November 3, 2020
Without reliable information, we rely on fear or luck.
“We are entering the most concerning and most deadly phase of this pandemic. This is not about lockdowns. It hasn’t been about lockdowns since March or April. It’s about an aggressive balanced approach that is not being implemented.”Dr. Birx, White House coronavirus response coordinator
“The US could not possibly be positioned more poorly to stem rising cases as more people gather indoors during the colder autumn and winter months. The US will need to make an abrupt change in public health precautions.”Dr. Fauci, Director of the National Institute of Allergy and Infectious Diseases
“The lockdowns will go down as an epic failure of public policy by people who were wrong, refused to accept they were wrong, didn’t know the data, didn’t care, and became a frenzy of stopping COVID-19 cases at all costs and those costs are massive.”Scott Atlas, White House coronavirus advisor
Situation Report Summary:
- Cases Increasing Across World At Rapid Rate
- Case Fatality Rate Is Decreasing
- Lockdowns Increasing Across the World (as is Opposition to them)
- Risk of Supply Chain Disruption Is Increasing
1. Cases & Tests
3. Top 5 States in Cases, Deaths, Hospitalizations & Positivity
O. Linked Stories
- Convalescent plasma therapy for C19: Where are we now?
- Death Rates Have Dropped for Seriously Ill Covid Patients
- C19: What role does vitamin D play?
- Spike in prescribing dexamethasone to C19 patients may do more harm than good
- How Coronavirus Can Be Stopped: 3D Atomic Map of C19’s Viral Replication Mechanism
- NEJM: clinical trial indicates monoclonal antibody lowered hospitalizations and emergency visits
- Coronavirus Infection Revealed in “Mini-Lungs” Shows How C19 Damages the Lungs
- Coronavirus might attack red marrow and block new erythrocytes formation
- Study provides clues on curbing the aggressive nature of coronavirus
- After Coming Down With Symptoms, Scientist Develops New Way to Test for C19 Antibodies
- Despite C19 Pandemic, Risky Sexual Behavior and STIs Are Rising
- Norwegian Researchers Are Collecting Sperm From C19 Patients to Determine Impact on Future Generations
- Potential impact of C19 school closures on academic achievement
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A. The Pandemic As Seen Through Headlines
(In no particular order)
- Pre-election COVID-19 spike creates concerns for polling places
- In people without symptoms, a rapid test misses more infections than it spots, a study says
- NY Gov. Cuomo announces mandatory quarantine and COVID-19 testing for out-of-state travelers
- Dr. Fauci: U.S. ‘In for a Whole Lot of Hurt’ Due to Rising Virus Cases, Deaths
- Trump hints he may fire Dr. Fauci after the election
- Public health experts see timeline for returning to normal slipping into late 2021 or 2022
- Record number of American children (> 61,000) tested positive for COVID-19 last week
- Pregnant women with Covid-19 are more likely to need intensive care, a new C.D.C. study finds
- States say they lack federal funds to distribute coronavirus vaccine as CDC tells them to be ready by Nov. 15
- A relentless virus surges, burying the Mountain West and pushing many states to the brink
- ‘Clearly, Coloradans have lapsed’: New virus cases are setting records in Colorado
- New COVID-19 test can deliver accurate results in 30 minutes
- States undercount positive rapid tests, masking the spread of disease
- Israel begins human trials for COVID-19 vaccine
- China’s race for Covid-19 vaccine raises safety questions
- “We’re Not Guinea Pigs!” – Brazilians Protest São Paulo Governor’s Mandatory Vaccination Push
- Black Americans Hesitant On Vaccine
- The death risk from Covid-19 for elderly people varies sharply among countries
- In the hunt for the source of the virus, the W.H.O. let China take charge
- “A Lot Of People Are Leaving”: COVID Shutdowns Have Turned San Francisco Into A Ghost Town
- Europe’s COVID-19 cases double in five weeks, total infections surpass 10 million
- European leaders driven to new lockdowns by surge in virus
- Merkel likens the pandemic to the challenges Germany faced after World War II as a new lockdown begins
- Anti-Lockdown Protests Erupt Across Spain As State Of Emergency Extended
- As new lockdowns are ordered across Europe, Swedish COVID death rate has fallen sharply
- ‘Le Grand Escape’ From Paris: Footage Shows Record-Breaking Traffic Gridlock Hours Before Lockdown
- Japan opens airport COVID-19 test lab for departing travelers
- UK Police Chief: It’s A “Civic Duty” To Snitch On Neighbors Violating COVID Restrictions
- UK Prime Minister Johnson announces 1 month lockdown
- With delayed death counts, popular COVID tracking sites mislead public, fuel alarm
- As cases soar, an El Paso judge ordered a shutdown, but the Texas AG says the judge has ‘no authority’
- A wave of ransomware hits US hospitals as coronavirus spikes
- North Dakota worst-hit state
- Covid-19: Mexico acknowledges 50 000 more deaths than official figures show
- Midwestern states see near-record cases
- Texas hospitalizations climb
- Cases climb in key election states
- Florida becomes 4th state to top 17,000 COVID-19 deaths
- France reports 50,000+ new cases in latest record
- CureVac vaccine shows positive response in early trial
- Sunak says England lockdown could be extended
- South Korea confirms 97 new cases
- India reports 45,231 new cases as outbreak continues to slow
- New cases in Iran fall
- China reports 33 new cases
- Poland reports 21,000 new cases
- Brazil strikes deal to buy Chinese vaccine
- France reports most new deaths since April 20
- Belgium announces 6-week lockdown
- CDC unveils guidance for cruise lines
- Italy suffers 2nd straight record
- New Jersey cases, hospitalizations highest since May
- Regeneron follows Eli Lilly, halts enrollment of seriously ill patients (but continues to treat moderately ill patients)
- Iceland tightens restrictions
- Sweden introduces new economic support
- Czech Republic won’t shut down manufacturing as country braces for new restrictions
- Taiwan celebrates record COVID-19 free streak, best growth in developed world
- UK accelerates vaccine approval
- Germany reports record jump
- Japan tops 100,000 cases
- HK customs agents seize counterfeit masks
- Indonesia reports most cases in 2 months
- Schools in Cambodia can begin reopening
- Slovakia Aims To Test All 5 Million Citizens In New Approach To Combat COVID-19
- Michigan Bars, Restaurants Will Require Customer’s Names And Phone Numbers Starting Monday
- Black-Owned Businesses Lead Rebound To Pre-Pandemic Levels
- Global Wine Production Slumps For Second Year As Industry Crushed By Virus
- The Crashing Rental Market Could Set Off The Next Housing Crisis
- In Moment Of Brutal Honesty, JPMorgan Says Economic Disaster And More Lockdowns Will Be Great For Stocks
- Friendly’s Restaurant Files For Bankruptcy, Expect Many More
- ‘CommonPass’: New COVID-19 Security Measures Will Make Health A Prerequisite For Travel
- As many as 10,000 attend Utah rave billed as a ‘protest’ against COVID-19 restrictions
- Skidmore College has suspended almost 50 students for violations of virus rules
- Nearly 150 COVID-19 cases linked to Massachusetts church
- Overnight retreat spurred 116 coronavirus cases after student developed symptoms
- Foot-operated vending machine is a germaphobe’s dream
- Private Jet Traffic Soars As Elites Panic Exit Cities Amid Virus, Elections
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
- Worldwide Cases:
- Total Cases = 47,313,868
- New Cases = 472,997
- New Cases (7 day average) = 502,135 (+8,615) (+1.8%)
- Record high 7 day average number of new cases
- 7 day average has been rapidly increasing since 10/5
- Since 10/5, the 7 day average has increased by more than 200,000, and increase of 40.2%
- US Cases & Testing:
- Total Cases = 9,567,543
- New Cases = 88,905
- New Cases (7 day average) = 86,055 (+2,685) (+3.2%)
- Percentage of New Global Cases (7 day average) = 17.2%
- Total Number of Tests = 149,694,768
- Percentage of positive tests (7 day average) = 8.1%
- Record high 7 day average of new cases
- 7 day average has been rapidly increasing since 10/5
- Since 10/5, 7 day average has increased from 44,491 to 88,905, an increase of 99.8%
- 7 day average percentage of positive tests increases from 5.1% to 8.1% since 10/5, an increase of 58.9%
- Rapid increases in new cases and percentage of positive tests could foreshadow an increase in the number of new deaths
- Worldwide Deaths:
- Total Deaths = 1,211,022
- New Deaths = 5,706
- New Deaths (7 day average) = 6,659 (+85) (+1.3%)
- 7 day average of new deaths have been rapidly increasing since 10/13
- 7 day average has exceeded the 2nd peak on 8/11 by 658, an increase of 11%
- 7 day average is approaching the 1st peak on 4/18 (7,070)
- Total Deaths = 236,997
- New Deaths = 522
- New Deaths (7 day average) = 850 (-1) (-0.1%)
- Percentage of Global New Deaths = 12.8%
- 7 day average of new deaths has been mostly increasing since 10/5
- Since 10/5, 7 day average has increased from 711 to 850, an increase of 19.5%
- 7 day average case fatality rate = 0.99% (vs. 7.7% on 4/21, a decrease of 87.1%)
3. Top 5 States in Cases, Deaths, Hospitalizations & Positivity (11/2)
- The positivity rate continues to rise across the country
- Nationally, the average 7-day positivity rate was 8.1% — up from 6.3% as of 10/19.
- More than 50% of all tests are now positive in ND and SD.
- Four states (KS, IA, WI, ID) 7-day positivity rates greater than 30%
- Four states (NE, MO, IN, WY) had 7-day positivity rates greater than 20%.
- In total, 39 states have 7-day positivity rates greater than 5% (+1 states since 10/19)
- Hospitalizations in the US increased to 48,470, up 28% since 10/19.
- 40 states have had increases of hospitalized patients of more than 10% since 10/19
- Of states with more than 1,000 hospitalized patients, the notable increases include: MI (+87%), IL (+61%), OH (+58%), PA (+56%), NJ (+46%), and TX (+33%).
- MA, and HI – only states with a drop in hospitalizations since 10/19
4. U.S. 7 Day Average of New Cases Hits New High
- Just days after the U.S. recorded the highest daily number of new coronavirus cases since the pandemic began, Sunday’s numbers were lower, but the seven-day average is now the highest the country has seen, at 81,493 cases.
- The seven-day average, which smooths out irregularities in the data, has been steadily increasing since Sept. 12, when the average was 34,350 cases.
- In total, confirmed U.S. cases topped 9.2 million, according to data compiled by Johns Hopkins University.
- Hospitalizations are also on the rise. Nationwide, there were 47,502 people in hospitals due to C19 on Sunday, the highest total since Aug. 12, according to the Covid Tracking Project.
- States continue to break daily records as well, as the vast majority of states experience a rise in new cases.
- The Tennessee Department of Health reported more than 3,000 new cases Monday, the fourth time the state’s daily case total was above 3,000 since the pandemic began. All four instances have happened in the past 15 days. Indiana also registered over 3,000 cases Monday, a number it surpassed on Thursday for the first time. Daily numbers in the state rarely exceeded 1,000 cases a day until early August.
- Ohio registered nearly 3,000 new cases Monday, after hitting a record 3,845 new infections on Friday. The state was averaging just over 1,000 new cases in September and nearly 2,000 in October, according to a Wall Street Journal analysis of Johns Hopkins University data.
- Michigan reported more than 4,000 new cases for Sunday, its third-highest reading since the pandemic began, after hitting a record last week, according to Johns Hopkins data. Other states that have seen elevated numbers recently reported lower daily figures for Sunday, including Wisconsin and Pennsylvania.
- The number of new cases reported tends to be lower at the beginning of the week because fewer people get tested over the weekend.
C. New Scientific Findings & Research
1. If You Have This on Your Skin, You Could Have Severe C19
- By now, we’re all familiar with the most common COVID symptoms: we know that fever, cough, and loss of smell or taste—and especially a combination of these—could easily spell trouble. But there’s one symptom that’s rarely talked about, yet associated with some of the worst COVID cases. A new analysis of patients with long-COVID—those who experience prolonged coronavirus symptoms for 60 days or longer—reveals that one dermatological symptom almost universally ends in a hospital visit. That symptom is called retiform purpura, a necrotic rash resulting from compromised blood vessels.
- If this sounds a bit frightening, it’s because it most definitely is. The analysis, conducted by the European Academy of Dermatology and Venereology (EADV), explains that out of the 990 cases analyzed for the study, every patient that presented with retiform purpura was hospitalized. COVID patients with this symptom have in many cases suffered vascular damage, indicating that the virus has deeply infiltrated the organs. A net-like pattern appears under the skin as the blockage of blood flow worsens.
- According to Esther Freeman, MD, director of Global Health Dermatology at Massachusetts General Hospital, these types of dermatological symptoms can offer much needed clues about a patient’s condition. “The skin can provide a visual window into inflammation that may be going on elsewhere in the body,” she explained.
- COVID toes are perhaps the best known skin-related coronavirus symptom. These are chilblain sores that look red, irritated, and inflamed, and they can serve as a dead giveaway that it’s time to be tested. The good news? According to the aforementioned study, “COVID toes travel with relatively mild disease, with only 16 percent [of patients] hospitalized.” And for more surprising COVID symptoms, find out why A Rash in This Spot May Mean You Have COVID.
- If you notice a dry, scaly rash on your skin combined with any of the more common COVID symptoms, it’s definitely time to get tested. This particular rash is typically red, pink, purple, or brown in color and can be shaped like a bullseye (similar to a rash from Lyme disease) or in smaller circles on the skin. One study noted that this rash was found most commonly in the COVID outbreak in Lombardy, Italy.
- If you find that you suddenly break out in hives with no known allergy to explain it, this may very well be a COVID symptom. Speak with your doctor about any skin abnormalities you may notice, especially if you present with any other COVID symptoms. And for a comprehensive list of COVID warning signs, check out The Most Common COVID Symptoms You Could Have.
- These skin lesions are characterized by scaly papules or plaques—basically a red, scaly, inflamed skin rash. Doctors believe this is caused by “high levels of pro-inflammatory cytokines,” as part of the patient’s immune response to C19. And for more warning signs of severe coronavirus, know that If You Have These 2 COVID Symptoms, You Could End Up in the Hospital.
2. Chances Are High Your Grocery Store Clerk Has Silent C19
- When we sing the praises of frontline workers—the doctors, nurses, and other medical teams that are tackling the COVID crisis head on—we often forget others that put their lives at risk daily for the sake of their jobs. As one study published in the journal Occupational & Environmental Medicine reveals, grocery store clerks face a shockingly high risk of COVID infection—which could in turn put customers at risk while shopping. As the study revealed, grocery workers at one store were 20 times more likely to be infected than the general population, and those with customer facing jobs were 5 times more likely to be infected than their colleagues in other positions.
- The study centered on one grocery store in Boston, Massachusetts with 104 employees. In May of this year, the entire team was subjected to coronavirus tests, as part of a mandatory testing policy issued by the city. “One in five (21 out of 104) workers tested positive for the coronavirus (SARS-CoV-2), indicating a prevalence of 20% at that point in time. This was significantly higher than the prevalence of the infection in the local community at the time: 0.9-1.3%,” the study explains.
- Perhaps even more disturbingly, 76% of these cases were completely asymptomatic, presenting with no known symptoms of COVID. Among those who tested positive, 91% had a customer facing role, compared with 59% of those employees who tested negative.
- “This is the first study to demonstrate the significant asymptomatic infection rate, exposure risks, and associated psychological distress of grocery retail essential workers during the pandemic,” the researchers said. Of course, beyond the harrowing impact on the grocery store workers themselves, these findings also demonstrate a significant COVID risk to the more general population. “Once essential workers are infected with SARS-CoV-2, they may become a significant transmission source for the community they serve,” the study notes.
- So the next time you shop at the grocery store, practice extreme COVID precautions: practice social distancing, touch as little as possible, and be sure to wear a mask. And for goodness’ sake, be kind and patient with your checkout clerk—their day is stressful enough already. Read on for more places that could be spreading COVID, and for more on minimizing your risk, check out Your Risk of Catching COVID at Home Is This High.
3. Tiny variants in genes may dictate severity of C19
- It has been one of the most baffling aspects of the C19 pandemic. Healthy young men and women have become infected with the virus and developed life-threatening side effects. But at the same time, many of their contemporaries have simply shrugged off the condition.
- Unknown factors are clearly leaving some people vulnerable to the pandemic’s worst effects even though some of them are young, are not overweight and do not suffer from other obvious health problems. Scientists think that tiny genetic differences are causing some to be struck down while many others are spared.
- And these differences in DNA are now being tracked by researchers who believe they offer a route to developing new drugs that could halt many of the worst consequences of suffering from C19.
- Key developments include research which indicates that interferon – a molecular messenger that stimulates immune defences against invading viruses – may play a vital role in defending the body. Scientists have found that rare mutations in some people may leave them unable to make adequate supplies of the interferon they need to trigger effective immune responses to Covid. Trials using interferon as Covid treatments are now under way at several centers.
- “These genetic findings give us very clear insights,” said Martin Hibberd, professor of emerging infectious diseases at the London School of Hygiene and Tropical Medicine. “They are natural biological experiments which suggest that people who make more interferon when infected have a better response to the disease. And that in turn tells us that patients could well benefit from treatment with interferon.”
- Research is also focusing on a gene known as TYK2. Some variants of this gene are involved in triggering some auto-immune diseases such as rheumatoid arthritis (RA) and also seems to be involved in causing severe Covid. A drug developed to treat RA, baricitinib, has a genetic common denominator with Covid and this has led to it being used in clinical trails against the virus. Last month the pharmaceutical company Eli Lilly announced that early results showed the drug helped Covid patients recover.
- “The crucial point is that by understanding the impact of gene variants in the body we can now think about finding drugs that could block their pathways and help patients,” said Jeffrey Barrett, of the Wellcome Sanger Institute’s C19 genomic surveillance programme. “The bad news is that it can take years of experiments to find treatments this way. The good news is that there are now so many scientists working on this kind of thing that we might still some quick answers.”
- Other research – pioneered by Kenneth Baillie, of Edinburgh University, and outlined in a recent issue of Science – has uncovered several other genes that appear to be important. These include OAS genes that are triggered by interferon and which code for proteins that are involved in breaking down viral RNA, from which the C19 virus is made. Baillie’s research has yet to be peer reviewed and he has counselled caution in interpreting this work. Nevertheless, he told Science that he hoped his results would speed the development of treatments “because the epidemic is progressing at such an alarming rate, even a few months of time saved will save lots of lives”.
- In addition, other researchers point out that there are other ways of using genetics to combat Covid. Dr Dipender Gill of Imperial College London has, with colleagues, used genetic data to predict how different interventions could affect disease reactions.
- Gill said: “We looked at five traits that have been linked to increased risk of getting severe C19: obesity, high blood pressure, poor cholesterol, smoking and diabetes. Then we looked to see if these traits could be modified in order to reduce that risk of severe infection.”
- To do that, Gill – working with a team of British, Norwegian and American scientists – analyzed data from thousands of patients, using genetic variants that increase individuals’ risk of acquiring these conditions. They were then able to carry out studies that would show if action taken to modify these traits would reduce susceptibility to severe C19. The team made two key discoveries.
- “We found there is a causal link between obesity and the risk of having a severe C19 [reaction]. We also found the same effect for smoking. This indicates that losing weight and giving up smoking will have a direct impact in improving your chances of surviving C19. That is the power of genetic studies like these.”
4. Household spread of coronavirus is common and quick
- The spread of C19 among members in a household after one person is infected is “common” and occurs quickly after illness onset, according to a new study from the US Centers for Disease Control and Prevention.
- The person exposed or suspected of having C19 should be isolated before getting tested and before test results come back to protect others in the home, said the study, published Friday in the CDC’s Morbidity and Mortality Weekly Report.
- “Because prompt isolation of persons with C19 can reduce household transmission, persons who suspect that they might have C19 should isolate, stay at home, and use a separate bedroom and bathroom if feasible,” wrote a CDC-led team of researchers.
- In addition, all members of the household should wear masks at all times in common spaces, the team said.
Infection of others happened within days
- The research, part of an ongoing CDC-supported study, followed 101 people initially infected with C19 in Nashville, Tennessee, and Marshfield, Wisconsin, between April and September.
- Infection was quick: Over half of the people (53%) who lived with someone battling C19 became infected within a week, researchers found. Some 75% of these secondary infections occurred within five days of the first symptoms in the initial patient.
- “Substantial transmission occurred whether the index patient was an adult or a child,” researchers said.
- A 53% household infection rate, the study said, is higher than what has been documented so far. To date, related research has reported only a 20% to 40% infection rate.
- “An important finding of this study is that fewer than one half of household members with confirmed that coronavirus (SARS-CoV-2) infections reported symptoms at the time infection was first detected,” the study authors wrote.
- “Many reported no symptoms throughout 7 days of follow-up, underscoring the potential for transmission from asymptomatic secondary contacts and the importance of quarantine.”
Isolate yourself or your loved one
- Staying isolated from other household members can be challenging, especially if you are in a small space or there are children in the home.
- “If you have somebody at home who’s older or immunocompromised, you may want to isolate them to one side of the house so the kids and everybody else aren’t around them on a regular basis,” said pediatrician Dr. Tanya Altmann, editor in chief of the American Academy of Pediatrics’ book “Caring for Your Baby and Young Child: Birth to Age 5 and The Wonder Years,” in a prior interview.
- “If it’s a child that you have to care for, then you may have to make the decision to isolate one adult with the child,” she added. “That adult would be caring for the child, and the other adult would be responsible for the rest of family.”
- And of course, all of this will be extremely difficult for a single parent “who might be the only one,” said pediatrician Dr. Jenny Radesky, a spokesperson for the American Academy of Pediatrics, in a prior interview.
- “Know who your neighbors are, even what your neighborhood social network might be,” said Radesky, an assistant professor of pediatrics at the University of Michigan. “You may not be that close interpersonally, but someone may be willing to do a grocery store drop-off, or pick-up medications because we’re all in this together.”
- The rest of the family should practice isolation as well, Radesky added.
- “Unfortunately you need to keep the whole household under isolation,” she said. “The patterns of C19 spread suggest that clusters of people who live close together are at highest risk of getting it from one another. If children are part of that household, they may show minimal symptoms but still be contagious.”
- If you live alone, your challenge is to monitor your symptoms and care for yourself when you’re not feeling well. Be sure to have a plan in place to get food and medications delivered to your home, and find someone who can be responsible for virtually checking in on you on a regular basis.
- Stock or ask loved ones to provide the room with all relevant forms of entertainment: TV, computer, iPad, books, even games that you could play via FaceTime or Skype.
A supply checklist
- Don’t hesitate to order online or ask loved ones to provide basic supplies:
- A working thermometer to monitor fever, which is considered to be 100 degrees Fahrenheit (37.7 degrees Celsius), and a method to clean it, such as isopropyl alcohol
- Fever-reducing medications, such as acetaminophen
- A box of rubber or latex disposable gloves and face masks
- A 60- or 90-day supply of necessary prescription medicines
- Regular soap and 70% alcohol-based hand sanitizer (antibacterial soap isn’t necessary if you wash properly, and that way you won’t contribute to the world’s growing antibiotic-resistant superbugs)
- Tissues to cover sneezes and coughs. But there is really no need to hoard toilet paper — this is a respiratory disease
- Regular cleaning supplies, kitchen cleaning gloves and trash can liners
- Disinfectant cleaning supplies — the CDC suggests picking from a list that meets the virus-fighting standards of the US Environmental Protection Agency, but says you can also make your own version by using 1/3 cup unexpired bleach per gallon of water or 4 teaspoons bleach per quart of water. Never mix bleach with ammonia or any other cleanser — it produces toxic gases
Cover up and disinfect
- If you’re sick, the CDC says to use a face mask around other people, such as when going to the doctor or hospital.
- Try to keep it on at home too, unless you or your loved one is having “trouble breathing” or is “unconscious, incapacitated, or otherwise unable to remove the mask without assistance,” the CDC says.
- Maximize isolation and protective actions, Altmann stressed.
- “You can have a healthy person leave the sick one food and drinks at the door, and then go wash their hands,” Altmann explained. “Wear gloves to pick up the empty plates, take them back to the kitchen and wash them in hot water with soap, or preferably with a dishwasher, and wash your hands again.”
- Do not share drinking glasses, cups, forks or other eating utensils or dishes, the CDC says. Don’t share towels or bedding with other people in your home. When doing laundry, don’t shake the sick person’s dirty clothes to “minimize the possibility of dispersing virus through the air.”
- And caregivers should wear disposable gloves when handling that dirty laundry, the CDC says, throwing them away after each use.
- “If using reusable gloves, those gloves should be dedicated for cleaning and disinfection of surfaces for C19 and should not be used for other household purposes. Clean hands immediately after gloves are removed,” the CDC advises.
- Dedicate a lined trash can for any tissues or other paper or disposable products used by a sick person, the CDC says, adding that caregivers should “use gloves when removing garbage bags, handling and disposing of trash. Wash hands after handling or disposing of trash.”
- And remember: Call 911 immediately if you or your loved ones have any of these symptoms: increased or sudden difficulty breathing or shortness of breath; a persistent pain or pressure in the chest; and any sign of oxygen deprivation, such as new confusion, bluish lips or face, or you can’t arouse the sick person.
- While these are key danger signs, this is not an exhaustive list, said American Medical Association President Dr. Patrice Harris, so call if anything concerns you.
- “If the symptoms don’t get better or they worsen you should call your health care provider, the urgent care or the emergency department,” Harris said. “And if the shortness of breath is severe, immediately call 911.”
Keeping everyone else from getting sick
- To be clear: After a positive C19 diagnosis, everyone in the house needs to isolate themselves from the outside world as much as possible.
- “I would recommend that families find friends who can drop off essential groceries or medications, not go to work, and not play with other children — even outside,” Radesky said.
- “If you don’t have friends who can drop off groceries or essential items, see if the local stores can deliver the items for you — I’m sure they would appreciate not having a potential C19 exposure in their store,” she added.
- If a family member without symptoms believes it is absolutely essential to go outside to the grocery store, pharmacy or to check on a family member, be aware that you may well be contagious and anything you touch could transfer the virus — even without symptoms.
- “I would urge people not to do this,” Radesky said. “The way we will beat this virus is by reducing the number of times that each infected person transmits the virus to another person. So the more you can do to stop the virus in its tracks — in other words, your family doesn’t give it to anyone else, and you don’t bring it to your workplace or a local store — the sooner we will be done with this!”
- To reduce virus transfer inside your home, try to keep an air flow in the rest of the home with opened windows or doors with screens, if weather permits. You can also add air filtering devices to your home.
- “Improving ventilation helps remove respiratory droplets from the air,” the CDC says.
- Have everyone wash their hands at every opportunity. Clean and disinfect all those commonly shared surfaces — don’t forget the refrigerator and microwave handles!
- Keep everyone as stress-free as possible — a hard task for sure — and focus on healthy eating, regular exercise and quality sleep.
- Even though there is no indication that pets can give or get C19, the CDC suggests keeping pets away from sick people.
- “Since animals can spread other diseases to people, it’s always a good idea to practice healthy habits around pets and other animals,” the CDC says. “If you must care for your pet or be around animals while you are sick, wash your hands before and after you interact with pets.”
When is your home isolation over?
- If you tested positive but had no symptoms, you can stop isolating at home 10 days after the date you had your positive test, the CDC says.
- For those with symptoms, the CDC says you can be around others when:
- It’s been 10 days or more since symptoms first appeared
- AND you’ve gone 24 hours with no fever without the use of fever-reducing medications
- AND other symptoms of C19 are improving
- “A limited number of persons with severe illness may produce replication-competent virus beyond 10 days that may warrant extending duration of isolation and precautions for up to 20 days after symptom onset,” the CDC says. Consider consultation with infection control experts, the agency says.
- A loss of taste and smell can remain for weeks or even months after recovery, the CDC notes, but that does not mean you need to remain isolated.
- However, if you have a severely weakened immune system or were more severely sick with C19 — such as being admitted to a hospital and needing oxygen — the rules change, according to the CDC:
- “Your healthcare provider may recommend that you stay in isolation for longer than 10 days after your symptoms first appeared (possibly up to 20 days),” the CDC says.
- “Persons who are severely immunocompromised may require testing to determine when they can be around others. Talk to your healthcare provider for more information.”
- These are scary times, but hopefully these tips will help ease your anxiety and prepare you and your family for the worst, while hoping and striving for the best.
5. How two immune system chemicals may trigger C19’s deadly cytokine storms
- Exactly how the coronavirus kills is a mystery. But part of the problem may be a partnership between just two immune system chemicals that triggers deadly organ damage.
- In mice, a combination of immune chemicals called TNF alpha and gamma interferon trips a domino chain of biochemical reactions that ultimately leads to three types of cell death, researchers report October 29 at bioRxiv.org. That wave of cell death further feeds an escalation of immune chemicals, known as a cytokine storm, that leads to more cell death and causes tissue and organ damage and failure.
- If the same process happens in people with severe C19, the research points to several existing drugs that might help calm the cytokine storm and prevent severe disease or aid recovery. The preliminary results, however, have not yet been reviewed by other scientists.
- Study after study has found that people with severe C19 have elevated levels of inflammation-stimulating chemicals called cytokines in their blood compared with healthy people, says immunologist Thirumala-Devi Kanneganti of St. Jude Children’s Research Hospital in Memphis, Tenn. But the mechanism by which cytokines can lead to organ failure and death isn’t known.
- Kanneganti and colleagues selected eight of the most commonly elevated cytokines in severely ill C19 patients to see how the cytokines affect cells growing in lab dishes. Alone, none of cytokines caused harm to infection-fighting macrophage cells. But when the researchers treated macrophages with a cocktail of all eight cytokines, “we were seeing dramatic cell death, unbelievable, through the roof,” Kanneganti says. The team then tried various combinations of cytokines and discovered that only the pairing of TNF alpha and gamma interferon was deadly to macrophages.
- That’s surprising, says Mohamed Lamkanfi, an immunologist at Ghent University in Belgium who was not involved in the study. Those cytokines have been studied for decades and weren’t previously implicated in killing cells.
- This deadly duo doesn’t just kill cells. “When we injected the combination of TNF and interferon gamma, mice are dead like flies. Within 10 hours they just drop dead,” Kanneganti says. And those mice had symptoms similar to those seen in people with severe C19, such as low numbers of infection-fighting T cells and signs of liver and tissue damage.
- Next, Kanneganti and her colleagues deciphered how the two cytokines kill cells and mice. In a series of experiments, the researchers found that the combo triggers three kinds of cell death: apoptosis, pyroptosis and necroptosis.
- Apoptosis is a quiet kind of programmed cell death that happens often, even in healthy people. It’s necessary for proper development and health, including avoiding cancer. Cells infected with a virus will often set off this self-destruct mechanism. Their deaths and removal from the body may help shield other cells from becoming infected.
- Pyroptosis and necroptosis are messier, causing cells to spill their guts and release cytokines and debris that can trigger more inflammation. Researchers knew that these gorier deaths are involved in some inflammatory conditions, but apoptosis wasn’t previously known to rile up the immune system, Kanneganti says.
- Activating all three types of cell death together — an inflammation-producing process Kanneganti calls PANoptosis — leads to an ever-escalating cytokine storm, “like a hurricane,” she says.
- Researchers have thought that those three varieties of cell death were triggered by different biochemical switches. But Kanneganti’s group found that all three types of death can result from a single chain reaction, or pathway. At the trailhead of the biochemical pathway sit proteins known as STAT1 and JAK. Inappropriate chemical actions by both have been implicated in some types of cancer, and inhibitors of these proteins are being tested in cancer therapies.
- One inhibitor of JAK, a drug called baricitinib, is already being tested against the coronavirus (SN: 5/13/20). Preliminary evidence suggests that when given to hospitalized patients along with the antiviral drug remdesivir, baricitinib can shorten hospital stays even more than remdesivir alone has been shown to do.
- The researchers also found that blocking TNF alpha and gamma interferon protected mice infected with the coronavirus (SARS-CoV-2) from dying. Mice with other inflammatory conditions were also protected from dying when both cytokines were blocked, and to a lesser extent when only one was blocked. Those findings suggest that both cytokines must be blocked to have an effect, Lamkanfi says.
- Drugs and antibodies that block the two immune chemicals exist and are used to treat some autoimmune diseases. For instance, TNF alpha inhibitors are used to treat Crohn’s disease, ulcerative colitis, and rheumatoid and psoriatic arthritis.
- Kanneganti’s data are convincing that the two cytokines may be involved in what’s going wrong in severely ill C19 patients, says Craig Coopersmith, a sepsis researcher and director of the Emory Critical Care Center in Atlanta. “It’s mechanistically fascinating and gives multiple potential [drug] targets that are worth exploring,” he says.
- But he’s skeptical that blocking the two cytokines will be as effective in people as it was in mice. “I have cured mouse sepsis 15 times, and I know my colleagues have cured mouse COVID,” he says. But “most of the time when you do the trials in people, they turn out to be negative.”
- And just because a drug could plausibly work doesn’t mean it will, of course. For instance, an antibody drug called tocilizumab, which blocks another cytokine called IL-6, did not show a benefit for treating C19 in recent clinical trials (SN: 10/23/20).
- In people, the triad of cell death triggered by TNF alpha and gamma interferon isn’t necessarily the only thing killing C19 patients, Coopersmith emphasizes. Blood clotting and cardiovascular issues and lung damage from mechanical ventilation are also big problems. Nevertheless, the new “mechanistically phenomenal study” gives researchers a good place to start teasing out what goes wrong in people with severe C19, he says, and learning how to fix it.
6. It’s Evolving: Coronavirus Genetic Mutation May Have Made C19 More Contagious
- A study involving more than 5,000 C19 patients in Houston finds that the virus that causes the disease is accumulating genetic mutations, one of which may have made it more contagious. According to the paper published in the peer-reviewed journal mBIO, that mutation, called D614G, is located in the spike protein that pries open our cells for viral entry. It’s the largest peer-reviewed study of the coronavirus (SARS-CoV-2) genome sequences in one metropolitan region of the U.S. to date.
- The paper shows “the virus is mutating due to a combination of neutral drift — which just means random genetic changes that don’t help or hurt the virus — and pressure from our immune systems,” said Ilya Finkelstein, associate professor of molecular biosciences at The University of Texas at Austin and co-author of the study. The study was carried out by scientists at Houston Methodist Hospital, UT Austin and elsewhere.
- During the initial wave of the pandemic, 71% of the novel coronaviruses identified in patients in Houston had this mutation. When the second wave of the outbreak hit Houston during the summer, this variant had leaped to 99.9% prevalence. This mirrors a trend observed around the world. A study published in July based on more than 28,000 genome sequences found that variants carrying the D614G mutation became the globally dominant form of SARS-CoV-2 in about a month. SARS-CoV-2 is the coronavirus that causes C19.
- So why did strains containing this mutation outcompete those that didn’t have it?
- Perhaps they’re more contagious. A study of more than 25,000 genome sequences in the U.K. found that viruses with the mutation tended to transmit slightly faster than those without it and caused larger clusters of infections. Natural selection would favor strains of the virus that transmit more easily. But not all scientists are convinced. Some have suggested another explanation, called “founder’s effects.” In that scenario, the D614G mutation might have been more common in the first viruses to arrive in Europe and North America, essentially giving them a head start on other strains.
Most coronavirus strains circulating in Houston in the summer of 2020 had the D614G mutation in the spike protein.
- The spike protein is also continuing to accumulate additional mutations of unknown significance. The Houston Methodist-UT Austin team also showed in lab experiments that at least one such mutation allows spike to evade a neutralizing antibody that humans naturally produce to fight SARS-CoV-2 infections. This may allow that variant of the virus to more easily slip past our immune systems. Although it is not clear yet whether that translates into it also being more easily transmitted between individuals.
- The good news is that this mutation is rare and does not appear to make the disease more severe for infected patients. According to Finkelstein, the group did not see viruses that have learned to evade first-generation vaccines and therapeutic antibody formulations.
- “The virus continues to mutate as it rips through the world,” Finkelstein said. “Real-time surveillance efforts like our study will ensure that global vaccines and therapeutics are always one step ahead.”
- The scientists noted a total of 285 mutations across thousands of infections, although most don’t appear to have a significant effect on how severe the disease is. Ongoing studies are continuing to surveil the third wave of C19 patients and to characterize how the virus is adapting to neutralizing antibodies that are produced by our immune systems. Each new infection is a roll of the dice, an additional chance to develop more dangerous mutations.
- “We have given this virus a lot of chances,” lead author James Musser of Houston Methodist told The Washington Post. “There is a huge population size out there right now.”
- Several other UT Austin authors contributed to the work: visiting scholar Jimmy Gollihar, associate professor of molecular biosciences Jason S. McLellan and graduate students Chia-Wei Chou, Kamyab Javanmardi and Hung-Che Kuo.
- The UT Austin team tested different genetic variants of the virus’s spike protein, the part that allows it to infect host cells, to measure the protein’s stability and to see how well it binds to a receptor on host cells and to neutralizing antibodies. Earlier in the year, McLellan and his team at UT Austin, in collaboration with researchers at the National Institutes of Health, developed the first 3D map of the coronavirus spike protein for an innovation that now factors into several leading vaccine candidates’ designs.
- The researchers found that SARS-CoV-2 was introduced to the Houston area many times, independently, from diverse geographic regions, with virus strains from Europe, Asia, South America and elsewhere in the United States. There was widespread community dissemination soon after C19 cases were reported in Houston.
7. 7 different ‘disease forms’ identified in mild C19
- n a study recently published in the top journal “Allergy“, a team of MedUni Vienna scientists led by immunologist Winfried F. Pickl and allergologist Rudolf Valenta (both from the Center for Pathophysiology, Infectiology and Immunology) showed that there are seven “forms of disease” in C19 with mild disease course and that the disease leaves behind significant changes in the immune system, even after 10 weeks. These findings could play a significant role in the treatment of patients and in the development of a potent vaccine.
- In the study involving 109 convalescents and 98 healthy individuals in the control group, the researchers were able to show that various symptoms related to C19 occur in symptom groups. They identified seven groups of symptoms:
1) “flu-like symptoms” (with fever, chills, fatigue and cough),
2) “common cold-like symptoms” (with rhinitis, sneezing, dry throat and nasal congestion),
3) “joint and muscle pain”,
4) “eye and mucosal inflammation”,
5) “lung problems” (with pneumonia and shortness of breath),
6) “gastrointestinal problems” (including diarrhoea, nausea and headache) and
7) “loss of sense of smell and taste and other symptoms”.
- “In the latter group we found that loss of smell and taste predominantly affects individuals with a ‘young immune system’, measured by the number of immune cells (T lymphocytes) that have recently emigrated from the thymus gland. This means that we were able to clearly distinguish systemic (e.g., groups 1 and 3) from organ-specific forms (e.g., groups 6 and 7) of primary C19 disease,” says Pickl.
C19 fingerprint in the blood
- At the same time, the scientists established that C19 leaves behind long detectable changes in the blood of convalescents, very similar to a fingerprint. For example, the number of granulocytes, which are otherwise responsible in the immune system for fighting bacterial pathogens, is significantly lower than normal in the C19 group. Pickl explains: “However, both the CD4 and CD8 T cell compartment developed memory cells and CD8 T cells remained strongly activated. This indicates that the immune system is still intensively engaged with the disease several weeks after initial infection.
- At the same time, the regulatory cells are greatly diminished – and that is likely a dangerous mix, which could lead to autoimmunity.” Furthermore, increased levels of antibody-producing immune cells were detected in the blood of convalescents – the higher the fever of the affected patient during the mild course of the disease, the higher were the antibody levels against the virus.
- “Our findings contribute to a better understanding of the disease and help us in the development of potential vaccines, since we now have access to promising biomarkers and can perform even better monitoring,” the scientists emphasize.
- “Above all, the study shows that the human immune system “doubles up” when defending against C19 with the combined action of immune cells and antibodies – like the defence in a modern soccer team – and that the cells are also able to memorise certain “moves” on the part of the virus and respond to them. Now it is a matter of implementing these findings and using them for the development of highly-effective C19 vaccines.”
8. New cause of C19 blood clots identified – existing drug may reduce clotting
- Blood clots continue to wreak havoc for patients with severe C19 infection, and a new study explains what may spark them in up to half of patients.
- The culprit: an autoimmune antibody that’s circulating in the blood, attacking the cells and triggering clots in arteries, veins, and microscopic vessels. Blood clots can cause life-threatening events like strokes. And, in C19, microscopic clots may restrict blood flow in the lungs, impairing oxygen exchange.
- Outside of novel coronavirus infection, these clot-causing antibodies are typically seen in patients who have the autoimmune disease antiphospholipid syndrome. The connection between autoantibodies and C19 was unexpected, says co-corresponding author Yogen Kanthi, M.D., an assistant professor at the Michigan Medicine Frankel Cardiovascular Center and a Lasker Investigator at the National Institutes of Health’s National Heart, Lung, and Blood Institute.
- “In patients with C19, we continue to see a relentless, self-amplifying cycle of inflammation and clotting in the body,” Kanthi says. “Now we’re learning that autoantibodies could be a culprit in this loop of clotting and inflammation that makes people who were already struggling even sicker.”
‘Some of the worst clotting we’ve ever seen’
- Co-corresponding author Jason Knight, M.D., Ph.D., a rheumatologist at Michigan Medicine, has been studying antiphospholipid syndrome antibodies in the general population for years.
- “Half of the patients hospitalized with C19 were positive for at least one of the autoantibodies, which was quite a surprise,” says Knight, also an associate professor of internal medicine and a leading expert on diseases caused by autoantibodies.
- In the new Science Translational Medicine publication, they found about half of the patients who were very sick with C19 were exhibiting a combination of high levels of both the dangerous antibodies and super-activated neutrophils, which are destructive, exploding white blood cells. In April, the team was the first to report that patients hospitalized for severe C19 had higher levels of neutrophil extracellular traps in their blood.
- To learn more, they studied the explosive neutrophils and the C19 antibodies together in mouse models to see if this could be the dangerous combination behind the clots.
- “Antibodies from patients with active C19 infection created a striking amount of clotting in animals – some of the worst clotting we’ve ever seen,” Kanthi says. “We’ve discovered a new mechanism by which patients with C19 may develop blood clots.”
Attacking C19 blood clots from all angles
- The researchers say these findings aren’t yet ready for clinical practice, but they add a new perspective to the robust thrombosis and inflammation research in patients with C19.
- Kanthi, Knight, first author Yu (Ray) Zuo, M.D., and colleagues now want to know whether severely ill patients with high levels of these antibodies would have better outcomes if the antibodies are blocked or removed.
- If so, that might warrant an aggressive treatment like plasmapheresis, which is commonly used in severe autoimmune diseases, Zuo explains. It involves draining blood through an IV, filtering it and replacing it with fresh plasma that doesn’t contain those antibodies associated with blood clots.
- “We know people with the highest levels of autoantibodies did worse in terms of respiratory function, and the antibodies caused inflammation even in healthy cells” says Zuo, an assistant professor of internal medicine and a rheumatologist at Michigan Medicine.
- “We don’t yet know what is triggering the body to produce these antibodies, so the next step would be additional research to identify the triggers and the targets of the antibodies,” Knight adds.
- In addition, these findings bring up new questions surrounding the use of convalescent plasma as a possible C19 treatment, but the team says more research is needed to examine this concern.
- “We’re now investigating how long these antibodies remain in circulation after recovery from the novel coronavirus,” Knight says.
- The researchers are also currently running a randomized clinical trial called DICER, which is testing a well-known anti-clotting agent, dipyridamole, in patients with C19 to determine whether it’s more effective than a placebo in reducing excessive blood clots.
- “Dipyridamole is an old drug that is safe, inexpensive, and scalable,” Kanthi says. “The FDA approved it 20 years ago to prevent clotting, but we only recently discovered its potential to block this specific type of inflammation that occurs in COVID.”
9. T-cell C19 immunity ‘present in adults six months after first infection’
- Cellular (T-cell) immunity against the virus that causes C19 is likely to be present within most adults six months after primary infection, with levels considerably higher in patients with symptoms, a study suggests.
- The data offers another piece of the puzzle that could be key to understanding whether previous Sars-CoV-2 infections – the virus behind C19 – can prevent reinfection, and if so, for how long.
- The study, led by the UK coronavirus immunology consortium, evaluated 100 non-hospitalised healthcare workers in March and April after antibody responses were detected in them. It is yet to be peer-reviewed.
- It is the first study to offer data on T-cell levels six months after infection in people with mild or asymptomatic disease that is likely to represent the majority of infections, the authors say.
- The results of the study are likely to be viewed positively, after previous studies suggested antibody levels can decline within the first few months post-infection.
- Data released from a 100,000-person sample in August indicated about 6% of the population of England had antibodies – proteins produced in response to an infection – but antibody levels dropped by more than a quarter in three months, researchers revealed in late October.
- Once the virus enters the body, it is greeted by a cavalry of cells that mount a counterattack that is swift, broad and generic. This so-called innate immune system is meant to arrest the infection in its tracks. If that mission is foiled, it buys time until the “experts” show up.
- These experts constitute two types of white blood cells: B-cells and T-cells, that work like brothers-in-arms. If the virus makes it past the initial assault, some T-cells are slayers, annihilating respiratory cells the pathogen has colonised.
- Meanwhile, helper T-cells take on a supportive role – including stimulating B-cells to produce molecules called antibodies that render the virus immobile or thwart it from penetrating other cells. The adaptive system also retains memory – but in the case of C19, it is unclear how much and for how long.
- After being tracked for six months, researchers found that every person had detectable T-cell levels, and levels were 50% higher in people who had experienced symptoms at the time of infection.
- This could mean that either there will be more protection in people with more severe initial disease, or conversely, that people with asymptomatic disease are able to control the virus with lower levels of T-cells, they said.
- A bigger set of patients would be tracked for a longer time period to get a better sense of cellular immunity, given that T-cells could survive for long periods, said one of the study’s authors, Paul Moss, a professor at the University of Birmingham.
- The authors also saw that T-cells levels were strongly correlated with the peak level of the antibody response. Cellular immune responses could even help to protect against the decline in antibody levels over time, they added.
- Overall, the results offer evidence that T-cell immunity may last longer than antibodies – but whether these persistent T-cells offer protection against reinfection remains unclear.
- “I think this data is reassuring, potentially even encouraging — but it does not mean that people cannot get reinfected,” Moss said. “We now need large-scale population studies to show how the antibody and cellular profiles act together to protect people over time.”
- In the study, some people lost detectable levels of antibodies. But that did not mean that B-cells, which make antibodies, were not around to spring into action if challenged again, the authors explained.
- Ideally, testing for B-cells and T-cells in the community would provide a conclusive idea of how much the antibody response was actually predicting large-scale immunity, and whether there were people who did not have antibodies but were protected by cellular immunity, cautioned the author Shamez Ladhani, a consultant epidemiologist for Public Health England.
- “But at the moment, there is little evidence to suggest that there is widespread cell-mediated immunity without an antibody response.”
- Paul Morgan, a professor at Cardiff University, who was not involved in the study, said: “The work provides a welcome dose of optimism that Sars-CoV2 infection (and immunization?) can induce a robust and sustained protective immune response, although this does not yet prove immunity to further infections which will require longer-term surveillance and larger cohorts.”
10. Trends in C19 Risk-Adjusted Mortality Rates
- Early reports showed high mortality from coronavirus disease 2019 (C19). Mortality rates have recently been lower, raising hope that treatments have improved. However, patients are also now younger, with fewer comorbidities. We explored whether hospital mortality was associated with changing demographics at a 3-hospital academic health system in New York. We examined in-hospital mortality or discharge to hospice from March through August 2020, adjusted for demographic and clinical factors, including comorbidities, admission vital signs, and laboratory results.
- Among 5,121 hospitalizations, adjusted mortality dropped from 25.6% (95% CI, 23.2-28.1) in March to 7.6% (95% CI, 2.5-17.8) in August. The standardized mortality ratio dropped from 1.26 (95% CI, 1.15-1.39) in March to 0.38 (95% CI, 0.12-0.88) in August, at which time the average probability of death (average marginal effect) was 18.2 percentage points lower than in March. Data from one health system suggest that mortality from C19 is decreasing even after accounting for patient characteristics.
- Early reports showed high mortality from coronavirus disease 2019 (C19), while current United States data mortality rates are lower, raising hope that new treatments and management strategies have improved outcomes. For instance, CDC data show that 6.7% of (confirmed) cases resulted in death in April, compared with 1.9% in September.
- However, the demographics of those infected have also changed, and more available testing may mean more comprehensive identification and earlier treatment. Nationally, for instance, the median age of confirmed cases was 38 years at the end of August, down from 46 years at the start of May. Therefore, whether decreasing C19 mortality rates simply reflect changing demographics or represent actual improvements in clinical care is unknown. The objective of this analysis was to assess outcomes over time in a single health system, accounting for changes in demographics, clinical factors, and severity of disease at presentation.
- We included 5,121 hospitalizations, of which 5,118 (99.94%) had known outcomes (death or hospital discharge). Peak hospitalizations occurred in late March to mid-April, which accounted for 53% of the hospitalizations. Median length of stay for patients who died or were discharged to hospice was 8 days (interquartile range, 4-15; max 140 days). The median age and the proportion male or with any comorbidity decreased over time (Table). For instance, the proportion with any chronic condition decreased from 81% in March to 72% in August.
- Adjusted mortality dropped each month, from 25.6% in March to 7.6% in August (Table and Figure). The SMR declined progressively over time, from 1.26 (95% CI, 1.15-1.39) in March to 0.38 (95% CI, 0.12-0.88) in August (Table). The adjusted average marginal effect was also significantly lower than in March in every subsequent month, reaching a maximum of an average 18.2 (95% CI, 12.0-24.4) percentage point decrease in probability of death in August, accounting for changes in demographics and clinical severity (Table and Appendix B). The decrease in unadjusted mortality over time was observed across age groups (Appendix C).
- Results of the two sensitivity analyses were similar (Appendices D and E), though attenuated in the case of the sepsis/respiratory cohort, with adjusted mortality falling from 31.4% to 14.4%, SMR decreasing from 1.28 (95% CI, 1.16-1.41) to 0.59 (95% CI, 0.16-1.50), and AME in August 17.0 percentage points (95% CI, 6.0-28.1).
- In this study of C19 mortality over 6 months at a single health system, we found that changes in demographics and severity of illness at presentation did not fully explain decreases in mortality seen over time. Even after risk adjustment for a variety of clinical and demographic factors, including severity of illness at presentation, mortality was significantly and progressively lower over the course of the study period.
- Similar risk-adjusted results have been preliminarily reported among intensive care unit patients in a preprint from the United Kingdom. Incremental improvements in outcomes are likely a combination of increasing clinical experience, decreasing hospital volume, growing use of new pharmacologic treatments (such as systemic corticosteroids, remdesivir, and anticytokine treatments), nonpharmacologic treatments (such as placing the patient in the prone position, or proning, rather than on their back), earlier intervention, community awareness, and, potentially, lower viral load exposure from increased mask wearing and social distancing.
- Strengths of this study include highly detailed electronic health record data on hospitalizations at three different hospitals, a diverse patient population,6 near-complete study outcomes, and a lengthy period of investigation of 6 months. However, this study does have limitations. All patients were from a single geographic region and treated within a single health system, though restricting data to one system reduces institution-level variability and allows us to assess how care may have evolved with growing experience.
- Aggregating data from numerous health systems that might be at different stages of local outbreaks, provide different quality of care, and contribute different numbers of patients in each period introduces its own biases. We were also unable to disentangle different potential explanatory factors given the observational nature of the study. Residual confounding, such as a higher proportion of particularly frail patients admitted in earlier periods, is also a possibility, though the fact that we observed declines across all age groups mitigates this concern. Thresholds for hospital admission may also have changed over time with less severely ill patients being admitted in the later time periods. While changing admission thresholds could have contributed to higher survival rates in the latter portions of the study, our inclusion of several highly predictive clinical and laboratory results likely captured many aspects of disease severity.
- In summary, data from one health system suggest that COVID-19 remains a serious disease for high-risk patients, but that mortality rates are improving over time.
D. Vaccines & Testing
1. Ultrapotent C19 Nanoparticle Vaccine Designed via Computer
- An innovative nanoparticle vaccine candidate for the pandemic coronavirus produces virus-neutralizing antibodies in mice at levels 10 times greater than is seen in people who have recovered from C19 infections. Designed by scientists at the University of Washington School of Medicine in Seattle, the vaccine candidate has been transferred to two companies for clinical development.
- Compared to vaccination with the soluble coronavirus (SARS-CoV-2) Spike protein, on which many leading C19 vaccine candidates are based, the new nanoparticle vaccine produced 10 times more neutralizing antibodies in mice, even at a sixfold lower dose. The data also show a strong B-cell response after immunization, which can be critical for immune memory and a durable vaccine effect.
- When administered to a single nonhuman primate, the nanoparticle vaccine produced neutralizing antibodies targeting multiple different sites on the Spike protein. Researchers say this may ensure protection against mutated strains of the virus, should they arise. The Spike protein is part of the coronavirus infectivity machinery.
- The findings were published on October 30, 2020, in Cell. The lead authors of this paper are Alexandra Walls, a research scientist in the laboratory of David Veesler, a UW associate professor of biochemistry; and Brooke Fiala, a research scientist in the lab of Neil King, UW assistant professor of biochemistry.
- The vaccine candidate was developed using structure-based vaccine design techniques invented at UW Medicine. It is a self-assembling protein nanoparticle that displays 60 copies of the SARS-CoV-2 Spike protein’s receptor-binding domain in a highly immunogenic array. The molecular structure of the vaccine roughly mimics that of a virus, which may account for its enhanced ability to provoke an immune response.
- “We hope that our nanoparticle platform may help fight this pandemic that is causing so much damage to our world,” said King, inventor of the computational vaccine design technology at the Institute for Protein Design. “The potency, stability, and manufacturability of this vaccine candidate differentiate it from many others under investigation.”
- Hundreds of candidate vaccines for C19 are in development around the world. Many require large doses, complex manufacturing, and cold-chain shipping and storage. An ultrapotent vaccine that is safe, effective at low doses, simple to produce and stable outside of a freezer could enable vaccination against C19 on a global scale.
Production schematic shows how coronavirus proteins are added to a computer-designed nanoparticle platform to create a candidate vaccine against C19. The vaccine candidate was designed and tested in animal models by researchers at the University of Washington School of Medicine.
- “I am delighted that our studies of antibody responses to coronaviruses led to the design of this promising vaccine candidate,” said Veesler, who spearheaded the concept of a multivalent, receptor-binding, domain-based vaccine.
- The lead vaccine candidate from this report is being licensed non-exclusively and royalty-free during the pandemic by the University of Washington. One licensee, Icosavax, a Seattle biotechnology company co-founded in 2019 by King, is currently advancing studies to support regulatory filings and has initiated the FDA’s Good Manufacturing Practice. To accelerate progress by Icosavax to the clinic, Amgen has agreed to manufacture a key intermediate for these initial clinical studies. Another licensee, SK bioscience of South Korea, is advancing its own studies to support clinical and further development.
E. Improved & Potential Treatments
1. New drug candidate for the treatment of C19
- Researchers from the University of Kent, the Goethe-University in Frankfurt am Main (Germany), and the Hannover Medical School (Germany) have identified a drug with the potential to provide a treatment for C19.
- The international team led by Professor Martin Michaelis, Dr Mark Wass (both School of Biosciences, University of Kent), and Professor Jindrich Cinatl (Institute of Medical Virology, Goethe-University) found that the approved protease inhibitor aprotinin displayed activity against the coronavirus (SARS-CoV-2) in concentrations that are achieved in patients. Aprotinin inhibits the entry of SARS-CoV-2 into host cells and may compensate for the loss of host cell protease inhibitors that are downregulated upon SARS-CoV-2 infection.
- Aprotinin aerosols are approved in Russia for the treatment of influenza and could be readily tested for the treatment of C19.
- Professor Martin Michaelis said: ‘The aprotinin aerosol has been reported to be tolerated extremely well in influenza patients. Hence, it may have a particular potential to prevent severe C19 disease when applied early after diagnosis.’
F. Concerns & Unknowns
1. First known case in Bay Area of dual coronavirus-flu infection
- The first known case in the Bay Area of a dual coronavirus-influenza infection was confirmed Thursday in Solano County, prompting health officials to urge residents to hurry up and get flu shots and double down on social distancing and mask wearing.
- The Solano County Department of Health and Social Services described the unlucky patient as an otherwise healthy individual under the age of 65, but the county did not release any personal information.
- Bela Matyas, the Solano County health officer, said the victim is older than 20, works in the “health care realm” and appears to have recovered from the co-infection.
- “This is a very clear indication of the potential for this to occur,” Matyas said. “We now have flu in our community at the same time we have COVID … Contracting either disease may weaken your immune system and make you more susceptible to the other disease.”
- Not much is known about how contracting the flu would impact someone with C19, but infectious disease specialists have long warned that co-infection could cause more severe illness.
- “It certainly can’t be good to be infected with both and it may well be a greater challenge to the person who has both infections, and that could make the outcomes worse,” said John Swartzberg, an infectious disease specialist at the UC Berkeley School of Public Health. “So we should do everything we can to prevent infections.”
- The fact that the Solano County patient recovered from the two viruses may not be indicative of what is likely to occur in the overall population. It is just not a large enough sample to determine how the two viruses interact with each other, said Robert Siegel, an infectious-disease specialist at Stanford University.
- That’s why doctors are forced to rely on common sense, which dictates that two diseases in one body put greater stress on the immune system.
- “People who have respiratory problems generally do worse with the coronavirus, and the flu causes those problems,” Siegel said. “We want to err on the side of caution.”
- But there is some contradictory information.
- A small study in New York found no difference in outcomes when they compared patients with C19 with patients who had both influenza and C19. The data, released on Oct. 23 in IDWeek, looked at a small group of patients in the Bronx who tested positive for both tests early in the pandemic.
- A Stanford study in April found that 20.7% of people infected with the coronavirus (SARS-CoV-2) were also co-infected with at least one other respiratory pathogen.
- What doctors do know is that severe symptoms — high fever, headache and body aches — are more likely to manifest themselves early with the flu. With C19, severe symptoms including fever, cough and shortness of breath, may appear from two to 14 days after exposure. Neither is treatable with antibiotics.
- Pregnant women, children under 5 and older people with pre-existing conditions, like heart disease, asthma and diabetes, are the biggest concern with either virus, Matyas said. Fortunately, the way to prevent spread is the same with both — masks, social distancing, washing hands and staying home when you are sick.
- The vaccine will also help, he said.
- “Getting a flu vaccine this year is more important than ever,” Matyas said. “Vaccination not only reduces the risk of catching the flu, it also reduces the chance that you’ll be hospitalized. In other words, the flu vaccine will provide some protection and reduce your chances of needing to be hospitalized if you do get sick.”
2. Brain Scans Show a Whole Spectrum of C19 Abnormalities We Can’t Fully Explain
- Among the many serious symptoms of C19, the strange neurological effects experienced by many patients count as perhaps the most mysterious.
- A sudden loss of smell and taste was one of the first unusual symptoms reported by C19 patients, but stroke, seizures, and swelling of the brain (called encephalitis) have all been described.
- Some patients diagnosed with C19 also experience confusion, delirium, dizziness, and have difficulty concentrating, according to case reports and reviews.
- For several months, doctors have been relentlessly trying to understand this disease, and its many manifestations that seem to affect the brain in ways we can’t fully explain.
- To synthesize some of the rapidly accumulating data, two neurologists have now conducted a review of research exploring how C19 disturbs patterns of normal brain function, which can be measured by an EEG.
- An EEG, short for electroencephalogram, records electrical activity in different parts of a person’s brain, typically by using electrodes placed on their scalp.
- In their review, the researchers collated data on nearly 620 COVID-positive patients from 84 studies, published in peer-reviewed journals and pre-print servers, where the EEG waveform data were available to analyse.
- Looking at EEG results could indicate some form of COVID-related encephalopathy in these patients – signs of impairment or disturbance to brain function.
- Approximately two-thirds of the patients in the studies were male, and the median age was 61 years old. Some people also had a pre-existing condition, such as dementia, that could alter an EEG reading, which the researchers considered when evaluating their test results.
- Among the 420 patients where the basis for ordering an EEG was recorded, the most common reason was an altered mental state: close to two-thirds of the patients studied had experienced some delirium, coma, or confusion.
- Around 30% of patients had had a seizure-like event, which prompted their doctor to order an EEG, while a handful of patients had speech issues. Others experienced a sudden cardiac arrest, which could have interrupted blood flow to the brain.
- The patients’ EEG scans showed a whole spectrum of abnormalities in brain activity, including some rhythmic patterns and epileptic-like spikes in activity. The most common abnormality noted was diffuse slowing, which is an overall slowing of brain waves that indicates a general dysfunction in brain activity.
- In the case of COVID, this impairment could be the result of widespread inflammation, as the body mounts its immune response, or possibly reduced blood flow to the brain, if the heart and lungs are weak.
- As for localized effects, a third of all abnormalities detected were detected in the frontal lobe, the part of the brain which handles executive thinking tasks, such as logical reasoning and decision-making. The frontal lobe also helps us to regulate our emotions, control our behaviour, and is involved in learning and attention.
- “These findings tell us that we need to try EEG on a wider range of patients, as well as other types of brain imaging, such as MRI or CT scans, that will give us a closer look at the frontal lobe,” said neurologist and co-author Zulfi Haneef from Baylor College of Medicine in Houston.
- In time, an EEG could help cement a C19 diagnosis or hint at possible complications. Doing so might help doctors monitor the long-term complications of C19, and detect any long-lasting effects on a patient’s brain function.
- Unfortunately, as it stands the results don’t give any indication of how rare or common these brainwave disturbances are in the broader population, since only C19 patients who had an EEG test were included in the analysis.
- But it does add to mounting evidence that the novel coronavirus can have a serious impact on our neurological health.
- “More research is needed, but these findings show us these are areas to focus on as we move forward,” Haneef said.
- “EEG abnormalities affecting the frontal lobe seem to be common in C19 encephalopathy, and has been proposed as a potential biomarker if recorded consistently,” the authors wrote in their paper.
- As the pandemic rolls on, we’ve come to understand just how stubborn C19 can be, with patients dubbed ‘long haulers‘ describing how they can’t shake symptoms, and still feel fatigued months after they were diagnosed.
- “A lot of people think they will get the illness, get well, and everything will go back to normal,” Haneef said in a statement.
- “But these findings tell us that there might be long-term issues, which is something we have suspected and now we are finding more evidence to back that up.”
- The study was published in Seizure: European Journal of Epilepsy.
3. C19 Deaths Fall Heavily on Middle-Aged Men
- In the U.S., federal data show men represent about two-thirds of Covid-19 deaths among middle-aged people, and similar trends have emerged overseas. Scientists say there are a constellation of likely reasons, including health problems like high blood pressure and diabetes that men tend to have more often and that can lead to worse Covid-19 outcomes.
- But researchers also are homing in on potential biological factors, including women’s more able immune systems. And research has shown men are more prone to poor hand hygiene, lax mask-wearing habits and delaying medical care. Identifying the factors at play is important, health experts say, to help guide both effective prevention and treatment.
- “This is more than a significant trend. This clearly is a reality that this disease is more aggressive in men than women,” said Lawrence Young, professor of molecular oncology at the University of Warwick, in England.
- Covid-19 has hit women hard too. U.S. death-certificate data show women make up about 60% of all Covid-19 deaths among people at least 85 years old, the most affected age group. This is a stage in life when there are far fewer men still alive, since women live longer. There are also more women in nursing homes, which have been devastated by Covid-19 outbreaks.
- Overall, however, men make up about 54% of U.S. deaths, and a significantly higher portion in middle age. The death-certificate data through late October show men make up nearly 66% of more than 42,000 Covid-19 deaths occurring among people between their mid-30s and mid-60s.
- In Europe, the European Center for Disease Prevention and Control says men represent 73% of deaths of those from 40 to 69 years old. Data there also show men are 62% of the hospitalized population aged 40 to 69, and nearly three-quarters of the sickest patients in that age bracket.
- More broadly, a global database effort spanning 183 countries called the Sex, Gender and Covid-19 Project based at University College London found about 11 known Covid-19 cases among males for every 10 cases among females, and 14 male deaths for every 10 female deaths. There are some variations within these trends, and some countries aren’t reporting detailed sex-based data, which researchers say is sorely needed to help identify risks.
- The chance for severe illness and death with Covid-19 rises steeply with age but is also closely tied to a person’s underlying health. Multiple studies have found people with conditions including diabetes, cardiovascular disease and hypertension tend to be at greater risk of a bad outcome if they catch the virus—conditions that men are more likely to have in general, or at earlier ages.
- Beyond underlying health, differences in immune systems between the sexes may be guiding some of the disparity in how people respond to Covid-19, scientists say. The X chromosome, which women have two of and men one, contains many immunity-related genes, while the female sex hormone estrogen plays a role in moderating the body’s immune response, said Prof. Young, from the University of Warwick.
- In a recent Yale University study, researchers focused mainly on patients beyond middle age and found distinctions in how males and females respond to Covid-19 infections, including women’s stronger activation of virus-fighting T-cells, and weak activation of these cells correlated to worse outcomes in men. Men had higher levels of certain inflammatory proteins that can build to a level that damages lungs and other organs.
- Some scientists are probing possible treatments for Covid-19 pegged to sex-based differences, though research is halting and preliminary. Stony Brook University, for instance, began a small trial looking at estrogen as a treatment for men and older women with Covid-19, but the trial was halted because researchers couldn’t find enough eligible patients.
- Trying to address nonbiological risks may be an easier path, some researchers say.
- “We can’t control our genes, we can’t control how many X chromosomes we were born with, but we can control our behaviors,” said Erin Michos, director of women’s cardiovascular health at Johns Hopkins University School of Medicine. “A lot of this might be mitigated by behavioral habits. Not smoking, hand washing, mask wearing.”
- Sarah Richardson, who directs the Gender Sci Lab at Harvard University, believes male Covid-19 deaths are driven by external factors like job-based exposure and underlying health problems. Statistics can also be skewed, Dr. Richardson said: For example, front-line female health workers tend to be healthy, to fare well when sick and to be tested frequently, which can create a bigger pool of positive tests. Men with other kinds of occupational exposure may be tested less and be less healthy at baseline, she said.
- “I’m very concerned that if we continue to look at this as a biological problem we’re missing true patterns of vulnerability,” Dr. Richardson said. This includes racial disparities such as worse Covid-19 outcomes for minority women than white men, she said. Death records have already shown minorities are enduring a disproportionate hit from the disease.
4. Doctors Begin to Crack C19’s Mysterious Long-Term Effects
- Nearly a year into the global coronavirus pandemic, scientists, doctors and patients are beginning to unlock a puzzling phenomenon: For many patients, including young ones who never required hospitalization, C19 has a devastating second act.
- Many are dealing with symptoms weeks or months after they were expected to recover, often with puzzling new complications that can affect the entire body—severe fatigue, cognitive issues and memory lapses, digestive problems, erratic heart rates, headaches, dizziness, fluctuating blood pressure, even hair loss.
- What is surprising to doctors is that many such cases involve people whose original cases weren’t the most serious, undermining the assumption that patients with mild C19 recover within two weeks. Doctors call the condition “post-acute Covid” or “chronic Covid,” and sufferers often refer to themselves as “long haulers” or “long-Covid” patients.
- “Usually, the patients with bad disease are most likely to have persistent symptoms, but Covid doesn’t work like that,” said Trisha Greenhalgh, professor of primary care at the University of Oxford and the lead author of an August BMJ study that was among the first to define chronic Covid patients as those with symptoms lasting more than 12 weeks and spanning multiple organ systems.
- For many such patients, she said, “the disease itself is not that bad,” but symptoms like memory lapses and rapid heart rate sometimes persist for months.
- In October, the National Institutes of Health added a description of such cases to its C19 treatment guidelines, saying doctors were reporting C19-related long-term symptoms and disabilities in people with milder illness.
- Estimates about the percentage of C19 patients who experience long-haul symptoms range widely. A recent survey of more than 4,000 C19 patients found that about 10% of those age 18 to 49 still struggled with symptoms four weeks after becoming sick, that 4.5% of all ages had symptoms for more than eight weeks, and 2.3% had them for more than 12 weeks. The study, which hasn’t yet been peer reviewed, was performed using an app created by the health-science company Zoe in cooperation with King’s College London and Massachusetts General Hospital.
- Another preliminary study looking mostly at nonhospitalized Covid patients found that about 25% still had at least one symptom after 90 days. A European study found about one-third of 1,837 nonhospitalized patients reported being dependent on a caregiver about three months after symptoms started.
- With more than 46 million cases world-wide, even the lower estimates would translate into millions living with long-term, sometimes disabling conditions, increasing the urgency to study this patient population, researchers said. What they find could have implications for how clinicians define recovery and what therapies they prescribe, doctors said.
- Doctors say anxiety caused by social isolation and uncertainty surrounding the pandemic may exacerbate symptoms, though that isn’t likely the primary cause.
- Other viral outbreaks, including the original SARS, MERS, Ebola, H1N1 and the Spanish flu, have been associated with long-term symptoms. Scientists reported that some patients experienced fatigue, sleep problems and joint and muscle pain long after their bodies cleared a virus, according to a recent review chronicling the long-term effects of viral infections.
- What differentiates C19 is the far-reaching nature of its effects. While it starts in the lungs, it often affects many other parts of the body, including the heart, kidneys and the digestive and nervous systems, doctors said.
- “I haven’t really seen any other illness that affects so many different organ systems in as many different ways as Covid does,” said Zijian Chen, medical director for Mount Sinai Health System’s Center for Post-Covid Care.
- He described colleagues who were energetic, but after getting sick, had trouble getting through the day. He said he has seen up close how C19 still affects their ability to do the things they love.
- “We thought it was a virus that, once it does what it does, you recover and you go back to normal,” he said. Sometimes that isn’t the case, and that “is really scary,” he said.
- A leading explanation for long-Covid symptoms is that immune-system activity and ensuing inflammation continue to affect organs or the nervous system even after the virus is gone, researchers said.
- Some of the most compelling evidence for the inflammation theory comes from C19 patients with signs of heart inflammation and injury months after illness. One study looking at 100 C19 patients two months after getting sick found that 78 had abnormal findings on cardiac magnetic resonance imaging, while 60 had cardiac MRIs indicating heart-muscle inflammation. The study included hospitalized, nonhospitalized and asymptomatic patients.
- “Even those who had no symptoms and were young and fit…even in those patients we saw abnormalities,” said Eike Nagel, one of the lead authors and director of the Institute for Experimental and Translational Cardiovascular Imaging at the University Hospital Frankfurt in Germany.
- Some patients had scarring on their heart imaging, he said, which worried him. The scarring wasn’t too serious, he said, but “we know from other studies that this is related to worse outcomes.”
- Doctors also are reporting cases of long-Covid patients with gastrointestinal issues. Recent work has found the new coronavirus, known as SARS-CoV-2, in fecal matter and intestinal lining of some C19 patients, suggesting the virus can infect and damage the cells of the gut. The intestines have a high density of ACE2 receptors, a type of protein on the surface of cells, which SARS-CoV-2 uses to infiltrate cells.
- Many patients report issues with concentration and memory, sometimes referred to as “brain fog.” Some say they forget what they’re trying to say or do. Neurologists seeing such patients say cognitive problems are among the most common symptoms.
- Some neurologists say they are seeing patients with signs of dysautonomia, or dysregulation of the autonomic nervous system. The autonomic nervous system regulates involuntary functions such as breathing, digestion and heart rate.
Taste and Smell
- Patients say it can take weeks or months to regain their senses of smell and taste. They say the loss of these senses affects not just their diet but their mental health.
- Some patients report persistent shortness of breath. Doctors often prescribe asthma inhalers and breathing exercises to help improve lung function. The exact cause is unknown. It could be related to aberrant nervous system function, lung injury or a compromised cardiovascular system.
- Many patients experience a racing heartbeat, or tachycardia, as well as extreme blood pressure changes. Some physicians think this could be related to an issue with the nervous system, particularly the autonomic arm, which deals with involuntary functions like heart rate and blood pressure.
- Some patients have signs of heart-muscle inflammation weeks or months after infection, doctors and researchers say. In some cases, they don’t report any symptoms, while others say they have shortness of breath and chest pain.
- Patients report issues with abdominal pain and diarrhea weeks or months after coming down with C19. Some physicians are recommending avoiding certain foods, such as dairy and gluten.
- Some patients report mild muscle and joint aches. Others have more severe pain.
- Many patients also report persistent fatigue weeks or months after coming down with C19, even when they had a mild or moderate course of illness and didn’t require hospitalization. The fatigue can be debilitating and get in the way of regular daily activities, like work and spending time with family.
A Persistent Multifront Attack
- The virus also might cause changes in gut bacteria, said Brennan Spiegel, a gastroenterologist and director of health services research at Cedars-Sinai Health System, who has had patients come in with abdominal pain and diarrhea weeks or months after coming down with C19.
- Ms. Moore, the Indiana lawyer, got C19 in March and initially felt better by the end of April. “I thought I beat this thing. I was ecstatic,” said Ms. Moore, who tested positive for coronavirus antibodies in May.
- That month, her health took a sharp turn for the worse. She struggled with tachycardia, or a racing heartbeat, and blood-pressure fluctuations. Those symptoms improved, but she still has gastrointestinal problems. A recent test found stomach-lining inflammation. Pepcid, antihistamines and avoiding dairy products have provided some relief, but other symptoms such as memory deficits persist.
- “I feel like there has to be some sort of next step,” she said, “because I’m not ready to accept this as my new reality.”
- She enrolled in a research study at the Neuro C19 Clinic at Northwestern Medicine in Chicago, one of several clinics across the country aiming to find solutions for patients.
- Some symptoms could be collateral damage from the body’s immune response during the acute infection, researchers said. Some patients might harbor an undetectable reservoir of infectious virus or have bits of noninfectious virus in some cells that trigger an immune response, they said.
- Another possibility is that the virus causes some people’s immune systems to attack and damage their own organs and tissues, researchers said. A June study found roughly half of 29 hospitalized ICU patients with C19 had one or more types of autoantibodies—antibodies that mistakenly target and attack a patient’s own tissues or organs.
- Doctors say some patients appear to be developing dysautonomia, or dysregulation of the autonomic nervous system, the part of the nervous system that regulates involuntary functions like breathing, digestion and heart rate, some researchers and doctors said.
- David Putrino, director of rehabilitation innovation at Mount Sinai Health System in New York City, said the majority of the more than 300 long-Covid patients being seen at its Center for Post-Covid Care appear to have developed a dysautonomia-like condition. About 90% of such patients report having symptoms of exercise intolerance, fatigue and elevated heartbeats. About 40% to 50% also report symptoms such as gastrointestinal issues, headaches and shortness of breath.
- Dr. Putrino said inflammation from the virus might be disrupting the normal functioning of the vagus nerve—the body’s longest cranial nerve—which relays messages to the lungs, gut and heart.
- The constellation of such neurological symptoms, along with persistent fatigue, joint pain and headaches, resembles myalgic encephalomyelitis, also known as chronic fatigue syndrome, said Anthony Komaroff, a Harvard Medical School professor of medicine who has studied the syndrome for decades. The condition can follow certain viral and bacterial infections, he said. He thinks the condition likely follows C19, too, at least in a portion of patients. A 2009 study of 233 SARS survivors found 27% met criteria for chronic fatigue syndrome four years after getting sick.
- It still isn’t known whether the new coronavirus gets into the brain itself, or if C19’s neurological symptoms stem from a body-wide inflammatory response, scientists say.
- In autopsies of some C19 patients, doctors have observed encephalitis, or inflammation of the brain. Small autopsy studies also have found preliminary evidence of coronavirus particles in regions of the brain important for smell. With other infections, viral particles have been found in the brains of patients with encephalitis, though it is rare, said Walter Royal, a neurovirologist and director of Morehouse School of Medicine’s Neuroscience Institute. What is more common is that the virus infects the lining of the blood vessels, causing damage and inflammation that in turn affects the brain.
- How long it will take long-Covid patients to recover remains unknown. Dr. Putrino said most of them won’t get better on their own, and will need at least six months of structured rehabilitation.
- “What tends to happen to people who don’t get treatment and don’t get the recognition they need is they slump down to a new normal of function,” he said.
G. The Road Back?
1. The Simple Rule That Could Keep C19 Deaths Down
- During the first C19 surge of the spring, the mantra was “Flatten the curve”—to buy time, using every tool available.
- Seven months later, it’s possible to measure what that time has bought: The death rate for C19 has fallen dramatically. Hospitals in most places are not overburdened, and treatments are improving in many small but cumulative ways. In one study of patients hospitalized in a New York City health system, the adjusted death rate fell from 25.6% in March, at the pandemic’s onset, to 7.6% in August.
- This change cannot be explained by C19 patients getting younger and healthier. The study’s authors adjusted the mortality rates for age and other risk factors. “People should take this as validation of all the hard work and sacrifices they have been making,” says Leora Horwitz, an internist and the study’s lead author. “It has made a difference.” Similar patterns hold throughout New York City and in the U.K., and they underscore the reason for flattening the curve. The longer we can prevent infections, the better prepared we will be to treat the people that might eventually get it.
- What was true about flattening the curve in March is still true now. As the U.S. faces a third coronavirus surge, Horwitz warns that “these numbers are not static.” We are still learning about how to treat C19, and truly game-changing therapies have yet to arrive. When hospitals become overburdened—as they are starting to in El Paso, Utah, Wisconsin—death rates may rise again. The axiom from the beginning of the C19 pandemic still applies today. “If I have to choose to have it, probably the later, the better,” says Sanja Jelic, a pulmonologist at Columbia University Medical Center.
- Jelic was among the doctors treating C19 patients in New York in the spring, when hundreds of people were turning up at the city’s hospitals everyday unable to breathe. Patients were crammed into hallways; doctors were overworked. Normally, Jelic says, she might have seen 8 or 10 patients in a day. In April, she and two fellows were responsible for 60, any of whom might crash and need to be intubated.
- Lack of knowledge about the virus constrained what doctors did. Hospitals initially favored ventilation in part because doctors feared that high-flow therapy oxygen could aerosolize the virus and spread it to staff who didn’t have adequate supplies of personal protective equipment. (Now, of course, we know that the virus can be spread through aerosols generated from just normal talking and exhaling.) In some cases, aggressive intubation might have done more harm than good in patients who didn’t need it. Doctors stopped putting every patient on a ventilator once they realized the benefits of less invasive oxygen therapy and even turning patients onto their bellies, also known as proning.
- Because C19 can, like many conditions, manifest so differently from person to person, knowing which patients might benefit—or be hurt—by a treatment is a key part of the learning curve. “There isn’t a one-size-fits-all treatment,” says Nicholas Caputo, a doctor at Lincoln Hospital in the Bronx, who was one early advocate of proning. Ventilation is one example of a treatment that can help or hurt depending on the patient. Another is dexamethasone, a steroid that suppresses the immune system. The drug has been shown to reduce mortality in patients with severe C19, whose immune systems have become hyperactive, but might harm patients with milder cases whose immune systems are still trying to clear the virus.
- Doctors have also learned to watch out for C19’s more unusual symptoms. The disease has been linked to kidney failure; those patients might need dialysis. It’s also linked to blood clots; patients who show warning signs might need blood thinners. Seeing more cases of C19 has also allowed doctors to refine details like the size of tubing used with ECMO, an artificial-lung technology for the sickest patients who aren’t doing well on ventilators.
- A lot of this experience has been shared in real time and informally. J. Eduardo Rame, a cardiologist at Thomas Jefferson University Hospitals, helps convene a regular Zoom forum where doctors discuss the latest, such as how to use ECMO. “Experiential learning,” as Rame puts it, has been vital for sharing information about a new disease. But doctors are also trained to rely on data and randomized, controlled trials, not anecdotes. “We’re nowhere near the inflection point where we can have medical care dictated by evidence,” Rame says, which puts doctors in a strange position. For now, they have experience to go on, which is better than nothing. But it’s not data.
- Randomized, controlled trials can be difficult to run in the middle of a pandemic. Hospitals under stress might not have the time and resources. Doctors may be loath to deprive patients of an experimental drug that just might help, as is necessary for placebo-controlled trials. These trials, though, are valuable for identifying not just what works but what common experimental treatments don’t work and might even cause harm. The list of drugs that have failed in rigorous trials includes hydroxychloroquine, tocilizumab, sarilumab, interferon, and antivirals already used to treat HIV. Nearly all of the trials in this first group have involved repurposing drugs used to treat other conditions.
- Another set of clinical trials involve monoclonal antibodies, which mimic the proteins the human body naturally makes against pathogens. Monoclonal antibodies are the best near-term shot for a targeted therapy against C19. President Trump gave them a huge boost of visibility after receiving Regeneron’s antibody infusion, which very early data now suggest could reduce doctor visits for C19. The trials still need to run to completion though, and availability will be limited, because antibodies are particularly difficult to manufacture. Regeneron said in early October it has doses for 50,000 patients, which is fewer than the number of people getting C19 each day in the U.S. right now. Antibody therapy will get better in the future too, as researchers try to engineer cheaper and more potent versions.
- All of this means that C19 treatments are likely to become both more effective and more accessible in the future. And eventually there will be a vaccine. At some point, C19 will become a manageable disease, akin to the flu. There will never be a good time to get the coronavirus, but getting it later will almost certainly be better than getting it today, tomorrow, next week, or even next month.
H. Back to School!?
1. Why schools probably aren’t C19 hotspots
- Data gathered worldwide are increasingly suggesting that schools are not hot spots for coronavirus infections. Despite fears, C19 infections did not surge when schools and day-care centres reopened after pandemic lockdowns eased. And when outbreaks do occur, they mostly result in only a small number of people becoming ill.
- However, research also shows that children can catch the virus and shed viral particles, and older children are more likely than very young kids to pass it on to others. Scientists say that the reasons for these trends are unclear, but they have policy implications for older children and teachers.
- Schools and childcare centres seem to provide an ideal setting for coronavirus transmission because large groups gather indoors for extended periods of time, says Walter Haas, an infectious-diseases epidemiologist at the Robert Koch Institute in Berlin. Yet, globally, C19 infections are still much lower among children than among adults, he says. “They seem rather to follow the situation than to drive it.”
- Data collected globally have previously shown that schools can reopen safely when community transmission is low.
- But even in places where community infections were on the rise, outbreaks in schools were uncommon, particularly when precautions were taken to reduce transmission. More than 65,000 schools in Italy reopened in September, as case numbers were climbing in the community. But only 1,212 campuses had experienced outbreaks four weeks later. In 93% of cases, only one infection was reported, and only one high school had a cluster of more than 10 infected people.
- In the state of Victoria, Australia, where a second wave of C19 infections surged in July, large outbreaks linked to schools and childcare centres were also rare, although schools were only partially open. Two-thirds of the 1,635 C19 infections in schools were limited to a single case, and 91% involved fewer than 10 people.
- In the United States, community transmission remained high in many places when schools started to reopen in August, and the proportion of infections in children continued to climb, says Ashlesha Kaushik, a paediatrician in Sioux City, Iowa, and a spokesperson for the American Academy of Pediatrics.
- But it is unclear how often outbreaks that originate in schools contribute to community transmission, because other factors, including the easing of restrictions on businesses and gatherings, have also contributed to community spread. Increased testing later in the pandemic has probably also boosted case numbers, says Kaushik.
- Data on school outbreaks in England have also shown that adults were often the first to be infected. Most of the 30 confirmed school outbreaks in June involved transmission between staff members, and only 2 involved student-to-student spread.
Young children transmit less
- Researchers suspect that one reason schools have not become C19 hot spots is that children — especially those under the age of 12–14 — are less susceptible to infection than adults, according to a meta-analysis4 of prevalence studies. And once they are infected, young children, including those aged 0–5 years, are less likely to pass the virus on to others, says Haas. In an analysis of German schools, Haas’s team found that infections were less common in children aged 6–10 years than in older children and adults working at the schools. “The potential to transmit increases” with age, and adolescents are just as likely to transmit the virus as adults, he says. Teenagers and teachers should be the focus of mitigation measures, such as wearing masks or a return to online lessons when community transmission is high, says Haas.
- This gradient in infectiousness is emerging in other data sets, too. In the United States, the rate of infection is twice as high in children aged 12–17 years as it is among 5–11-year-olds. According to data on 200,000 school students across 47 US states gathered by economist Emily Oster at Brown University in Providence, Rhode Island, incidence was highest in high-school students, followed by those in middle school and then elementary school.
- But “we don’t actually understand the natural history of transmission in children, because we mitigate against it”, says paediatrician Fiona Russell at the University of Melbourne, Australia, who was involved in the Victoria school-outbreaks study. Children aren’t in a typical school environment — instead, they’re social distancing, wearing masks and following other precautions.
- Evidence gleaned from national C19 statistics also has shortcomings. In the United States, for example, asymptomatic infections are still being missed because of policies that only people who develop symptoms are tested.
- Why young children seem less likely to spread the new coronavirus to others is unclear, says Haas. One possibility is that because they have smaller lungs, they are less able to project infectious aerosols than are adults. Haas says that this occurs in tuberculosis. But in tuberculosis, infection is spread from lesions in the lungs; coronavirus (SARS-CoV-2) infections are different, because the virus infects the upper airways. The question “puzzles me”, Haas says.
- Another possibility is that children tend to transmit less virus because they are more commonly asymptomatic. In a UK study of 2–15-year-olds, up to 50% of infected children developed no symptoms7.
- “There’s no such thing as zero transmission or zero risk,” says Russell. But the risk of infection at school is low, especially when community transmission is low, she says.
- Read the study here: doi: https://doi.org/10.1038/d41586-020-02973-3
2. How Congress Can Get Kids Back to Class
Opinion by Dr Scott Gottlieb, Former Commission of the FDA
- The U.K., France and other European countries are closing businesses in another wave of lockdowns, as C19 cases and hospitalizations rise. But unlike in the spring, schools are open. Infections are also surging across the U.S., where in many places in-person classrooms are closed and distance learning has become the norm. But there’s growing evidence schools can open safely, with reasonable precautions and, perhaps soon, regular testing.
- The ABC Science Collaboratives, supported by Duke University researchers, are working with school boards, superintendents, principals, teachers, health departments and the state of North Carolina to share data and best practices among more than 50 districts. The findings so far suggest that spread is limited when cases occur in North Carolina districts that are open for some in-person instruction.
- Six districts that completed their first nine weeks of instruction have seen a total of fewer than 20 secondary infections, where infected children or adults pass on the virus to someone else at school. One large district of nearly 35,000 students and staff had fewer than 100 cases over a nine-week period, only eight secondary infections—and no cases of child-to-adult transmission.
- These districts used “hybrid” models, in which children were in class only two days a week to reduce classroom density and allow distancing. Masks were required at all times except meals and water breaks. Even in counties where the prevalence of infection was high, this experience suggests schoolhouse outbreaks can be contained.
- Policy makers should take three steps to support opening schools more widely. First, the Centers for Disease Control and Prevention and the Education Department should expand research like the North Carolina project. Questions and concerns remain about how easily children can transmit the virus, and whether outbreaks in schools spread into the broader community. Because many children are asymptomatic, outbreaks can go undetected.
- Second, Congress should treat teachers like first responders and fund their protective equipment. Older teachers and those with medical risk factors should be allowed to work remotely. The government should provide teachers N95 masks and offer training on how to fit them.
- Third, Congress should provide more funding for testing in schools as a further layer of protection. Schools in poor communities or areas with high spread are most likely to benefit. Many of these districts lack resources to retrofit ventilation systems, and some school buildings may not allow for much distancing.
- Prompt testing for those with symptoms and regular testing for those without can detect cases earlier, helping schools take isolation measures and avoid broad shutdowns. The growing availability of inexpensive antigen tests, similar to rapid flu tests, makes routine testing feasible. These tests can be run by a school nurse or other trained worker and provide results in minutes. Schools will need to consider plans for follow-up testing on possible false positives.
- Regular testing has been used by sports leagues, universities and private schools to help prevent outbreaks. The federal government has begun purchasing and distributing some tests to states for school use, and the Rockefeller Foundation is supporting pilot studies to determine the most effective testing strategies. Executing these steps now will make schools more willing to reopen later this fall and winter as the current surge subsides.
- In France, bars and restaurants are closed but schools are open. In many parts of the U.S., schools are closed while bars and restaurants are largely open for business. The priority in the weeks and months ahead should be helping more schools reopen—and stay open—so American children can stop losing out on their education.
3. C19: Mathematical Modeling to Identify an Optimal School Return Approach
- In a recent study, NYU Abu Dhabi Professor of Practice in Mathematics Alberto Gandolfi has developed a mathematical model to identify the number of days students could attend school to allow them a better learning experience while mitigating infections of C19.
- Published in Physicsa D journal, the study shows that blended models, with almost periodic alternations of in-class and remote teaching days or weeks, would be ideal. In a prototypical example, the optimal strategy results in the school opening 90 days out of 200, with the number of C19 cases among the individuals related to the school increasing by about 66%, instead of the almost 250% increase, which is predicted should schools fully reopen
- The study features five different groups; these include students susceptible to infection, students exposed to infection, students displaying symptoms, asymptomatic students, and recovered students. In addition, Gandolfi’s study models other factors, including a seven hour school day as the window for transmission, and the risk of students getting infected outside of school.
- Speaking on the development of this model, Gandolfi commented: “The research comes as over one billion students around the world are using remote learning models in the face of the global pandemic, and educators are in need of plans for the upcoming 2020 – 2021 academic year. Given that children come in very close contact within the classrooms, and that the incubation period lasts several days, the study shows that full re-opening of the classrooms is not a viable possibility in most areas. On the other hand, with the development of a vaccine still in its formative stages, studies have placed the potential impact of C19 on children as losing 30% of usual progress in reading and 50% or more in math.”
- He added: “The approach aims to provide a viable solution for schools that are planning activities ahead of the 2020 – 2021 academic year. Each school, or group thereof, can adapt the study to its current situation in terms of local C19 diffusion and relative importance assigned to C19 containment versus in-class teaching; it can then compute an optimal opening strategy. As these are mixed solutions in most cases, other aspects of socio-economic life in the area could then be built around the schools’ calendar. This way, children can benefit as much as possible from a direct, in class experience, while ensuring that the spread of infection is kept under control.”
- Using the prevalence of active C19 cases in a region as a proxy for the chance of getting infected, the study gives a first indication, for each country, of the possibilities for school reopening: schools can fully reopen in a few countries, while in most others blended solutions can be attempted, with strict physical distancing, and frequent, generalized, even if not necessarily extremely reliable, testing.
I. Innovation & Technology
1. Nanofiber Membranes Boost Cloth Masks to Block Up to 99% of C19
- The cloth masks many are sporting these days offer some protection against C19. However, they typically provide much less than the professional N95 masks used by healthcare workers.
- That may soon change. Recently, students from BYU’s College of Engineering teamed up with Nanos Foundation to develop a nanofiber membrane that can be sandwiched between the cloth pieces in a homemade mask.
- While today’s typical cloth mask might block fewer than 50% of virus particles, the membrane — which can be made using simple, inexpensive materials — will be able to block 90 to 99% of particles, increasing effectiveness while preserving breathability.
- The membranes are made through a process called “electrospinning,” which involves dissolving a polymer plastic in a solution and then using an electrical current to move a droplet of the polymer downward through a needle. As the droplet accelerates, it stretches into a very small fiber that retains a static charge.
- “Those nanofibers randomly land on a collector to create a sort of non-woven mesh,” said Katie Varela, a BYU mechanical engineering senior on the project team.
- The remaining charge in the fibers is beneficial, she explained, because virus particles also have a static charge. “When they come close to your mask, they will be statically attracted to the mask and will not be able to go through it, and so it prevents you from inhaling viruses.”
- In addition to the dramatic improvement in efficacy, another key benefit of the nanofiber masks is that unlike traditional N95 masks, which have a reputation for being hot and stuffy, they allow for the circulation of (filtered) air, water, and heat.
- A close up look at some nanofibers recently spun and placed on a disk for testing. (Photo above)
- “Not only is it hard to find an N95 mask these days, but the best mask is useless if you won’t wear it,” said Will Vahle, director at Nanos Foundation. “Our nanofiber membranes are six times easier to breathe through than existing N95 masks, making them cooler, drier, and more comfortable.”
- The group plans to make the instructions for creating the membranes open source. They hope that non-profit organizations will use the instructions to set up local sites where people can bring in their masks to be fitted with a membrane. They also hope other engineers will use their work as a springboard to produce more effective filters.
- “We had our own proprietary nanofiber production process,” said Vahle of the project’s origins, “but we realized, hey, we have some expertise in this — why don’t we get this together and release a version that anybody can do?”
- When Vahle and his colleagues approached BYU to collaborate on the project, BYU “jumped at the opportunity,” Vahle said. In addition to providing funding and facilities, the university connected the company with “fantastic students, who’ve really demonstrated an incredible work ethic and a drive to help people in need.”
- Using cutting-edge science to make an immediate positive impact has also been highly valuable for the BYU students on the project.
- “This experience makes things very real,” said Varela. “I’m really glad that I’m able to help with this fight against C19 to help people all around the world and in my community.”
J. Projections & Our (Possible) Future
1. 10 States on the Verge of COVID Surges
- With COVID case numbers rising across the country, it’s not a question of which states are experiencing outbreaks, but how severe those outbreaks will be. No state has been untouched by the coronavirus pandemic, and it’s not clear when the latest COVID spikes will start to diminish. Looking at the data, it’s easy to see which states are currently seeing the highest numbers of new cases, hospitalizations, and deaths, but how can we know which states are on the verge of COVID surges?
- The New York Times keeps a regularly updated list of every U.S. state broken down into different categories. One of the most significant might be states “where new cases are lower but going up.” These are states that had a daily average of fewer than 15 new coronavirus cases per 100,000 people over the past week, but where the numbers are rising. If you are wondering where COVID will spike next, these are the states to pay attention to—while some of the increases are small, this is where the data shows movement in the wrong direction.
- With that in mind, these are the 10 states that could be on the precipice of new coronavirus surges. And for a look at how every state is faring, This Is How Bad the COVID Outbreak Is in Your State.
- While Arizona was once one of the epicenters of the pandemic in the U.S., it made great strides in containing the virus. Now, however, the state might have to be on high alert again. Over the past 14 days, there has been a 55 percent increase in new cases, according to The New York Times, along with a 4 percent rise in deaths and a 24 percent rise in hospitalizations. To be clear, these percentage increases represent the change from the average two weeks prior. COVID Act Now says Arizona has a high infection rate of 1.14, meaning “cases are rapidly increasing.”
- Like many New England states, Connecticut overcame COVID’s early onslaught in the Northeast. Sadly, the virus is rearing its head again. Connecticut has seen a 66 percent rise in new cases over the last two weeks. Significantly, there has also been a 114 percent rise in coronavirus deaths and a 64 percent rise in hospitalizations from the previous average. The infection rate is higher than Arizona’s at 1.20, per COVID Act Now. And for ways that states are trying to contain their outbreaks, These 4 States Are Showing the First Signs of Another Lockdown.
- Another former epicenter that seemed to have turned the corner, Florida is backsliding with a 29 percent increase in new cases over the past 14 days. Just over the last week, The New York Times reports more than 20,900 new cases, contributing to Florida’s 762,525 cases overall. Currently, COVID Act Now says the state has a high daily new case rate of 13.9 cases per 100,000 people, a “very large number of new cases.”
- Georgia’s early resistance to coronavirus mitigation measures made it a state to watch, but it did seem to have managed the crisis—at least to a point. And currently, the state is seeing the curve rise again, with a 15 percent increase in cases over the last two weeks. The 10,000 new cases in the last seven days represent a troubling rate of 94 weekly cases per 100,000 people.
- Massachusetts is seeing a 14-day increase in every area, The New York Times reports: an 18 percent rise in new cases, a 32 percent rise in deaths, and an 11 percent rise in hospitalizations from the average two weeks prior. Over the past week, there have been nearly 5,175 new cases in Massachusetts, or 75 weekly cases per 100,000 people. And for more on how coronavirus spreads, The CDC Now Says You Can Catch COVID From Someone in Exactly This Long.
6. New Hampshire
- New Hampshire is a state that hasn’t been on many people’s radars during the pandemic. But while containment of the virus had been effective, New Hampshire has now experienced a 54 percent increase in new cases in the last 14 days. While the daily new case rate of 6 cases per 100,000 people means COVID is “at low levels,” according to COVID Act Now, the infection rate of 1.13 reflects the fast escalation of new cases.
7. New Jersey
- Like its neighbor New York, New Jersey was hit hard in the early days of the pandemic, then had a significant recovery. Unlike New York, however, there have been more bumps in the road for the Garden State, and the latest bump is beginning to look suspiciously like the start of a new curve. The New York Times reports a 57 percent rise in cases over the last 14 days, an 80 percent rise in deaths, and a 45 percent rise in hospitalizations from the average two weeks before. New Jersey now has a high daily new case rate of 11.6 cases per 100,000 people, COVID Act Now says. And for more on the state’s outbreak, New Jersey’s Governor Just Urged Residents “Not to Travel” Due to COVID.
- As with New Jersey, Pennsylvania has seen 14-day increases in the three key areas from the state’s previous average two weeks before: a 40 percent rise in COVID cases, a 13% rise in deaths, and a 45% rise in hospitalizations. According to COVID Act Now, Pennsylvania is quite close to New Jersey when it comes to current coronavirus containment. Both states are seeing 11.6 daily new cases per 100,000 people, but Pennsylvania has a slightly lower (though still high) infection rate of 1.10.
- After a series of highs and lows throughout the pandemic, Virginia is in danger of another upswing, per The New York Times. Cases are up 32 percent over the last two weeks, along with deaths and hospitalizations. In the last week, Virginia saw just over 7,160 new cases, which equals 84 weekly cases per 100,000 people. COVID Act Now shows the state’s daily new case rate is 12 cases per 100,000 people. And for more up-to-date information, sign up for our daily newsletter.
- The situation may not be as dire in Washington—another early COVID hotspot in the U.S.—but the state is still seeing modest increases that could point to another coronavirus surge. Over the last 14 days, cases are up 16 percent, The New York Times reports, with hospitalizations from COVID up 11 percent. There have been more than 4,555 new cases in Washington in the last week, or 60 weekly cases per 100,000 people. To date, the state has seen nearly 104,625 coronavirus cases.
1. Why People Have Had Enough of Lockdowns
- The history of epidemics is rife with examples of society rebelling against tough public-health edicts, such as the breach of plague quarantine in 18th-century Marseille or protests against face masks during the 1918 influenza pandemic. The grim consequence is a fresh wave of deadly infections.
- C19’s million deaths may pale in comparison to the estimated 50 million lives lost in 1918, but the cycle risks unfolding again. France, the U.K. and Spain face a triple threat: A jump in cases, a population exhausted by lockdown-induced recession, and rising resistance to tougher measures.
- Curfews and closures of restaurants and bars have seen business owners literally throw their keys to the ground in present-day Marseille. In Madrid, protesters have bristled at a targeted local lockdown they view as discriminatory. It’s not just conspiracy theorists on the streets in London and Berlin who are angry.
- Those protesting shouldn’t be dismissed as the selfish exceptions to the rule. Beyond the vocal minority, there are signs that the silent majority is also losing faith in increasingly bureaucratic strictures. Policymakers need to restore it.
- While respect for mask-wearing and personal hygiene is broadly high, according to YouGov surveys of European countries, support for quarantine and self-isolation is wavering. In France, only 48% of people currently support quarantining those who’ve had contact with infected patients, down from 78% in March. It has also fallen in the U.K. and Spain, though to a lesser degree.
- There’s mounting evidence that people who are asked to stay at home aren’t doing so. A recent King’s College London survey in the U.K. of over 30,000 people between March and August found that only 18.2% reported remaining at home after developing symptoms and a measly 10.9% after being alerted by contact tracers. That’s worrying given the critical importance of self-isolation in breaking chains of transmission before they reach the vulnerable and the elderly.
- Obviously being cooped up is nobody’s idea of fun, and it brings the psychological stress of altruistically choosing long-term pain over short-term pleasure. But for those who don’t have the luxury of jobs they can do from their kitchen table, isolation also means being deprived of a decent wage. Around 10%-11% of respondents cited “going out to work” among reasons for non-compliance. That echoes an earlier finding that half of Britain’s low-income workers couldn’t actually afford to self-isolate because mandatory sick pay is so low, according to the Trades Union Congress. Other reasons given included caring for a vulnerable person (10%-12%) and mental stress (8%-11%).
- This isn’t the case for all countries. In Austria, where quarantined workers are entitled to be paid as normal, compliance is over 98%, according to the Washington Post. A lot of focus has been put on European countries’ approach to lockdown, but relatively little on their welfare systems, reckons Joan Ramon Villalbi of Barcelona’s Public Health Agency. The OECD is rightly encouraging countries to extend sick leave and other benefits to more workers, especially the self-employed. Europe should, too.
- Rewarding those who self-isolate should ideally be accompanied by punishment for those who don’t. But this requires confidence in the rules and their enforcement, which has been lacking. Test-and-trace infrastructure is bursting at the seams in several countries, with delays so long that people don’t see the point in following official guidelines. And in the U.K., increasingly complex limits such as “the rule of six” are patently unenforceable, with politicians encouraging people to spy on their neighbors and rat them out. More testing capacity and rules that can actually be enforced with fines would help.
- On top of carrots and sticks, transparency and education can help compliance. New rules such as closing restaurants and bars at 10 p.m. rather than 11 p.m. haven’t been justified with any scientifically backed explanations, the kind of thing that can chip away at public trust. Worse, some doctors reckon they may simply shift parties to private homes indoors. Clear and understandable rules tend toward better obedience, according to Joan Costa-Font, associate professor at the London School of Economics’s health policy department. This is one area where Sweden, despite criticism of its more individualist approach to stay-at-home curbs, is doing well.
- Given the public is starting to lose trust in rules handed down from above, the least policymakers could do is stick to their own guidance. Yet they are proving their own worst enemy, whether it’s Dominic Cummings flouting lockdown or French Prime Minister Jean Castex’s feeble “I no longer take the metro” excuse for not downloading France’s contact-tracing app. Apparently the U.K. government doesn’t even understand its own rules, judging by three confusing errors by officials explaining new restrictions in just three hours on Tuesday — one by Prime Minister Boris Johnson himself.
- C19 disobedience goes deeper than we think. Those whose fingers are hovering on the lockdown button can, and should, do more to curb it.
L. Practical Tips & Other Useful Information
1. A Guide to Safely Holiday Road-Tripping Through a Pandemic
- The reality is scary. The pandemic may be entering its worst phase yet, with coronavirus cases and hospitalizations surging all over the map. But the social cost of keeping families apart is rising too. My parents are elderly, and these many months of isolation and postponed medical appointments have walloped their health. They haven’t even met their youngest grandchild. Finding a way to see them—safely—has become one of my highest priorities.
- For me that means a multiday journey down Interstate 80. Some road-tripping advice hasn’t changed from the summer, when cooped-up travelers sprinted for the closest campsite. But winter weather—and a surge in case loads—adds complications. Here’s my checklist for traveling long distances while limiting your chances of spreading or contracting the virus.
Talk to Your Family
- Traveling will increase your risk of spreading and potentially contracting C19. So the first thing to do is to talk to the people you’re visiting. Make sure they actually want you to come. Are they comfortable with your lifestyle and choices? Are they as Covid-cautious as you’d like them to be? Hash out a plan for what you’ll do before you reunite. Will all parties quarantine or get tested? The answer will affect how you plan your trip.
- Once everyone agrees to a plan, it’s time to think about your vehicle.
Prepare Your Car
- You never want your car to break down in the middle of a desert, but you especially don’t want that to happen in a pandemic. This year the American Automobile Association has seen an uptick in service calls, especially for faulty batteries, spokesperson Aldo Vazquez says. It makes sense: During the lockdown, more cars sat idle in garages for longer periods, endangering their batteries. So before you hit the road, take your car in for a full check-up of the battery, tire pressure, fluid levels, and more.
- Renting a car is a good option. The big rental-car companies have all instituted more-intense cleaning regimens, including disinfection of high-touch areas such as the door handles, dashboard controls, and steering wheel. If you seek more peace of mind, you can do your own quick wipe-down, roll down the windows to air out the interior, and wash your hands before touching your face.
- Whatever you’re driving, you’ll want to pick up an emergency kit or at least procure the basics: jumper cables, a multitool, some duct tape, a blanket, a first aid kit. If you think you might hit a winter storm, grab some snow chains too.
Get Your Tech in Order
- You’re about to venture into the great beyond. Possibly even, dare I say it, into a cell phone dead zone. Before you leave home, download your maps so they’re available offline. To do so on Google Maps, search for a place of interest. Once it pops up, click the name of the place at the bottom, and the option to download that map should appear. You can then drag a window to customize the area you’re capturing.
- Then immediately go find a car phone charger, put it in your car, and never remove it. For bonus points, pack an extra power brick. To offset a scintilla of road-tripping climate guilt, consider one from Nimble, which makes environmentally responsible charging accessories. (If you’re traveling with young children, you might need to top up an iPad mid-drive.) Even more bonus points: paper maps.
- If your trip spans several days and you want to maximize social distance, you’ll need to pack more stuff than in a normal year. And that means being highly strategic about cargo space.
- We’re a family of four with two car seats in the back, so our space is extremely limited. I’m measuring every inch to see how much I can pack—and how to best pack it. You can boost your available volume with a roof cargo box, rack, or bag. Roof boxes are the most elegant but also run in the many hundreds of dollars. All those options drag down your fuel economy. As a minimalist packer, I’m hoping to fit all of our stuff in the car’s interior. Everyone will get a couple of packing cubes for their clothes. Eagle Creek has an extensive line of them; I use these. If I run out of space, my cheapskate backup plan is to shove those packing cubes into a surfboard bag and strap it to the roof.
Eat Like a Backpacker
- Food can take up a shocking amount of space. My approach is bare-bones: Bring enough to last roughly four days, patronize the occasional drive-thru, contract scurvy. The dry ingredients are the easy part. I’m considering a bag of rice, lentils, some cans of beans, and tortillas. Fill a pillbox with your favorite spices and you’ll feel like a veritable Anthony Bourdain. You can make an easy, delicious meal out of a jar of internet-famous Rao’s pasta sauce and some spaghetti. Dried fruit and nuts make an energy-dense snack. And, of course, the staple of American travel: peanut butter.
- For perishables, consider dividing your food between two coolers instead of jamming it all into one large one. You can dip into the more accessible cooler for the day’s drinks and snacks, and tuck the second one into a harder-to-reach part of the car. I’ll be packing a WIRED-favorite Pelican 20QT Elite, whose slim profile allows it to fit into the space behind the front seats.
- And let’s not forget coffee, that elixir of life and safe driving. You can’t go wrong with an Aeropress Go, a very compact way to make delicious coffee.
Book a Safe Place to Stay
- With temperatures dropping, you’ll need more than a tent to get through the night. The AAA has a route-planning tool and a map of C19 travel restrictions (such as mask requirements) and caseloads across the country. Several hotel and motel chains have upped their cleaning game. Airbnb has too, and it now requires all guests and hosts to wear masks and practice social distancing while interacting. Because I’d rather cook than patronize restaurants, I’ll be booking Airbnbs for my trip. I’m not too worked up about wiping down surfaces, but I’ll still bring a box of disinfecting wipes, and I might throw the windows open for a few minutes to flush out the air before settling in.
- Eventually nature will call. Should you use a public restroom? While the virus could hang out in the air and on surfaces, it’s probably not a major risk factor. You can mitigate your risk by wearing a mask, being swift about your business, and washing your hands thoroughly. But if you prefer to avoid restrooms, technically you can. Set up your own toilet stall using a bucket such as this one and a pop-up privacy tent. Try out the contraption at home first—a freezing-cold parking lot is not the place to discover you suffer from performance anxiety (parcopresis is the technical term). It’s also not the spot to wrestle with your equipment for the first time. My pop-up tent arrived without instructions, but a quick Youtube search solved the mystery of how to fold it back up.
Testing vs. Quarantining
- Once you arrive at your destination, you have one more hurdle: Figuring out if you might be infected. The only way to get to near-zero risk of transmission is to quarantine for 14 days. Testing can provide some peace of mind, but it can’t offer a guarantee. Even the most accurate tests (the ones that require a nasal swab) can fail to detect an infection around 20 percent of the time. But even that unimpressive figure has a catch: It comes from studying symptomatic people. The unfortunate reality is there is no solid data on how well coronavirus tests perform on asymptomatic individuals, says Steve Woloshin, an expert at Dartmouth on risk communication in medicine. If you decide to take a diagnostic test, keep in mind they are most reliable five to seven days after a potential exposure, says Keri Althoff, an epidemiologist at Johns Hopkins. Their reliability drops slowly thereafter.
- Personally, I plan to quarantine. It’s a hassle, but in my case it feels essential. As Woloshin puts it, the decision on whether to travel comes down to anticipated regret: How much you imagine you’ll suffer from missing the visit—or from potentially infecting a person you love.
M. Johns Hopkins COVID-19 Update
November 2, 2020
1. Cases & Trends
- The WHO COVID-19 Dashboard reports 46.17 million cases and 1.19 million deaths as of 08:40 am EST on October 26. The WHO reported a new record high for global weekly incidence for the sixth consecutive week. The global weekly total reached 3.33 million cases—an increase of more than 17% over the previous week, continuing a trend of rapid increase. The WHO reported 223,280 new cases on Monday.
- Total Daily Incidence (change in average incidence; change in rank, if applicable)
- Per Capita Daily Incidence (change in average incidence; change in rank, if applicable)
- Andorra: 1,455 (+233)
- Belgium: 1,271 (-25;↑ 1)
- Czech Republic: 1,115 (-9;↓ 1)
- Luxembourg: 1,045 (+233; ↑ 1)
- Slovenia: 873 (+199; ↑ 2)
- Switzerland: 832 (+355; new)
- French Polynesia: 745 (-272; ↓ 3)
- Armenia: 706 (+25; ↓ 2 )
- Liechtenstein: 697*** (+169)
- France: 603 (+74; ↓ 2)
- This week, the US continued to remain the country with the highest cumulative incidence and is reporting the highest number of global daily cases. The US, India, and Brazil continue to lead in cumulative incidence, with few signs of leveling off. The United Kingdom is experiencing a resurgence and is among the top 10 countries with highest cumulative incidence this week, with an 18% increase in incidence compared to last week. Germany has also reported an increase of over 5,000 new cases on average per day compared to last week, currently positioned at number 10 among the top 10 countries for daily incidence. Italy’s daily incidence has also shot up 3 spots to number 4 among the top 10 countries for daily incidence, whereas incidence in Brazil and Russia have both decreased.
- Belgium now has the second highest per capita daily incidence this week, replacing the Czech Republic which is now in third place. Italy’s daily incidence grew the most this week, moving up to position 7 from position 9 last week. While still not among the top 3 countries with highest per capita incidence, Luxembourg has experienced a 29% increase compared to last week. Additionally, Switzerland has now entered the top 10 countries, with a 74% increase in per capita incidence compared to last week.
- The US CDC reported 9.1 million total cases and 229,932 deaths. The average daily C19 incidence is currently at 80,932 new cases, which is a slight decrease from 83,851 new cases per day reported last week. Last week, the US set a new record peak for new daily incidence with 101,273 cases on October 31, which is about 20,000 cases higher than the record from last week. Following the expected dip in reporting over the weekend, we will continue to track whether a new record peak will be set later this week.
- The US C19 mortality decreased slightly from 900 to currently around 823 new deaths per day; however, data over the weekend generally provides an underestimate of actual death counts. Currently mortality at the national level appears to be stagnating at this level, but it is unclear whether this will remain a longer term trend.
- More than half of all US states have reported more than 100,000 cases, including 11 with more than 200,000 cases:
- The Johns Hopkins CSSE dashboard reported 9.2 million US cases and 231,011 deaths as of 11:20 AM November 2.
2. HOUSEHOLD TRANSMISSION
- A new publication from the Morbidity and Mortality Weekly Report examines the risk of SARS-CoV-2 transmission among household members. The authors described findings from a prospective study involving 191 initially asymptomatic household contacts of 101 index patients in Tennessee and Wisconsin. Among 102 of the household contacts who tested negative upon enrollment in the study, 53% later tested positive for SARS-CoV-2. Secondary infection rate was notably lower for index patients aged 12-17 (38%) but not for index patients under the age of 12 (53%) – although only 14 of the index patients enrolled were under the age of 18.
- Notably, 75% of household infections were identified within the first five days of index patients becoming symptomatic. These secondary infection rates may be an underestimate as household contacts were enrolled 2-4 days after illness onset of index patients, so earlier household transmission may not have been included in the identification of secondary infection rates. Authors recommend that symptomatic individuals promptly isolate from household members as soon as possible after illness onset, even while waiting for testing results and that household members adopt mask usage and distancing when housed with a confirmed infection.
3. US TESTING DATA
- Journalists from The New York Times have recently pointed out inconsistencies in types of testing data reported across states. 37 states combine antigen testing with diagnostic testing to report C19 case statistics, six states report antigen testing separately and seven states and D.C. do not report antigen testing results. These inconsistencies can lead to undercounting of C19 cases or an unclear picture of whether public health mitigation measures are sufficiently succeeding in quelling outbreaks. Notably, antigen testing is less sensitive and specific than testing via PCR, but the CDC recommends that states report C19 case statistics using both PCR and antigen testing data.
- Other issues with testing data interpretation can also arise due to testing refusals. The New York Times recently alleged that community members in Kiryas Joel, a village in Orange County, New York, may have actively discouraged individuals from seeking or accepting C19 testing in order to artificially lower the village’s C19 test positivity rate. The village reportedly reduced testing positivity from 34% to 2% in only two weeks.
4. RISK TO HEALTH CARE PERSONNEL
- Three recent publications have drawn attention to the C19 risked faced by health workers and their households. One study in the Morbidity and Mortality Weekly Report (MMWR) discussed exposure factors and infections among 21,406 Minnesota health worker exposure events. 5,374 of the exposure events included close and prolonged contact with an infected case while not wearing suitable personal protective equipment (i.e. within six feet for at least 15 minutes).
- While two thirds of high-risk exposure events happened in the patient care setting, one third of exposures involved infected coworkers, household contacts or social contacts. The authors highlighted the need for health workers to remain vigilant regarding C19 prevention measures when not in the patient care setting. Health care personnel working in long-term care or congregate living were also found to be more likely to continue working while symptomatic or after receiving positive test results than those working in acute care settings, emphasizing the need for flexible sick leave policies, access to testing and access to personal protective equipment.
- The other two publications discussed hospitalization of health workers and their households due to C19. The study in BMJ identified risk factors for hospital admission across 158,445 health workers and 229,905 household members of health workers in the United Kingdom. 17.2% of C19 hospital admissions in the UK among individuals aged 18-65 were hospital workers or their household members. Risk factors for hospital admission largely mirrored risk factors previously identified for the general population (e.g. age, certain underlying medical conditions) but also included in-person care of patients or being a household member of a health worker who provided in-person care of patients.
- Health workers in “front door” roles such as paramedics or those working in emergency rooms had a higher risk of hospital admission due to C19 than other in-person patient care workers. The absolute risk of hospital admission due to C19 for healthcare workers and their households was calculated to be 0.5%, similar to the general population.
- Meanwhile, an additional MMWR study discussed US hospitalization data for 6,760 adult hospitalized C19 patients of whom 438 were health care personnel. Notably, 36% of hospitalized health care personnel were in an nursing-related profession, 71.9% were female, 52% were non-Hispanic Black and 89.8% had an underlying condition, largely represented by individuals reported as obese (73%). The median age of hospitalization for health care personnel (49) was notably lower than for those hospitalized among the general population (62). One in four health workers in the data set were also admitted to an intensive care unit, which is in line with the proportion admitted to intensive care units among general population C19 hospitalizations for adults aged 18 to 64.
5. WHO DIRECTOR-GENERAL
- Director-General of the World Health Organization, Tedros Adhanom Ghebreyesus, is now working from home while self-quarantining following exposure to a C19 case, according to a tweet posted on Sunday. The Director-General has not reported any symptoms of C19 thus far.
6. UNITED KINGDOM
- On Saturday night, Prime Minister Boris Johnson announced a swath of new restrictions aimed at reducing the spread of C19 within the United Kingdom. New policies included closure of bars, in-person dining at restaurants and other non-essential businesses. Educational institutions and childcare facilities will remain open. A stay-at-home order will also be in place with individuals only allowed to leave their residences for work if remote work is not possible, education, exercise, caregiving or essential shopping. Amateur sports are recommended to cease activities. The measure to pay 80% of wages for furloughed workers has also been extended. New restrictions are slated to be in place through December 2. Parliament will be voting on the new measures this Wednesday. The United Kingdom notably has the highest official death toll for the C19 pandemic in Europe.
7. ELI LILLY
- A recent study published in the New England Journal of Medicine last week reported that convalescent plasma derived monoclonal antibody treatment (LY-CoV555), developed by Eli Lilly, showed clinical benefit in patients. The study found that patients experienced decreased viral loads and severity, and had no serious adverse effects in outpatients. The phase II trial involved outpatients that had mild to moderate C19. A total of 452 patients participated, receiving either low, medium or high concentration of the antibody, or placebo.
- Researchers measured the change in viral load after 11 days of treatment, and the study has reported on interim findings. Patients receiving the medium dose (2800 mg) had about a 3 fold reduction in viral load. Differences among placebo and treatment groups were non-significant and smaller for both the low and the high dosage categories. However, patients receiving any antibody dose had lower symptom severity as well as lower hospitalization rates than placebo. Additionally, the percentage of adverse events was similar across treatment and placebo groups.
- The report came after an announcement from the NIH that it was going to halt a trial investigating the antibody after the trial’s Data Safety Monitoring Board reviewed the data on October 26th and recommended that no further participants enroll, as it concluded there was a “low likelihood that the intervention would be of clinical value” for hospitalized patients. Scientists currently believe that while there may be possible benefit among outpatients, as observed in the NEJM study, the longer course of infection and severity among hospitalized patients reduces likelihood of benefit for the treatment. An additional hurdle is that there are highly limited doses of antibody treatments available for both the Eli Lilly and Regeron cocktails. Eli Lilly reportedly anticipates it can ship 100,000 doses of its monoclonal antibody once allowed, and that it can produce as much as a million doses by the end of the year; however, that is at the lowest dosage concentration, which was currently not found to yield significant benefit in the NEJM study.
8. BEHAVIORAL DIFFERENCES BY AGE
- A recent CDC study published in the MMWR assessed self-reporting of recommended behaviors to mitigate SARS-CoV-2 transmission, including mask-wearing, hand washing, social distancing, and staying home when sick. The Data Foundation COVID Impact Survey collected national data on reported mitigation behaviors from April to June among adults. The study found that mask use increased from 78% in April to 89% in June. Other crucial mitigation measures, including hand washing, social distancing, and avoiding crowded areas, stagnated or declined.
- The prevalence of reported behaviors was lowest among those aged 18-29 years old and highest among those over 60 years. Across all age groups, however, mask wearing increased. Handwashing decreased across all groups from April to June, with the greatest decrease occurring among those aged 30-44 years old (from about 92% to 87%) and those over 60 years old (96.5% to 93%). The proportion of respondents who cancelled social activities and avoided crowded places generally stagnated or decreased from April to June, particularly for those aged 18-29 and 30-44 years old.
- The study concluded that understanding the factors leading to uptake of each mitigation behavior is important, particularly among the younger age groups. While news media, particularly earlier in the year, generally emphasized and criticized the lack of social distancing among young people at parties and other social events, other factors such as job type could also play a large role in disproportionately preventing younger people from distancing.