding it hard to resist the urge to reunite.
- Zoe Sharp, a 43-year-old human-resources leader in Washington, D.C., has been stringent with her family throughout the pandemic, sanitizing elevator buttons, airing out packages and microwaving the newspaper. Her 4-year-old son Hank even created a no-cuddle list to protect family members who are more vulnerable to the virus, like his grandparents.
- A week ago, however, something snapped. Ms. Sharp booked a trip to visit her father-in-law in Memphis, Tenn., replete with a stop at the local theme park. Grandpa is now off the no-cuddle list.
- “I need something to look forward to,” Ms. Sharp says, adding that her children “want to see their grandfather. They’re worried about him, and they talk about him a lot.”
- The collective exhaustion—known as pandemic fatigue—has emerged as a formidable adversary for governments that are counting on a high degree of public cooperation with the latest rounds of restrictions to flatten the infection curve. Too much pandemic fatigue, authorities say, can fuel a vicious cycle: A tired public tends to let its guard down, triggering more infections and restrictions that in turn compound the fatigue.
- That is part of what is driving the recent spate of policy reversals. Bars and cafes that reopened after the spring lockdown are suddenly off limits again. Workers who were told to return to their offices are now being asked to work from home if possible. In France, authorities recently halved the length of quarantines to one week, believing it would boost compliance.
- “It’s a matter of balance. To be able to enforce a new rule, we need to make sure first that people can accept it,” French Education Minister Jean-Michel Blanquer said in an interview.
- Surveys on both sides of the Atlantic show people are better at keeping up with the latest rules and advice when it comes to personal hygiene, like hand-washing and masks. Weekly Gallup polls of between 2,714 and 9,353 people in the U.S. found that 91% of respondents said they had worn a mask in the past seven days as of Sept. 27, compared with 80% as of May 10.
- Problems begin when the rules run up against the need for social connection. Gallup polling over the same May-to-September period showed the number of Americans avoiding small gatherings with family and friends had fallen from 71% to 45%.
- A government survey in France found that 72% of people said they were avoiding gatherings and face-to-face meetings as of mid-May, right after the country’s lockdown ended. By Sept. 23, that figure had fallen to 32%. In the same time frame, the percentage who said they greeted others without shaking hands or embracing fell from 88% to 69%.
- The resolve to wear masks also appears to weaken in certain social settings. A U.K. survey found that 98% of people reported wearing a mask over a seven-day period ended Oct. 11. That figure dropped to 19%, however, when it involved one-on-one social activity.
- That is a problem, epidemiologists say, as winter sets in. More people will socialize indoors, where the virus spreads most efficiently, and at close quarters.
- Younger people, wary of becoming vectors of infection, are walking a tightrope before they head home for the holidays.
- When the lockdown hit London in March, the Diamond family went all-in. They set up a home office, bought a spin bike and limited their outings to a weekly stop at a grocery store where social distancing was strictly enforced.
- They kept up the routine for seven months—even after the U.K. eased restrictions over the summer, allowing people to go back to restaurants, pubs and the gym. “We were really conscientious about it,” says 36-year-old Lawrence Diamond.
- On Oct. 10, they decided it was time to socialize again. They met friends in a pub and invited people over for Sunday lunch.
- “We were feeling much more confident, the virus seemed under control and it didn’t feel like we were putting anyone at risk by meeting up,” says Megan Diamond, his 35-year-old wife.
- A few days later, Londoners were banned from having other people in their homes or going to the pub with people outside their household.
- “Winter is long in Britain,” Mr. Diamond says. “No one’s not bored of this.”
5. Analyzing web searches can help experts predict, respond to C19 hot spots
- Web-based analytics have demonstrated their value in predicting the spread of infectious disease, and a new study from Mayo Clinic indicates the value of analyzing Google web searches for keywords related to C19.
- Strong correlations were found between keyword searches on the internet search engine Google Trends and C19 outbreaks in parts of the U.S., according to a study published in Mayo Clinic Proceedings. These correlations were observed up to 16 days prior to the first reported cases in some states.
- “Our study demonstrates that there is information present in Google Trends that precedes outbreaks, and with predictive analysis, this data can be used for better allocating resources with regards to testing, personal protective equipment, medications and more,” says Mohamad Bydon, M.D., a Mayo Clinic neurosurgeon and principal investigator at Mayo’s Neuro-Informatics Laboratory.
- “The Neuro-Informatics team is focused on analytics for neural diseases and neuroscience. However, when the novel coronavirus emerged, my team and I directed resources toward better understanding and tracking the spread of the pandemic,” says Dr. Bydon, the study’s senior author. “Looking at Google Trends data, we found that we were able to identify predictors of hot spots, using keywords, that would emerge over a six-week timeline.”
- Several studies have noted the role of internet surveillance in early prediction of previous outbreaks such as H1N1 and Middle East respiratory syndrome. There are several benefits to using internet surveillance methods versus traditional methods, and this study says a combination of the two methods is likely the key to effective surveillance.
- The study searched for 10 keywords that were chosen based on how commonly they were used and emerging patterns on the internet and in Google News at that time.
- The keywords were:
- COVID symptoms
- Coronavirus symptoms
- Sore throat+shortness of breath+fatigue+cough
- Coronavirus testing center
- Loss of smell
- Face mask
- Coronavirus vaccine
- COVID stimulus check
- Most of the keywords had moderate to strong correlations days before the first C19 cases were reported in specific areas, with diminishing correlations following the first case.
- “Each of these keywords had varying strengths of correlation with case numbers,” says Dr. Bydon. “If we had looked at 100 keywords, we may have found even stronger correlations to cases. As the pandemic progresses, people will search for new and different information, so the search terms also need to evolve.”
- The use of web search surveillance data is important as an adjunct for data science teams who are attempting to predict outbreaks and new hot spots in a pandemic. “Any delay in information could lead to missed opportunities to improve preparedness for an outbreak in a certain location,” says Dr. Bydon.
- Traditional surveillance, including widespread testing and public health reporting, can lag behind the incidence of infectious disease. The need for more testing, and more rapid and accurate testing, is paramount. Delayed or incomplete reporting of results can lead to inaccuracies when data is released and public health decisions are being made.
- “If you wait for the hot spots to emerge in the news media coverage, it will be too late to respond effectively,” Dr. Bydon says. “In terms of national preparedness, this is a great way of helping to understand where future hot spots will emerge.”
- Mayo Clinic recently introduced an interactive C19 tracking tool that reports the latest data for every county in all 50 states, and in Washington, D.C., with insight on how to assess risk and plan accordingly. “Adding variables such as Google Trends data from Dr. Bydon’s team, as well as other leading indicators, have greatly enhanced our ability to forecast surges, plateaus and declines of cases across regions of the country,” says Henry Ting, M.D., Mayo Clinic’s chief value officer.
- Dr. Ting worked with Mayo Clinic data scientists to develop content sources, validate information and correlate expertise for the tracking tool, which is in Mayo’s C19 resource center on mayoclinic.org.
- The study was conducted in collaboration with the Mayo Clinic Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery. The authors report no conflicts of interest.
1. Government scientists have blown apart their own case for lockdown
- Sir Patrick Vallance, who has until now been an avowed purveyor of the official Government doctrine that finding a vaccine will be the ultimate solution to the problem of Covid, made a statement to a Commons committee which blew that idea out of the water. Appearing before the Joint Committee on National Security Strategy, the Chief Scientific Officer asserted that the notion “of eliminating Covid is not right”. Even if a vaccine was available by the spring, it “would not wipe out the virus” which would, in fact, become endemic in Britain. We will simply have to live with this disease, he said, and learn to manage it in the best possible way.
- Excuse me? What are we arguing about then? As I understood it, the experts who were demanding repeated lockdowns of varying degrees in ever more numerous locations were basing their entire case on the promise of eventual deliverance by a vaccine. When those of us who were protesting against these measures claimed that they were, in the literal sense of the word, inhuman, we were assured that they must persist Until We Have a Vaccine. Any case that was put forward for managing the virus in ways that did not involve the shutdown of life as we knew it was dismissed outright and, indeed, caricatured in outlandish terms, as if everyone opposed to lockdown was a callous fanatic.
- The official doctrine occasionally tripped over its own feet when the experts, and even the Prime Minister, blurted out the terrible possibility that an effective vaccine might never be found. But those moments of doubt were always cancelled out as soon as any lockdown sceptic uttered the unanswerable questions: “So what happens then? How can we ever get out of this doom loop?” There would then follow a rapid scuttle back into the accepted dogma: we must continue with this self-inflicted destruction Until We Have a Vaccine.
- To make it absolutely clear, the two opposing sides of this dispute were: on the one hand, on-and-off lockdowns are the only solution in the absence of a vaccine, and, on the other, we should learn to cope with the virus by protecting those who are most at risk for as long as necessary while allowing the rest of society to return to something like normal. But Sir Patrick’s devastating remarks change the parameters of this discussion entirely.
- Let me put this as plainly as possible. If a vaccine is not going to put a definitive end to the virus, and we are still going to have to manage it in the most effective ways that can be found – why won’t Government ministers even engage with the possibility that we should be managing it in sensible, less destructive ways right now? Boris Johnson dismisses the idea that the vulnerable elderly could be given such special protection in half a sentence: it is “unrealistic”, he says, because so many of them live in multi-generational families. But that is surely not an insoluble problem – if you treat this as a serious possibility.
- It is a pity that Andy Burnham’s spectacular campaign against the Government came down in the end to a rather squalid haggle about a (relatively speaking) small amount of money when there was a more interesting argument to be had over the suggestion by Sir Richard Leese, the leader of Manchester City Council, in favor of simply protecting the high-risk population. I would bet that at a fraction of the cost that the Treasury is spending to support zombie businesses, a full service of care, and even alternative accommodation, could be offered to those who are in real danger. If younger family members wish to care for them, special provision could be made for them too.
- It cannot be beyond the wit of officials who are currently spending their time drawing up vastly complicated tier restrictions (and enormous amounts of money ameliorating the effects of them) to devise ways of managing the risks to specific groups with compassion and sensitivity. All it would take is a political decision to grant that such a proposition is acceptable. And Sir Patrick himself – the voice of “the science” – has just said that it is not only acceptable but inevitable.
- But it has probably gone too far for that. The Government is in too deep, locked into a plan with devastating consequences that has no obvious endgame or criteria for escape, even though its experts and spokesmen contradict one another – and themselves. At last Thursday’s press conference, Sir Patrick did not reiterate his game-changing statement to the parliamentary committee.
- He reverted to the status quo ante position of probably no proper vaccination program until next spring (which is not quite never) and made no mention of the prospect that even that would not get rid of the virus. So which version of his opinion is the one he actually stands by? Does Boris Johnson secretly know the answer to this? He was visibly relieved at the press briefing by what he called Sir Patrick’s “optimism” about a vaccine. What is the Government’s actual view?
- Do they condemn the “managing risk” option in defamatory terms just to make their own claim to be taking a middle way between extremes – national lockdown vs protection of the vulnerable – seem reasoned and sensible? Unfortunately, these questions are not being put into the mainstream debate, largely because the broadcast media journalists who dominate Downing Street press conferences are too busy scoring easy points about the failures of track and trace.
- So the same non-questions are asked, and the same non-answers are given. And Government ministers spew out more and more fatuous bluster. Matt Hancock said last week that “with science on our side” we will win this fight. Does he really believe that “science” (as opposed to particular scientists) can be on anybody’s side? I despair.
2. C19 lockdown reduced mental health, sleep, exercise
- A first-of-its-kind global survey shows the initial phase of the C19 lockdown dramatically altered our personal habits, largely for the worse.
- “The stay-at-home orders did result in one major health positive. Overall, healthy eating increased because we ate out less frequently. However, we snacked more. We got less exercise. We went to bed later and slept more poorly. Our anxiety levels doubled,” said Leanne Redman, PhD, Associate Executive Director for Scientific Education at Pennington Biomedical Research Center.
- The global survey evaluated the inadvertent changes in health behaviors that took place under the pandemic’s widespread restrictions. Researchers found that the lockdown’s effects were magnified among people with obesity.
- “Overall, people with obesity improved their diets the most. But they also experienced the sharpest declines in mental health and the highest incidence of weight gain,” Dr. Redman said. “One-third of people with obesity gained weight during the lockdown, compared to 20.5% of people with normal weight or overweight.”
- The online survey study ran during the month of April. More than 12,000 people worldwide took a look at the survey and 7,754 completed the detailed online questionnaire. The majority of the respondents were in the United States, with half from Louisiana. Residents of Australia, Canada, the United Kingdom, and more than 50 other countries also responded.
- Those who took the survey reacted to the pandemic in largely the same way whether they live in Louisiana, elsewhere in the United States or abroad.
- The research team would like physicians and scientists to modify the way they manage patients with obesity in two ways, said Emily Flanagan, PhD, lead author of the study and a postdoctoral researcher in Dr. Redman’s Reproductive Endocrinology and Women’s Health Laboratory.
- By increasing the number of mental health screenings during and after the pandemic.
- By remaining connected to patients/study participants through remote visits and telehealth to prevent irreversible health effects from the pandemic. So-called virtual visits can assuage patients’ concerns about the safety of in-person visits.
- The results of the full study can be found at: https://onlinelibrary.wiley.com/doi/epdf/10.1002/oby.23066
L. Practical Tips & Other Useful Information
1. A Timeline of the Immune Response to C19
- Pictured above: after the initial exposure, patients typically develop symptoms within 5-6 days (incubation period). C19 generates a diverse range of clinical manifestations, ranging from mild infection to severe disease accompanied by high mortality. In patients with mild infection, initial host immune response is capable of controlling the infection. In severe disease, excessive immune response leads to organ damage, intensive care admission, or death. The viral load peaks in the first week of infection, declines thereafter gradually, while the antibody response gradually increases and is often detectable by day 14.
A summary of a study recently published in BMJ
- SARS-CoV-2 is genetically similar to SARS-CoV-1 (“SARS”), but characteristics of SARS-CoV-2—e.g., structural differences in its surface proteins and viral load kinetics—may help explain its enhanced rate of transmission
- In the respiratory tract, peak SARS-CoV-2 load is observed at the time of symptom onset or in the first week of illness, with subsequent decline thereafter indicating the highest infectiousness potential just before or within the first five days of symptom onset.
- PCR tests can detect SARS-CoV-2 RNA in the upper respiratory tract for a mean of 17 days; however, detection of viral RNA does not necessarily equate to infectiousness, and viral culture from PCR positive upper respiratory tract samples has been rarely positive beyond nine days of illness.
- Symptomatic and pre-symptomatic transmission (1-2 days before symptom onset), is likely to play a greater role in the spread of C19 than asymptomatic transmission.
- A wide range of virus-neutralising antibodies have been reported, and emerging evidence suggests that these may correlate with severity of illness but wane over time.
L. Johns Hopkins COVID-19 Update
October 26, 2020
1. Cases & Trends
- The WHO C19 Dashboard reports 42.75 million cases and 1.15 million deaths as of 5:15am EDT on October 26. The WHO reported a new record high for global weekly incidence for the sixth consecutive week. The global total reached 2.85 million cases—an increase of more than 14% over the previous week. Additionally, the WHO reported 223,026 new cases on Monday.
- Total Daily Incidence (change in average incidence; change in rank, if applicable)
- Per Capita Daily Incidence (change in average incidence; change in rank, if applicable)
- Andorra: 1,222 daily cases per million population (-36)
- Czech Republic: 1,123 (+366)
- Belgium: 1,052 (+174; ↑ 2)
- French Polynesia: 1,017 (+455 ; new)
- Luxembourg: 811*** (+518 ; new)
- Armenia: 680 (+283; ↓ 2)
- Slovenia: 673 ( +366; ↑ 1)
- France: 528 (+173; ↓ 1)
- Liechtenstein: 528 (+206)
- Netherlands: 522 (+74 ;↓ 6)
- This week, the US retook the number one global position for cumulative incidence and is reporting the highest number of global daily cases. The US, India, and Brazil remain significantly higher than any other country in terms of cumulative incidence with little signs of leveling off. While India’s daily cumulative incidence remains high, their daily incidence decreased by 16% compared to last week.
- Belgium has moved into the top 10 countries for daily incidence this week, replacing the Czech Republic. Italy’s daily incidence grew the most this week, moving up to position 7 from position 9 last week. This growth represents an 88% increase over last week. In keeping with the past 3 weeks, France’s daily incidence has approximately doubled again at a 49% increase from last week. Argentina and Montenegro fell out of the top 10 in terms of per capita daily incidence, and they were replaced by French Polynesia and Luxembourg. Not only did these two countries enter the top 10 per capita daily incidence group, but they also jumped to #4 and #5 globally, respectively. French Polynesias’s daily incidence increased by 81% compared to the previous week, Luxembourg’s increased by 177%, and Slovenia’s increased by 119%. However, #1 position Andorra’s daily per capita incidence decreased by 3% this week compared to last week.
- The US CDC reported 8.55 million total cases and 224,221 deaths. The daily C19 incidence continues to increase, now up to 83,851 new cases per day, the highest since August 3. Last week, the US set a new record peak for new daily incidence with 85,329 cases on October 24. Following the expected dip in reporting over this past weekend, we will continue to track whether a new record peak will be set later this week.
- The US C19 mortality continues to hover around 900 deaths per day. Last week on October 22, daily new deaths reached 1,135, making it the worst day since September 24 when 1,104 deaths were recorded. It is still too early to determine if this is the beginning of a longer-term trend, but it is concerning that the mortality deviated to such a degree from a trend that persisted for nearly 3 weeks.
- More than half of all US states have reported more than 100,000 cases, including 11 with more than 200,000 cases:
>400,000: New York
- The Johns Hopkins CSSE dashboard reported 8.64 million US cases and 225,247 deaths as of 10:24am EDT on October 26.
2. WHITE HOUSE INFECTIONS
- Marc Short, the US Vice President’s Chief of Staff, tested positive on Saturday. Four other aides have also tested positive, including political adviser Marty Obst and personal aide Zach Bauer. While Vice President Mike Pence and his wife have thus far tested negative on Saturday and Sunday. Devin O’Malley, a spokesperson for the Vice President, recently announced that the Vice President does not plan to quarantine and will continue campaigning as he is considered “essential personnel” – a reasoning typically only applicable to critical infrastructure workers who cannot work remotely, such as firefighters and police officers. These essential personnel may defer quarantine after exposure as long as they remain asymptomatic and additional precautions are put in place such as mask usage and social distancing. Health experts have condemned the Vice President’s decision to skip quarantine and continue attending in-person events – including his presence at a Sunday evening rally in North Carolina and his expected attendance at the Senate vote to confirm Judge Amy Coney Barrett to the Supreme Court today. Concerns have specifically been based on the Vice President’s past behavior of inconsistent mask wearing and from recorded increases in C19 cases associated with campaign rallies.
3. US COUNTY HOTSPOTS
- A recent publication from CDC’s Morbidity and Mortality Weekly Report explored the potential association between social vulnerability and C19. Authors compared C19 incidence for counties to their score with the CDC’s 2018 Social Vulnerability Index – an index that scores counties on fifteen social factors, such as the prevalence of poverty or crowded housing, in order to identify vulnerable counties that may require additional assistance to respond to disasters or outbreaks. Findings noted that counties with crowded housing and a high proportion of racial and ethnic minority residents were significantly more likely to be identified as a C19 hotspot; although, other social vulnerability factors also showed positive associations with likelihood to be identified as a C19 hotspot. Authors recommended that leaders at the local, state and federal level take additional measures to address social vulnerability factors in the context of C19 such as culturally sensitive risk communication messaging, provision of temporary housing, and other supportive measures for C19 patients residing in crowded housing units.
4. EFFECTIVENESS OF CONTROL MEASURES
- A recently published article in Lancet Infectious Diseases has taken a look at potential associations between country-level reproduction numbers (R) and non-pharmaceutical interventions introduced and lifted throughout the course of the pandemic. For context, R is an epidemiological metric that calculates the average number of people infected by one infected individual; an R value of 1 or higher indicates sustained transmission leading to a growing outbreak while an R value under 1 indicates a shrinking outbreak. Findings from the modeling study noted decreases in R associated with school closures, business or office closures, public event bans, stay-at-home orders and other movement restrictions. However, public event bans were the only measure significantly associated with a reduction of R to a value of 1 or less.
- Increases in R were associated with relaxing of the following measures: school closures, public event bans, bans on gatherings greater than ten people, stay-at-home orders and other movement restrictions. However, the only significant associations for increases in R above 1 were school reopening and lifting bans on gatherings over 10 people. Authors noted that the full effect of introducing or lifting non-pharmaceutical interventions took 1-3 weeks on average from the date of implementation. Authors made further recommendations regarding the use of non-pharmaceutical interventions by national governments, noting that other factors, such as population compliance, also influence the success of non-pharmaceutical interventions and may not be fully captured in the study.
- As of last night, Prime Minister Pedro Sánchez has announced that Spain has declared a national state of emergency and implemented an evening curfew in response to a new rise in C19 cases in the country. The evening curfew will be in place from 11pm to 6am nightly. Businesses and other establishments open to the public will need to close by 9pm each night to meet curfew requirements. Other new measures to control the spread of C19 include a ban on travel between regions and a limit on gatherings to six people. These new measures will remain in place for at least the next 15 days, but may be extended to six months if parliament allows. Local officials will have some flexibility on implementation of measures, but thus far reactions to the new measures have been positive with some localities seeking greater restrictions. Madrid has imposed a ban on mixing households for overnight stays. The Canary Islands, a tourist destination, have been excluded from the newly implemented measures.
6. CONVALESCENT PLASMA
- A study published last week in BMJ discussed the results of an open-label, Phase 2 PLACID trial of convalescent plasma in adults in India. In this multi-center, randomized control trial, 464 adult patients with moderate C19 were separated into intervention and control groups and followed for 28 days post-enrollment. Despite general public hope for the use of convalescent plasma in treating C19, this study found no evidence that convalescent plasma was associated with a reduction in disease severity or a reduction in all-cause mortality for their study population. This study is one of the first full RCTs for convalescent plasma rather than an observational study. While convalescent plasma transfusion appears to be a safe procedure, the actual benefits for C19 patient recipients remains questionable. However, convalescent plasma transfusion is not without risks of its own; blood clotting is a potential risk of the procedure, and is particularly concerning among C19 patients since blood clots are already a clinical manifestation of C19. The authors of the study have called for more randomized control trials of convalescent plasma to further evaluate its efficacy in C19 patients, even as its use has been authorized in many countries.
7. VACCINE TRIAL RESTART
- Two major vaccine trials, those of AstraZeneca and Johnson & Johnson, are positioned to restart after being paused over potential safety concerns. The AstraZeneca trial was paused on September 6th, but after independent monitoring of the adverse event several trial sites in other countries resumed later in September. The US FDA held off on restarting AstraZeneca trial sites in the US through October in order to further investigate the event with their own team. The Johnson & Johnson vaccine trial was paused on October 11 after a participant suffered a stroke. This adverse event was also independently reviewed and a final report was sent to the US FDA that recommends the vaccine trial continue. The Johnson & Johnson trial can start re-enrolling participants as early as next week. This vaccine is of particular interest to many since it is a one-dose vaccine which would greatly simplify the process of quickly inoculating millions of people. The AstraZeneca vaccine has already shown promising preliminary results and seems to produce an immunogenic response in elderly participants as well as in younger ones. It is important that any eventual vaccine can produce immunogenic responses in the eldery, in children, and in those with underlying conditions. The Pfizer vaccine has begun to enroll a cohort of children between the ages of 12-18 to test its efficacy in this age group. 16- and 17-year-old volunteers are the first to be enrolled in this study, with researchers soon looking to enroll their younger peers.
- A recently published study in the New England Journal of Medicine assessed the efficacy of the drug tocilizumab, an interleukin-6 receptor blockade, in patients hospitalized with C19 in a randomized, double-blind placebo-controlled trial. It was hypothesized that administration of this drug could potentially disrupt the cytokine storm associated with C19. The study involved 243 patients, 45% of whom were Hispanic or Latino, and about half of participants had a BMI above 30 and hypertension. Additionally about 31% of the participants had known diabetes mellitus. Patients were randomized 2:1 to receive standard care and a simple dose of tocilizumab or placebo, and key outcomes assessed included receiving time to intubation or death. A total of 11.2% of patients were intubated within 28 days or had died prior to intubation.
- The proportion of patients who experienced these outcomes in the tocilizumab group was about 2% lower than in the control group, though these results were not statistically significant. The authors concluded that the study data do not provide sufficient evidence supporting early administration of tocilizumab as an effective treatment for moderately ill patients hospitalized with C19. Given the wide confidence intervals, the authors stated they could not draw any conclusions about whether the drug exhibits benefits or harms for C19 treatment, and acknowledged that their study yielded different results than open label trials and non-randomized case series that had shown more positive results for using the treatment.
8. POOLED TESTING
- A pre-print publication has recently reported on findings from a large-scale trial aimed at assessing the efficiency of using a pooled-testing strategy within an Israeli population from April to September 2020. The study analyzed 133,816 samples using 17,945 pools to determine how many tests could be spared compared to traditional testing approaches (efficiency), the diagnostic sensitivity, and the operational feasibility of implementing this approach. Despite fluctuating prevalence in the study population, the authors concluded that they spared 76% of potential PCR reactions compared to individual testing; however, the authors noted that there was an “acceptable” reduction in sensitivity. As the prevalence rate increased from 1% to 6% in the population, they switched from 8 sample pooling to 5 sample pooling, with about 9% of the 8 sample pools and 22% of the 5 sample pools testing positive. The sensitivity decreased by 3 cycle threshold levels (Cts), which the authors believed was a clinically acceptable and expected reduction as a result of pooling. The study, though not peer-reviewed, indicates the possibility for using pooled-testing strategies to use limited testing resources with greater efficiency without sacrificing on sensitivity of testing.
9. DOWN SYNDROME
- A new paper from the Annals of Internal Medicine aimed to assess the mortality risk of C19 in individuals with Down syndrome. The study examined over 8 million individuals from the UK using a population-level primary care database, 4,053 of whom had Down syndrome. After adjusting for key demographic variables, the researchers estimated that individuals with Down Syndrome had a 4-fold increase of C19 hospitalization and a 10-fold increase of death. The researchers emphasize that this estimated association between Down syndrome and C19 is not a claim of a causal relationship, but argue that they warrant further investigation. Down syndrome is not currently listed as a C19 risk factor within the United Kingdom or United States.
M. Johns Hopkins COVID-19 Update
October 23, 2020
1. Cases & Trends
- The WHO C19 Dashboard reports 41.57 million cases and 1.13 million deaths as of 9:30am EDT on October 23.
- The US surpassed India in terms of daily incidence, resuming the #1 position globally with approximately 60,000 new cases per day. This means that the US is again increasing its lead over #2 India in terms of cumulative C19 incidence.
- The current C19 resurgence in Europe and the US have been well covered globally, as well as India’s epidemic and the high-profile success of countries like New Zealand. Today, we briefly discuss global trends in C19 incidence, with a specific focus on parts of the world that are receiving less attention recently.
- Notably, Central and South America, which were major global hotspots several months ago, are largely reporting decreasing C19 incidence, as is the nearby Caribbean region. While there are some exceptions, many countries in Sub-Saharan Africa are reporting decreasing incidence as well. Additionally, daily incidence is decreasing in most of the Eastern Mediterranean region, which includes numerous countries that previously reported among the highest per capita incidence in the world. This trend continues across much of South and Southeast Asia as well, including India, which has reported a decrease of 40% over the past 5 weeks.
- These trends can also be observed on a continental level, with incidence decreasing in South America and Asia (driven principally by India), increasing moderately in North America, and increasing more sharply in Europe (nearly doubling over the past 2 weeks). Incidence in Oceania is increasing sharply as well, but Oceania has generally reported very low incidence over the course of the pandemic, so even minor absolute increases result in large relative changes. Similarly, incidence in Africa appears to be increasing at approximately the same rate as North America, but this is a result of a much smaller absolute change due to Africa’s generally low incidence, particularly on a per capita basis.
- The US CDC reported 8.31 million total cases and 221,438 deaths. The daily C19 incidence continues to increase, now up to 59,699 new cases per day, the highest since August 3. Following the previous peak (66,960 new cases per day on July 24), the US daily incidence fell by 48% to its most recent low (34,371 new cases per day on September 12). Since that time, however, the US has climbed more than 75% of the way back to its highest peak, and still increasing steadily.
- The US C19 mortality increased for the third consecutive day, up from approximately 700 deaths per day to 773—a 10% increase and the highest average since September 19. It is still too early to determine if this is the beginning of a longer-term trend.
- More than half of all US states have reported more than 100,000 cases, including 10 with more than 200,000 cases:
>400,000: New York
- Wisconsin is averaging more than 3,500 new cases per day over the past week, so we expect it to surpass 200,000 cumulative cases in the next several days.
- The Johns Hopkins CSSE dashboard reported 8.43 million US cases and 223,289 deaths as of 12:30pm EDT on October 21.
2. LOMBARDY, ITALY
- Early in the C19 pandemic, Italy’s Lombardy region was one of the most severely affected parts of the world. According to Italy’s Ministry of Health, the region has reported more than 143,000 total cases, including more than 17,000 deaths. The initial patient surge overwhelmed Lombardy’s health system, and approximately 12,000 healthcare workers were infected. In order to better understand the impacts and drivers of the epidemic, the Regional Council of Lombardy created a “C19 investigative commission.”
- The commission will “analyze the sequence of events and the specific choices that led to so many infections and deaths” with the aim of learning and sharing lessons and providing “accountability [for] the Italian people.” The commission will assess a variety of data and include input from technical experts in order to characterize the C19 epidemiology, response, and effects on the region. A member of the commission indicated that this effort is the first of its kind in Europe, and possibly globally.
- Ireland is implementing one of the most restrictive sets of social distancing measures in Europe in response to its “second wave” of C19. This week, Ireland entered Phase 5 “lockdown,” the highest level in Ireland, which includes restrictions on social gatherings (indoors and outdoors), including weddings and funerals; religious services; retail businesses, restaurants, cafes, and pubs; essential services; sporting events and outdoor activities; and travel, hotels, and public transportation. Notably, schools and childcare services will remain open in Phase 5.
- Households are permitted to form a “support bubble” with one other household, under specific circumstances. The Irish government is also increasing financial assistance for unemployed individuals under Phase 5. The Phase 5 restrictions are currently scheduled to last at least 6 weeks. In early October, when Ireland was at Phase 2, senior medical experts in Ireland reportedly called on the government to move immediately to Phase 5, arguing that this was the only option to contain transmission while keeping schools open; however, Ireland moved one step to Phase 3, which still permitted many aspects of social and economic activity to continue. Ireland has reported nearly 55,000 cases and more than 1,800 deaths, and its daily incidence has increased by a factor of 11 since early September, setting new records there.
- Following efforts by the Kenyan government to ease social and economic restrictions, Kenya is reporting a second surge in C19 incidence. The policy changes included shifting the start of a nationwide curfew to a later hour in order to support bars and restaurants and a partial reopening of public schools. Kenyan President Uhuru Kenyatta announced the changes during a national address in late September, in which he discussed the challenges Kenya endured over the early stage of the pandemic and called for continued vigilance by Kenyans to contain the virus. The restrictions implemented in response to Kenya’s “first wave” of transmission enabled the country to largely bring its epidemic under control; however, Kenya has seen a steady increase in C19 activity since mid-to-late September. Since its low of 118 new cases per day on September 21, Kenya’s daily incidence has increased by a factor of 5. It has nearly returned to the height of its first peak and is still increasing rapidly.
- The government’s response to C19 has added fuel to protests in Kyrgyzstan that started in opposition to disputed results of the country’s parliamentary election. In addition to concerns about the validity of the election results, protestors expressed frustration with the lack of government support during the national “lockdown.” According to a report by Reuters, some protestors indicated that citizens were largely left to “fend for themselves,” which has contributed to growing anger and opposition toward government leadership. Kyrgyzstan relies on external travel with China and Russia to support the national economy, and many have argued that the government did not do enough to support their citizens financially following the border closure and travel restrictions. C19 daily incidence has been increasing in Kyrgyzstan since its low in mid-September, increasing from approximately 57 new cases per day to more than 500 over that time.
6. WHO REFORM
- The German government and the EU reportedly drafted a document calling for reforms that aim to increase transparency by the WHO. The WHO has received criticism over the course of the C19 pandemic, including for a perceived shortage of information shared publicly in the pandemic’s early stages. US President Donald Trump has repeatedly cited a lack of transparency, with a particular focus on China, as one of the primary reasons for his decision to withdraw the US from the WHO. According to a report by Reuters, the document is part of an ongoing EU effort to improve WHO’s capabilities. The report also indicates that the EU proposal aims to reduce the impact of “political influence” on WHO activities and reporting as well as increase funding and address the WHO’s lack of legal authority to take and compel action around health issues. The proposal is still in draft form and, to our knowledge, has not yet been published publicly.
- Following a recent surge to more than 10,000 new cases per day, Germany issued travel warnings for nearby European countries, including popular tourist destinations such as Austria, Italy, and Switzerland. Returning travelers from these countries must self-quarantine for 10 days; however, if the individual tests negative after the fifth day, they can end their quarantine period early. The new travel policies take effect on October 24, and they are an expansion of previously issued warnings corresponding for more than 10 European countries, based on the Robert Koch Institute’s list of high-risk areas. Countries across Europe are facing a severe resurgence of C19, worse than the “first wave” in many countries. While the new measures may impact tourism to affected regions or countries, other tourist regions such as Spain’s Canary Islands have recently been removed from the Robert Koch Institute’s list of high-risk areas.
- Additionally, German Health Minister Jens Spahn recently tested positive for SARS-CoV-2. While Minister Spahn is in isolation and reportedly exhibiting “cold-like symptoms,” no other members of Chancellor Angela Merkel’s cabinet will be subjected to quarantine, despite having contact with Minister Spahn earlier in the week. The extent of the contact between Minister Spahn and other cabinet members is unclear; however, government officials indicated that quarantine is not warranted, based on Germany’s public health guidelines.
8. US CDC UPDATES “CLOSE CONTACT” DEFINITION
- The US CDC published updated guidance regarding the definition of “close contact” for C19. The new iteration of the guidance indicates that even brief contact with infectious individuals could result in transmission. Both the previous version and the newest iteration define close contact as being within 6 feet of an infectious individual for 15 minutes, but the new version notes that the time is cumulative over a 24-hour period. This could include being within 6 feet of an infectious individual for 3 separate periods of 5 minutes each, whereas the previous version was generally understood as referring to a single, prolonged exposure period. The CDC guidance continues to emphasize that it is difficult to concretely define what qualifies as close contact and that the guidance is an “operational definition for contact investigation.”
- The change was reported motivated by a case study recently published in the US CDC’s MMWR. The study documents suspected SARS-CoV-2 transmission over the course of multiple short exposure periods. The event occurred at a correctional facility in Vermont (US), and a correctional officer was infected after “multiple brief encounters with six incarcerated…persons” who were awaiting the results of SARS-CoV-2 tests after their arrival at the facility. All 6 individuals ultimately received positive test results. Review of video surveillance showed that the correctional officer was not within 6 feet of any of the individuals for a 15-minute period, and therefore, he was not identified as a close contact. The officer was not included in contact tracing efforts, and he was permitted to continue working. He later developed C19 symptoms and tested positive for SARS-CoV-2. Further evaluation of the surveillance video found that the correctional officer was within 6 feet of the infected incarcerated individuals at least 22 times, totaling approximately 17 minutes over the course of an 8-hour shift. This example illustrates that SARS-CoV-2 transmission can occur over much shorter periods of contact than suggested by previous CDC guidance.
9. REMDESIVIR APPROVED
- The US FDA announced that it approved remdesivir as treatment for C19, the first drug to obtain full regulatory approval (as opposed to an Emergency Use Authorization [EUA]). According to the official announcement, the approval applies to hospitalized C19 patients aged 12 or older and weighing at least 88 pounds (40 kg). Remdesivir’s EUA remains in effect for hospitalized pediatric patients under the age of 12 and weighing at least 7.7 pounds (3.5 kg) and for hospitalized patients aged 12 and older and weighing 7.7-88 pounds (3.5-40kg). The FDA’s decision was based on the findings from 3 randomized controlled trials that demonstrated a statistically significant effect in terms of speeding recovery among hospitalized C19 patients. However, the trials did not identify an improvement in the odds of recovery/reduction in mortality.
10. VACCINE CLINICAL TRIALS
- Moderna Therapeutics completed enrollment of the Phase 3 clinical trial for its candidate SARS-CoV-2 vaccine. The trial enrolled 30,000 participants, including more than 12,000 Americans who are over the age of 65 or have high-risk health conditions. Approximately 42% of the total trial population is at elevated risk for severe C19 disease and death, including those with a myriad of underlying health conditions: diabetes (36%), severe obesity (25%), severe cardiac disease (19%), and chronic lung disease (18%). Additionally, 37% of enrollees are racial or ethnic minorities. Notably, 10% of all enrollees are Black, 20% are Hispanic or Latinx, and 4% are Asian. Black enrollment in the study is slightly lower than the proportion of Black individuals in the overall US population, but the diversity of the participants has been viewed positively, particularly considering that Moderna faced challenges enrolling participants from certain racial and ethnic minority groups.
- It was widely reported this week that a participant enrolled in the Phase 3 clinical trial for the AstraZeneca/Oxford candidate vaccine trial died, raising concerns about the safety of the vaccine and the clinical trial timeline. The participant was a 28-year-old physician in Brazil who treated C19 patients. However, according to multiple reports, the patient was a member of the control group, and did not receive the candidate SARS-CoV-2 vaccine. Rather, the participant received an approved meningitis vaccine. Because the death was not attributable to an adverse event associated with the candidate vaccine, the trial can continue. Focus has remained centered on developments in the AstraZeneca clinical trials around the world, particularly after the trials in the UK and other countries were paused after a participant was diagnosed with transverse myelitis. The trial has since resumed in the UK and other countries, but not in the US.