December 7, 2020
“We’re now looking literally at 2021 being the worst humanitarian crisis year since the beginning of the United Nations, and we’re going to have to step up as some 270 million people are on the pathway towards starvation.”David Beasley, Head of UN World Food Program
“That plastic sheet keeps moving closer. I’m trying not to panic, but where am I supposed to go? It’s not like I can jump up and make a run for it. I’m in a wheelchair and am a sitting duck that can’t afford to wait for a vaccine.”Bruce MacGillis, resident of Ohio nursing home that called 911 to be rescued
“Is there anyone in the York Hospital, Hershey Hospital, Penn State, Temple or Maryland Hospitals that has connections to the COVID ICU? My mom is not doing well and is maxed out at Hanover Hospitals capabilities. We are looking for a hospital that has an ECMO machine and a bed so Hanover can transfer her to you. I’m sorry to be blunt but FB is the fastest way to get news out. Hanover Hospital is making calls, but I can’t move forward without giving it my best shot.”Shawn Rider, pleading for help for his mom from Facebook friends
“We’ve had Operation Warp Speed in developing vaccines but Operation Turtle Speed in reviewing the results.”Dr. Marty Makary, a professor at the Johns Hopkins University School of Medicine and Johns Hopkins Bloomberg School of Public Health, lambasting the Food and Drug Administration for lacking urgency in greenlighting a coronavirus vaccine, suggesting that the agency’s bureaucratic process is costing lives
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Highlighted stories includes information we found interesting. An (!) indicates a story that includes new, promising/breakthrough or unexpected/surprising information. A (*) indicates information that may be useful in connection with your plans and preparations regarding the coronavirus and C19. And © indicates that a story contains information that may contradict or be inconsistent with other information.
- Cases & Tests
- Top 5 States in Cases, Deaths, Hospitalizations, Patients in ICU & Positivity
- New Infections Reported in U.S. Topped 1.3 Million in a Week
- The virus is devastating the U.S., and leaving an uneven toll
- Asymptomatic Spread Not a Significant Source of C19 (!) ©
- C19: When Are You Most Infectious? (!) (*)
- Should Isolation Periods Be Shorter for People With C19?
- Scientists find link between TB vaccination and C19 spread
- Blood Tests May Be Key To Future C19 Vaccine Development
- Here’s what scientists want to know about the vaccines (*)
- Find your place in line. When will you get the vaccine? (*)
- A Rapid Covid Test That’s Also Accurate? The NFL Says It Has One
- Florida requiring labs to report critical ‘cycle threshold’ of C19 tests
- The U.S. Has Passed the Hospital Breaking Point
- What happens when the immune response is out of sync?
- The Vaccine: Is it safe? Should I get one? (*)
- Train Your Body to Work Out—or Just Hang Out—in Colder Weather (*)
- How Airflow Inside a Car May Affect C19 Transmission Risk – What Works Best for Windows and Ventilation (*)
K. Linked Stories
- Researchers urge priority vaccination for individuals with diabetes
- ‘Do people understand what’s happening here? Do they care?’: The excruciating wait for a vaccine inside a covid-infected nursing home
- Once hospitalized, Black patients with C19 have lower risk of death than white
- Lung tissue from C19 patients and others reveals promising target to treat lung fibrosis
- C19 advice may have reduced exposure to heart attack triggers
- Scientist’s decades of mRNA research led to both COVID-19 vaccines
- The vaccine miracle: how scientists waged the battle against C19
- Woman with C19 eats super-spicy meal after losing sense of taste, documents body’s ‘weirdest’ reaction
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A. Pandemic Headlines
(In no particular order)
- US cases top 200,000 cases for four consecutive days (Wednesday through Saturday)
- US deaths highest since springtime peak
- The Midwest is showing signs of progress against the virus, but will it last?
- HHS Secretary Azar Says COVID Vaccine Approval Could Arrive “Within Days”
- Azar says vaccines widely available by second quarter of 2021
- Russia begins a mass vaccination campaign in Moscow, with a vaccine that is not fully tested.
- Britain’s vaccine rollout gives Boris Johnson a chance to improve his reputation
- The World Watches as Russia and Britain Lead the Way in Mass Vaccinations
- China prepares large-scale rollout of coronavirus vaccines
- “There Will Absolutely Be A Black Market” For COVID Vaccines, Bioethicists Warn
- The U.S. debate over which group should get vaccine priority is getting heated
- NYC Mayor de Blasio will take COVID vaccine publicly to prove its safety
- Dr Birx: COVID-19 vaccine won’t ‘save us from this current surge’
- Most of California to enter new sweeping virus lockdown
- California Sheriff Slams Gov. Newsom’s ‘Dictatorial’ Lockdowns, Won’t Be ‘Blackmailed, Bullied Or Used As Muscle’ To Enforce
- CA chef refuses to close restaurants, calls Gov. Newsom an ‘a—hole’
- COVID-19 now leading cause of death in US topping heart disease
- CDC Asks Americans To Wear Masks Indoors Unless At Home
- Coronavirus Immunity Passports ‘Likely to Be Possible’, Say UK Govt Science Advisers
- Chief Medical Officer Says Canadians Who Refuse Vaccine Won’t Have “Freedom To Move Around”
- Dr. Fauci says he ‘absolutely’ accepted offer to be Biden’s chief medical adviser
- 82% Of Americans Say They Couldn’t Afford $500 Emergency Thanks To COVID-19
- NJ reports record 6,000+ new cases
- NYC COVID-19 numbers still rising in ‘cluster zones,’ positive rate dips statewide
- NYC positivity rate tops 5%
- San Francisco Bay Area to begin month-long COVID-19 lockdown
- With Covid-19 hospitalizations at a high, Tennessee asks the National Guard for help
- Once a model for how to contain the virus, New Rochelle now mourns its return
- Bavaria orders new lockdown
- Italy outbreak improves
- Tokyo reports a record number of cases
- Indonesia receives first shipment of Sinovac doses
- Polish deaths slow
- Government officials will ease coronavirus restrictions in Portugal over the Christmas holiday
- Paris Plunges Into Chaos As Protesters Denounce New Security Law
- Even Sweden toughens up restrictions after refusing to order COVID-19 lockdown
- COVID Is Exposing The Cancerous Underbelly Of US Healthcare
- Queen Elizabeth, Prince Philip may get UK’s COVID-19 vaccine to dispel fears
- Seven COVID-19 deaths reported at nursing home after staffers attend wedding
- Oregon suspends license of anti-mask doctor
- Covid-19 may cause erectile dysfunction
- Homeschooling More Than Doubles During the Pandemic
- K-12 experiment in distant learning has failed
- Minority Students Crushed By Lockdowns; 600% Increase In Math Failures, 500% English
- More high school seniors skip out on college planning amid COVID-19
- Condo Interest In NYC Suburbs Erupts As Exodus Accelerates
- Hawaii hopes its pandemic-battered economy will get a boost from mainlanders working remotely
- Should I just give up and retire if I can’t get a new job at 64?
- Mexico is urging citizens to cancel Christmas
- ‘We’re just scraping by’: Defiant NYC bar reopens despite COVID restrictions
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 New Cases: 67,377,463
- New Cases (7 day average) = 610,177
- Record high 7 day average of new cases
- Record high number of new cases on 12/3
- 7 day average began increasing again on 11/30
- From 11/30 to 12/6, the 7 day average increased from 578,182 to 610,177, an increase of 5.5%
US Cases & Testing:
- Total Cases = 15,159,529
- New Cases (7 day average) = 200,012
- Percentage of New Global Cases = 32.8%
- Total Number of Tests = 207,456,975
- Percentage of positive tests (7 day average) = 12.9%
- Record High 7 day average of new cases
- After declining from 11/25 to 11/30, the 7 day after has been rapidly growing
- From 11/30 to 12/6, the 7 day average increased from 166,904 to 200,012, an increase in 19.8% in one week (!)
- Percentage of positive tests continues to increase
- Total Deaths = 1,541,373
- New Deaths (7 day average) = 10,807
- Record high 7 day average of new deaths
- Total Deaths = 288,906
- New Deaths (7 day average) = 2,258
- Percentage of Global New Deaths = 20.9%
- Record high 7 day average of new deaths
- After declining from 11/25 to 11/29, the 7 day average has been increasing at a rapid rate
- Since 11/29, the 7 day average has increased from 1,522 to 2,258, an increase of 48.6% in one week (!)
- US percentage of Global New Deaths is also increasing at a rapid rate
- The rapid increase in new cases and positive test rate indicate that new deaths will continue to increase at rapid rate
3. Top 5 States in Cases, Deaths, Hospitalizations, ICU Patients & Positivity (12/6)
- For the 5th straight day following Thanksgiving, the US positivity % increased 12.9%, an increase from 11.8% on 11/29.
- ND retains the lead at 52.3%, but the rate continues to decline, falling from 54.2% a week ago
- Overall, 7 states reported lower positivity rates over the last seven days.
- Seven states (SD, KS, ID, MO, NE, IA, IN) 7-day positivity rates greater than 40%. (+4 since 11/29)
- Six states (NV, WI, PA, UT, AL, RI) 7-day positivity rates greater than 30%. (unch since 11/29)
- Six states (MN, AZ, WY, CO, DE, NH) had 7-day positivity rates greater than 20%. (-2 since 11/29)
- In total, 45 states have 7-day positivity rates greater than 5% (+2 since 11/29)
- Hospitalizations in the US reached an all-time high of 101,487, up 8.7% since 11/29. Hospitalizations are increasing, but the rate of growth is slowing. The growth rate on 11/29 was 11.4%.
- 24 states have had increases of hospitalized patients of more than 10% since 11/29. (-6 since 12/3)
- 32 states have more than 1,000 hospitalized patients (+1 since 12/3)
- 12 states saw decreases in the number of hospitalized patients (IA, NE, IL, ND, WI, SD, IN, MN, WY, CO, HI, NM). (+2 since 12/3)
- ICU Patients in the US reached an all-time high of 20,145, up from 18,437 (+9.3%) a week ago. While ICU patients have increased, the weekly percentage increase has fallen from 15.3% on 11/24
- 18 states have seen the number of ICU patients increase by more than 10% since a week ago (unch since 12/3)
- 32 states have more than 100 patients in ICU, (+1 states since 12/3)
- 11 states (HI, IA, MT, ME, IL, WI, MN, MO, AR, KY, VT) saw decreases in the number of ICU patients since a week ago (unch since 12/3)
4. New Infections Reported in U.S. Topped 1.3 Million in a Week
What to Know
- The number of reported deaths in the U.S. neared 282,000.
- The U.S. reported 213,875 new cases.
- Total reported infections in the U.S. surpassed 14.7 million on Sunday.
- Nationally, the seven-day average hit a record of 190,948 infections a day.
- Nationally, the number of people hospitalized because of C19 was 101,190 on Saturday, the most recent data available from the Covid Tracking Project show, after hitting a single-day record of 101,276 on Friday, nearly double the 52,086 hospitalizations recorded one month earlier, on Nov. 4.
- Newly reported Covid-19 cases in the U.S. were above 200,000 for the fourth straight day, as the number of deaths linked to the virus in the country neared 282,000.
- Nationally, 213,875 new cases were reported on Saturday, according to data compiled by Johns Hopkins University, down from 227,885 a day earlier. The Johns Hopkins data showed 2,254 new deaths.
- Days earlier, the U.S. broke single-day records for deaths and hospitalizations.
- The United States is winding up a particularly devastating week, one of the very worst since the coronavirus pandemic began nine months ago.
- The country set a single-day record for new daily infections on Thursday, with more than 217,000, only to jump to a new high of more than 228,000 on Friday. Many other data points that illustrated the depth and spread of a virus that has killed more than 279,000 people in the United States, more than the entire population of Lubbock, Texas; or Modesto, Calif.; or Jersey City, N.J.
- “It’s just an astonishing number,” said Caitlin Rivers, a senior scholar at the Johns Hopkins Center for Health Security. “We’re in the middle of this really severe wave and I think as we go through the day to day of this pandemic, it can be easy to lose sight of how massive and deep the tragedy is.”
- As the virus has spread, infectious disease experts have gained a better understanding of who among the nation’s nearly 330 million residents is the most vulnerable.
- Nursing home deaths have consistently represented about 40% of the country’s C19 deaths since midsummer, even as facilities kept visitors away and took other precautions and as the share of infections related to long-term care facilities fell substantially.
- Underlying conditions have played a pivotal role in determining who survives the virus. Americans who have conditions like diabetes, hypertension and obesity — about 45% of the population — are more vulnerable.
- And new evidence has emerged that people in lower-income neighborhoods experienced higher exposure risk to the virus because of their need to work outside the home.
- The poor, in particular, have been more at risk than the rich, according to analyses of those who have been sickened by the virus or succumbed to it.
- Studies suggest that the reason the virus has affected Black and Latino communities more than white neighborhoods is tied to social and environmental factors, not any innate vulnerability.
- According to one recent study of cellphone data, people in lower-income neighborhoods experienced significantly higher exposure risk to the virus because they were compelled to go to jobs outside their homes.
C. New Scientific Findings & Research
1. Asymptomatic Spread Not a Significant Source of C19
- The most recent study from China on the prevalence of infection after a lockdown found no transmission of the coronavirus among people who were in close contact with asymptomatic patients, contradicting the current narrative that asymptomatic transmission plays a major role in the pandemic.
- An asymptomatic carrier is someone who has not displayed symptoms after being infected, but may spread the virus to others. This is different from someone who is presymptomatic, meaning the person doesn’t feel or look sick, but eventually shows symptoms later, and does transmit the virus during that presymptomatic phase.
- The study, published in Nature, identified 300 asymptomatic positive cases through a massive screening program of more than nine million Chinese citizens post-lockdown in Wuhan—where the coronavirus originated—from May 4 to June 1, using PCR tests.
- Samples of all the asymptomatic cases were also cultured in the lab and “no viable virus” was found, meaning it cannot transmit a virus. The authors also found that 190 of the 300 asymptomatic samples tested positive for antibodies (IgG and/or IgM), indicating a possible recent C19 infection or the PCR test resulted in a false positive.
- The scientists identified and followed 1,174 close contacts of the asymptomatic cases and found that none of the contacts tested positive for C19. They noted, “Compared with symptomatic patients, asymptomatic infected persons generally have low quantity of viral loads and a short duration of viral shedding, which decrease the transmission risk of the coronavirus (SARS-CoV-2).”
- “This study confirms what physicians have known and non-scientists have suspected for millennia: namely, that asymptomatic transmission has never been the primary cause of outbreaks,” Dr. Simone Gold, MD, and founder of America’s Frontline Doctors told The Epoch Times in an email.
- Prior to the coronavirus pandemic, guidance for treatment and diagnosis of a respiratory viral outbreak—including the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak and the 2012 Middle East Respiratory Syndrome (MERS) outbreak—predominantly focused on symptomatic cases to stop the transmission of the disease.
- The Infectious Diseases Society of America’s most updated guidance on diagnosing, treating, and managing outbreaks during flu season recommends only people with symptoms get tested for influenza.
- Sweden, which has not resorted to lockdowns, universal testing of its citizens, or mandated mask-wearing since the pandemic began, doesn’t believe that asymptomatic spread is common. “Based on the experience of C19 and other similar diseases, the assessment is that the spread of infection from people without symptoms accounts for a small proportion,” according to the Swedish Public Health Agency.
- To avoid infection, Swedes are encouraged to not touch their face, physically distance in public places, practice hand hygiene, sneeze or cough into the arm fold, and stay home when feeling sick.
- There is evidence that indicates asymptomatic spread is not as prevalent as earlier studies claimed it to be, as high as 81%, and that the risk of transmission from asymptomatic patients is low.
- In a systematic review and meta-analysis that included 79 studies, scientists found that asymptomatic carriers “demonstrated faster viral clearance” that suggests a “shorter infectious period.”
- In a different meta-analysis study published online on October 9, researchers found that their “estimates of the prevalence of asymptomatic C19 cases and asymptomatic transmission rates are lower than many highly publicized studies.”
- The overall rate of asymptomatic cases was 17%, and asymptomatic carriers were 42% less likely to spread the Coronavirus compared to symptomatic individuals.
- The study involved 21,708 people from 13 studies that followed patients for “at least 7 days to distinguish asymptomatic cases from pre-symptomatic cases.”
- Several highly publicized studies like the Diamond Princess cruise ship, the Iceland study, and the homeless shelter in Boston, cited by many governments and public health officials to justify some of their policies were excluded from this study for their lack of follow-up on the patients to determine if they were truly asymptomatic or presymptomatic.
- The first report to suggest asymptomatic spread outside China was also excluded. The report made national headlines before it was found to be flawed. The authors relied only on the accounts of the four German patients without speaking to the “asymptomatic” businesswoman from Shanghai, who had developed symptoms while in Germany.
- The authors addressed the mistake by submitting a supplementary appendix (pdf) attached to the bottom of the paper, instead of making a correction to the paper itself.
Testing of Healthy People
- Several countries are universally testing and masking healthy people as an effort to mitigate asymptomatic spread, despite inconclusive evidence to support asymptomatic infections being a driver of the pandemic.
- The CDC in its updated guidance for why cloth masks should be worn in the community claim there is a 50% transmission rate of asymptomatic people, without differentiating between asymptomatic and presymptomatic individuals.
- “Masks are primarily intended to reduce the emission of virus-laden droplets (“source control”), which is especially relevant for asymptomatic or presymptomatic infected wearers … who are estimated to account for more than 50% of transmissions.”
- Universities across the United States, Canada, and the UK have propped up makeshift testing sites to test students and staff, while Washington Mayor Muriel Bowser has implemented an asymptomatic testing protocol for students and staff participating in the state’s public schools in-person learning program.
- “We are proud of the very robust testing system we have built in [the District of Columbia], and now we can use that infrastructure to support this program,” Bowser said in a press release on Dec. 2.
- Students whose parent or guardian have signed a consent form will be able to receive a “PCR nasal-swab test” about every 10 days at school, while staff is offered a mailed testing kit once a week, all at no cost.
2. C19: When Are You Most Infectious?
- To understand when people with C19 are most likely to be infectious, our team conducted a study which was recently published in The Lancet Microbe.
- We investigated three things: viral load (how the amount of the virus in the body changes throughout infection), viral shedding (the length of time someone sheds viral genetic material, which does not necessarily mean a person is infectious), and isolation of the live virus (a better indicator of a person’s infectiousness, as the live virus, is isolated and tested to see if it can replicate in the laboratory).
- We found that viral load reached its peak in the throat and nose (which is thought to be the main source of transmission) very early in the disease, particularly from the first day of symptoms to day five of symptoms – even in people with mild symptoms.
- We also found that genetic material can still be detected in throat swab or stool samples for several weeks. But no live virus was found in any sample collected beyond nine days of symptoms. Although some people, especially those with severe illness or with a weakened immune system (say from chemotherapy), may have longer viral shedding, the results suggest that those infected with SARS-CoV-2 are most likely to be highly infectious a few days before symptoms start and the following five days.
- In comparison, the viral load of Sars peaks at 10-14 days and for Mers at 7-10 days after symptoms start (Sars and Mers are both diseases caused by coronaviruses). This explains why the transmission of these viruses was effectively reduced by immediately finding and isolating people who had symptoms. It also explains why it has been so difficult to contain C19 as it spreads very quickly early in the disease course.
- Contact tracing and modeling studies also show that transmission is highest in the first five days of experiencing symptoms. According to a recent study, the period of highest infectiousness is within about five days of symptoms starting. A contact tracing study from Taiwan and the UK found that most contacts got infected if they were exposed to the infected person within five days of their symptom onset.
- By the time most people get their test results, they may already be beyond their most infectious period. This early viral load peak suggests that to prevent onward transmission, a person with C19 needs to self-isolate as soon as symptoms start without waiting for test results.
- According to a UK survey, only one in five people are able to self-isolate. Barriers include having a dependent child at home, having low income, experiencing greater financial hardship during the pandemic, and being a key worker, such as a nurse or teacher.
Governments Could Do More To Help
- How will a diagnosis help if your living situation doesn’t allow for isolation, if you have a job that can’t be done from home, and your work doesn’t provide sick leave? And how will a diagnosis help if your family depends on your income to meet basic needs, or your access to care is linked to your employment?
- This highlights why we must focus on supporting people with C19 to self-isolate early in the disease course. Here are four ways to help people self-isolate:
- Income relief to avoid undue pressure to work when sick (the proportion of salary covered by sick pay is 29% in the UK).
- Housing for disadvantaged communities, especially those living in crowded houses and those living with vulnerable people, as has been successfully done in Vermont, in the US.
- Services to support people who are self-isolating, as is done in New York and many southeast Asian countries.
- Remove barriers to accessing healthcare and consider making isolation periods shorter – five to seven days after symptoms begin. This could cover the most infectious period and might improve people’s ability to comply with isolation. In September, France dropped the isolation period for cases to seven days, and Germany is considering shortening it to five days. The benefit of shortening isolation may more than offset any risk to the community.
- With these measures in place, we should be in a much better position to beat the pandemic.
3. Should Isolation Periods Be Shorter for People With C19
- People with C19 are most infectious about two days before symptoms begin and for five days afterward, according to a new analysis of previous research.
- A few patients who are extremely ill or have impaired immune systems may expel — or “shed” — the virus for as long as 20 days, other studies have suggested. Even in mild cases, some patients may shed live virus for about a week, the new analysis found.
- The accumulating data presents a quandary: Should public health officials shorten the recommended isolation time if it means more infected people will cooperate? Or should officials opt for longer periods in order to prevent transmission in virtually all cases, even if doing so takes a harsher toll on the economy?
- The CDC recommends that infected people isolate for a minimum of 10 days from the beginning of their illness. The agency is considering shortening the recommended isolation period and may issue new guidelines as early as next week, according to two federal officials with knowledge of the discussions.
- In September, France dropped its required period of isolation to seven days from 14 days, and Germany is considering shortening it to five days. (Isolation refers to people who are ill; quarantine refers to people who have been exposed to the virus and may become ill.)
- Setting the isolation period at five days is likely to be much more palatable and may encourage more infected people to comply, said Dr. Muge Cevik, an infectious disease expert at the University of St Andrews in Scotland who led the new analysis, published in the journal The Lancet Microbe.
- A recent survey in the United Kingdom showed that only one in five people were able to isolate for 10 days after developing symptoms. “Even if we do more testing, if we can’t ensure people self-isolate, I don’t think we’ll be able to control the spread,” Dr. Cevik said.
- In the United States, many people don’t get tested for the infection until a day or two after they begin to feel ill. With the current delays, many receive results two or three days later, toward the end of the period during which they are infectious.
- “Even if you were to get the P.C.R. test right on the very first day that you could, by the time you get the results back, 90 percent of your shedding has been completed,” said Dr. Michael Mina, a virologist at the Harvard T.H. Chan School of Public Health. “This meta-analysis shows just how short your transmission window is.”
- Dr. Cevik and her colleagues set out to analyze the so-called kinetics of the coronavirus over the course of an infection, and to compare the pathogen to the closely related SARS and MERS viruses.
- The researchers considered nearly 1,500 studies published from 2003 to June 2020 on the timing of infection in thousands of people, most of whom were sick enough to be hospitalized. The team drew data from 79 studies of the new coronavirus, 11 studies of MERS and eight studies of SARS.
- People who never develop symptoms seem to carry about the same amount of the new coronavirus as symptomatic patients, Dr. Cevik and her colleagues found. But asymptomatic people seem to clear the virus more quickly from their bodies.
- People with C19 usually are most infectious a day or two before the onset of symptoms until about five days after, the analysis concluded. Yet patients may carry genetic fragments from the virus in their noses and throats for an average of 17 days, and, in some cases, for up to three months.
- A few patients may carry infectious virus in their lungs — as opposed to the nose and throat — for as long as eight days after symptoms begin, noted Dr. Megan Ranney, an emergency physician at Brown University. For these patients, at least, isolation periods should probably be longer than five days, if only they could be identified.
- “The trouble is, who has Covid pneumonia versus who doesn’t is not always fully apparent just based on physical exam,” she said. “They wouldn’t know it on their own.”
- Older people tend to be infectious for longer than younger people, but no study in the analysis detected live virus beyond nine days of symptom onset. The results suggest that positive tests after that point find only genetic fragments, rather than whole live virus, Dr. Cevik said.
- Because the infectious period seems to peak relatively quickly in the course of the illness, health care workers at community clinics may be at higher risk of becoming infected than those working in I.C.U. units, where patients tend to be in the later stages, Dr. Cevik added.
- The analysis underscores data that has accumulated since March. In July, based on similar evidence, the C.D.C. truncated its recommendation for isolation to 10 days from 14 days.
- But even at 10 days, the isolation period may be too long for many people, experts said. Patients may be financially unable to isolate for so long, or they may not feel sick enough to want to do so.
- “If you could make that shorter for people, I think that would really help people comply with the public health guidelines,” said Angela Rasmussen, a virologist affiliated with the Center for Global Health Science and Security at Georgetown University, referring to the recommended isolation period.
- But the new analysis is limited by the fact that only a few of the included studies looked at live virus, she added.
- Some people who are older or very sick may be infectious for longer than a week. But if a shorter recommended period encourages more people to isolate, the benefit will more than offset any risk to the community from the small amount of virus that a few patients may still carry after five days, said Dr. Stefan Baral, an epidemiologist at Johns Hopkins University.
- “There’s a sweet spot there, I would imagine, but I haven’t figured out where that is,” said Dr. Taison Bell, a critical care and infectious disease physician at the University of Virginia.
- Dr. Cevik and other experts suggest that people can isolate as soon as they experience even mild symptoms, such as a sore throat or head and body aches — without venturing out for a P.C.R. test right when they are most infectious.
- But Dr. Bell said he was unsure how this would work in practice, because these early symptoms were similar to those from other viral infections, including the common cold.
- Dr. Cevik said a P.C.R. test could be performed after isolation ended to confirm the diagnosis. Alternately, it may make sense to take a rapid antigen test — which can detect high amounts of virus — while isolating, so as to confirm an active coronavirus infection.
- Other experts also endorsed the use of at-home rapid tests. “I think that’s a lovely solution,” Dr. Ranney said. “If you have symptoms, and you have a reliable test that you can do at home, stay home, test at home and isolate for five days.”
- Over all, the new analysis underscores how quickly the coronavirus blooms in the body and the speed with which both patients and doctors must respond to keep it contained, Dr. Baral said. Levels of the MERS virus peak at seven to 10 days from symptom onset, and those of the SARS virus peak at Days 10 to 14.
- By contrast, the new coronavirus “moves quick,” Dr. Baral said. “It’s a very difficult virus to control, as compared to SARS.”
- Home isolation is safe for most of those newly infected with the coronavirus, he added — essentially the model of care that doctors use for patients suspected of having influenza.
- Some countries already have adopted policies to make it easier for people to isolate. Vietnam provides income support to people who need to take time off work. Until May, the Japanese government asked patients who were young and had mild symptoms to stay home for four days before seeking testing.
- Japan’s guidelines now ask patients to consult by phone with their doctors and to seek testing only if they seem likely to be infected. Anyone who tests positive is admitted to a hospital or a hotel to isolate. In the United States, New York City and Vermont have made similar accommodations available to infected patients.
- Even if the rest of the country doesn’t implement such policies, having patients isolate at home — while wearing a mask, keeping windows open, cleaning high-touch surfaces and staying far from other household members — is more feasible for five days than for 10, Dr. Baral said.
- “I do think there’s an element of diminishing returns with those last four or five days,” he said. “An intense amount of isolation during that first five to seven days would avert a ton of infections — a ton.”
4. Scientists find link between TB vaccination and C19 spread
- Scientists from St. Petersburg University, Russia, have analysed data detailing C19 spread in several countries to find that “new coronavirus infection occurs more slowly where there is a large percentage of people vaccinated against tuberculosis with the BCG vaccine”.
- The effect of the Bacillus Calmette-Guerin (BCG) vaccine on immunity against C19 is currently being investigated across the world, with some earlier studies deriving similar conclusions as well. India is one of the countries where BCG, which guards against tuberculosis, is part of the immunisation programme for children.
- “This vaccination itself, given in early childhood, changes the immune system in such a way that the new coronavirus disease course tends to be less severe,” the Russian scientists said in a press release.
- The researchers from St. Petersburg University added that they “have analysed about 100 academic papers and statistics” on the spread of Covid in different countries to arrive at their conclusion. Their study has been published in the Russian peer-reviewed journal Juvenis scientia.
Analysis of Covid spread
- The researchers say they have found an “association” between countries where BCG is given on a long-term and regular basis, and “the incidence of C19, the course of acute interstitial pneumonia caused by infection, and the mortality rate from it”.
- “The mortality rate turned out to be lower in those countries and areas where national vaccine immunisation programmes have taken place for a long time or continue today, especially if revaccinations were practised,” the researchers said in the press release, issued in English.
- According to the study, this association was found in Finland, China and Japan, as well as in countries in Eastern Europe, Central and South Asia, Africa, and the former USSR.
- “The figures are significantly higher where large-scale BCG vaccination has never been practised or stopped more than 20 years ago, for example, in the USA, Italy, the Netherlands, Belgium, and Germany excluding the lands of the former East Germany,” the study authors said.
How it works
- Simply put, the BCG vaccine triggers a “trained” or innate and adaptive immune system response within our bodies, which could offer protection against severe C19, the researchers state.
- According to the St. Petersburg scientists, “it is the early and long-term influence of the vaccine strain on the developing immune system that provides an adjuvant effect — it enhances the body’s immune reaction to various antigens, including many infectious ones”.
- In other words, this protection is most likely when the vaccine is given at a young age, in countries that have practised BCG immunisation for a long period of time.
- “There is reason to believe that in adults and elderly people who were not vaccinated in early childhood, the effect of late vaccine administration will be significantly less,” said Leonid Churilov, the scientist who supervised the study, as quoted in the press release.
- “At the same time, there are research papers by scientists from the Netherlands, where BCG is not given in childhood. They indicate that BCG administration to adults does not worsen, and, perhaps, somewhat attenuates the course of the disease when infected with the new coronavirus,” he added.
- In October, scientists from the ICMR National Institute for Research in Tuberculosis found, in a non-peer-reviewed study, that administering BCG vaccine could increase the trained, adaptive immunity in older adults, which could help protect against C19.
- “When the BCG vaccine is given at a young age, one can get lots of T memory cells which can help fight a coronavirus infection. But there are studies that show BCG can also mount an immune response in adults,” said Dr Gobardhan Das, professor of molecular medicine at JNU and among the early proponents of using the BCG vaccine against C19.
- “When coronavirus enters BCG-vaccinated individuals, the innate memory generated by BCG paves the way for generating Covid-antigen-specific T cells. This may lead to generation of specific vaccine efficacy against Covid, which may protect in future exposure,” he added.
D. Vaccines & Testing
1. Blood Tests May Be Key To Future C19 Vaccine Development
- News today from Harvard’s Center for Virology and Vaccine Research may help solve a problem that future C19 manufacturers are sure to face: how to make sure that new and potentially better vaccines actually work without doing extremely large and expensive studies.
- Writing in the journal Nature, the researchers show that a certain class of antibodies in a monkey’s blood predicted protection from C19. If that hold true for humans, a relative simple blood test may show whether an experimental vaccine is working.
- Here’s the dilemma: Once a vaccine is approved, it’s unethical to test it against a placebo. Approving a new vaccine would require researchers to compare two vaccines against each other, instead of having a vaccine and a placebo–which would take a lot more people than the 30,000 for the initial trials.
- Most researchers agree the key to solving this problem is finding something known as correlates of immunity.
- “Correlates of immunity are very important because they give us insight into how vaccines work, says Dan H. Barouch, M.D., Ph.D., Principal Investigator at the Harvard vaccine center.
- The idea is if you could measure something in a people’s blood that would show whether a vaccine works or not, you could then focus more on whether the vaccine was safe–because researchers would already know it’s likely effective.
- “So it would be much more convenient for future testing of C19 vaccines to have a well-established correlate of protection,” Barouch says.
- This approach is already used in approving the annual flu vaccine. “There’s a new influenza vaccine that’s licensed every year,” he says, because of genetic changes in the influenza virus.
- “It would not be possible to do a large-scale clinical efficacy trial of an influenza vaccine candidate every single year,” says Barouch, so regulators rely on correlates of protection.
- The correlate of protection for the coronavirus vaccine, Barouch and his colleagues found, was neutralizing antibodies. These are antibodies that can prevent a virus from infecting cells. It’s possible to test for the presence of these antibodies in people’s blood.
- It’s been assumed all along that neutralizing antibodies were necessary for a vaccine to induce to be effective, but no one know for sure if neutralizing antibodies alone were enough.
- The new research conducted with rhesus macaque monkeys suggests they are.
- Researchers took blood from monkeys that had been infected with the coronavirus that causes C19, and then recovered. That blood contained neutralizing antibodies to the coronavirus that helped the monkeys fight off the infection.
- “We isolated [those antibodies], we purified them and then we transfer them alone into naïve animals,” Barouch says. Naïve animals are ones who had never been sick.
- They then exposed the monkeys to the coronavirus. Most showed no signs of infection, and of those receiving a higher amount of antibodies, none showed signs of infection.
- The implication is if a vaccine can induce someone’s immune system to make those antibodies, that alone might be sufficient to believe the vaccine will work. Some scientists have argued that vaccines must provoke other kinds of immune responses known a cellular immunity. This research suggests that might not be the case.
- There are some caveats. The study was done in a small number of monkeys. Also, it’s possible that human neutralizing antibodies won’t work as well as the monkey neutralizing antibodies did.
- Nonetheless, Barouch is bullish about the implications of this research. “This is good news for vaccines because this level of neutralizing antibodies should be readily achievable by a variety of different vaccine candidates,” says Barouch.
2. Here’s what scientists want to know about the vaccines
- With striking speed, the United Kingdom has become the first country to approve a C19 vaccine that has been tested in a large clinical trial. On 2 December, UK regulators granted emergency-use authorization to a vaccine from drug firms Pfizer and BioNTech, just seven months after the start of clinical trials. British front-line health-care workers, as well as care-home staff and residents, could receive their first doses next week.
- China and Russia had approved vaccines already, but before they’d completed the final round of tests in people. Regulators in the United States and Europe are expected to issue their decisions in the coming weeks.
- Tests on more than 43,000 people have shown that the Pfizer vaccine is 95% effective at preventing disease when measured a week after its second dose, the New York City-based firm said in November when it and BioNTech, in Mainz, Germany, submitted a request for emergency approval to the US Food and Drug Administration. The UK approval is based on data from only 170 infections, and real-world efficacy might be lower than in a trial, but it is still an extraordinarily promising result, says immunologist Danny Altmann of Imperial College London: “This is brilliant news.”
- The approval is a historic moment. But scientists still have many questions about how this and other vaccines will perform as they’re rolled out to millions of people.
Do the vaccines prevent transmission of C19?
- In addition to the Pfizer vaccine, regulators are poring over data from another similar vaccine made by Moderna of Cambridge, Massachusetts, and a third vaccine produced by AstraZeneca of Cambridge, UK, and the University of Oxford, UK. All three of these vaccines have been tested in large clinical trials, and have shown promise in preventing disease symptoms.
- But none has demonstrated that it prevents infection altogether, or reduces the spread of disease in a population. This leaves open the chance that those who are vaccinated could remain susceptible to asymptomatic infection — and could transmit that infection to others who remain vulnerable. “In the worst case scenario, you have people walking around feeling fine, but shedding virus everywhere,” says virologist Stephen Griffin of the University of Leeds, UK.
- Pfizer has said that its scientists are looking at ways to assess disease transmission in future studies. For now, AstraZeneca and the University of Oxford may be able to provide the first hints as to whether a vaccine can protect against such transmission. Although they have yet to publish complete results, their trial did test participants routinely for SARS-CoV-2, allowing investigators to pick up on asymptomatic infections. Early indications are that the vaccine may have reduced the frequency of such infections. That would suggest that disease transmission might also be reduced.
How long will vaccine-induced immunity last?
- There is no quick way to determine how long immunity to the SARS-CoV-2 virus will last, and researchers will need to monitor this closely in the coming months and years.
- There have been some reports of reinfection and falling antibody levels months after an initial bout of C19, but it is still unclear how prevalent reinfection is. And there are signs that the immune system preserves a memory of coronavirus infection in the form of specialized memory cells that could kick into action rapidly if the virus is encountered again. And vaccines, Altmann says, are deliberately designed to provoke strong responses from the immune system.
- Still, it will be important for public health officials to monitor immunity – and to know when it begins to wane. One way to do that, in addition to keeping track of infections among people who have received the shots, is to periodically assess levels of antibodies and immune cells.Tracking the kinetics of these immune responses could give an early indication of when they are waning to worrisome levels, says Altmann. But the wide variation in people’s immune responses could make it a challenge to work out the circumstances in which a vaccine doesn’t work, and such studies will need to track many people. “You need to have a good stab at some high-level population analysis to work out whether you’re winning or losing,” says Altmann. “Otherwise, you might be a government kidding yourself in years’ time.”
How well do the vaccines work in groups such as old people and children?
- The major vaccine trials to date have enrolled tens of thousands of people, but their conclusions about effectiveness are drawn from infections in fewer than 200 of them. As a result, it can be difficult to break up that data into different groups — such as people who are obese or elderly — without losing statistical power. “We need to see more data in terms of effects of vaccines across different demographics,” says Michael Head, an infectious disease researcher at the University of Southampton, UK.
- There are early indications that the three leading vaccines may protect people over 65. But it will likely require real-world data from large numbers of vaccinated people before researchers can achieve the demographic granularity needed to ensure that parts of the population aren’t left unprotected.
- There is no data yet on how the vaccine fares in children and pregnant women. Such trials often lag behind tests in other groups of people, to ensure that as much safety data as possible has been collected before those studies begin. On 2 December, Moderna unveiled plans to test its vaccine in children.
How do the vaccines stack up against each other?
- All three leading vaccines have probably beaten the goal of achieving 50% efficacy, and all look to be safe, based on the clinical trial data so far. But there might be differences in how well they work, and in which contexts, that could shape the course of the pandemic.
- Vaccines from Pfizer and Moderna rely on RNA, encased in a lipid particle that ferries the RNA into cells where it is used as a template to generate a viral protein that stimulates the immune system. AstraZeneca’s vaccine, however, uses DNA that is shuttled into cells within a harmless virus, unrelated to coronavirus.
- Early data suggest that the RNA approach may be more effective for preventing disease. But there are subtle differences in the immune response provoked by each approach, notes Griffin. Researchers might eventually find that one approach works better than another in certain groups of people, or that one is the best at limiting transmission.
- Difference in cost and logistics will also shape which vaccine is best for which region. Shortly after announcing the authorization of the Pfizer vaccine, UK officials acknowledged that getting the vaccine to individual care homes to vaccinate residents would be a challenge because the vaccine needs to be stored at extremely low temperatures (–70C). The other two vaccines do not need to be kept at such low temperatures, and the AstraZeneca vaccine is likely to be the easiest and cheapest to store of the three, says Head.
- Comparisons between the effectiveness of the different vaccines are important and should be done, but until then, the path forward is clear, says Altmann. “Grab any vaccine that your government can buy,” he says. “All I want is out of this mess and my family not to be in danger, and any one of the vaccines that we’re talking about will get us there.”
Could the virus evolve to evade immunity given by vaccines?
- Some viruses, like the wily influenza virus, are notorious for mutating and moving around bits of their genomes. The SARS-CoV-2 genome, however, so far appears to be fairly stable. Most of the vaccines being developed, including the three that lead the pack, target a protein called spike that the virus needs to infect cells. And immune responses elicited by those vaccines will likely target multiple sites along that protein.
- All of this gives researchers some reassurance that the virus might not evolve ways to evade immunity conferred by vaccines. But mass vaccination campaigns will, for the first time, put enormous pressure on SARS-CoV-2 to adapt, and will select for any strain of the virus that might be able to escape immune defences. “We’ve never seen a virus like this under selective pressure,” says Griffin. “So we don’t know how it’s going to respond.”
- As a result, researchers will need to monitor SARS-CoV-2 isolates for signs of change, says Charlie Weller, head of vaccines at the Wellcome Trust in London. “Robust surveillance with ongoing sampling and sequencing will be key to assessing any potential impact on public health and picking up any mutations,” she says, “as will the continued research in developing the next generation of C19 vaccines.”
- It will be handy to have vaccines against other targets ready, in case they need to be deployed against a SARS-CoV-2 that has become resistant to the vaccines that target sSpike, says Altmann. “It’s not high up on my list of panics,” he says. “But never say never: there could be emergent versions where we’d need to have vaccines against other targets up our sleeves.”
How will scientists monitor for long-term safety concerns?
- “The public’s safety has always been at the forefront of our minds,” says a statement from June Raine, chief executive of the MHRA, that accompanied the UK approval of the Pfizer vaccine.
- The vaccine has only completed a few months of its two-year clinical trial period — which it will need to complete before it is approved to be sold freely on the market — so health officials, clinicians and people receiving the vaccine will be watching closely for as-yet unobserved signs of danger. Many governments already have reporting systems in place that are designed to track vaccine safety.
- Vaccines are rigorously vetted for potential side effects in clinical trials that combine self-reporting from participants and data collection by research clinicians. The Pfizer–BioNTech vaccine is given in two doses at least three weeks apart. For a week after each dose, participants keep tabs on their health status using an electronic diary or smart phone app. Blood is taken the day after a dose is given and one week after each injection to look for anything that might indicate a dangerous reaction.
- Pfizer’s trials revealed that some recipients experienced pain at the injection site, fever, fatigue, sore muscles and headaches — although these symptoms usually lasted only a few days and are generally not considered serious. But they can stoke fear. “When the reaction to the vaccine and to the disease have the same characteristics, people get worried,” says Jerome Kim, director-general of the International Vaccine Institute in Seoul.
- MHRA’s assurance that the vaccine is safe is based on monitoring hundreds of patients for at least two months after their second dose. By then, serious complications usually don’t happen, says Kim.
- But after a vaccine is approved, whether with full approval or only for emergency use, clinicians are expected to continue reporting any adverse reactions. Most countries have some kind of agency, such as the US Vaccine Adverse Event Reporting System (VAERS), which collects reports of serious symptoms that occur after people receive a vaccine. US doctors are legally bound to report such symptoms. For C19 drugs and vaccines, the United Kingdom has set up a specialized Coronavirus Yellow Card Reporting Site for such data collection.
- Kim says such systems work. “You still need strong surveillance. These rare events can be important,” he says.
3. Find your place in line. When will you get the vaccine?
- A vaccine may be around the corner, but how long will it be until you get the shot? Health officials are considering vaccine timelines that give some Americans priority over others. If you’re a healthy American, you may wait many months for your turn.
- To put this in perspective, we worked with the Surgo Foundation and Ariadne Labs using their vaccine tool to calculate the number of people who will need a vaccine in each state and county — and where you might fit in that line.
- To find out your place in line, click here.
4. A Rapid Covid Test That’s Also Accurate? The NFL Says It Has One
- The Baltimore Ravens woke up in Pittsburgh on Wednesday morning in need of a C19 test that was both immediate and accurate. Ravens personnel had registered new positives for 10 straight days, causing their game against the Steelers to be rescheduled three times. The teams needed to know quickly and for certain whether it was finally safe to play.
- The NFL and a pair of biotech companies, BioReference Laboratories and Mesa BioTech, believed they had a solution. In recent weeks, they have quietly studied a different kind of Covid test: one that they say delivers on-the-spot results, in 30 minutes, with as much accuracy as existing tests that are sent out to labs for processing that can take days.
- The NFL’s rapid PCR test, developed by Mesa, has been tested on a selection of league personnel across five teams, who also submitted their usual samples for standard PCR tests. The 917 tests using both methods each produced 27 positive samples and 890 negative samples, a perfect match.
- The league used the rapid PCR test to clear the Ravens and Steelers to play on Wednesday, and it’s the type of development these companies hope could have broad public health implications soon beyond football—possibly helping airlines, schools and more safely return to a semblance of normalcy.
- “When you do a trial, you don’t expect results that accurate,” said Christopher Halpin, NFL executive vice president and chief strategy and growth officer.
- There are two widely available C19 testing options, and each has a critical shortfall. PCR tests are seen as the gold-standard for accuracy but often have turnaround times that can last many days for the general public, and even for the NFL are described as “overnight.”
- Antigen tests provide turnarounds in a matter of minutes, but research has continued to indicate they are not nearly as sensitive as the PCR tests and can fail to detect the virus, particularly in asymptomatic people.
- The NFL worked as a testing ground because its highly resourced, highly motivated owners wanted an unrivaled level of testing to play through a pandemic, which also provided the infrastructure that allowed for a quick study of this new test.
- “All of this information is because we had essentially a captured population of people that we were testing every day,” said BioReference’s executive chairman Jon Cohen.
- It’s an investment that can’t be easily replicated, however. Cohen wouldn’t put a price-tag on how much it cost to run each test, noting that it would depend on the scale of an operation. For now, running it requires the use of a designated machine for 30 minutes for each person tested, with laboratory staff on hand to interpret the results. With enough machines and a very large staff, Cohen said, it would be possible to run several thousand in a day, or 600 an hour “if we had to.”
- “Eventually we want to be in people’s homes,” said Ingo Chakravarty, Mesa Biotech’s president and chief executive. In the interim it could have broad applications for institutions willing to invest in it. He said other clients examining the technology include major hospitals, care facilities, first responders and an island.
- That NFL was a natural test partner for these biotech companies because it could run the test on a population that was already being given a standard PCR test, to compare the results. Since Aug. 1, the league has conducted more than 700,000 tests on its players and personnel.
- The NFL is now planning to use this as its point-of-care option for all 32 teams, and its ever-evolving pandemic protocols may continue to change around this new test, Halpin said. The league doesn’t plan to use the tests for every player, every day.
- Instead, the NFL sees it as a tool to swiftly test personnel in circumstances where near-instant turnarounds are critical, such as during outbreaks, to confirm positive results or to check potential false positives.
- The league is still weathering a series of pandemic-caused crises. As cases have reached all-time highs in the country, they also have risen in the NFL. From Nov. 21 to Nov. 28, the NFL had 86 players and staff test positive—more than the first six weeks of the season combined.
- The results have been messy. The Denver Broncos were forced to play without a quarterback on Sunday after a backup tested positive and the others were sidelined due to contact tracing. The San Francisco 49ers were forced to relocate to Arizona because of local health restrictions.
- Commissioner Roger Goodell took the extraordinary step of closing most team facilities on Monday and Tuesday to regroup from Thanksgiving. There was also the outbreak on the Ravens, which mounted each day as their game against the Steelers was postponed from last Thursday, to Sunday, to Tuesday and then to Wednesday.
- On Wednesday morning, the Ravens received these new tests to determine whether the 3:40 p.m. game that day could go forward. By noon, they had the results: all negative.
5. Florida requiring labs to report critical ‘cycle threshold’ of C19 tests
- The Florida Department of Health is requiring that all labs in the state report the critical “cycle threshold” level of every C19 test they perform.
- In a press release this week, the department said that, regarding C19 tests, “cycle threshold (CT) values and their reference ranges, as applicable, must be reported by laboratories to FDOH via electronic laboratory reporting or by fax immediately.”
- “Cycle thresholds” are the level at which widely used polymerase chain reaction test can detect a sample of the C19 virus. The higher the number of cycles, the lower the amount of viral load in the sample; the lower the cycles, the more prevalent the virus was in the original sample.
- Numerous epidemiological experts have argued that cycle thresholds are an important metric by which patients and the public can make an informed decision about how infectious and/or sick an individual with a positive C19 test might be. However, health departments across the country are failing to collect that data.
E. Improved & Potential Treatments
1. Potential of Hepatitis C Drugs to Treat C19 by Stopping the Virus From Spreading
- Experiments led by researchers at the Department of Energy’s Oak Ridge National Laboratory have determined that several hepatitis C drugs can inhibit the coronavirus (SARS-CoV-2) main protease, a crucial protein enzyme that enables the novel coronavirus to reproduce.
- Inhibiting, or blocking, this protease from functioning is vital to stopping the virus from spreading in patients with C19. The study, published in the journal Structure, is part of efforts to quickly develop pharmaceutical treatments for C19 by repurposing existing drugs known to effectively treat other viral diseases.
- “Currently, there are no inhibitors approved by the FDA that target the SARS-CoV-2 main protease,” said ORNL lead author Daniel Kneller. “What we found is that hepatitis C drugs bind to and inhibit the coronavirus protease. This is an important first step in determining whether these drugs should be considered as potential repurposing candidates to treat C19.”
- The SARS-CoV-2 coronavirus spreads by expressing long chains of polyproteins that must be cut by the main protease to become functional proteins, making the protease an important drug target for researchers and drug developers.
- In the study, the team looked at several well-known drug molecules for potential repurposing efforts including leupeptin, a naturally occurring protease inhibitor, and three FDA-approved hepatitis C protease inhibitors: telaprevir, narlaprevir, and boceprevir.
- The team performed room temperature X-ray measurements to build a three-dimensional map that revealed how the atoms were arranged and where chemical bonds formed between the protease and the drug inhibitor molecules.
- The experiments yielded promising results for certain hepatitis C drugs in their ability to bind and inhibit the SARS-CoV-2 main protease — particularly boceprevir and narlaprevir. Leupeptin exhibited a low binding affinity and was ruled out as a viable candidate.
- To better understand how well or how tightly the inhibitors bind to the protease, they used in vitro enzyme kinetics, a technique that enables researchers to study the protease and the inhibitor in a test tube to measure the inhibitor’s binding affinity, or compatibility, with the protease. The higher the binding affinity, the more effective the inhibitor is at blocking the protease from functioning.
- “What we’re doing is laying the molecular foundation for these potential drug repurposing inhibitors by revealing their mode of action,” said ORNL corresponding author Andrey Kovalevsky. “We show on a molecular level how they bind, where they bind, and what they’re doing to the enzyme shape. And, with in vitro kinetics, we also know how well they bind. Each piece of information gets us one step closer to realizing how to stop the virus.”
- The study also sheds light on a peculiar behavior of the protease’s ability to change or adapt its shape according to the size and structure of the inhibitor molecule it binds to. Pockets within the protease where a drug molecule would attach are highly malleable, or flexible, and can either open or close to an extent depending on the size of the drug molecules.
- Before the paper was published, the researchers made their data publicly available to inform and assist the scientific and medical communities. More research, including clinical trials, is necessary to validate the drugs’ efficacy and safety as a C19 treatment.
- “The research suggests that hepatitis C inhibitors are worth thinking about as potential repurposing candidates. Immediately releasing our data allows the scientific community to start looking at the interactions between these inhibitors and the protease,” said ORNL corresponding author Leighton Coates. “You can’t design a drug without knowing how it works on a molecular level, and the data we’re providing is exactly what developers need to design stronger, more tightly binding drugs for more effective treatments.”
- The X-ray measurements and synthesis of the protease samples used in the experiments were performed with support from the Center for Structural and Molecular Biology using facilities located at the Spallation Neutron Source.
- The research team plans to conduct neutron scattering experiments to locate the hydrogen atom positions and the network of chemical bonds between the protease and the inhibitor molecules.
F. Concerns & Unknowns
1. The U.S. Has Passed the Hospital Breaking Point
- Since the beginning of the pandemic, public-health experts have warned of one particular nightmare. It is possible, they said, for the number of coronavirus patients to exceed the capacity of hospitals in a state or city to take care of them. Faced with a surge of severely ill people, doctors and nurses will have to put beds in hallways, spend less time with patients, and become more strict about whom they admit into the hospital at all. The quality of care will fall; Americans who need hospital beds for any other reason—a heart attack, a broken leg—will struggle to find space. Many people will unnecessarily suffer and die.
- “If, in fact, there’s a scenario that’s very severe, it is conceivable that will happen,” Anthony Fauci, the nation’s top infectious-disease doctor, said in mid-March. “We’re doing everything we can to not allow that worst-case scenario to happen.”
- Fear of this scenario drove many of the most stringent stay-at-home orders in the spring. “There will be no normally functioning economy if our hospitals are overwhelmed,” Liz Cheney, a leading House Republican, said a week and a half later.
- Yet that worst-case scenario never came to pass at a national level. At the springtime peak, even as northeastern hospitals faced a deluge, 60,000 people were hospitalized nationwide. When the Sun Belt frothed with cases this summer, hospitalizations again reached the 60,000 mark before they started to fall.
- A month ago, in early November, hospitalizations passed 60,000—and kept climbing, quickly. On Wednesday, the country tore past a nauseating virus record. For the first time since the pandemic began, more than 100,000 people were hospitalized with C19 in the United States, nearly double the record highs seen during the spring and summer surges.
- The pandemic nightmare scenario—the buckling of hospital and health-care systems nationwide—has arrived. Several lines of evidence are now sending us the same message: Hospitals are becoming overwhelmed, causing them to restrict whom they admit and leading more Americans to die needlessly.
- The current rise in hospitalizations began in late September, and for weeks now hospitals have faced unprecedented demand for medical care. The number of hospitalized patients has increased nearly every day: Since November 1, the number of people hospitalized with C19 has doubled; since October 1, it has tripled.
- Throughout that time, health-care workers have worried that hospitals would soon be overwhelmed. “The health-care system in Iowa is going to collapse, no question,” an infectious-disease doctor told our colleague Ed Yong early last month. The following week, a critical-care doctor in Nebraska warned, “The assumption we will always have a hospital bed for [you] is a false one.”
- These catastrophes seem to be coming to pass—not just in Iowa and Nebraska, but all across the country. A national breakdown in hospital care is now starkly apparent in the coronavirus data.
- It is clearest in a single simple statistic, recently observed by Ashish Jha, the dean of the Brown University School of Public Health. For weeks, the number of people hospitalized with C19 had been about 3.5 percent of the number of cases reported a week earlier. But, he noticed, that relationship has broken down. A smaller and smaller proportion of cases is appearing in hospitalization totals.
- “This is a real thing. It’s not an artifact. It’s not data problems,” Jha told us.
- Why would this number change? As hospitals run out of beds, they could be forced to alter the standards for what kinds of patients are admitted with C19. The average American admitted to the hospital with C19 today is probably more acutely ill than someone admitted with C19 in the late summer. This isn’t because doctors or nurses are acting out of cruelty or malice, but simply because they are running out of hospital beds and must tighten the criteria on who can be admitted.
- Many states have reported that their hospitals are running out of room and restricting which patients can be admitted. In South Dakota, a network of 37 hospitals reported sending more than 150 people home with oxygen tanks to keep beds open for even sicker patients. A hospital in Amarillo, Texas, reported that C19 patients are waiting in the emergency room for beds to become available. Some patients in Laredo, Texas, were sent to hospitals in San Antonio—until that city stopped accepting transfers. Elsewhere in Texas, patients were sent to Oklahoma, but hospitals there have also tightened their admission criteria.
- The COVID Tracking Project has found the same phenomenon by looking at a different variable in the data produced by the Department of Health and Human Services: the number of people admitted to the hospital every week. (Jha was analyzing the number of people currently hospitalized.)
- In August and September, about 9.5 percent of C19 cases were admitted to hospitals nationwide, according to federal data. As October began, this case-hospitalization proportion held for about a week. But then cases began to explode, especially in the Midwest and Great Plains, and hospitals suffered strain. In the last week of October, the average number of new C19 cases surged past its all-time high of 66,000 new cases a day. Less than 8 percent of those cases made it into the hospital, a 16 percent drop in the proportion of sick people admitted versus September.
- As the pandemic intensified, the fall continued. On November 10, the U.S. recorded more virus hospitalizations than ever before, passing the previous high set during the spring and summer surges. More than 100,000 Americans were diagnosed with the virus every day last month, on average, and more than ever were hospitalized as well. But as facilities ran short on bed space, the fraction of admitted cases fell. Ultimately, only 7.4 percent of C19 cases were hospitalized in November—the lowest percentage yet.
- This change may not seem ominous at first. You might expect to see such a divergence, for instance, if testing rapidly increased, so that states were suddenly detecting many more mild cases of C19. But the data don’t show any evidence of this kind of “casedemic”—if anything, they show the opposite. Last month, the number of total C19 tests increased by about a third compared with October, but the number of total cases discovered more than doubled. More people are getting sick.
- At the same time, the virus seems to be killing a slightly higher fraction of people diagnosed with it. Using a method that accounts for clinical- and data-reporting lags between cases and deaths, for most of October and November, about 1.7 percent of cases resulted in death. But in the middle of November, that number lurched to more than 1.8 percent. While this change may seem small, it represents hundreds of deaths, because many more people are getting sick every day.
- In other words, we’re observing exactly the opposite of what you’d expect from a rash of mild cases in the data. The virus seems to be killing more people. And that makes sense: As Yong and our colleague Sarah Zhang have both written, many of our medical triumphs over the virus have come from more attentive and knowledgeable hospital care for C19 patients. Yet a smaller fraction of people are now receiving that expert and conscientious care.
- Since March, most of our writing about the pandemic has focused on the near-term future. We’ve described data as worrying or ominous, words implying that the worst is soon to arrive. There’s a good reason for this forward-looking approach: It gives people a sense of what’s coming, and it helps people make decisions to protect themselves or their family.
- But ominous no longer fits what we’re observing in the data, because calamity is no longer imminent; it is here. The bulk of evidence now suggests that one of the worst fears of the pandemic—that hospitals would become overwhelmed, leading to needless deaths—is happening now. Americans are dying of C19 who, had they gotten sick a month earlier, would have lived. This is such a searingly ugly idea that it is worth repeating: Americans are likely dying of C19 now who would have survived had they gotten September’s level of medical care.
- The first doses of the vaccine will almost certainly go out by Christmas. Tens of millions of Americans could have protective immunity within eight weeks. As the days lengthen and the weather warms, the vaccine will become easier to get; more than 100 million Americans may have immunity by the end of February.
- Many indicators suggest that next summer will be happy and prosperous, and we will gather indoors and outdoors and grin at one another like children in June. But the world will be reduced, and not as wise, because tens of thousands of Americans will be dead when they should be alive.
2. What happens when the immune response is out of sync?
- Various components of the immune system are fine-tuned and coordinated for the protection and maintenance of tissue homeostasis in various organs. Evolution has ensured the precise activation and synchronization of specific immune components at a given time to provide proper defense and regeneration environment to tissues of our body. Any disorders may lead to imperfect protection and uncontrolled tissue damages. A new study from the Sette and Crotty group just reported in Cell demonstrated that C19 patients, especially at elder ages, suffered the most when the immune components were asynchronous (i.e., not in sync).
- In the Figure above, the coronavirus (SARS-CoV-2) antigen-specific CD8+ T cells, CD4+ T cells, and neutralizing antibodies. a Troika combating C19 infection. A coordinated response involving CD8+ cytotoxic T cells, CD4+ helper T cells, and neutralizing antibodies is required to provide the best protective effects for SARS-CoV-2 infections. However, in older patients whose CD8+ T and CD4+ T cell responses are compromised, the diseases are prone to progress to severe stages
- Like most viral infections, SARS-CoV-2 elicits strong inflammatory responses. It has been proposed that the immune responses induced by SARS-CoV-2 infection are two-phased. Specific adaptive immune responses are critical for the elimination of the virus during the incubation and non-severe stages and for stopping disease progression to severe stages.
- When the protective immune responses are insufficient, due to genetic predisposition or preexisting medical conditions, the virus will propagate and massive destruction of the affected tissues, such as lungs, will occur. Most studies are focused on the inflammation and tissue damages at severe stages. However, recent investigations on non-severe or convalescent patients have provided clues to the understanding of protective immune responses.
- In an effort to understand human CD4+ and CD8+ T cell responses to SARS-CoV-2 infection, the same research group employed human leukocyte antigen (HLA) class I and II predicted peptide “megapools” and CD8+ and CD4+ T cells from convalescent patients and found that 87% and 93% of these recovered patients possessed SARS-CoV-2-specific CD8+ and CD4+ T cells, respectively.1 Remarkably, when antibodies (Abs) made from B cell clones derived from convalescent patients were tested for their ability to neutralize SARS-CoV-2 virus in vitro in plastic and in vivo in hamsters, it was found that the receptor binding domain (RBD) specific Ab provided strong protection.
- Upon until now, the most comprehensive study on SARS-CoV-2 virus-specific adaptive immunity in humans is by the Sette and Crotty group just published in Cell, which is the subject highlighted herein. It not only involved a larger number of convalescent and acutely infected patients, but also divided adaptive immune responses into viral protein-specific CD4+ T cells, CD8+ T cells, and Abs, the three most critical components of the adaptive immune responses. Although each component can work separately, together, the three components bring best protection.
- In the vaccinia virus system, based on the pooled viral peptides, it was shown that CD8+ T cell, CD4+ T cell, and Ab responses tend to recognize different antigens with distinct characteristics, CD8+ T cells recognize early antigens, and CD4+ T cells and Abs recognize later antigens. This same pattern is also demonstrated by Moderbacher et al. in SARS-CoV-2 infection, during which all three arms work together to bring the best protection and if these adaptive immune responses are not synchronized C19 patients are in trouble.1 In this coordinated process, B cell-produced Abs are able to attach to and neutralize extracellular SARS-CoV-2 virus. For various reasons, if the Abs are unable to stop the virus from entering cells, CD8+ T cells are called in to destroy the infected cells. Regarding CD4+ T cells, the third arm, they are helpers and coordinators for production of Abs and the activation of CD8+ killer T cells (Fig. 1).
- Moderbacher et al. analyzed the blood of C19 patients suffering from mild to ultimately fatal infection. Their immune responses were compared to those of convalescents and unexposed control individuals. The Ab levels alone did not correlate with C19 severity. Those worst cases of C19 had low levels of CD8+ killer T cells and CD4+ T helper cells. It is highly possible that T cells play a more important role than Abs in combating ongoing C19 infections. In fact, the authors identified one case that had no detectable neutralizing antibodies and resolved infection without hospitalization. In addition, some infected children recovered before developing an Ab response, again arguing for the importance of T cells.
- When blood samples from the older participants (≥65 years old) with acute infections were analyzed, it was found that they were far more likely to have asynchronous immune responses among CD4+ T cells, CD8+ T cells, and Abs than younger infected patients. In older patients, high levels of Abs could be seen, while one of the T cell responses remained weak. Interestingly, older C19 patients tended to also have smaller populations of the “naive” T cells, which could recognize the new SARS-CoV-2 virus and then develop into mature CD8+ killer T cells and CD4+ T helpers, which otherwise mounts a coordinated attack against SARS-CoV-2.
- There is much talk about the cytokine storm in C19 patients. It should be recognized that due to the lymphopenia in severe patients, the cytokine storm in these patients should not be expected to be the same as that observed in other patients such as chimeric antigen receptor T cell recipients. In the lack of T cells, the antibody response is unable to constrain SARS-CoV-2 and allows the virus to replicate to high levels. The innate immune cells release high levels of cytokines, which, in the absence of T cell cytokines, further damage the adaptive immunity and vital organs such as the lungs, kidneys, and cardiovascular system. It should be clearly recognized that such a cytokine storm without T cells is distinctly different from that in other overreactions of the immune system during infections or some other pathological conditions.
- Although the mechanisms underlying the diminishment of T cells in severe C19 patients are not known, it is clear that immunity-damaging agents such as dexamethasone should be used cautiously, especially during the early phase of the infections, when adaptive immune responses are required to prevent the progression of the disease.
- The information from the analysis of Moderbacher et al. also provided important clues to vaccine development. T cell responses should be accentuated. So far, C19 vaccine development efforts are mostly focused on the S protein of SARS-CoV-2 with the hope to induce SARS-CoV-2 neutralizing antibodies. Ironically, only antibodies against the RBD region of the S protein provide strong virus neutralization. Based on the requirement of the synchrony of CD8+ T cells, CD4+ T cells, and Abs, effective vaccines should elicit both antibody and T cell responses and strong T cell responses may require M proteins and NP proteins in addition to S proteins. Additionally, T cell responses should also be used to evaluate SARS-CoV-2 vaccines.
- This is one of the most comprehensive analyses of SARS-CoV-2-specific immunity in patients. It provided critical information for the understanding of how to stop disease progression and how to design efficacious treatments and how to develop better vaccines.
G. The Road Back?
- In the ongoing conversation about how to defeat the coronavirus, experts have made reference to the “Swiss cheese model” of pandemic defense.
- The metaphor is easy enough to grasp: Multiple layers of protection, imagined as cheese slices, block the spread of the virus that causes C19. No one layer is perfect: Each has holes, and when the holes align, the risk of infection increases. But several layers combined — social distancing, masks, hand-washing, testing and tracing, ventilation, government messaging — significantly reduce the overall risk. Vaccination will add one more protective layer.
- “Pretty soon you’ve created an impenetrable barrier, and you really can quench the transmission of the virus,” said Dr. Julie Gerberding, executive vice president and chief patient officer at Merck, who recently referenced the Swiss cheese model.
- “But it requires all of those things, not just one of those things,” she added. “I think that’s what our population is having trouble getting their head around. We want to believe that there is going to come this magic day when suddenly 300 million doses of vaccine will be available and we can go back to work and things will return to normal. That is absolutely not going to happen fast.”
- In October, Bill Hanage, an epidemiologist at the Harvard T.H. Chan School of Public Health, retweeted an infographic rendering of the Swiss cheese model, noting that it included “things that are personal *and* collective responsibility — note the ‘misinformation mouse’ busy eating new holes for the virus to pass through.”
- The Swiss cheese concept originated with James T. Reason, a cognitive psychologist, now a professor emeritus at the University of Manchester, England, in his 1990 book, “Human Error.” A succession of deadly disasters in the 1980s — including the Challenger space shuttle explosion; the toxic gas leak in Bhopal, India; and the nuclear accident in Chernobyl, Ukraine — motivated the concept, and it became known as the “Swiss cheese model of accidents,” with the holes in the cheese slices representing errors that accumulate and lead to adverse events.
- The metaphor now pairs well with the coronavirus pandemic. Ian M. Mackay, a virologist at the University of Queensland in Brisbane, Australia, saw a version on Twitter, but thought that it could do with more slices and more information. So he created, with collaborators, the “Swiss Cheese Respiratory Pandemic Defense.”
H. Innovation & Technology
1. New C19 Test Uses Smartphone Camera and Genetic Technology
- Imagine swabbing your nostrils, putting the swab in a device, and getting a read-out on your phone in 15 to 30 minutes that tells you if you are infected with the C19 virus. This has been the vision for a team of scientists at Gladstone Institutes, University of California, Berkeley (UC Berkeley), and University of California, San Francisco (UCSF). And now, they report a scientific breakthrough that brings them closer to making this vision a reality.
- One of the major hurdles to combating the C19 pandemic and fully reopening communities across the country is the availability of mass rapid testing. Knowing who is infected would provide valuable insights about the potential spread and threat of the virus for policymakers and citizens alike.
- Yet, people must often wait several days for their results, or even longer when there is a backlog in processing lab tests. And, the situation is worsened by the fact that most infected people have mild or no symptoms, yet still carry and spread the virus.
- In a new study published in the scientific journal Cell, the team from Gladstone, UC Berkeley, and UCSF has outlined the technology for a CRISPR-based test for C19 that uses a smartphone camera to provide accurate results in under 30 minutes.
- “It has been an urgent task for the scientific community to not only increase testing, but also to provide new testing options,” says Melanie Ott, MD, PhD, director of the Gladstone Institute of Virology and one of the leaders of the study. “The assay we developed could provide rapid, low-cost testing to help control the spread of C19.”
- The technique was designed in collaboration with UC Berkeley bioengineer Daniel Fletcher, PhD, as well as Jennifer Doudna, PhD, who is a senior investigator at Gladstone, a professor at UC Berkeley, president of the Innovative Genomics Institute, and an investigator of the Howard Hughes Medical Institute. Doudna recently won the 2020 Nobel Prize in Chemistry for co-discovering CRISPR-Cas genome editing, the technology that underlies this work.
- Not only can their new diagnostic test generate a positive or negative result, it also measures the viral load (or the concentration of SARS-CoV-2, the virus that causes C19) in a given sample.
- “When coupled with repeated testing, measuring viral load could help determine whether an infection is increasing or decreasing,” says Fletcher, who is also a Chan Zuckerberg Biohub Investigator. “Monitoring the course of a patient’s infection could help health care professionals estimate the stage of infection and predict, in real time, how long is likely needed for recovery.”
A Simpler Test through Direct Detection
- Current C19 tests use a method called quantitative PCR—the gold standard of testing. However, one of the issues with using this technique to test for the coronavirus (SARS-CoV-2) is that it requires DNA. Coronavirus is an RNA virus, which means that to use the PCR approach, the viral RNA must first be converted to DNA. In addition, this technique relies on a two-step chemical reaction, including an amplification step to provide enough of the DNA to make it detectable. So, current tests typically need trained users, specialized reagents, and cumbersome lab equipment, which severely limits where testing can occur and causes delays in receiving results.
- As an alternative to PCR, scientists are developing testing strategies based on the gene-editing technology CRISPR, which excels at specifically identifying genetic material.
- All CRISPR diagnostics to date have required that the viral RNA be converted to DNA and amplified before it can be detected, adding time and complexity. In contrast, the novel approach described in this recent study skips all the conversion and amplification steps, using CRISPR to directly detect the viral RNA.
- “One reason we’re excited about CRISPR-based diagnostics is the potential for quick, accurate results at the point of need,” says Doudna. “This is especially helpful in places with limited access to testing, or when frequent, rapid testing is needed. It could eliminate a lot of the bottlenecks we’ve seen with C19.”
- Parinaz Fozouni, a UCSF graduate student working in Ott’s lab at Gladstone, had been working on an RNA detection system for HIV for the past few years. But in January 2020, when it became clear that the coronavirus was becoming a bigger issue globally and that testing was a potential pitfall, she and her colleagues decided to shift their focus to C19.
- “We knew the assay we were developing would be a logical fit to help the crisis by allowing rapid testing with minimal resources,” says Fozouni, who is co-first author of the paper, along with Sungmin Son and María Díaz de León Derby from Fletcher’s team at UC Berkeley. “Instead of the well-known CRISPR protein called Cas9, which recognizes and cleaves DNA, we used Cas13, which cleaves RNA.”
- In the new test, the Cas13 protein is combined with a reporter molecule that becomes fluorescent when cut, and then mixed with a patient sample from a nasal swab. The sample is placed in a device that attaches to a smartphone. If the sample contains RNA from SARS-CoV-2, Cas13 will be activated and will cut the reporter molecule, causing the emission of a fluorescent signal. Then, the smartphone camera, essentially converted into a microscope, can detect the fluorescence and report that a swab tested positive for the virus.
- “What really makes this test unique is that it uses a one-step reaction to directly test the viral RNA, as opposed to the two-step process in traditional PCR tests,” says Ott, who is also a professor in the Department of Medicine at UCSF. “The simpler chemistry, paired with the smartphone camera, cuts down detection time and doesn’t require complex lab equipment. It also allows the test to yield quantitative measurements rather than simply a positive or negative result.”
- The researchers also say that their assay could be adapted to a variety of mobile phones, making the technology easily accessible.
- “We chose to use mobile phones as the basis for our detection device since they have intuitive user interfaces and highly sensitive cameras that we can use to detect fluorescence,” explains Fletcher. “Mobile phones are also mass-produced and cost-effective, demonstrating that specialized lab instruments aren’t necessary for this assay.”
Accurate and Quick Results to Limit the Pandemic
- When the scientists tested their device using patient samples, they confirmed that it could provide a very fast turnaround time of results for samples with clinically relevant viral loads. In fact, the device accurately detected a set of positive samples in under 5 minutes. For samples with a low viral load, the device required up to 30 minutes to distinguish it from a negative test.
- “Recent models of SARS-CoV-2 suggest that frequent testing with a fast turnaround time is what we need to overcome the current pandemic,” says Ott. “We hope that with increased testing, we can avoid lockdowns and protect the most vulnerable populations.”
- Not only does the new CRISPR-based test offer a promising option for rapid testing, but by using a smartphone and avoiding the need for bulky lab equipment, it has the potential to become portable and eventually be made available for point-of-care or even at-home use. And, it could also be expanded to diagnose other respiratory viruses beyond SARS-CoV-2.
- In addition, the high sensitivity of smartphone cameras, together with their connectivity, GPS, and data-processing capabilities, have made them attractive tools for diagnosing disease in low-resource regions.
- “We hope to develop our test into a device that could instantly upload results into cloud-based systems while maintaining patient privacy, which would be important for contact tracing and epidemiologic studies,” Ott says. “This type of smartphone-based diagnostic test could play a crucial role in controlling the current and future pandemics.”
I. Projections & Our (Possible) Future
1. Winter Offers Perfect Conditions for C19 Spread
- Winter outbreaks of C19 might be worsened by colder weather and drier indoor air that boost transmission of the coronavirus, but it is too soon to know whether it will become truly seasonal, according to new research by scientists studying the disease.
- In a dozen new studies, scientists have marshaled evidence that airborne transmission of the coronavirus (SARS-CoV-2) responsible for the disease is strongly affected by changes in temperature and humidity.
- Winter’s colder air will promote survival of the virus and drive people indoors where the drier air of many heated homes can have an even stronger influence on how long it remains infectious, the scientists said. Some scientists already see the consequences of cooler weather in near-record numbers of people hospitalized with C19 during recent weeks.
- “I think we are seeing an uptick in transmission in the Northern Hemisphere as weather gets colder and people spend more time indoors,” said Dylan Morris, a bio-mathematician at the University of California in Los Angeles who models how viruses spread. “Dry indoor air is a dangerous thing because it’s poorly ventilated; it helps virus stability; and it might also harm our immune defenses.”
- In several studies of coronaviruses and infection rates, epidemiologist Rachel Baker at Princeton University and her colleagues found that even a small seasonal change can have a substantial impact if safety measures aren’t widely followed.
- “Cold, dry winterlike conditions would be the optimal time for transmission,” said Dr. Baker, who investigates the effect of climate on infectious diseases. “It could be that the climate in winter would push you over the edge by giving you this relatively small boost in transmission.”
- Generally, many factors combine to drive seasonal infection trends for contagious respiratory diseases such as influenza, chickenpox and other coronaviruses, including the biochemistry of the virus, the physics of airborne droplets and the psychology of public health. These contagions are seasonal, even though many of them can be controlled by effective vaccines.
- No one knows yet what impact C19 vaccines now gaining approval might have on the long-term prospects for the disease. When widely adopted, they will likely significantly curb the current pandemic, leaving the coronavirus more driven by climate factors. Until then, the seasonal influence can be offset by people following public-health-control measures, including mask wearing and social distancing, the scientists say.
- “We are still observing that human behavior is the main driver of transmission,” said Mauricio Santillana, director of the Machine Intelligence Lab at Harvard University, who develops forecasts of C19 outbreaks. “A very large part of the population is still susceptible to the coronavirus, and that is eclipsing other factors for now.”
- Earlier this year, some public-health authorities predicted a seasonal lull in the pandemic during hot, humid summer months. While cases dipped slightly, C19 continued its spread through temperate and tropical areas world-wide such as North America, Brazil and India. The tempering effect of weather was overshadowed by the sheer number of people vulnerable to the disease, the scientists said.
- Researchers at the Yale School of Public Health and Columbia University’s Mailman School of Public Health tracked daily temperatures, humidity and C19 trends in 913 U.S. counties this past summer. In unpublished preliminary findings posted online in November, they determined that C19 cases were fractionally higher in northern counties than in southern counties, influenced most strongly by differences in humidity.
- “Our findings indicated a potential increased SARS-CoV-2 transmission in the coming winter,” said epidemiologist Kai Chen, the project’s senior scientist, at the Yale Center on Climate Change and Health.
Dr. Morris of UCLA, working with colleagues at the Rocky Mountain Laboratories in Hamilton, Mont., and at Princeton in New Jersey, recently conducted laboratory experiments to see how SARS-CoV-2 and four other coronaviruses responded to variations in temperature and relative humidity. They tested combinations of temperatures ranging from 50 degrees Fahrenheit to 80.6 degrees Fahrenheit, and levels of relative humidity from 40% to 85%.
In preliminary research posted online in November, they found that SARS-CoV-2 survived for more than 24 hours at 50 degrees and 40% relative humidity before starting to seriously break down, but only about an hour and a half at 80 degrees and 65% relative humidity. In the cold, the coronavirus survived best at extremes of low or high humidity.
- “We’re basically supposing there is some chemical reaction which is driving this inactivation of the virus,” said Jamie Lloyd-Smith, a UCLA professor of ecology and evolutionary biology who studies emerging diseases. “We don’t know what it is exactly.”
- Broadly, the odds of catching C19 indoors are about 18 times higher than in open-air environments, where sunlight and better ventilation are mitigating factors, according to the Centers for Disease Control and Prevention. In part, the spread of C19 has been driven by superspreader events linked to cool, dry indoor settings from recreational hockey rinks to the business-class section of a 10-hour commercial jet flight, according to a study published last month in the journal Emerging Infectious Diseases and other research.
- Indoor humidity and temperatures vary widely depending on regional climate, construction, heating systems and personal preferences.
- During a typical January, indoor residential temperatures in the Southeast average about 72 degrees Fahrenheit with a relative humidity of about 52%. In the Northeast, indoor temperatures average almost 65 degrees Fahrenheit with a relative humidity of 36%. In the Northwest, it averages about 63 degrees Fahrenheit with 50% humidity, according to the U.S. Department of Housing and Urban Development.
- During winter, air is drier inside New York City apartments than in detached two-story homes in Boston, according to a 2017 study by Columbia University public-health experts published in the journal Science of the Total Environment. The bigger the apartment building, the drier the air.
- “There are particular mitigation measures that make sense for the winter like humidifying the indoors, committing to a slightly higher heating bill, and cracking the windows to get more fresh air,” said Dr. Morris. “It’s possible to mitigate the effects while we wait for a vaccine.”
J. Practical Tips & Other Useful Information
1. The Vaccine: Is it safe? Should I get one?
- The primary advantage of a vaccine is that it’s predictable and safe.
- But what do we know about how the immunity from a prior infection compares with the protection given by the new vaccines? And what if you have already had Covid — is it safe to be vaccinated? We asked experts to weigh in on the latest evidence.
Which produces a stronger immune response: a natural infection or a vaccine?
- The short answer: We don’t know. But C19 vaccines have predictably prevented illness, and they are a far safer bet, experts said.
- Vaccines for some pathogens, like pneumococcal bacteria, induce better immunity than the natural infection does. Early evidence suggests that the C19 vaccines may fall into this category. Volunteers who received the Moderna shot had more antibodies — one marker of immune response — in their blood than did people who had been sick with C19.
- In other cases, however, a natural infection is more powerful than a vaccine. For example, having mumps — which can cause sterility in men — generates lifelong immunity, but some people who have received one or two doses of the vaccine still get the disease.
- Natural immunity from the coronavirus is fortunately quite strong. A vast majority of people infected produce at least some antibodies and immune cells that can fight off the infection. And the evidence so far suggests that this protection will persist for years, preventing serious illness, if not reinfection.
- But there is a “massive dynamic range” in that immune response, with a 200-fold difference in antibody levels.
- In people who are only mildly ill, the immune protection that can prevent a second infection may wane within a few months. “Those people might benefit more from the vaccine than others would,” said Bill Hanage, an epidemiologist at the Harvard T.H. Chan School of Public Health.
- The diversity in the immune response from natural infection might be because of differences in the amount of virus to which the person was exposed.
- With a vaccine, everyone gets the same dose. “We know the dose that is being administered, and we know that that dose is effective at eliciting an immune response,” Dr. Gommerman said. “So that becomes a variable that’s taken off the table when you get the vaccine.”
I’m young, healthy and at low risk of Covid. Why not take my chances with that rather than get a rushed vaccine?
- The experts were unanimous in their answer: C19 is by far the more dangerous option.
- “It’s clear that one is less problematic for the body to recover from them than the other — there’s more risk with natural infection,” said Marion Pepper, an immunologist at the University of Washington in Seattle.
- People who are obese, or who have diseases like diabetes are particularly susceptible to severe cases of C19. On average, the virus seems to be less risky for younger people, and women tend to fare better than men. But beyond those broad generalizations, doctors don’t know why some people get very sick and die while others have no symptoms.
- For example, people who harbor certain mutations in immune genes are more susceptible to the disease, several studies have shown. “So there’s a risk factor that has nothing to do with age,” Dr. Gommerman said.
- In a study of more than 3,000 people, ages 18 to 34, who were hospitalized for Covid, 20 percent required intensive care and 3 percent died.
- “It’s true that most people aren’t going to be hospitalized, most people aren’t going to get in the intensive care unit or die,” said Dr. Yvonne Maldonado, who represents the American Academy of Pediatrics at the meetings of the federal Advisory Committee on Immunization Practices.
- But “nobody is immune to severe disease,” she said. And even if people are not at high risk of Covid themselves, their friends or family could be.
- As many as one in three people who recover from Covid have chronic complaints, including exhaustion and a racing heart, for months afterward. This includes people under 35 with no previous health conditions. Some survivors of Covid also show troubling signs that their body has turned on itself, with symptoms similar to those of lupus and rheumatoid arthritis.
- Covid vaccines, in contrast, carry little known risk. They have been tested in tens of thousands of people with no serious side effects — at least so far. “Once you start vaccinating millions, you might find very, very rare events,” Dr. Hanage said. “But we have to know that they are very, very rare and much more rare than the adverse events associated with natural infection.”
I had C19. Is it safe for me to get a vaccine? If so, when could I get one?
- It’s safe, and probably even beneficial, for anyone who has had Covid to get the vaccine at some point, experts said.
- “There’s nothing deleterious about getting a boost to an immune response that you’ve had before,” Dr. Pepper said. “You could get an actually even better immune response by boosting whatever immunity you had from the first infection by a vaccine.”
- In fact, at a meeting on Wednesday, Dr. Moncef Slaoui, chief adviser to Operation Warp Speed, said up to 10 percent of participants in clinical trials for the vaccines had been infected with the virus without knowing it. Their immune responses to the vaccine are being analyzed, he said.
- If you’ve already had C19, you can afford to wait awhile for the vaccine.
- Studies from Dr. Pepper’s team and others have shown that the immune response evolves over the first few months after infection, but everyone who has had Covid has some level of protection during that time.
- “We didn’t see anybody who didn’t develop some sort of an immune response,” she said. “I don’t think those people need to rush out and go get the vaccine in the same way that people who are highly susceptible really do.”
- The A.C.I.P., which makes recommendations to the Centers for Disease Control and Prevention about vaccine distribution, said at a meeting on Wednesday that people who had not been infected should get priority over those who contracted the virus in the past 90 days.
- “At some point we’ll need to figure out whether 90 days is the right number,” Dr. Maldonado said. But for now, “people who have evidence of infection recently should probably not be vaccinated at first in line because there’s so little vaccine available.”
2. Train Your Body to Work Out—or Just Hang Out—in Colder Weather
- So you hate the cold.
- With coronavirus surging, restaurants and bars closed and the homes of even friends and family off-limits, does that mean your winter social life is doomed?
- No, according to a host of scientists, professors and trainers who are experts on the physiological impact of frigid weather on humans. Adapting to cold isn’t fun— who loves to shiver?—but it’s possible, scientists say. And as a bonus: Cold, like exercise, makes you healthier.
- “I literally do cold exposure training every day,” says Dave Whitley, a motivational speaker, coach, strongman and author of “Superhuman You.” He either turns his shower water to cold or submerges in a big freezer of nearly freezing water in his outdoor shed. “At first it’s really miserable, then bearable, then kind of pleasant,” he says.
- If practiced consistently, training for cold can potentially transform a lonesome indoor winter. “If people follow a progressive intelligent path of delivering cold exposure, they will be able to tolerate the cold better, go out with friends and hang out outdoors on New Year’s Eve,” Mr. Whitley says.
- This isn’t for everybody. People who hole up indoors likely will have a harder time adjusting. The elderly and those with cardiovascular and other health conditions must take extra care. Cold exposure can weaken the immune system, at least for a short time.
- But kooky as it sounds, getting uncomfortably cold is good for you. “People are very thermostatic. We like our thermal systems at one temperature,” says Christopher Minson, a physiology professor at the University of Oregon, who studies the body’s response to extreme environments and works with professional and Olympic athletes and sports teams. While that’s comfortable, it’s not healthy long-term, he says. When temperature pushes you out of your comfort zone, “your metabolic rate goes up, your heart works a little harder, the blood vessels constrict. Every single cell of your body is challenged a little bit, the same as with exercise,” he says.
- This type of training doesn’t require a trainer or special equipment. You can begin by taking simple (though not necessarily pleasant) steps like turning the thermostat down, shedding clothes and going outside in the cold air as often as possible. When it comes to temperature, “humans are very stimulus-oriented,” says John Castellani, a research physiologist for the U.S. Army who has studied how people adapt to and perform in the cold.
- It’s the receptors in skin that alert the brain to cold. The hypothalamus, which acts as the body’s thermostat, responds to signals from the skin by causing vasoconstriction of the blood vessels, reducing blood flow to the extremities to protect the core and prevent heat loss, according to Dr. Minson.
- If the cold doesn’t abate, shivering starts; the muscle contractions generate heat to ward off deadly hypothermia, even in conditions that don’t come close to being dangerous, like waiting at a bus stop in winter. With repeated exposures, though, the brain begins to get it. “It perceives cold as less of a threat,” says Dr. Minson. Shivering subsides and research shows that the body begins to generate heat biochemically. Scientists aren’t sure exactly how, but progressively, we feel more comfortable. That’s why a cold day in September feels less so in March.
- Researchers and trainers have come up with all sorts of different ways to acclimate. Michael McTate, founder of the Chilled Out Wellness Center in Fort Collins, Colo., has dozens of practical methods for the beginner to the advanced, including ice packs on the back of the neck, hands in cold water and wearing shorts in 40-degree weather. Dr. Minson, who experiments on himself, bikes to work in a T-shirt in cold weather and does yoga outside.
- If you really want to be ready, say, for ice skating or an outdoor New Year’s Eve, subject yourself to really cold water. Scientists have found that humans cool two to five times more quickly in water than in air. For some, this method can be as extreme as an ice bath in a tub chilled literally with blocks of ice or a chest freezer—the kind usually used to store food or game.
- Or it can be as simple as adjusting your shower. “Everybody has a shower and everybody takes a shower,” Mr. Whitley says. At the end of yours, he suggests, turn the water as cold as you can comfortably stand for 30 seconds. If that’s too much, try ten or 15 seconds.
- Dr. Minson, who has put himself through a year of daily “cold shower challenges,” recommends starting at 15 seconds of cold water daily the first week and increasing the time incrementally in subsequent weeks. If you start to shiver, “back off, get out and warm up,” says Mr. McTate. “It’s training. You want gradual unforced exposure. You don’t have to break world records.”
- Scientists used to think that human adaptation to cold would take way longer and be more painful. In 2014, a group of Lithuanian scientists studied physiological adaptations in 14 men who had agreed to spend up to three hours a day in 57 degree water for nearly three weeks. Marius Brazaitis, a Lithuanian Sports University scientist and an author of that study, recently conducted similar research—this time to see if 12 young people could adapt to the cold water by spending just 10 minutes a day in it.
- “Ten minutes worked very well,” he says, acknowledging he feels “a little bit guilty” over the stressful protocol of the earlier study. Ten minutes, he says, was enough to observe a decrease in heart rate and hyperventilation over the course of the yet unpublished study, a delayed immune response and improved cognitive function including attention and memory. “The cold is very good for your brain,” he says.
- Based on the new research, “it’s a good recommendation to try cold showers,” he says. “Start from a higher temperature—just two or three minutes—and day after day, decrease water temperature and increase the time spent. I think you will get adapted.”
How to Acclimate to the Cold
- First week: Turn shower water to cold for 15 seconds every day for four or five days.
- Subsequent weeks: Lengthen the cold burst five or ten seconds until you can take an entirely cold shower.
- Buy a timer. This is not the time to be fiddling with your smartphone.
- Be consistent or the body won’t take the challenge seriously.
- If you’re really hooked, take an ice bath chilled with blocks of ice or buy a chest freezer. Use a pool thermometer.
- Don’t overdo it. If you start to shiver, back off and warm up.
- Can’t stand the water? Go outside—a lot. Wear fewer clothes. The point is to feel the cold, not fight it.
- Outdoors on New Year’s Eve? Better bundle up. Alcohol has the opposite effect of a cold shower. It expands blood vessels making it easier to lose heat from the skin.
3. How Airflow Inside a Car May Affect C19 Transmission Risk – What Works Best for Windows and Ventilation
- A new study of airflow patterns inside a car’s passenger cabin offers some suggestions for potentially reducing the risk of C19 transmission while sharing rides with others.
- The study, by a team of Brown University researchers, used computer models to simulate the airflow inside a compact car with various combinations of windows open or closed. The simulations showed that opening windows — the more windows the better — created airflow patterns that dramatically reduced the concentration of airborne particles exchanged between a driver and a single passenger. Blasting the car’s ventilation system didn’t circulate air nearly as well as a few open windows, the researchers found.
- “Driving around with the windows up and the air conditioning or heat on is definitely the worst scenario, according to our computer simulations,” said Asimanshu Das, a graduate student in Brown’s School of Engineering and co-lead author of the research. “The best scenario we found was having all four windows open, but even having one or two open was far better than having them all closed.”
- Das co-led the research with Varghese Mathai, a former postdoctoral researcher at Brown who is now an assistant professor of physics at the University of Massachusetts, Amherst. The study is published in the journal Science Advances.
A study published recently in Science Advances looks at how airflow patterns inside the passenger cabin of a car might affect the transmission of SARS-CoV-2 and other airborne pathogens. The simulations produced some potentially counterintuitive findings. For example, one might expect that opening windows directly beside each occupant might be the simplest way to reduce exposure. The simulations found that while this configuration is better than no windows down at all, it carries a higher exposure risk compared to putting down the window opposite each occupant. “When the windows opposite the occupants are open, you get a flow that enters the car behind the driver, sweeps across the cabin behind the passenger and then goes out the passenger-side front window,” said Kenny Breuer, a professor of engineering at Brown and a senior author of the research. “That pattern helps to reduce cross-contamination between the driver and passenger.” Credit: Breuer lab / Brown University
- The researchers stress that there’s no way to eliminate risk completely — and, of course, current guidance from the CDC notes that postponing travel and staying home is the best way to protect personal and community health. The goal of the study was simply to study how changes in airflow inside a car may worsen or reduce risk of pathogen transmission.
- The computer models used in the study simulated a car, loosely based on a Toyota Prius, with two people inside — a driver and a passenger sitting in the back seat on the opposite side from the driver. The researchers chose that seating arrangement because it maximizes the physical distance between the two people (though still less than the 6 feet recommended by the CDC). The models simulated airflow around and inside a car moving at 50 miles per hour, as well as the movement and concentration of aerosols coming from both driver and passenger. Aerosols are tiny particles that can linger in the air for extended periods of time. They are thought to be one way in which the SARS-CoV-2 virus is transmitted, particularly in enclosed spaces.
- Part of the reason that opening windows is better in terms of aerosol transmission is because it increases the number of air changes per hour (ACH) inside the car, which helps to reduce the overall concentration of aerosols. But ACH was only part of the story, the researchers say. The study showed that different combinations of open windows created different air currents inside the car that could either increase or decrease exposure to remaining aerosols.
- Because of the way air flows across the outside of the car, air pressure near the rear windows tends to be higher than pressure at the front windows. As a result, air tends to enter the car through the back windows and exit through the front windows. With all the windows open, this tendency creates two more-or-less independent flows on either side of the cabin. Since the occupants in the simulations were sitting on opposite sides of the cabin, very few particles end up being transferred between the two. The driver in this scenario is at slightly higher risk than the passenger because the average airflow in the car goes from back to front, but both occupants experience a dramatically lower transfer of particles compared to any other scenario.
- The simulations for scenarios in which some but not all windows are down yielded some possibly counterintuitive results. For example, one might expect that opening windows directly beside each occupant might be the simplest way to reduce exposure. The simulations found that while this configuration is better than no windows down at all, it carries a higher exposure risk compared to putting down the window opposite each occupant.
- “When the windows opposite the occupants are open, you get a flow that enters the car behind the driver, sweeps across the cabin behind the passenger and then goes out the passenger-side front window,” said Kenny Breuer, a professor of engineering at Brown and a senior author of the research. “That pattern helps to reduce cross-contamination between the driver and passenger.”
- It’s important to note, the researchers say, that airflow adjustments are no substitute for mask-wearing by both occupants when inside a car. And the findings are limited to potential exposure to lingering aerosols that may contain pathogens. The study did not model larger respiratory droplets or the risk of actually becoming infected by the virus.
- Still, the researchers say the study provides valuable new insights into air circulation patterns inside a car’s passenger compartment — something that had received little attention before now.
- “This is the first study we’re aware of that really looked at the microclimate inside a car,” Breuer said. “There had been some studies that looked at how much external pollution gets into a car, or how long cigarette smoke lingers in a car. But this is the first time anyone has looked at airflow patterns in detail.”
- The research grew out of a C19 research task force established at Brown to gather expertise from across the University to address widely varying aspects of the pandemic. Jeffrey Bailey, an associate professor of pathology and laboratory medicine and a coauthor of the airflow study, leads the group. Bailey was impressed with how quickly the research came together, with Mathai suggesting the use of computer simulations that could be done while laboratory research at Brown was paused for the pandemic.
- “This is really a great example of how different disciplines can come together quickly and produce valuable findings,” Bailey said. “I talked to Kenny briefly about this idea, and within three or four days his team was already doing some preliminary testing. That’s one of the great things about being at a place like Brown, where people are eager to collaborate and work across disciplines.”