October 5, 2020
Without reliable information, we rely on fear or luck.
“An estimated 750 million, or 10% of the world’s population, have been infected by Covid-19.”Dr. Michael Ryan, Executive Director, WHO Health Emergencies Program
[Note: Assuming 750,000,000 have been infected as estimated by WHO, the case-fatality rate is approximately 0.13%, which is slightly more lethal than the flu, which is far less lethal than previously estimated by WHO.]
“Ever since we wrote that letter, signed by 239 scientists, I have been waiting for the landslide. The evidence is now simply overwhelming that the virus is spread through aerosols. The idea it’s mainly droplets is a myth. It’s scandalous and absurd the WHO and CDC refuse to give correct guidance.”Jose-Luis Jimenez, a chemistry professor at the University of Colorado, Boulder, who has studied aerosols for 20 years
“I’m not going to a restaurant because I know they’re not safe.”Richard Corsi, PhD, dean of the College of Engineering and Computer Science at Portland State University, who studies indoor air quality [Note: See story below on risks of indoor dining and ways to reduce risk]
“The President is receiving all of the standard of care and beyond for routine, international COVID protocols. He’s the president. I didn’t want to hold anything back. If there was any possibility that it would add value to his care and expedite his return, I wanted to take it.”Navy Cmdr. Sean Conley, the president’s physician
1. Cases & Tests
3. Top 5 States in Cases, Deaths, Hospitalizations & Positivity
4. Coronavirus hospitalizations grow in the Midwest amid climbing cases
1. What we won’t know about a vaccine
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A. The Pandemic As Seen Through Headlines
(In no particular order)
- Trump’s Condition Substantially Improved, But He’s “Not Out Of The Woods Yet”, Doctor Says
- Covid mortality rate for a 74 year old man – such as Trump – is 2.68%, or roughly 1 in 37
- Trump Could Be Released from Hospital Monday
- New York Times: Trump’s oxygen levels dropped and he was given dexamethasone, potentially signaling a ‘severe’ case of Covid-19
- Michigan Supreme Court Strikes Down Gov. Whitmer’s Lockdown Edicts
- NYTimes Admits WHO’s Decision Not To Close Borders At Start Of Pandemic Was Based On “Politics”, Not Science
- Pfizer CEO Says COVID-19 Vaccine “Will Be Ready At The Speed Of Science”
- The White House coronavirus outbreak shows that testing alone is not enough
- With Trump hospitalized, Covid-19 continues its onslaught in the U.S.
- Mike Pence tested negative again on Sunday and will keep campaigning, despite C.D.C. guidelines
- The National Security Council now requires masks for staff members
- New York City is ‘on the edge of a precipice’ as coronavirus cases grow, former CDC director says
- NYC Seeks Permission from NY State to Close Schools, Restaurants In 9 COVID-19 “Hots Spots” In First Rollback Since Start Of Pandemic
- NY Suffers Another 1,500+ New COVID-19 Cases As Gov. Cuomo Threatens To Fine “Non-Compliant” Communities
- New York City’s school testing plan may miss large outbreaks, a study suggests
- Colorado officials urge parents to enroll kids in schools
- Florida governor says closing schools to stop spread of COVID-19 was a mistake
- Colleges learn how to suppress the virus: extensive testing
- Six Months After The Pandemic Started: Manhattan Offices Are Only 10% Full
- India’s Covid-19 death toll tops 100,000 as infections spike
- Britain’s coronavirus cases rise sharply to record level
- UK Prime Minister Boris Johnson says “Eat Out” drive may have spread Covid
- Mecca’s Grand Mosque admits umrah pilgrims for the first time since March
- The virus upends South Korea’s Thanksgiving
- German officials worry about the virus in Spain
- World’s Best Airport Warns of ‘Daunting’ Future Amid Pandemic
- The number of empty rental apartments in Manhattan has tripled compared to last year
- US Unemployment Rate Unexpectedly Plunges Below 8% As 661,000 Jobs Added
- The U.S. economy is facing a tidal wave of long-term unemployment
- Rising Homicides This Year May Be Yet Another Side-Effect Of COVID Lockdowns
- Apartment sales in Manhattan plunged by 46% in the third quarter (10,000 units unsold), as homebuyers continued to flow to the suburbs and Florida
- San Francisco Rents Crash Most On Record Amid Mass Exodus
- More Than One Million New Jerseyans To Become “Food Insecure” By Year-End
- Say Goodbye To Millions Of Jobs As Events Unfold
- Performing arts are near the point of no return
- Pope Francis, denouncing the lack of global solidarity, says the virus exposes “our false securities.”
- Stanford professor: To fully eliminate COVID-19, we would have to ‘destroy our entire society’
- Millennials Say They’re Even Less Likely To Have Kids Now Thanks To COVID-19
B. Numbers & Trends
Note: Unless otherwise noted, (i) all cases/deaths are confirmed cases/deaths that have been reported, (ii) all numbers reported in this update are as of the end of the most recent reporting period, and (iii) all changes reflect changes since the preceding day.
1. Cases & Tests
- Total Cases = 35,389,694
- New Cases = 239,546
- New Cases (7 day average) = 288,231 (-1,549) (-0.5%)
- 7 day average is slightly lower than peak on 9/29
- Since 9/29, 7 day average has declined from 291,142 to 288,231, a decrease of 1%
- 1,000,000 cases every 3.5 days (based on 7 day average)
US Cases & Testing:
- Total Cases = 7,636,912
- New Cases = 34,066
- Percentage of New Global Cases = 14.2%
- New Cases (7 day average) = 43,804 (+31) (-0.1%)
- Total Number of Tests = 111,470,266
- Percentage of positive tests (7 day average) = 5.1%
- 7 day average of new cases has been steadily rising since 9/12, which is a negative trend that could foreshadow an increase in deaths
- Since 9/12, 7 day average has increased from 35,542 to 43,804, and increase of 23.2%
- 7 day average of the percentage of positive tests has decreased from 5.5% to 5.1% during the last 30 days, which is a positive trend
- Total Deaths = 1,041,543
- New Deaths = 4,043
- New Deaths (7 day average) = 4,970 (+35) (+0.7%)
- 7 day average of new deaths has mostly declined since 2nd peak on 8/11
- Since 8/11, 7 day average has declined from 5,979 to 4,970, a decrease of 16.9%
- Total Deaths = 214,611
- New Deaths = 332
- Percentage of Global New Deaths = 8.2%
- New Deaths (7 day average) = 736 (+7) (+1.0%)
- 7 day average of new deaths has been slowly declining since 9/15
- Since 2nd peak on 8/4, 7 day average has declined from 1,178 to 736, a decrease of 37.5%
3. Top 5 States in Cases, Deaths, Hospitalizations & Positivity (10/4)
- Hospitalizations in the US increased +4.7% over the last two weeks while new 7-day cases decreased -2.3% over the prior two weeks. Average 7-day deaths decreased -11.4% over the prior 2-week period
- Wisconsin reported 1,800 positive cases on Sunday. This breaks a five day streak of the state adding more than 2,000 cases a day.
- Hospitalizations in the US increased 4.7% over the last two weeks while new 7-day cases decreased 2.3% over the prior two weeks.
4. Coronavirus hospitalizations grow in the Midwest amid climbing cases
- Growing coronavirus outbreaks across the American West and Midwest have started to take an alarming turn as some states report growing C19 hospitalizations and a shrinking supply of beds for patients.
- Six states reached record high C19 hospitalizations, based on a weekly average to smooth out the reporting, as of Friday, according to a CNBC analysis of data compiled by the Covid Tracking Project, an independent volunteer organization launched by journalists at The Atlantic.
- Most of the states are based in the Midwest, including Missouri, Wisconsin, North Dakota and South Dakota.
- There were at least 663 people in the hospital with C19 in Wisconsin as of Friday, well beyond the state’s previous highs in April when roughly 400 people were hospitalized. Only 19% of the state’s hospital beds are available and 27% of the state’s C19 patients are in the intensive-care unit, according to its data dashboard.
- In Missouri, there were at least 1,137 people hospitalized with C19 on Friday, the state’s highest number of patients so far, according to the Covid Tracking Project. Missouri, which tracks the weekly average of coronavirus patients, has reported a steady increase in patients and a slight decline in available intensive-care unit beds since early September.
- Public health experts watch hospitalizations closely because they can indicate how severe an outbreak is in an area. It’s considered a better measure than new cases because it’s not as reliant on the availability of testing.
- Nationwide, coronavirus cases were growing by 5% or more, based on a weekly average, in 27 states as of Friday, according to a CNBC analysis of data compiled by Johns Hopkins University. Kentucky, Wisconsin, Nebraska and Montana reached record-high averages.
- “What we’re seeing is community based transmission right now in the upper Midwest and the Northwest,” Health and Human Services Secretary Alex Azar told lawmakers on Friday during a U.S. House Select Subcommittee on the Coronavirus Crisis hearing.
- “What we’re facing now is just plain old community spread as we saw in the Southeast and Southwest that comes from individuals not practicing the three W’s: wash your hands, watch your distance, wear your face coverings.”
Wisconsin reports ‘alarming trends’
- Wisconsin Gov. Tony Evers on Thursday urged residents to stay at home as much as possible and to wear face coverings when in public. Evers extended Wisconsin’s mask mandate last week as he warned of an “alarming increase” in cases across the state, especially on college campuses.
- “I’m concerned about the alarming trends of C19 we’re seeing across our state,” Evers reiterated during a press briefing Thursday, a day after the state reported 27 new C19 deaths — it’s highest daily total on record.
- Wisconsin reported 2,745 new C19 cases on Friday, continuing a trend of climbing infections at a level the state has yet to witness in its response to the pandemic, according to Johns Hopkins data.
- “For a long stretch there we were kind of smoldering along, but never really got to a point where we would say that our resources were overwhelmed,” said Dr. Nasia Safdar, an infectious disease physician and the medical director for infection prevention at the University of Wisconsin School of Medicine and Public Health.
- “It was kind of a slow burn, and now it’s clearly a forest fire,” Safdar said.
- The recent surge in C19 cases is one of the first big challenges for Wisconsin since the start of the pandemic, she said, adding that “no one has a giant surplus” of supplies like hospital beds, personal protective equipment and health care workers.
- “I think this is probably the worst possible time for us to be seeing this because of the fact that there’s the pending flu season,” Safdar said.
- Bellin Health, which runs a hospital in Green Bay, Wisconsin, said in a statement that its emergency department has had several instances in the past week where it was at capacity and placed patients in beds in hallways, Reuters reported Thursday.
- Evers signed an emergency order that same day to ease licensing rules for health-care workers so they can practice in Wisconsin facilities and help with the surge of C19 patients.
A ‘disturbing trend’ in Nebraska
- Nebraska has also reported record-high numbers of C19 hospitalizations this week. It’s weekly average of patients grew by more than 16% compared with a week ago as of Friday, according to a CNBC analysis of Covid Tracking Project data.
- “We’re seeing a disturbing trend with increasing hospitalizations and diminishing bed capacity,” said Dr. Angela Hewlett, a member of the Infectious Disease Society of America and an associate professor of infectious diseases at the University of Nebraska Medical Center.
- “In our Omaha metro area, we currently have the highest number of hospitalizations in patients with Covid since the spring,” she said.
- Daily coronavirus cases have grown by more than 37% compared with a week ago in Nebraska, moving to a seven-day average above 540 on Friday, according to Johns Hopkins data.
- Most of Nebraska’s positive cases are among those aged 20 to 34, according to the state’s dashboard, but the coronavirus appears to now be infecting older adults who are at greater risk of serious illness, Hewlett said.
- “My concern is that we’re sitting here on a curve and potentially we’ll see an increasing number of deaths once our higher risk individuals become infected,” she said.
Iowa hospitalizations on the rise
- Iowa hospitals reported a more than 27% increase in C19 patients on Friday compared with a week ago, climbing toward record highs last seen in May, according to Covid Tracking Project data.
- On Friday, Gov. Kim Reynolds allowed bars, restaurants, breweries and wineries to reopen in Johnson and Story counties, two of Iowa’s most populated areas where the University of Iowa and Iowa State University are located.
- The businesses were shuttered in late August as coronavirus cases climbed, students returned to university campuses for the fall semester and in-person classes resume at K-12 schools. Some infectious disease experts applauded the actions but said they were likely “too little too late.”
- As hospitalizations in Iowa rise, the problem goes beyond the state’s hospital bed and ventilator capacity, said Dr. Megan Srinivas, an infectious disease physician based in Fort Dodge.
- “There’s also the issue of staffing and needing nurses, doctors,” she said. “As we have hospitalizations increase, that is really going to be a limiting factor, especially in many rural parts of the state.”
C. Trump & The Coronavirus
1. Doctors Throw Kitchen Sink at President Trump: monoclonal antibodies, remdesivir, dexamethasone and more
- President Trump’s physicians are giving him several different treatments — including investigational drugs — in the hope of relieving his C19 symptoms and possibly shorten his course of illness.
- As some experts put it, doctors are throwing “the kitchen sink” at him.
- While many questions remain about the President’s condition and when he was first diagnosed with the coronavirus that causes C19, here is what has been revealed so far about what he was been treated with — and when.
Regeneron’s monoclonal antibody therapy
- On Friday afternoon, the White House said in a letter that President Donald Trump was treated with an 8-gram dose of the experimental antibody therapy cocktail made by the biotechnology company Regeneron.
- To make its monoclonal antibody therapy, Regeneron scientists selected two antibodies that best neutralized a version of the novel coronavirus in the lab. Antibodies are proteins the body makes to fight infection. The scientists copied those two antibodies to make a treatment for C19.
- The investigational cocktail, known by its investigational name REGN-COV2, has been in clinical trials since June. On Tuesday, the company announced early data from a trial with 275 non-hospitalized patients showing the treatment was safe and seemed to reduce viral levels and improve symptoms. The data, issued via news release, have not been peer-reviewed.
- The greatest improvements were seen in patients who had not mounted a natural response to the coronavirus infection.
- The treatment also seemed to reduce the need for medical visits for the patients, none of whom were sick enough to be hospitalized at the start of this trial, according to Regeneron.
- More patient data will need to be analyzed to know for sure how well the treatment works.
- Regeneron’s therapy is not approved for any use and has not received emergency use authorization from the US Food and Drug Administration — but Regeneron is in talks with regulators to see if the FDA would consider an EUA.
- The New York-based company confirmed that it provided the drug under a “compassionate use” request from the President’s physicians, but did not specify when it received the request. “There is limited product available for compassionate use requests that have been approved under rare, exceptional circumstances on a case-by-case basis,” Regeneron said in a statement released Friday. These requests must be initiated by a physician.
- Some may be able to receive the treatment as part of a clinical trial, where they might receive the therapy or a placebo, or dummy treatment.
- President Trump is being given a five-day course of the antiviral drug remdesivir, one of the doctors treating him said during a briefing on Saturday. The treatment is intended to shorten recovery time for C19 patients.
- “Yesterday evening he received his first dose of IV remdesivir and our plan is to continue a five-day treatment course for remdesivir,” Dr. Brian Garibaldi, one of the team of doctors treating Trump at the Walter Reed National Military Medical Center, told reporters on Saturday.
- In a Phase 3 clinical trial,remdesivir was found to speed recovery in moderately ill patients with pneumonia from C19, according to results published in the medical journal JAMA in August.
- The trial included nearly 600 patients randomly assigned to receive either the current standard of care for C19; a five-day course of remdesivir in addition to the current standard of care; or 10 days of the drug plus care. The recovery of each patient was tracked and examined.
- The study found patients with moderate C19 who received a five-day course of remdesivir were more likely to get better after 11 days compared to those who received standard care alone.
- In May, remdesivir became the first therapy drug issued an emergency use authorization for C19 in the United States.
- The FDA originally authorized the emergency use of remdesivir for C19 in May, but only to treat patients with severe coronavirus who needed extra oxygen or mechanical ventilation to help their breathing. Then on August 28, the FDA extended the emergency use authorization for remdesivir to all patients hospitalized with C19, regardless of the severity of their disease.
- This type of FDA authorization means that physicians can administer the drug to their C19 patients as an emergency treatment.
- President Trump was given the corticosteroid drug dexamethasone on Saturday after his oxygen level transiently dipped, White House physician Dr. Sean Conley said during a briefing on Sunday.
- “We decided that in this case the potential benefits early on in the course probably outweighed the risks,” Conley said.
- Dr. Rochelle Walensky, chief of infectious diseases at Massachusetts General Hospital, said the use of dexamethasone for Trump’s care had some “scratching our heads.”
- “Generally you start the dexamethasone when you’re starting to worry that they’re heading down the wrong path,” Walenksy said. “So, what happened today? Either he progressed or people are like, well, let’s just throw the kitchen sink at him.
- “It’s unclear to me why they would have given him that if he did not require supplemental oxygen.”
- The drug is typically given to patients on supplemental oxygen or needing ventilation.
- In the United States, dexamethasone has been used to treat some C19 patients since early on in the pandemic — but some doctors previously have warned “it is not a treatment for mild disease.”
- In June, preliminary results from a large, randomized study in the United Kingdom found that a low-dose regimen of dexamethasone for 10 days reduced deaths by a third among hospitalized patients requiring ventilation.
- That trial included about 6,400 hospitalized C19 patients, a third of whom who were randomized to receive dexamethasone, and the rest given the usual standard of care at their hospitals.
- In the early trial, dexamethasone was provided at a dose of 6 mg once a day for up to 10 days, either as an injection or orally. The researchers reported no serious adverse events among the patients taking dexamethasone.
- The National Institutes of Health says in its guidelines on treating coronavirus infections that “patients with severe C19 can develop a systemic (all-of-body) inflammatory response that can lead to lung injury and multisystem organ dysfunction.” Based on the results of this one trial, the NIH panel of experts recommended giving dexamethasone to C19 patients who need oxygen.
- “The Panel recommends against using dexamethasone for the treatment of C19 in patients who do not require supplemental oxygen,” the NIH guidelines read.
- In the study on dexamethasone, about 23% of patients who got dexamethasone died, compared to about 26% of those who did not.
- “No survival benefit was seen among participants who did not require oxygen therapy at enrollment,” the NIH said. There’s a reason for this — the drug reduces inflammation, but in doing so, can impair the body’s ability to fight off infection.
- Steroids are widely available and already commonly used to treat seriously ill C19 patients.
- After previously telling reporters on Saturday that Trump “is not on oxygen right now,” White House physician Conley said during a briefing on Sunday that the President had been given supplemental oxygen and had two episodes of transient drops in his oxygen level.
- Late Friday morning, “the President had a high fever and his oxygen saturation was transiently dipping below 94%,” Conley said. A normal blood oxygen saturation level is 95% or higher.
- The President initially was “fairly adamant that he didn’t need” oxygen. “He was not short of breath. He was tired, had the fever, and that was about it,” Conley said.
- However, the President was given oxygen.
- “And after about a minute on only two liters, his saturation levels were back over 95%. He stayed on that for about an hour maybe, and was off and gone,” Conley said.
- Oxygen therapy, or supplemental oxygen, is a treatment that delivers oxygen gas for patients to breathe who may have difficulty breathing. Oxygen can be delivered through tubes resting in the nose, a face mask or tube placed in the trachea or windpipe.
- The NIH notes that hypoxemia, or a low level of oxygen in the blood, is common in C19 patients.
Zinc, vitamin D, famotidine, melatonin and daily aspirin
- On Friday afternoon, Conley said in a White House letter that Trump also has taken zinc, vitamin D, the heartburn drug famotidine, melatonin and a daily aspirin.
- Zinc is a nutrient naturally found in the body that helps the immune system fight off outside bacteria and viruses — but while zinc supplements are often taken to reduce the length of colds, there is no evidence that they can be used to treat C19.
- The FDA has issued warning letters to some companies that have tried to claim there is a link between their zinc products and reduced risk of C19.
- As for vitamin D, it is good for bone health and can be absorbed through food, sunlight and supplements and is appropriate for those who are deficient — but there is no evidence that vitamin D will directly reduce the risk of C19. The FDA also has issued warning letters to some companies tying to sell their vitamin D products to reduce risk of C19 or treat illness.
- Taking too much vitamin D can lead to a toxic buildup of calcium in the blood, causing confusion, disorientation and problems with heart rhythm, as well as bone pain, kidney damage and painful kidney stones.
- The White House letter also noted that the President has been taking famotidine, commonly used to treat ulcers, heartburn and indigestion by reducing the amount of acid in the stomach.
- Ten C19 patients who were taking the drug while treating their illness at home may have found relief, according to a study published in June in the medical journal Gut. Famotidine is the active ingredient in Pepcid AC.
- A coauthor of the study emphasized that it was in a small group of patients.
- More research is needed to determine the efficacy of famotidine as a potential C19 treatment.
- Melatonin was also given to the President and more research is needed to determine its potential benefits for C19 patients, but some studies suggest it could help C19 patients who also have diabetes and obesity.
- A paper published in the European Journal of Pharmacology reviewed previously published studies on melatonin — a hormone that the brain produces — and its effects on viruses, obesity, diabetes and inflammation.
- “A common trend exists between the increased number of SARS-COV-2-infected cases and the low levels of blood melatonin in people with chronic metabolic diseases and elderly people,” the researchers, from Mansoura University in Egypt wrote in the paper.
- “The ability of melatonin to decrease viral infections in obese and diabetic patients is attributed to its characteristics such as potent antioxidant effects, improving the endogenous antioxidant system, immunomodulatory, and the strong anti-inflammatory capability,” the researchers wrote.
- As for aspirin, the over-the-counter drug can help reduce the risk of blood clotting — and evidence has shown that C19 can trigger the formation of blood clots in some patients.
- Studies at Xijing Hospital in China and Louisiana State University Health Sciences Center in New Orleans are investigating possible effects aspirin could have in C19 patients.
- It’s not clear what dose of aspirin Trump was taking and whether he had already been taking it. Many people are prescribed low-dose aspirin for heart health.
2. Charting Trump’s C19 Infection
- It’s too soon to tell whether President Trump’s illness will follow a typical course, or how severe his symptoms may become. And with millions of people sickened worldwide, no single timeline can encompass the range of Covid cases. But months of data have helped scientists home in on the general portrait of a symptomatic coronavirus case.
Exposure and incubation
- The time between initial exposure to the virus and the appearance of symptoms is known as the incubation period. This period is typically four to five days, although it can last up to 14 days, or perhaps even longer in rare cases.
- It remains unclear who infected Mr. Trump, although there are many potential candidates, several of whom gathered with the president during events last weekend and have traveled with him to crowded campaign rallies.
Symptoms and recovery
- Most people who come down with Covid recover within a couple weeks and do not require hospitalization. Mr. Trump has reportedly experienced only mild symptoms so far.
- Severe cases, however, may take far longer to resolve. And a growing cohort of coronavirus survivors, called long-haulers, has reported symptoms and side effects — including fatigue, impaired memory and heart problems — that can linger for months.
- People who develop severe cases of Covid tend to be hospitalized within two weeks or so of the emergence of symptoms. But many of the factors that catapult certain people toward severe forms of the disease remain a scientific mystery. Scientists know that people who are male, older and obese — all descriptors of President Trump — are at higher risk for more serious effects of Covid.
- After an initial exposure, the number of virus particles in a person’s body, or viral load, takes time to build up as the pathogen infiltrates cells and copies itself repeatedly. Mathematical models indicate that the viral load tends to peak before symptoms appear, if they appear at all, and starts to decline rather quickly in the days following the first signs of illness.
- Experts have said that people are more likely to be contagious when their viral loads are high. If so, the window of peak infectiousness might be only a few days long, beginning a day or two before symptoms appear, and closing within a week thereafter.
- This also means that people can be highly contagious during the so-called presymptomatic stage, in the days before they develop symptoms. Separately, asymptomatic carriers of the coronavirus have also been repeatedly pinpointed as the source of transmission events, although how the virus behaves in the bodies of such people is less understood.
- If Mr. Trump’s symptoms appeared on Wednesday or Thursday, he may have exposed several people in the days prior. He likely remains contagious now. In a series of tweets early Friday morning, the president confirmed that he and Mrs. Trump would isolate themselves — a move that swiftly canceled several events in the tense lead-up to the Nov. 3 election. Later, Mr. Trump was taken to Walter Reed for a stay of a few days. He has also been given an experimental antibody treatment developed by drug maker Regeneron and an antiviral drug called remdesivir.
Testing for the virus
- For months, the White House has screened people coming into close contact with Mr. Trump. Many of these screenings are rapid tests, delivering actionable results within minutes without needing to send samples to a laboratory. Such speed and convenience can come at the cost of accuracy: Rapid tests are worse at picking up on low viral loads and very recent infections, and more often produce false negatives or false positives. Some experts argue that true positives from rapid tests might coincide with the period in which people are most contagious, although this has not yet been confirmed. Rapid tests like the much-discussed Abbott ID Now and BinaxNOW have been an emergency FDA greenlight only for sick people who are within seven days of the start of symptoms. Use on individuals who don’t feel ill is considered off-label, and negative results from such tests can’t rule out an infection or contagiousness.
- People with known exposure to an infected person — like Mr. Trump — or who have already developed symptoms may need to take a more sensitive test. Experts often recommend laboratory tests that rely on a technique called P.C.R. (polymerase chain reaction) that can detect very small amounts of the virus, but that usually takes several hours to run on sophisticated, expensive machines.
- Because a P.C.R. test is more sensitive to low viral loads, it may be able to detect a coronavirus infection very early on. But the diagnostic test can also pick up harmless bits of the virus that linger in the body after symptoms have resolved, and perhaps after a person stops being contagious.
- Antibodies are produced by the body in response to an invading pathogen, starting about a week or so into an infection, and can persist in the blood for months. Another type of test, called a serology test, looks for these antibodies instead of the virus. Experts do not consider antibody tests to be a reliable way to determine whether a person is harboring the coronavirus.
- Because the virus can be transmitted by people who feel healthy, experts have stressed the importance of deploying multiple public health measures to combat its spread. While no single tactic can confer complete protection, combining actions like mask-wearing, physical distancing, handwashing and avoiding crowded spaces rapidly ratchets down risk.
- Masks and face coverings that swaddle the nose and mouth can block much of transmission, and seem especially effective at waylaying outbound virus from an infected individual. But there’s evidence that masks can thwart some percentage of inbound pathogens as well, even if they don’t make the wearer impervious to infection.
- Mr. Trump has repeatedly shirked masks for much of the pandemic. On Tuesday night, he mocked former Vice President Joseph R. Biden for his stringent commitment to face coverings and physical distancing.
- Infected people can also reduce the chance of passing on the virus by isolating themselves for at least 10 days after symptoms appear, as long as they continue to improve. Those who have been exposed to someone with a known case of the coronavirus should quarantine for two weeks and seek a test. Up to 40% of infections might lack symptoms, although some estimates have been even higher.
- Based on data gleaned from other respiratory viruses, researchers think there is likely to be a minimum infectious dose for the coronavirus, or the lowest number of virus particles necessary to establish an infection. That number likely varies from person to person, and there is not yet firm data on what a typical dose might be.
- The CDC notes that people with Covid are unlikely to be infectious for more than 10 to 20 days after their symptoms start.
Source: Charting a Coronavirus Infection
D. New Scientific Findings & Research
1. Low risk of C19 transmission of virus on surfaces
- A recent paper (here) highlighting experiments done under controlled laboratory conditions that suggest persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on inanimate surfaces for days, with potential implications for viral transmission
- Yet, at the same time, this paper laments the absence of real-life studies investigating the infectious potential of SARS-CoV-2 on contaminated inanimate material and patient fomites, particularly in high-risk hospital wards.
- A study done in a hospital environment showed that most surfaces were contaminated, including air-conditioning vents, bed rails, bedside lockers, and rarely, toilets.(here) Of note, environmental surface contamination declined after week one of illness, and intriguingly, no surface contamination was detected in intensive care unit (ICU) rooms.
- A limitation of the study (here) is that no attempt was made to culture SARS-CoV-2 from the environmental swabs, which would have helped to understand the significance of SARS-CoV-2 RNA positive samples in terms of infectious potential.
- We have done two sequential studies (See here, and here) seeking to determine on one hand the extent, if any, of contamination of inanimate surfaces in a standard infectious disease ward of a major referral hospital in northern Italy, and on the other hand whether the risk of contamination was higher in emergency rooms and sub-intensive care wards than on ordinary wards. Cleaning procedures were standard.
- A number of objects and surfaces were swabbed. Remarkably, only the continuous positive airway pressure helmet of one patient was positive for SARS-CoV-2 RNA.
- More importantly, attempts to culture the positive swabs on Vero E6 cells were unsuccessful, suggesting that patient fomites and surfaces are not contaminated with viable virus.
- Our findings suggest that environmental contamination leading to SARS-CoV-2 transmission is unlikely to occur in real-life conditions, provided that standard cleaning procedures and precautions are enforced.
2. Researchers Identify Key Biomarker That Predicts Who Will Have Severe C19
- KAIST researchers have identified key markers that could help pinpoint patients who are bound to get a severe reaction to C19 infection. This would help doctors provide the right treatments at the right time, potentially saving lives. The findings were published in the journal Frontiers in Immunology.
- People’s immune systems react differently to infection with the coronavirus (SARS-CoV-2), ranging from mild to severe, life-threatening responses.
- To understand the differences in responses, Professor Heung Kyu Lee and PhD candidate Jang Hyun Park from the Graduate School of Medical Science and Engineering at KAIST analysed ribonucleic acid (RNA) sequencing data extracted from individual airway cells of healthy controls and of mildly and severely ill patients with C19. The data was available in a public database previously published by a group of Chinese researchers.
- “Our analyses identified an association between immune cells called neutrophils and special cell receptors that bind to the steroid hormone glucocorticoid,” Professor Lee explained. “This finding could be used as a biomarker for predicting disease severity in patients and thus selecting a targeted therapy that can help treat them at an appropriate time,” he added.
- Severe illness in C19 is associated with an exaggerated immune response that leads to excessive airway-damaging inflammation. This condition, known as acute respiratory distress syndrome (ARDS), accounts for 70% of deaths in fatal C19 infections.
- Scientists already know that this excessive inflammation involves heightened neutrophil recruitment to the airways, but the detailed mechanisms of this reaction are still unclear.
- Lee and Park’s analyses found that a group of immune cells called myeloid cells produced excess amounts of neutrophil-recruiting chemicals in severely ill patients, including a cytokine called tumour necrosis factor (TNF) and a chemokine called CXCL8.
- Further RNA analyses of neutrophils in severely ill patients showed they were less able to recruit very important T cells needed for attacking the virus. At the same time, the neutrophils produced too many extracellular molecules that normally trap pathogens, but damage airway cells when produced in excess.
- The researchers additionally found that the airway cells in severely ill patients were not expressing enough glucocorticoid receptors. This was correlated with increased CXCL8 expression and neutrophil recruitment.
- Glucocorticoids, like the well-known drug dexamethasone, are anti-inflammatory agents that could play a role in treating C19. However, using them in early or mild forms of the infection could suppress the necessary immune reactions to combat the virus. But if airway damage has already happened in more severe cases, glucocorticoid treatment would be ineffective.
- Knowing who to give this treatment to and when is really important. C19 patients showing reduced glucocorticoid receptor expression, increased CXCL8 expression, and excess neutrophil recruitment to the airways could benefit from treatment with glucocorticoids to prevent airway damage. Further research is needed, however, to confirm the relationship between glucocorticoids and neutrophil inflammation at the protein level.
- “Our study could serve as a springboard towards more accurate and reliable C19 treatments,” Professor Lee said.
3. Scientists Discover Coronavirus Infection Can Relieve Pain – May Help Explain C19 Spread
- The coronavirus (SARS-CoV-2), can relieve pain, according to a new study by University of Arizona Health Sciences researchers.
- The finding may explain why nearly half of all people who get C19 experience few or no symptoms, even though they are able to spread the disease, according to the study’s corresponding author Rajesh Khanna, PhD, a professor in the UArizona College of Medicine – Tucson’s Department of Pharmacology.
- “It made a lot of sense to me that perhaps the reason for the unrelenting spread of C19 is that in the early stages, you’re walking around all fine as if nothing is wrong because your pain has been suppressed,” said Dr. Khanna. “You have the virus, but you don’t feel bad because your pain is gone. If we can prove that this pain relief is what is causing C19 to spread further, that’s of enormous value.”
- The paper, “SARS-CoV-2 Spike protein co-opts VEGF-A/Neuropilin-1 receptor signaling to induce analgesia,” was published recently in PAIN, the journal of the International Association for the Study of Pain.
- The CDC released updated data Sept. 10 estimating that 50% of C19 transmission occurs prior to the onset of symptoms and 40% of C19 infections are asymptomatic.
- “This research raises the possibility that pain, as an early symptom of C19, may be reduced by the SARS-CoV-2 spike protein as it silences the body’s pain signaling pathways,” said UArizona Health Sciences Senior Vice President Michael D. Dake, MD. “University of Arizona Health Sciences researchers at the Comprehensive Pain and Addiction Center are leveraging this unique finding to explore a novel class of therapeutics for pain as we continue to seek new ways to address the opioid epidemic.”
- Viruses infect host cells through protein receptors on cell membranes. Early in the pandemic, scientists established that the SARS-CoV-2 spike protein uses the angiotensin-converting enzyme 2 (ACE2) receptor to enter the body. But in June, two papers posted on the preprint server bioRxiv pointed to neuropilin-1 as a second receptor for SARS-CoV-2.
- “That caught our eye because for the last 15 years my lab has been studying a complex of proteins and pathways that relate to pain processing that are downstream of neuropilin,” said Dr. Khanna, who is affiliated with the UArizona Health Sciences Comprehensive Pain and Addiction Center and a member of the UArizona BIO5 Institute. “So we stepped back and realized this could mean that maybe the spike protein is involved in some sort of pain processing.”
- Many biological pathways signal the body to feel pain. One is through a protein named vascular endothelial growth factor-A (VEGF-A), which plays an essential role in blood vessel growth but also has been linked to diseases such as cancer, rheumatoid arthritis and, most recently, C19.
- Like a key in a lock, when VEGF-A binds to the receptor neuropilin, it initiates a cascade of events resulting in the hyperexcitability of neurons, which leads to pain. Dr. Khanna and his research team found that the SARS-CoV-2 spike protein binds to neuropilin in exactly the same location as VEGF-A.
- See a 3D rendering of neuropilin with VEGF-A (left), spike protein (middle) and small molecule inhibitor (right) in the binding pocket here:
- With that knowledge, they performed a series of experiments in the laboratory and in rodent models to test their hypothesis that the SARS-CoV-2 spike protein acts on the VEGF-A/neuropilin pain pathway. They used VEGF-A as a trigger to induce neuron excitability, which creates pain, then added the RS-CoV-2 spike protein.
- “The spike protein completely reversed the VEGF-induced pain signaling,” Dr. Khanna said. “It didn’t matter if we used very high doses of spike or extremely low doses – it reversed the pain completely.”
- Dr. Khanna is teaming up with UArizona Health Sciences immunologists and virologists to continue research into the role of neuropilin in the spread of C19.
- In his lab, he will be examining neuropilin as a new target for non-opioid pain relief. During the study, Dr. Khanna tested existing small molecule neuropilin inhibitors developed to suppress tumor growth in certain cancers and found they provided the same pain relief as the SARS-CoV-2 spike protein when binding to neuropilin.
- “We are moving forward with designing small molecules against neuropilin, particularly natural compounds, that could be important for pain relief,” Dr. Khanna said. “We have a pandemic, and we have an opioid epidemic. They’re colliding. Our findings have massive implications for both. SARS-CoV-2 is teaching us about viral spread, but C19 has us also looking at neuropilin as a new non-opioid method to fight the opioid epidemic.”
4. Better Vaccines Are in Our Blood: Using Red Blood Cells to Generate Targeted Immune Responses
- Red blood cells do more than shuttle oxygen from our lungs to our organs: they also help the body fight off infections by capturing pathogens on their surfaces, neutralizing them, and presenting them to immune cells in the spleen and liver. Now, a team of researchers from Harvard’s Wyss Institute for Biologically Inspired Engineering and John A. Paulson School of Engineering and Applied Sciences (SEAS) has harnessed this innate ability to build a platform technology that uses red blood cells to deliver antigens to antigen-presenting cells (APCs) in the spleen, generating an immune response. This approach successfully slowed the growth of cancerous tumors in mice, and could also be used as a biocompatible adjuvant for a variety of vaccines. The technology, called Erythrocyte-Driven Immune Targeting (EDIT), is reported in Proceedings of the National Academy of Sciences (PNAS).
- “The spleen is one of the best organs in the body to target when generating an immune response, because it is one of the few organs where red and white blood cells naturally interact,” said senior author Samir Mitragotri, Ph.D., a Wyss Core Faculty member who is also the Hiller Professor of Bioengineering and Hansjörg Wyss Professor of Biologically Inspired Engineering at SEAS. “Red blood cells’ innate ability to transfer attached pathogens to immune cells has only recently been discovered, and this study unlocks the door to an exciting array of future developments in the field of using human cells for disease treatment and prevention.”
Don’t eat me, just check me out
- Using red blood cells as delivery vehicles for drugs is not a new idea, but the vast majority of existing technologies target the lungs, because their dense network of capillaries causes cargoes to shear off of red blood cells as they squeeze through the tiny vessels. Mitragotri’s research team first needed to figure out how to get antigens to stick to red blood cells strongly enough to resist shearing off and reach the spleen.
- They coated polystyrene nanoparticles with ovalbumin, an antigenic protein known to cause a mild immune response, then incubated them with mouse red blood cells. The ratio of 300 nanoparticles per blood cell resulted in the greatest number of nanoparticles bound to the cells, retention of about 80% of the nanoparticles when the cells were exposed to the shear stress found in lung capillaries, and moderate expression of a lipid molecule called phosphatidyl serine (PS) on the cells’ membranes.
- “A high level of PS on red blood cells is essentially an ‘eat me’ signal that causes them to be digested by the spleen when they are stressed or damaged, which we wanted to avoid. We hoped that a lower amount of PS would instead temporarily signal ‘check me out’ to the spleen’s APCs, which would then take up the red blood cells’ antigen-coated nanoparticles without the cells themselves getting destroyed,” said Anvay Ukidve, a graduate student in the Mitragotri lab and co-first author of the paper.
- To test that hypothesis, the team injected red blood cells coated with their nanoparticles into mice, then tracked where they accumulated in their bodies. 20 minutes after injection, more than 99% of the nanoparticles had been cleared from the animals’ blood, and more nanoparticles were present in their spleens than their lungs. The higher nanoparticle accumulation in the spleen persisted for up to 24 hours and the number of EDIT red blood cells in the circulation remained unchanged, showing that the red blood cells had successfully delivered their cargoes to the spleen without being destroyed.
Effective, adjuvant-free vaccines
- Having confirmed that their nanoparticles were successfully delivered to the spleen in vivo, the researchers next evaluated whether the antigens on the nanoparticles’ surfaces induced an immune response. Mice were injected with EDIT once a week for three weeks, and then their spleen cells were analyzed. Treated mice displayed 8-fold and 2.2-fold more T cells displaying the delivered ovalbumin antigen than mice that were given “free” nanoparticles or were untreated, respectively. Mice treated with EDIT also produced more antibodies against ovalbumin in their blood than either of the other groups of mice.
- “Red blood cells could be used as a safe alternative to foreign adjuvants to increase vaccine efficacy and speed vaccine creation.” — Zongmin Zhao
- To see if these EDIT-induced immune responses could potentially prevent or treat disease, the team repeated their three-week prophylactic injection of EDIT into mice, then inoculated them with lymphoma cells that expressed ovalbumin on their surfaces. The mice that received EDIT had about three-fold slower tumor growth compared with the control group and the group that received free nanoparticles, and had lower numbers of viable cancerous cells. This outcome significantly increased the window of time during which the tumor could be treated before the mice succumbed to the disease.
- “EDIT essentially is an adjuvant-free vaccine platform. Part of the reason why vaccine development today takes so long is that foreign adjuvants delivered along with an antigen have to go through a full clinical safety trial for each new vaccine,” said Zongmin Zhao, Ph.D., a Postdoctoral Fellow in the Mitragotri lab and co-first author of the paper. “Red blood cells have been safely transfused into patients for centuries, and their ability to enhance immune responses could make them a safe alternative to foreign adjuvants, increasing the efficacy of vaccines and speed of vaccine creation.”
- The team is continuing to work on understanding exactly how an immune response that is specific to the antigen presented by EDIT is generated by the spleen’s APCs, and plans to test it with other antigens beyond ovalbumin. They hope to use this additional insight to drive their pursuit of the optimal clinical setting(s) for the technology.
- “The human body is a treasure trove of elegant solutions to healthcare problems, and while medicine has come a long way in understanding those mechanisms, we are still in the early stages of being able to harness them to improve the length and quality of human life. This research is an exciting step forward toward that goal, and could dramatically change how immune responses are modulated in patients,” said the Wyss Institute’s Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and Professor of Bioengineering at SEAS.
- Read the study here: DOI: 10.1073/pnas.2002880117
5. 35 Years of Research Into Coronavirus Infections Show Long-Term Immunity Is Unlikely
- Even once a person gets sick with a coronavirus that’s no guarantee they won’t contract it again, new research suggests.
- While the coronavirus (SARS-CoV-2) has the world’s attention right now, there are numerous others that we’ve known about for decades, which are not only known to infect humans, but are highly seasonal.
- Researchers have studied four species of these seasonal coronaviruses across the past 35 years, and found reinfection occurred frequently, around a year after the first bout.
- While that doesn’t necessarily say anything about the current global pandemic, it’s not a good sign for the hope of long-term immunity in a population.
- Analysing 513 serum samples collected since the 1980s from 10 healthy males living in Amsterdam, researchers noticed several spikes of an antibodies linked to coronaviruses.
- Each of these spikes was interpreted as a reinfection, and for all four seasonal coronaviruses studied – including HCoV-NL63, HCoV-229E, HCoV-OC43, and HCoV-HKU1 – the team found three to 17 infections per patient.
- Some rare reinfections showed up as early as six months after initial infection, but more frequently, they came back about a year after, “indicating that protective immunity is only short-lived.”
- To date, there are few confirmed cases of C19 reinfection, but many have faced dispute as it’s still too early to say how long acquired immunity to SARS-CoV-2 can last.
- Looking to other coronaviruses is one of our best clues, and unfortunately, this 35-year study suggests immunity for many coronavirus infections is not only temporary, it’s short-lived. What’s more, the authors say reinfection may be a common feature of all human coronaviruses.
- The study is limited in that antibody levels act only as a proxy for coronavirus infections – we can’t say for sure that each uptick in antibodies was definitely another reinfection.
- The research was also done on a small sample of participants, so larger cohort studies are needed.
- That said, it does have some perks that other research doesn’t.
- “Our serological study is unique because it avoids the sampling bias of previous epidemiologic studies based on symptoms-based testing protocols,” the authors of the new study write.
- Instead, patients were regularly tested, multiple times a year over several decades, even when they were feeling healthy. This is important as many coronavirus infections can remain asymptomatic, which means we could be overlooking many reinfections.
- Recent research, specifically on SARS-CoV-2, indicates that specific antibody levels begin to decrease within the first 2 months after infection, especially after mild cases (which is what most people get).
- The new study found a similar timeline.
- Blood samples, which were collected every 3 months before 1989 and every 6 months after (bar an unexplained six-year gap in the data), show most coronavirus infections in Amsterdam occurred in winter.
- “In our study, the months of June, July, August, and September show the lowest prevalence of infections for all four seasonal coronaviruses,” the authors write, “confirming the higher prevalence in winter in temperate countries, and SARS-CoV-2 might share this feature in the post-pandemic era.”
- This is similar to research on other human coronaviruses, which show infection rates slowing in summer.
- With the Northern Hemisphere now firmly in fall, that’s an extremely worrying result if the new findings apply to the current global pandemic.
- Whether SARS-CoV-2 follows the same trend as other coronaviruses remains to be seen. But if we want to be as careful as possible, we should not assume long-term immunity is a thing, because in the end, relying on vaccinations and natural immunity may only get us so far with this virus.
- Acquiring a long-lasting immune response from a vaccine could be difficult. It might be that we have to get regular updates, like we do with the seasonal flu.
- The study was published in Nature Medicine.
E. Vaccines & Testing
1. What we won’t know about a vaccine
- There’s never been anything like it in the history of vaccine development.
- Four Covid vaccines are hurtling toward the finish line in the U.S. nearly 9 months after deciphering the genetic code for the coronavirus that causes the disease. Moderna and Pfizer, along with its German partner BioNTech, are leading the pack with double-dose treatments, while a single-shot vaccine from Johnson & Johnson began a late-phase trial last week.
- “This is beyond unprecedented,” says Otto Yang, a viral immunologist at UCLA. “It is crazy fast.”
- Vaccines tend to be safe and effective. Just look at the childhood vaccine for measles, mumps and rubella. But by collapsing clinical trials that normally would take years to conclude, scientists are pushing their limits, taking new risks and raising concerns. President Donald Trump’s threat to override minimum requirements in order to get a vaccine to market even faster, ahead of the Nov. 3 election, is upping the angst.
- “What the public needs to know is how much do we really know,” said Merck Chief Executive Kenneth Frazier during an Economic Club of New York webinar on Oct. 1. “And how much do we not know.”
- The biggest unknown, at least initially, may be that doctors won’t know how well vaccines work at preventing serious illness rather than easing run of the mill sore throats or muscle aches.
- People are getting the message: Only 51% of American adults say they’re now likely to get a C19 vaccine, down from 72% in May, according to a Pew Research Center poll.
Source: Bloomberg Daily Coronavirus Prognosis
2. ‘Game Changing’ 15-Minute Covid-19 Test Cleared in Europe
- Becton Dickinson and Co.’s C19 test that returns results in 15 minutes has been cleared for use in countries that accept Europe’s CE marking, the diagnostics maker said Wednesday.
- The test is part of a new class of quicker screening tools named for the identifying proteins called antigens they detect on the surface of the coronavirus (SARS-CoV-2). Becton Dickinson expects to begin selling the test, which runs on the company’s cellphone-sized BD Veritor Plus System, in European markets at the end of October. It will likely be used by emergency departments, general practitioners and pediatricians.
- “It is really a game-changing introduction here in Europe,” said Fernand Goldblat, BD’s head of diagnostics for Europe. Europe was really at the epicenter of the pandemic in April and May, “and unfortunately I think we’re headed back in that direction. So the need will be extremely high,” he said.
- Antigen tests have emerged as a valuable tool because they produce results much more quickly than gold-standard PCR diagnostic assays. However, they are generally less accurate. In the U.S., for instance, instructions for BD’s system recommend that negative results be confirmed by a molecular testing method.
- Becton Dickinson said its antigen assay is 93.5% sensitive, a measure of how often it correctly identifies infections, and 99.3% specific, the rate of correct negative tests. The data, which differ from the U.S. label’s 84% sensitivity and 100% specificity, come from a new clinical study that was recently submitted to the U.S. Food and Drug Administration, spokesman Troy Kirkpatrick said.
- Rapid antigen testing has been making inroads in Europe as well as the U.S. Roche Holding AG said this month it would launch its own 15-minute antigen test to European markets accepting the CE mark. Another test developer, LumiraDx, received CE marking for its antigen test late last month. It said it planned to manufacture 2 million tests in September and as many as 10 million in December.
- Becton Dickinson’s Veritor system has been used largely to screen for flu in Europe to date, but the new assay could help drive wider antigen testing adoption, including for influenza and other respiratory viruses, said Goldblat.
- The company is currently having conversations in multiple European countries, largely with governments and health authorities, about “where and how our solutions would fit,” he said.
- The test is already available in the U.S. Becton Dickinson said it is on track to produce about 8 million each month by October across its global markets, and 12 million monthly by March 2021.
- Goldblat declined to comment on how those tests would be allocated in Europe and the U.S., except that “a good portion” would be coming to Europe. Pricing will depend on commitments made and the reimbursement environment in a given country, among other factors, he said.
- In the U.S., where regulators cleared the assay in July, the Veritor Plus System has an average selling price of $250 to $300, and the tests themselves are about $20 each.
3. Researchers say there’s “no reason” to keep doing painful COVID nasal swab tests
- Researchers in Japan announced “game changing” research this week that found simple saliva tests for C19 are just as reliable as the widely used, but more complicated and uncomfortable, swab tests. The study involved testing almost 2,000 people who were showing no symptoms of the coronavirus using both saliva and the familiar nasal swab.
- The results have already upended conventional wisdom about mass screening in Japan.
- “Now it’s clear by our data that sensitivity and specificity are the same” for saliva and swab tests, research team leader Takanori Teshima of Hokkaido University told CBS News. Given the importance public health experts put on mass-screening for asymptomatic carriers of the virus, Teshima said the strong evidence that simple, non-invasive saliva tests are just as effective as the far more common “PCR” tests is “game changing.”
- “We have no reason to continue to collect samples by swab,” Teshima said. “It’s costly, requires health care workers, and is painful.”
- Teshima presented the results of the research on 1,924 asymptomatic individuals this week. It was one of the largest studies to date directly comparing saliva tests and the nasal swab tests for reliability. Subjects were asked to spit into a cup, and undergo the established nasal swab procedure at local health clinics and at Tokyo’s Haneda airport and Kansai International airport in Osaka.
- Unlike swabbing, which requires trained medical staff in protective gear to collect each sample and risk infection themselves, giving a saliva sample is no more complicated than walking into a booth and drooling in a cup.
- The dual analyses were carried out using the standard polymerase chain reaction (PCR) method, and the RT-LAMP procedure that detects the virus in saliva. The simple viral diagnostic tool has been used for years to test for MERS, SARS and Ebola.
- The Hokkaido study concluded that saliva testing was about 90% accurate in identifying positive cases, with nearly no false positives, a performance rate almost exactly on par with nasal swab sampling. Both tests, Teshima said, accurately identified negatives in nearly all cases.
- But while both methods were found to be highly accurate, “saliva testing has significant logistic advantages over the commonly used nasopharyngeal swab testing,” Teshima said.
- The RT-LAMP machines used for the saliva tests are compact, require no special training to operate, and yield results in just 30 minutes. Japanese regulators approved the use of saliva testing over the summer, and in doing so helped eliminated long lines for passengers at airport screening points.
- Teshima said mass screening of asymptomatic people at large venues like airports will ultimately shift to a third method, antigen testing, which yields results more quickly. But to compensate for that method’s lower accuracy, he said borderline individual results from initial antigen screening (which is also quick and painless) can be re-tested using one of the more reliable methods.
- Saliva screening has been studied at Yale University, which researched its effectiveness on 500 NBA players and staff, and at the University of Illinois, which has pioneered an ambitious program of testing every person on campus — twice a week. (See the video at the top of this page for more on that).
- Teshima said the saliva testing regimen developed in Japan, unlike those in the U.S., does not add preservatives to saliva samples, which is thought to compromise accuracy.
- “That’s why our testing is very convenient, easy and costs less,” Teshima said. “Initially we thought the method should be easy, could be done in any small town, without specialized technicians. That was our goal.”
- As part of its planning for next year’s Olympic Games, the Japanese government is considering setting up a system to make screening as easy as dropping off saliva samples at the local drug store.
- Teshima said that large Japanese hospitals, including Hokkaido University’s, where he works, already routinely screen all patients prior to admission using spit cups, which has helped prevent in-hospital transmission of the coronavirus.
- “This is feasible because of saliva testing,” he said.
4. Tool to detect viral history in a drop of blood has gotten an upgrade
- A tool designed to detect viral history in a drop of blood has gotten an upgrade in the age of C19. VirScan, a technology that can determine which of more than 1,000 different viruses have infected a person, can now also detect evidence of infection from coronaviruses, including the coronavirus (SARS-CoV-2). In a paper published in Science, investigators from Brigham and Women’s Hospital and Harvard Medical School offer up a treasure trove of details about the antibody response to SARS-CoV-2 and how this response may differ in individuals who go on to have a more severe case of C19.
- “This may be the deepest serological analysis of any virus in terms of resolution,” said corresponding author Stephen Elledge, Ph.D., the Gregor Mendel Professor of Genetics at the Brigham and HMS. “We now understand much, much more about the antibodies generated in response to SARS-CoV-2 and how frequently they are made. The next question is, what do those antibodies do? We need to identify which antibodies have an inhibitory capacity or which, if any, may promote the virus and actually help it enter into immune cells.”
- In their analysis, Elledge and colleagues looked in depth at antibody responses to SARS CoV-2 by using VirScan to analyze blood samples from 232 C19 patients and 190 pre-C19 era controls. The team identified 800 sites of the virus that the immune system can recognize, known as epitopes. Not all epitopes are created equal; some may be recognized by neutralizing antibodies, which can elicit a response that eliminates the infection. However, if the body creates antibodies against other epitopes, it may launch a less effective response, giving the virus an advantage. In some cases, including the related coronavirus that causes SARS, viruses may even be able to benefit from the body’s antibody response, using antibodies to enter cells in a phenomenon known as antibody-dependent enhancement.
- In the case of SARS-CoV-2, the team detected a range of antibody frequencies against various epitopes. Many were public epitopes—regions recognized by the immune systems of large numbers of patients. One public epitope was recognized by 79 percent of C19 patients. Others are considered private and recognized by only a few or even one individual. Ten epitopes were in regions essential for viral entry and are likely recognized by neutralizing antibodies. The team used the most discriminatory epitopes to develop a rapid diagnostic test.
- The team’s epitope findings may have important implications for vaccines. If the immune system’s response to public epitopes isn’t found to be protective—or even gives the virus an advantage—vaccines will need to target other regions of the virus to give the immune system a boost.
- In addition, the team found that there are several epitopes conserved across coronaviruses, and that the immune system is likely to try to reuse antibodies against them when infected with SARS-CoV-2—a possible explanation for why so many serology tests for C19 produce false positives.
- The team further analyzed where and when different antibody responses occurred, finding that patients with severe C19 were more likely to launch a stronger, broader response against SARS-CoV-2, possibly because their initial immune response failed to control the infection early. Within hospitalized patients, males made more antibodies than females. The researchers also compared the viral histories of hospitalized and non-hospitalized C19 patients and found that hospitalized patients were much more likely to have had CMV and HSV-1, two common herpes viruses. However, the researchers note that it is difficult to draw conclusions about causality given that the group of non-hospitalized patients was younger and consisted of a higher percentage of white people and women, a demographic group that generally have lower CMV infection rates.
- Elledge envisions their studies as a stepping stone for identifying the most effective antibodies and eliciting them.
- “Our paper illuminates the landscape of antibody responses in C19 patients,” said Elledge. “Next, we need to identify the antibodies that bind these recurrently recognized epitopes to determine whether they are neutralizing antibodies or antibodies that might exacerbate patient outcomes. This could inform the production of improved diagnostics and vaccines for SARS-CoV-2.”
F. Improved & Potential Treatments
1. Regeneron’s C19 antibody may help non-hospitalized patients recover faster
- New data from the biotechnology firm Regeneron seem likely to add to the excitement about drugs called monoclonal antibodies as treatments for C19, but experts caution more data will be needed to know how potentially beneficial the medicines are.
- A high dose of the company’s antibody cocktail, REGN-COV2, led levels of the virus to decrease more quickly in infected, non-hospitalized patients, potentially indicating the treatment may help them get better, Regeneron reported Tuesday via press release. Full results will be published at a later date.
- “There’s nothing bad about these results, you just can’t say much about how transformative this is going to be,” said Eric Topol, director of the Scripps Research Translational Institute. As with data from a similar antibody, developed by Eli Lilly, he warned that the data so far should not be enough for the FDA to grant an emergency use authorization.
- “This doesn’t cut it, but it’s moving in the right direction, that’s for sure,” Topol said.
- In a notable finding, the data seem to show that the antibody had a bigger effect in patients who tested positive for the coronavirus (SARS-CoV-2) but had not created high levels of their own antibodies against the virus. In this group, even a lower dose of the Regeneron antibodies seemed to result in patients getting better faster.
- The data add to the early results from Eli Lilly, which showed a reduction in virus levels for patients at some doses and a tantalizing hint that the treatment might help keep patients out of the hospital.
- Monoclonal antibodies are synthetic versions of one of the immune system’s own weapons against invaders. From the start of the pandemic, some experts have been most hopeful about this technology to create new medicines to fight SARS-CoV-2. But that potential could be limited by the ability to manufacture large quantities of the treatments. Regeneron has reached an agreement with Roche, the Swiss drug giant, to increase its production capacity.
- Experts said longer studies, which are ongoing, will be needed to really know if the antibody treatments make patients better.
- “We are highly encouraged by the robust and consistent nature of these initial data, as well as the emerging well-tolerated safety profile, and we have begun discussing our findings with regulatory authorities while continuing our ongoing trials,” said George Yancopoulos, Regeneron’s chief scientific officer.
- The data are from a 275-patient portion of Regeneron’s study testing REGN-COV2 in patients who have tested positive for C19 but who are not in the hospital.
- Patients received either placebo, 2.4 grams of REGN-COV2, or 8 grams of REGN-COV2. (The antibody cocktail is delivered intravenously.)
- Those who received the high dose saw viral levels decrease by 0.60 log10 copies of the virus per milliliter compared to placebo after seven days, a result that was statistically significant. In the lower dose, there was a 0.23 log10 reduction, which was not statistically significant. Regeneron did not give the total amount of virus detected in its press release.
- At the beginning of the study, Regeneron tested patients not only to see if they had SARS-CoV-2, but also to see if they created their own antibodies against the virus. The company found that 45% of patients had created antibodies, 41% had not, and 14% had unclear results.
- Those without antibodies had higher levels of virus in swabs from their noses from the start. And those who had created their own antibodies got better much faster. Patients with their own antibodies in the placebo group saw symptoms disappear in seven days, while in those whose antibodies were not detected, it took 13 days for symptoms to go away.
- Giving the patients Regeneron’s synthetic antibody had a far greater effect on the amount of virus detected in those who did not have an antibody response before treatment. There was a reduction of 0.6 log10 copies/mL in the patients who received the high dose, and 0.51 in those who received the low dose, both of them statistically significant.
- The reductions were also greater in patients who had higher levels of virus. And in those patients who did not have detectable antibodies at the study’s outset, Regeneron’s antibody cocktail improved symptoms. In this group, symptoms were alleviated in 13 days on placebo, eight days in the high-dose group, and six days in the low-dose group.
- Among the 275 patients for whom data are being reported, 50% were Hispanic, 14% were African American, and the rest of the racial breakdown was not disclosed. On average, they were 45 years old. Forty-nine percent of participants were male and 51% were female.
- A second portion of the study will recruit 1,300 patients, who will be followed for 29 days, with virus levels in the upper respiratory tract tested every two to three days and clinical endpoints assessed by doctors running the study and patients themselves.
- Regeneron’s antibody cocktail is also being treated in hospitalized patients in the U.K. RECOVERY trial, which has yielded several important results about what medicines do and don’t work against C19, and in a study to see if it can prevent household contacts of infected people from becoming infected.
- Nahid Bhadelia, the medical director of the Special Pathogens Unit at Boston Medical Center, said that the results indicate it may be useful to test patients’ antibody response to identify those who may be headed toward worse clinical outcomes. “This is not currently done,” she wrote in an email to STAT, but there could be a place for it if the large study pans out.
- “We have made advances in reducing mortality in hospitalized patients, but we haven’t found anything yet that decreases chances of hospitalization in the first place,” Bhadelia wrote.
- What she needs to see now, she said, are results on hospitalization, disease worsening, and mortality in the ongoing larger study.
- On a conference call after the data were released, Yancopoulos said that the “consistent picture” provided by the data meant that it should be considered by the FDA.
- “I think it deserves to be discussed with the regulatory authorities because of all of the societal implications,” he said. “And I think it’s not up to us. I mean, you know, we’re not going to be the arbiter on this. We think that there is a lot of evidence here to suggest that this is a therapeutic solution that could really benefit quite a number of individuals and patients.”
- If the FDA were to clear the antibody, would Regeneron be able to make enough? Could a testing regimen be implemented on the fly?
- “This is something that we as a society are going to have to grapple with: How to utilize a potentially powerful weapon in the most powerful way to control and fight back against this pandemic,” Yancopoulos said.
2. Nitric Oxide a Possible Treatment for C19 – Only Substance to Have a Direct Effect on the Coronavirus
- Researchers at Uppsala University have found that an effective way of treating the coronavirus behind the 2003 SARS epidemic also works on the coronavirus. The substance concerned is nitric oxide (NO), a compound with antiviral properties that is produced by the body itself. The study is published in the journal Redox Biology.
- “To our knowledge, nitric oxide is the only substance shown so far to have a direct effect on the coronavirus,” says Åke Lundkvist, a professor at Uppsala University, who led the study.
- Since there is still no effective cure for C19, the main emphasis in the treatments tested has been on relieving symptoms. This can shorten hospital stays and reduce mortality. To date, however, it has not been possible to prove that any of these treatments has affected the actual virus behind the infection.
- Nitric oxide (NO) is a compound produced naturally in the body. Its functions include acting like a hormone in controlling various organs. It regulates, for example, tension in the blood vessels and blood flow between and within organs. In acute lung failure, NO can be administered as inhaled gas, in low concentrations, to boost the blood-oxygen saturation level. During the SARS (severe acute respiratory syndrome) coronavirus epidemic of 2003, this therapy was tried out with success. One key reason for the successful results was that inflammation in the patients’ lungs decreased. This property of nitric oxide — the protection it affords against infections, by being both antibacterial and antiviral — is the very one that now interests the researchers.
- Their study builds further on a discovery about the coronavirus that caused the first SARS epidemic. In 2003, NO released from S-Nitroso-N-acetylpenicillamine (SNAP) proved to have a distinct antiviral effect. The researchers from Uppsala University and Karolinska Institute have now investigated how the novel coronavirus involved in the current pandemic reacts to the compound. And SNAP was shown to a clear antiviral effect on this virus, too — and an effect that grew stronger as the dose was raised.
- “Until we get a vaccine that works, our hope is that inhalation of NO might be an effective form of treatment. The dosage and timing of starting treatment probably play an important part in the outcome, and now need to be explored as soon as possible,” Åke Lundkvist says.
- The research group are now planning to proceed by investigating the antiviral effects of NO emitted in gas form. To do so, they will construct a model in the laboratory in order to safely simulate a conceivable form of therapy for patients.
G. Concerns & Unknowns
1. Studies Begin to Untangle Obesity’s Role in C19
- In early April, Edna McCloud woke up to find her hands tied to her hospital bed.
- She had spent the past four days on a ventilator in a hospital in St. Louis County, Mo., thrashing and kicking under sedation as she battled a severe case of C19.
- “They told me, ‘You were a real fighter down there,’” recalled Ms. McCloud, a 68-year-old African-American retiree with a history of diabetes and heart problems. She weighed close to 300 pounds when she caught the coronavirus, which ravaged her lungs and kidneys. Nearly six months later, she feels proud to have pulled through the worst. “They said people with the conditions I have, normally, this goes the other way,” she said.
- As rates of obesity continue to climb in the United States, its role in C19 is a thorny scientific question. A flurry of recent studies has shown that people with extra weight are more susceptible than others to severe bouts of disease. And experiments in animals and human cells have demonstrated how excess fat can disrupt the immune system.
- But the relationship between obesity and C19 is complex, and many mysteries remain. Excess weight tends to go hand in hand with other medical conditions, like high blood pressure and diabetes, which may by themselves make it harder to fight C19. Obesity also disproportionately affects people who identify as Black or Latino — groups at much higher risk than others of contracting and dying from C19, in large part because of exposure at their workplaces, limited access to medical care and other inequities tied to systemic racism. And people with extra weight must grapple with persistent stigma about their appearance and health, even from doctors, further imperiling their prognosis.
- “A new pandemic is now laying itself on top of an ongoing epidemic,” said Dr. Christy Richardson, an endocrinologist at SSM Health in Missouri. Regarding obesity’s effects on infectious disease, she said, “We are still learning, but it’s not difficult to understand how the body can become overwhelmed.”
- The correlations between C19 and obesity are worrisome. In one report published last month, researchers found that people with obesity who caught the coronavirus were more than twice as likely to end up in the hospital and nearly 50 percent more likely to die of C19. Another study, which has not yet been peer-reviewed, showed that among nearly 17,000 hospitalized C19 patients in the United States, more than 77% had excess weight or obesity.
- Similar links were unmasked during the H1N1 flu pandemic of 2009, when researchers began to notice that infected people with obesity were more likely to wind up in the hospital and to die. Flu vaccines administered in subsequent years performed poorly in individuals with extra weight, who fell ill more often than their peers even after getting their shots.
- “Obesity resets human physiology,” said Dr. Anne Dixon, a pulmonologist at the University of Vermont Medical Center who studies how excess weight can affect respiratory conditions like asthma. “People who are very obese are living on sort of a precarious position. This is not just cosmetic.”
- Experts said part of obesity’s threat is mechanical: Large amounts of fat, for instance, can compress the lower parts of the lungs, making it harder for them to expand when people breathe in. The blood of people with obesity also seems to be more prone to clotting, plugging up delicate vessels throughout the body and starving tissues of oxygen.
- Fat, or adipose tissue, can also send out hormones and other signals that make nearby cells go haywire. “Adipose tissue is very active,” said Rebekah Honce, a virologist at St. Jude Children’s Research Hospital in Tennessee and an author on a recent review describing how metabolism intersects with immunity. “It’s not a dormant tissue.”
- One of fat’s most potent effects appears to involve quelling the body’s initial immune response to the virus, allowing the pathogen to spread unchecked.
- Eventually, the body’s immune soldiers get their act together. But this delayed assault might do more harm than good: When late-arriving immune cells and molecules finally rouse themselves into action, they go berserk, driving uncontrolled bouts of inflammation throughout the body.
- These aberrant early responses can have severe long-term consequences as well, said Melinda Beck, who studies how nutrition affects immunity at the University of North Carolina at Chapel Hill. The constant inflammation, she said, can wear away at the immune system’s ability to generate a long-lived population of “memory” cells, which store intelligence about past encounters with pathogens.
- Similar trends have been noted in the immune systems of elderly patients, who also struggle to marshal effective defenses against pathogens. When obesity enters the picture, Dr. Beck said, some of the immune cells found in 30-year-old people “look like those of an 80-year-old.”
- These problems could have a big impact on the first coronavirus vaccines, Dr. Beck said. If the immune systems of people with obesity are more prone to pathogen amnesia, then they may need different dosages of a vaccine. Some products might not work at all in people carrying extra weight.
- But little attention has been paid to these risks in ongoing vaccine trials. When asked if they were testing the effects of weight on vaccine effectiveness, representatives from Novavax and AstraZeneca, two of the leaders among companies in the race for a coronavirus vaccine, said there were no public plans to investigate the issue. Representatives from their competitors Moderna and Pfizer did not respond to repeated requests for comment.
- Johnson & Johnson, whose coronavirus vaccine candidate entered late-stage clinical trials this month, is enrolling people with obesity, according to a company spokesman, Jake Sargent. The company “will have the opportunity to evaluate this question during development,” he said.
- Like many other conditions that can exacerbate C19, excess weight does not have a quick fix — especially in areas where access to healthy food and opportunities for exercise are vastly uneven among communities.
- “If we don’t address these social underpinnings, I think we’ll continue to see a recurrence of what is happening now,” said Dr. Jennifer Woo Baidal, a pediatric weight management specialist at Columbia University.
- In her neighborhood in St. Louis County, where there have been more than 23,000 cases of the coronavirus since March, Ms. McCloud has struggled to find fresh, affordable produce at her local grocery store. Availability has plummeted further since the start of the pandemic, she said, and what little is on the shelves is often on the verge of rotting.
- “I have to cook it right away, or it starts to turn,” she said.
- Ms. McCloud will sometimes travel a bit further to buy salad mixes or leeks — a favorite that adds zing to her meals. But the closest store with any variety is an inconvenient car ride away. She estimates that since contracting C19, she has lost 20 or 30 pounds. She wants to keep her weight down, she said, but her circumstances have made that hard, and “it has only gotten worse since the pandemic started.”
- A few months after Ms. McCloud got sick, her younger sister, Elaine Franklin, 62, began to experience terrible headaches. When she spoke to family members, they asked why she sounded so out of breath. “My son said, ‘Mama, you need to go to urgent care,’” Ms. Franklin recalled. A test soon revealed that she, too, had caught the coronavirus.
- Ms. Franklin’s case of C19 was more moderate than her sister’s. But she still deteriorated quickly, to the point where she could no longer reach the bathroom without assistance. “I was so weak, I couldn’t balance myself,” she said.
- Her physical symptoms haven’t been the only hardship. Ms. Franklin, who is overweight, said she had been irritated by incessant messaging in news reports blaming illnesses like hers on excess fat.
- “The way they were saying it is that because you’re obese and didn’t take care of yourself, you’ll get this disease,” Ms. Franklin said. “I feel like that was unfair.”
- Even medical professionals show bias when caring for patients with excess weight, said Dr. Benjamin Singer, a pulmonologist at the University of Michigan and an author on a recent review of obesity’s influence on immunity. Studies have shown that doctors tend to be more dismissive of patients with obesity and may brush off worrisome symptoms as irrelevant side effects of their weight. Drug dosages and diagnostic machines are also often incompatible with patients carrying excess weight, making it difficult to tailor treatments. Such interactions can be a powerful disincentive to some of the people who most need care.
- “These are not easy conversations,” said Dr. Kanakadurga Singer, a pediatric endocrinologist at the University of Michigan. (She and Dr. Benjamin Singer are married.) Not everyone who weighs more than average is unwell, she said. “It’s more than just the numbers, and it’s not just the weight we should focus on.”
- In St. Louis County, Ms. McCloud and Ms. Franklin have recovered well, though both sisters still grapple with lingering symptoms. Ms. McCloud has occasional fatigue and an intermittent cough. “I can’t talk like I did before,” she said. Ms. Franklin’s headaches never disappeared, and her mind now feels constantly clouded by a fog.
- Both women have worried about their sons, who also developed C19. Chris McCloud, a teacher, was like his mother put on a ventilator, and spent several weeks in the hospital shortly before Ms. McCloud fell ill. He was overweight as well.
- Ms. Franklin suspects she might have contracted the coronavirus from her son Darren Catching, who most likely caught it from a former co-worker. He had recently lost a large amount of weight, Ms. Franklin said, and was not hospitalized either, instead recovering at home.
- In July, when she was infected, she sought medical attention twice. She had lupus, an autoimmune disease, and worried that she wouldn’t be able to fight off the virus. Thoughts of friends and acquaintances who had died from C19 rushed through her head.
- But both times, Ms. Franklin was sent home — first from an urgent care facility, and then from a hospital emergency room.
- She managed to heal on her own, she said. Still, she wonders if her weariness and brain fog might have been prevented by more attentive clinical care. “I’m not a doctor or anything,” she said. “But if I had been in the hospital, maybe it would have been better.”
2. Scientists study whether immune response wards off or worsens Covid
- British scientists have launched a major study aimed at uncovering the critical role that human antibodies and other immune defences play in the severity of C19 cases.
- Results could support some scientists’ belief that antibodies triggered by common colds could be protecting children against the disease. Alternatively, the study could confirm other researchers’ fears that some immune responses to the virus may trigger deadly inflammatory reactions that could bedevil attempts to create anti-Covid vaccines.
- “This study could go in two very different directions,” said Michael Levin, professor of paediatrics at Imperial College London. “It could reveal that cross-reacting antibodies explain why children are less likely to suffer from severe C19, or it might show patients’ own immune responses cause life-threatening effects.”
- The study is being carried out by Levin’s group, a team led by Professor George Kassiotis at London’s Francis Crick Institute, and scientists led by Dan Davis, University College London. They will use thousands of samples which have been collected as part of existing studies funded by the EU and Wellcome.
- Much of the groups’ work will focus on antibodies, key immune defence proteins that bind on to viruses to block their activity. When C19 first appeared, scientists began searching for antibodies against the virus in patients and healthy individuals and to their surprise found them not just in samples taken from recently infected people but in specimens that had been collected before the pandemic began.
- “We discovered a small group – about 6% of the UK population – already had antibodies that could recognise the new virus, although they’ve never been exposed to it,” said Kassiotis. “We realised there must be cross reactivity occurring between common cold coronaviruses and the new pandemic strain. Both are coronaviruses, after all.”
- Coronaviruses cause about a fifth of UK common colds and antibodies triggered by them latch on to the C19 virus. But could they actually be blocking Covid activity? “Our laboratory experiments suggest this may be the case,” Kassiotis said. “These antibodies may actually protect against C19.”
- Adults get common colds caused by coronaviruses once every two or three years. In contrast children get them five or six times a year because they constantly reinfect each other at school, said Kassiotis. As a result about 60% of them have coronavirus antibodies, 10 times the adult level.
- “Children do not generally get severe C19 and I believe that protection is provided by cross-reacting antibodies triggered by repeating coronavirus colds,” said Kassiotis.
- Crucially, it appears coronavirus antibody levels drop steeply when children leave school and that raises a worry: UK children may have lost immunity during the lockdown. “The next coronavirus to spread among them could be the pandemic strain, not the seasonal cold variety,” said Kassiotis. “That does not seem to be happening but it is a concern.”
- The new Crick-Imperial-UCL study will analyse samples from thousands of people to see if they possess antibodies against Covid and also determine if they display any other immune reactions that might have been triggered by coronaviruses, including responses in T-cells. It will also study how individuals fare as the pandemic progresses to see how well antibodies protect them.
- Kassiotis said many different types of antibodies are generated by the body’s immune system when the disease strikes. Some are specific to C19. Others lock on to sections shared by all coronaviruses – and by focusing on those sections, it might be possible to design a vaccine to protect against all coronaviruses. “We would then be better prepared for the next pandemic.”
- But there are other aspects of the body’s immune response to C19 that could have a very different impact. “After the pandemic began we started seeing severely ill, infected children with intense inflammation and multi-organ failure,” said Levin. “We were puzzled because their illness was occurring not at the height of their infection but several weeks afterwards – when the virus had gone but antibodies were high. We feared those antibodies might actually be causing the damage.”
- The culprit could be a phenomenon called antibody dependent enhancement of disease, Levin added. “The Dengue fever virus provides a good example. There are three strains of it. If you get infected with one strain that might not make you terribly ill.
- “But if you later get infected with a second, different strain, you could be in trouble. The antibodies your immune system first made can actually make the disease worse when you encounter a slightly different strain of the virus.”
- This drawback has plagued attempts to develop a vaccine for dengue fever. Triggering antibody production – as vaccines attempt to do – can enhance the disease’s impact, unless those antibodies are effective against all three dengue strains.
- Levin said he was concerned that the newly recognised childhood inflammatory disease associated with C19 could be due to antibodies that later cause inflammation and damage to organs. If so, coronavirus antibodies induced by a vaccine might cause a similar problem.
- “We need to understand whether antibodies which children develop against the common cold coronaviruses and C19 protect against severe disease, or alternatively whether some children and adults make antibodies that might make the disease worse. Hopefully, our study will give us answers and provide the essential information we need to develop safe vaccines.”
3. COVID nightmares are becoming frighteningly common
- Having nightmares about being stuck maskless in a crowd or coming down with C19? You’re not alone.
- A suite of new studies finds that pandemic dreams are remarkably common across multiple countries. People in Finland, Italy, the U.S., Canada and elsewhere around the world report many of the same themes, from dreams about becoming infected to anxiety dreams about social distancing. Some of the examples are metaphorical, such as a cluster of dreams about being attacked by bugs. This bug-attack metaphor seemed unique to the coronavirus pandemic compared with other wide-scale stressful experiences, said the author of that study, Harvard Medical School psychology professor Deirde Barrett.
- “I had never seen one of those after 9/11 or after World War II,” Barrett said, referring to studies she has done on the dreams of people who have witnessed trauma.
- Dreams are an interesting area of study, Barrett told Live Science, because they reflect inner worries and concerns, but in a highly dramatized way.
- “They make up a little highly visual drama, with a narrative and vivid images,” she said. “They often tell us something that may not have otherwise been center stage in our attention.”
- They also sometimes trigger empathy, she said — for ourselves and others. For example, one dreamer surveyed by Barrett had a nightmare in which she found out her 10-year-old’s entire class was coming to her house, and she was responsible for home-schooling them for the rest of the year. People who hear that dream immediately grasp the woman’s real-life anxiety about school shutdowns, Barrett said.
- For Barrett’s study, published in a special COVID-dream section on Sept. 25 in the journal Dreaming, she surveyed 2,888 men and women about their dreams between March 23 and July 15. About 2,000 of the respondents were American, with the others coming from 85 other countries.
- Consistent with previous research on crisis situations, Barrett found that people reported recalling more dreams during the pandemic compared with pre-pandemic. Stress tends to make dreams more intense, she said, which explains part of the enhanced recall. With stay-at-home orders and workplace closures, people also reported sleeping longer once the pandemic began, she said, and people who sleep longer report remembering more dreams. This is because the length of dream cycles stretches out the longer the sleep session goes.
- Both men and women experienced more anxiety dreams and more dreams about death, but women reported a greater rise in both. Women also reported an increase in dreams full of feelings of sadness and anger, while men didn’t dream more about those emotions. The difference may reflect the different ways men and women have been affected by the pandemic, Barrett said. Women are more likely to report dreams about caregiving for sick people, and women are more likely to be caregivers or work in caregiving careers in waking life. Dreams about homeschool stress also turned up more in women’s reports than in men’s, perhaps reflecting a gender divide in responsibility for children’s schooling. Women have also made up more of the unemployed during pandemic lockdowns.
- “For women, it’s affecting them in lots more ways that make them sad and angry as well as anxious,” Barrett said.
- Another paper, this one published in the journal Frontiers in Psychology on Oct. 1, finds that in a sample of more than 4,000 Finnish dreamers, 55% of all bad dreams during the C19 lockdown were pandemic-related. For that study, researchers used an artificial intelligence program to analyze nouns and verbs in dream reports and sort them into clusters. One common cluster, dubbed “disregard of distancing,” included word pairs like mistake/hug, distancing/crowd, and handshake/distancing. Another common theme was travel, said study author Anu-Katriina Pesonen, head of the Sleep & Mind Research Group at the University of Helsinki. People reported dreams about being stuck at the border or not having the proper papers to travel home. This reflected what was really going on in Europe during initial lockdowns, she told Live Science.
- In an Italian study of 796 people, published in the journal Dreaming, 20% of respondents’ most recent dreams in April and May had something to do with C19. People who knew someone who had been infected with SARS-CoV-2 or who had died of the virus reported that their dreams were more emotionally intense than those who weren’t personally impacted. These respondents reported dreams about being stuck in border checkpoints and dreams about leaving their homes for the first time after lockdown, only to realize they weren’t allowed to do so.
- In another online survey of more than 3,000 Americans, also published in Dreaming, 29% reported that they were recalling more dreams since the pandemic began (the survey was taken in early May). Similar to findings from Barrett’s study, women were more likely than men to report pandemic-related dreams. Respondents were asked about the impacts of the pandemic on their own lives, and the results revealed that those who reported greater impacts on their mental and physical health also reported more dreams about C19.
- A much smaller study on just 19 Canadian college students had the advantage of tracking daily dreams, rather than asking people to recall their dreams for a survey. These students had been enrolled in a dream-journal study in February and March that was eventually halted by the pandemic, in which they had been recording their dreams every morning. The researchers compared these dreams, which captured the early days of the pandemic, with dreams collected from an age- and sex-matched group during non-pandemic times. They found that the participants’ dreams during the early pandemic period resembled the dreams of people with anxiety disorders. They reported more location changes in their dreams, and more animal imagery, which previous research has found to be more common in anxious dreamers. That research was also published in the journal Dreaming.
- Barrett plans to continue studying people’s dream reports from across the pandemic. So far, interesting patterns have emerged as anxieties change, she said. Early on in the pandemic, when store shelves emptied, many people reported dreams of starvation or famine, for example. Those disappeared quickly as supply chains stabilized. People’s personal circumstances also seem to matter, she said. Those who reported isolating alone often dreamed of being imprisoned, while those isolating with family members sometimes reported dreams about overcrowded houses or claustrophobia.
- There are also intriguing hints about cross-cultural differences in dream reports. Dreams about bug attacks were relatively common among Americans, Barrett said, but didn’t show up in English samples. (Nor did any Finns report being attacked by bugs in their dream worlds, Pesonen said.) It’s not clear whether that difference would hold if more people from other different countries were sampled, but the findings are interesting, Barrett said — and an example of how poetic dreams can be.
- “Lots of very small objects that cumulatively can harm or kill you is really a very accurate metaphor for the virus,” she said.
H. The Road Back?
1. Is Understanding the Dispersion of Coronavirus the Way Back to Normalcy?
- There’s something strange about this coronavirus pandemic. Even after months of extensive research by the global scientific community, many questions remain open.
- Why, for instance, was there such an enormous death toll in northern Italy, but not the rest of the country? Just three contiguous regions in northern Italy have 25,000 of the country’s nearly 36,000 total deaths; just one region, Lombardy, has about 17,000 deaths. Almost all of these were concentrated in the first few months of the outbreak. What happened in Quito, Ecuador, in April, when so many thousands died so quickly that bodies were abandoned in the sidewalks and streets? Why, in the spring of 2020, did so few cities account for a substantial portion of global deaths, while many others with similar density, weather, age distribution, and travel patterns were spared? What can we really learn from Sweden, hailed as a great success by some because of its low case counts and deaths as the rest of Europe experiences a second wave, and as a big failure by others because it did not lock down and suffered excessive death rates earlier in the pandemic? Why did widespread predictions of catastrophe in Japan not bear out? The baffling examples go on.
- I’ve heard many explanations for these widely differing trajectories over the past 9 months—weather, elderly populations, vitamin D, prior immunity, herd immunity—but none of them explains the timing or the scale of these drastic variations. But there is a potential, overlooked way of understanding this pandemic that would help answer these questions, reshuffle many of the current heated arguments, and, crucially, help us get the spread of C19 under control.
- By now many people have heard about R0—the basic reproductive number of a pathogen, a measure of its contagiousness on average. But unless you’ve been reading scientific journals, you’re less likely to have encountered k, the measure of its dispersion. The definition of k is a mouthful, but it’s simply a way of asking whether a virus spreads in a steady manner or in big bursts, whereby one person infects many, all at once. After nine months of collecting epidemiological data, we know that this is an overdispersed pathogen, meaning that it tends to spread in clusters, but this knowledge has not yet fully entered our way of thinking about the pandemic—or our preventive practices.
- The now-famed R0 (pronounced as “r-naught”) is an average measure of a pathogen’s contagiousness, or the mean number of susceptible people expected to become infected after being exposed to a person with the disease. If one ill person infects three others on average, the R0 is three. This parameter has been widely touted as a key factor in understanding how the pandemic operates. News media have produced multiple explainers and visualizations for it. Movies praised for their scientific accuracy on pandemics are lauded for having characters explain the “all-important” R0. Dashboards track its real-time evolution, often referred to as R or Rt, in response to our interventions. (If people are masking and isolating or immunity is rising, a disease can’t spread the same way anymore, hence the difference between R0 and R.)
- Unfortunately, averages aren’t always useful for understanding the distribution of a phenomenon, especially if it has widely varying behavior. If Amazon’s CEO, Jeff Bezos, walks into a bar with 100 regular people in it, the average wealth in that bar suddenly exceeds $1 billion dollars. If I also walk into that bar, not much will change. Clearly, the average is not that useful a number to understand the distribution of wealth in that bar, or how to change it. Sometimes, the mean is not the message. Meanwhile, if the bar has a person infected with C19, and if it is also poorly ventilated and loud, causing people to speak loudly at close range, almost everyone in the room could potentially be infected—a pattern that’s been observed many times since the pandemic begin, and that is similarly not captured by R. That’s where the dispersion comes in.
- There are C19 incidents in which a single person likely infected 80% or more of the people in the room in just a few hours. But, at other times, C19 can be surprisingly much less contagious. Overdispersion and super-spreading of this virus are found in research across the globe. A growing number of studies estimate that a majority of infected people may not infect a single other person. A recent paper found that in Hong Kong, which had extensive testing and contact tracing, about 19% of cases were responsible for 80% of transmission, while 69 percent of cases did not infect another person. This finding is not rare: Multiple studies from the beginning have suggested that as few as 10 to 20% of infected people may be responsible for as much as 80 to 90% of transmission, and that many people barely transmit it.
- This highly skewed, imbalanced distribution means that an early run of bad luck with a few super-spreading events, or clusters, can produce dramatically different outcomes even for otherwise similar countries. Scientists looked globally at known early-introduction events, in which an infected person comes into a country, and found that in some places, such imported cases led to no deaths or known infections, while in others, they sparked sizable outbreaks. Using genomic analysis, researchers in New Zealand looked at more than half the confirmed cases in the country and found a staggering 277 separate introductions in the early months, but also that only 19% of introductions led to more than one additional case. A recent review shows that this may even be true in congregate living spaces, such as nursing homes, and that multiple introductions may be necessary before an outbreak takes off. Meanwhile, in Daegu, South Korea, just one woman, dubbed Patient 31, generated more than 5,000 known cases in a megachurch cluster.
- Unsurprisingly, SARS-CoV, the previous incarnation of the coronavirus (SARS-CoV-2) that caused the 2003 SARS outbreak, was also overdispersed in this way: The majority of infected people did not transmit it, but a few super-spreading events caused most of the outbreaks. MERS, another coronavirus cousin of SARS, also appears overdispersed, but luckily, it does not—yet—transmit well among humans.
- This kind of behavior, alternating between being super infectious and fairly noninfectious, is exactly what k captures, and what focusing solely on R hides. Samuel Scarpino, an assistant professor of epidemiology and complex systems at Northeastern, told me that this has been a huge challenge, especially for health authorities in Western societies, where the pandemic playbook was geared toward the flu—and not without reason, because pandemic flu is a genuine threat. However, influenza does not have the same level of clustering behavior.
- We can think of disease patterns as leaning deterministic or stochastic: In the former, an outbreak’s distribution is more linear and predictable; in the latter, randomness plays a much larger role and predictions are hard, if not impossible, to make. In deterministic trajectories, we expect what happened yesterday to give us a good sense of what to expect tomorrow. Stochastic phenomena, however, don’t operate like that—the same inputs don’t always produce the same outputs, and things can tip over quickly from one state to the other. As Scarpino told me, “Diseases like the flu are pretty nearly deterministic and R0 (while flawed) paints about the right picture (nearly impossible to stop until there’s a vaccine).” That’s not necessarily the case with super-spreading diseases.
- Nature and society are replete with such imbalanced phenomena, some of which are said to work according to the Pareto principle, named after the sociologist Vilfredo Pareto. Pareto’s insight is sometimes called the 80/20 principle—80% of outcomes of interest are caused by 20% of inputs—though the numbers don’t have to be that strict. Rather, the Pareto principle means that a small number of events or people are responsible for the majority of consequences. This will come as no surprise to anyone who has worked in the service sector, for example, where a small group of problem customers can create almost all the extra work. In cases like those, booting just those customers from the business or giving them a hefty discount may solve the problem, but if the complaints are evenly distributed, different strategies will be necessary. Similarly, focusing on the R alone, or using a flu-pandemic playbook, won’t necessarily work well for an overdispersed pandemic.
- Hitoshi Oshitani, a member of the National C19 Cluster Taskforce at Japan’s Ministry of Health, Labour and Welfare and a professor at Tohoku University who told me that Japan focused on the overdispersion impact from early on, likens his country’s approach to looking at a forest and trying to find the clusters, not the trees. Meanwhile, he believes, the Western world was getting distracted by the trees, and got lost among them. To fight a super-spreading disease effectively, policy makers need to figure out why super-spreading happens, and they need to understand how it affects everything, including our contact-tracing methods and our testing regimes.
- There may be many different reasons a pathogen super-spreads. Yellow fever spreads mainly via the mosquito Aedes aegypti, but until the insect’s role was discovered, its transmission pattern bedeviled many scientists. Tuberculosis was thought to be spread by close-range droplets until an ingenious set of experiments proved that it was airborne. Much is still unknown about the super-spreading of SARS-CoV-2. It might be that some people are super-emitters of the virus, in that they spread it a lot more than other people. Like other diseases, contact patterns surely play a part: A politician on the campaign trail or a student in a college dorm is very different in how many people they could potentially expose compared with, say, an elderly person living in a small household. However, looking at nine months of epidemiological data, we have important clues to some of the factors.
- In study after study, we see that super-spreading clusters of C19 almost overwhelmingly occur in poorly ventilated, indoor environments where many people congregate over time—weddings, churches, choirs, gyms, funerals, restaurants, and such—especially when there is loud talking or singing without masks. For super-spreading events to occur, multiple things have to be happening at the same time, and the risk is not equal in every setting and activity, Muge Cevik, a clinical lecturer in infectious diseases and medical virology at the University of St. Andrews and a co-author of a recent extensive review of transmission conditions for C19, told me.
- Cevik identifies “prolonged contact, poor ventilation, [a] highly infectious person, [and] crowding” as the key elements for a super-spreader event. Super-spreading can also occur indoors beyond the six-feet guideline, because SARS-CoV-2, the pathogen causing C19, can travel through the air and accumulate, especially if ventilation is poor. Given that some people infect others before they show symptoms, or when they have very mild or even no symptoms, it’s not always possible to know if we are highly infectious ourselves. We don’t even know if there are more factors yet to be discovered that influence super-spreading. But we don’t need to know all the sufficient factors that go into a super-spreading event to avoid what seems to be a necessary condition most of the time: many people, especially in a poorly ventilated indoor setting, and especially not wearing masks. As Natalie Dean, a biostatistician at the University of Florida, told me, given the huge numbers associated with these clusters, targeting them would be very effective in getting our transmission numbers down.
- Overdispersion should also inform our contact-tracing efforts. In fact, we may need to turn them upside down. Right now, many states and nations engage in what is called forward or prospective contact tracing. Once an infected person is identified, we try to find out with whom they interacted afterward so that we can warn, test, isolate, and quarantine these potential exposures. But that’s not the only way to trace contacts. And, because of overdispersion, it’s not necessarily where the most bang for the buck lies. Instead, in many cases, we should try to work backwards to see who first infected the subject.
- Because of overdispersion, most people will have been infected by someone who also infected other people, because only a small percentage of people infect many at a time, whereas most infect zero or maybe one person. As Adam Kucharski, an epidemiologist and the author of the book The Rules of Contagion, explained to me, if we can use retrospective contact tracing to find the person who infected our patient, and then trace the forward contacts of the infecting person, we are generally going to find a lot more cases compared with forward-tracing contacts of the infected patient, which will merely identify potential exposures, many of which will not happen anyway, because most transmission chains die out on their own.
- The reason for backward tracing’s importance is similar to what the sociologist Scott L. Feld called the friendship paradox: Your friends are, on average, going to have more friends than you. (Sorry!) It’s straightforward once you take the network-level view. Friendships are not distributed equally; some people have a lot of friends, and your friend circle is more likely to include those social butterflies, because how could it not? They friended you and others. And those social butterflies will drive up the average number of friends that your friends have compared with you, a regular person. (Of course, this will not hold for the social butterflies themselves, but overdispersion means that there are much fewer of them.) Similarly, the infectious person who is transmitting the disease is like the pandemic social butterfly: The average number of people they infect will be much higher than most of the population, who will transmit the disease much less frequently. Indeed, as Kucharski and his co-authors show mathematically, overdispersion means that “forward tracing alone can, on average, identify at most the mean number of secondary infections (i.e. R)”; in contrast, “backward tracing increases this maximum number of traceable individuals by a factor of 2-3, as index cases are more likely to come from clusters than a case is to generate a cluster.”
- Scarpino told me that overdispersion also enhances the utility of other aggregate methods, such as wastewater testing, especially in congregate settings like dorms or nursing homes, allowing us to detect clusters without testing everyone. Wastewater testing also has low sensitivity; it may miss positives if too few people are infected, but that’s fine for population-screening purposes. If the wastewater testing is signaling that there are likely no infections, we do not need to test everyone to find every last potential case. However, the moment we see signs of a cluster, we can rapidly isolate everyone, again while awaiting further individualized testing via PCR tests, depending on the situation.
- Unfortunately, until recently, many such cheap tests had been held up by regulatory agencies in the United States, partly because they were concerned with their relative lack of accuracy in identifying positive cases compared with PCR tests—a worry that missed their population-level usefulness for this particular overdispersed pathogen.
- To return to the mysteries of this pandemic, what did happen early on to cause such drastically different trajectories in otherwise similar places? Why haven’t our usual analytic tools—case studies, multi-country comparisons—given us better answers? It’s not intellectually satisfying, but because of the overdispersion and its stochasticity, there may not be an explanation beyond that the worst-hit regions, at least initially, simply had a few unlucky early super-spreading events. It wasn’t just pure luck: Dense populations, older citizens, and congregate living, for example, made cities around the world more susceptible to outbreaks compared with rural, less dense places and those with younger populations, less mass transit, or healthier citizenry. But why Daegu in February and not Seoul, despite the two cities being in the same country, under the same government, people, weather, and more? As frustrating as it may be, sometimes, the answer is merely where Patient 31 and the megachurch she attended happened to be.
- Overdispersion makes it harder for us to absorb lessons from the world, because it interferes with how we ordinarily think about cause and effect. For example, it means that events that result in spreading and non-spreading of the virus are asymmetric in their ability to inform us. Take the highly publicized case in Springfield, Missouri, in which two infected hairstylists, both of whom wore masks, continued to work with clients while symptomatic. It turns out that no apparent infections were found among the 139 exposed clients (67 were directly tested; the rest did not report getting sick). While there is a lot of evidence that masks are crucial in dampening transmission, that event alone wouldn’t tell us if masks work. In contrast, studying transmission, the rarer event, can be quite informative. Had those two hairstylists transmitted the virus to large numbers of people despite everyone wearing masks, it would be important evidence that, perhaps, masks aren’t useful in preventing super-spreading.
- Comparisons, too, give us less information compared with phenomena for which input and output are more tightly coupled. When that’s the case, we can check for the presence of a factor (say, sunshine or Vitamin D) and see if it correlates with a consequence (infection rate). But that’s much harder when the consequence can vary widely depending on a few strokes of luck, the way that the wrong person was in the wrong place sometime in mid-February in South Korea. That’s one reason multi-country comparisons have struggled to identify dynamics that sufficiently explain the trajectories of different places.
- Once we recognize super-spreading as a key lever, countries that look as if they were too relaxed in some aspects appear very different, and our usual polarized debates about the pandemic are scrambled, too. Take Sweden, an alleged example of the great success or the terrible failure of herd immunity without lockdowns, depending on whom you ask. In reality, although Sweden joins many other countries in failing to protect elderly populations in congregate-living facilities, its measures that target super-spreading have been stricter than many other European countries. Although it did not have a complete lockdown, as Kucharski pointed out to me, Sweden imposed a 50-person limit on indoor gatherings in March, and did not remove the cap even as many other European countries eased such restrictions after beating back the first wave. (Many are once again restricting gathering sizes after seeing a resurgence.) Plus, the country has a small household size and fewer multigenerational households compared with most of Europe, which further limits transmission and cluster possibilities. It kept schools fully open without distancing or masks, but only for children under 16, who are unlikely to be super-spreaders of this disease. Both transmission and illness risks go up with age, and Sweden went all online for higher-risk high-school and university students—the opposite of what we did in the United States. It also encouraged social-distancing, and closed down indoor places that failed to observe the rules. From an overdispersion and super-spreading point of view, Sweden would not necessarily be classified as among the most lax countries, but nor is it the most strict. It simply doesn’t deserve this oversize place in our debates assessing different strategies.
- Although overdispersion makes some usual methods of studying causal connections harder, we can study failures to understand which conditions turn bad luck into catastrophes. We can also study sustained success, because bad luck will eventually hit everyone, and the response matters.
- The most informative case studies may well be those who had terrible luck initially, like South Korea, and yet managed to bring about significant suppression. In contrast, Europe was widely praised for its opening early on, but that was premature; many countries there are now experiencing widespread rises in cases and look similar to the United States in some measures. In fact, Europe’s achieving a measure of success this summer and relaxing, including opening up indoor events with larger numbers, is instructive in another important aspect of managing an overdispersed pathogen: Compared with a steadier regime, success in a stochastic scenario can be more fragile than it looks.
- Once a country has too many outbreaks, it’s almost as if the pandemic switches into “flu mode,” as Scarpino put it, meaning high, sustained levels of community spread even though a majority of infected people may not be transmitting onward. Scarpino explained that barring truly drastic measures, once in that widespread and elevated mode, C19 can keep spreading because of the sheer number of chains already out there. Plus, the overwhelming numbers may eventually spark more clusters, further worsening the situation.
- As Kucharski put it, a relatively quiet period can hide how quickly things can tip over into large outbreaks and how a few chained amplification events can rapidly turn a seemingly under-control situation into a disaster. We’re often told that if Rt, the real-time measure of the average spread, is above one, the pandemic is growing, and that below one, it’s dying out. That may be true for an epidemic that is not overdispersed, and while an Rt below one is certainly good, it’s misleading to take too much comfort from a low Rt when just a few events can reignite massive numbers. No country should forget South Korea’s Patient 31.
- That said, overdispersion is also a cause for hope, as South Korea’s aggressive and successful response to that outbreak—with a massive testing, tracing, and isolating regime—shows. Since then, South Korea has also been practicing sustained vigilance, and has demonstrated the importance of backward tracing. When a series of clusters linked to nightclubs broke out in Seoul recently, health authorities aggressively traced and tested tens of thousands of people linked to the venues, regardless of their interactions with the index case, six feet apart or not—a sensible response, given that we know the pathogen is airborne.
- Perhaps one of the most interesting cases has been Japan, a country with middling luck that got hit early on and followed what appeared to be an unconventional model, not deploying mass testing and never fully shutting down. By the end of March, influential economists were publishing reports with dire warnings, predicting overloads in the hospital system and huge spikes in deaths. The predicted catastrophe never came to be, however, and although the country faced some future waves, there was never a large spike in deaths despite its aging population, uninterrupted use of mass transportation, dense cities, and lack of a formal lockdown.
- It’s not that Japan was better situated than the United States in the beginning. Similar to the U.S. and Europe, Oshitani told me, Japan did not initially have the PCR capacity to do widespread testing. Nor could it impose a full lockdown or strict stay-at-home orders; even if that had been desirable, it would not have been legally possible in Japan.
- Oshitani told me that in Japan, they had noticed the overdispersion characteristics of C19 as early as February, and thus created a strategy focusing mostly on cluster-busting, which tries to prevent one cluster from igniting another. Oshitani said he believes that “the chain of transmission cannot be sustained without a chain of clusters or a megacluster.” Japan thus carried out a cluster-busting approach, including undertaking aggressive backward tracing to uncover clusters. Japan also focused on ventilation, counseling its population to avoid places where the three C’s come together—crowds in closed spaces in close contact, especially if there’s talking or singing—bringing together the science of overdispersion with the recognition of airborne aerosol transmission, as well as presymptomatic and asymptomatic transmission.
- Oshitani contrasts the Japanese strategy, nailing almost every important feature of the pandemic early on, with the Western response, trying to eliminate the disease “one by one” when that’s not necessarily the main way it spreads. Indeed, Japan got its cases down, but kept up its vigilance: When the government started noticing an uptick in community cases, it initiated a state of emergency in April and tried hard to incentivizethe kinds of businesses that could lead to super-spreading events, such as theaters, music venues, and sports stadiums, to close down temporarily. Now schools are back in session in person, and even stadiums are open—but without chanting.
- It’s not always the restrictiveness of the rules, but whether they target the right dangers. As Morris put it, “Japan’s commitment to ‘cluster-busting’ allowed it to achieve impressive mitigation with judiciously chosen restrictions. Countries that have ignored super-spreading have risked getting the worst of both worlds: burdensome restrictions that fail to achieve substantial mitigation. The U.K.’s recent decision to limit outdoor gatherings to six people while allowing pubs and bars to remain open is just one of many such examples.”
- Could we get back to a much more normal life by focusing on limiting the conditions for super-spreading events, aggressively engaging in cluster-busting, and deploying cheap, rapid mass tests—that is, once we get our case numbers down to low enough numbers to carry out such a strategy? (Many places with low community transmission could start immediately.) Once we look for and see the forest, it becomes easier to find our way out.
1. Americans are one step closer to a national contact tracing app for C19
- It may have gotten off to a slow start, but digital C19 contact tracing apps are finally picking up steam in the United States — and may have surmounted one of their biggest obstacles to widespread use.
- States are now able to create contact tracing apps that work with those from other states, thanks to a national server that works with the exposure notification tool developed by Apple and Google and stores information about potential exposures from all states that use it. This gives us the potential for a nationwide digital contact tracing system. Some states are already incorporating this technology into their regional efforts: the latest are New York and New Jersey, which unveiled new apps on Thursday.
- While the national server has been around for a few months, the fact that a growing number of states are using it is a big deal. Because America’s federal government refuses to create a national contact tracing app, each state has so far needed to create its own, leading to a patchwork of apps across the country that used different technologies and couldn’t communicate with each other. Any given state app became effectively useless as soon as the device it was on crossed a state line.
- This is no longer the case. Some states — New Jersey, New York, Pennsylvania, and Delaware — have teamed up to form a regional alliance of apps with a common codebase. That means if you had the New York version of the app and traveled to New Jersey for a large, crowded superspreader event where you were exposed to the coronavirus, you’d still get a notification (assuming the infected person used one of those states’ apps and reported their positive results to the proper health authorities).
- The public health authorities behind these new digital contact tracing apps are using the Apple-Google exposure notification tool, which uses Bluetooth to exchange anonymous “keys” with any devices that come within a certain proximity (and have opted into the tool). If someone tests positive for the coronavirus, their keys are uploaded to a server. Individual devices check the server every day, and if any keys on the server match keys received by the device, it will alert its owner that they may have been exposed to the virus.
- Apple and Google worked together to make the tool interoperable with iOS and Android operating systems, and iOS 14 has the exposure notification tool baked into the system itself and notifies users about the feature, creating a relatively seamless process to enable it. While a contact tracing app doesn’t have to use the Apple-Google tool — in fact, some states and countries have elected to go their own way here — those apps have had technical and privacy issues, and can’t work with each other.
- The Association of Public Health Laboratories launched the new national key server in July specifically for the Apple-Google tool, which means any state apps that use the tool and this national server will basically work together. If someone with Wyoming’s app tests positive, their keys are uploaded to a server and can be accessed by devices using apps from Delaware, New Jersey, New York, North Carolina, North Dakota, Pennsylvania, and parts of California that are participating in a pilot program.
- Several other states, including Alabama, Nevada, Virginia, and the territory of Guam, are also using the Apple-Google exposure notification tool in their contact tracing apps, but they are not using the national key server. A few more — Colorado, Connecticut, Maryland, Oregon, Washingtons state, and Washington, DC — have announced plans to come out with their own apps powered by the Apple-Google tool.
- New Jersey and New York are the newest states to roll out their apps. Along with Pennsylvania and Delaware, they’re touting a sort of regional effort at contact tracing. They’re using the national server, and the four apps are all very similar, from their name (“COVID Alert [state]”) to their source code: The apps were built using an open source codebase called COVID Green, which was initially developed for Ireland’s app. That gives all four apps a uniform look and function, and it means the process of building them was relatively fast compared to the time it would have taken for each state to build their own app from scratch.
- The states were also assisted by the Linux Foundation Public Health (LFPH) initiative, which works with public health authorities to use open source software to fight the coronavirus.
- “We’re really focused on making sure to build out an ecosystem around exposure notification, and making sure that there’s open source options in order to get these apps out more quickly,” Jenny Wanger of LFPH told Recode. “And to make sure that they’re secure and trustworthy, as well as building a community for everybody who’s actually implementing these apps.”
- One testament to how the attitude toward digital contact tracing and the Apple-Google exposure notification tool in particular has changed: In May, Pennsylvania told Recode it was using a different digital contact tracing tool to assist human contact tracing efforts, while New York told Recode it was focusing on building its manual contact tracing program.
- Apple and Google also recently announced an “exposure notification express” option that allows states to enable exposure notifications without having to build a standalone app. Several states that are part of the so-called Western States Pact — Washington, Oregon, and California — are currently piloting projects based on the exposure notifications express technology.
- The new apps and region-wide efforts come at a time when there’s an increased awareness of and interest in contact tracing, and when infection rates are relatively low but could be on the verge of a fall spike — meaning contact tracing could come in handy very soon. As always, the effectiveness of the apps depends on how many people use them. With states working together, new technology allowing apps to work across state lines, and the device operating system updates in place that facilitate their use, we’re as close as we’ve ever been to having a nationwide digital contact tracing effort.
2. Lab tests suggest Israeli-made face mask eliminates over 99% of coronavirus
- The SonoMask displayed an ability to neutralize the novel coronavirus at an effectiveness of 99.34% within trials performed by the internationally accredited ATCC Testing laboratory, Ramat Gan-based Israeli fabric maker and developer Sonovia announced on Saturday.
- Sonovia’s reusable anti-viral masks are coated in zinc oxide nanoparticles that destroy bacteria, fungi and viruses, which it says can help stop the spread of the coronavirus.
- Results from the most recent round of testing showed that the mask has the ability to neutralize fallen traces of SARS-COV-2 within 30 minutes after making contact with the fabric. The SonoMask was also proven to maintain its protective properties throughout 55 wash cycles.
J. Projections & Our (Possible) Future
1. Lockdowns May Have Had Little Effect on C19 Spread
- In 1932, Supreme Court justice Louis Brandeis famously called the states “laboratories of democracy.” Different states can test out different policies, and they can learn from each other. That proved true in 2020. Governors in different states responded to the C19 pandemic at different times and in different ways. Some states, such as California, ordered sweeping shutdowns. Others, such as Florida, took a more targeted approach. Still others, such as South Dakota, dispensed information but had no lockdowns at all.
- As a result, we can now compare outcomes in different states, to test the question no one wants to ask: Did the lockdowns make a difference?
- If lockdowns really altered the course of this pandemic, then coronavirus case counts should have clearly dropped whenever and wherever lockdowns took place. The effect should have been obvious, though with a time lag. It takes time for new coronavirus infections to be officially counted, so we would expect the numbers to plummet as soon as the waiting time was over.
- How long? New infections should drop on day one and be noticed about ten or eleven days from the beginning of the lockdown. By day six, the number of people with first symptoms of infection should plummet (six days is the average time for symptoms to appear). By day nine or ten, far fewer people would be heading to doctors with worsening symptoms. If C19 tests were performed right away, we would expect the positives to drop clearly on day ten or eleven (assuming quick turnarounds on tests).
- To judge from the evidence, the answer is clear: Mandated lockdowns had little effect on the spread of the coronavirus. The charts below show the daily case curves for the United States as a whole and for thirteen U.S. states. As in almost every country, we consistently see a steep climb as the virus spreads, followed by a transition (marked by the gray circles) to a flatter curve. At some point, the curves always slope downward, though this wasn’t obvious for all states until the summer.
Lockdowns Not the Cause
- The lockdowns can’t be the cause of these transitions. In the first place, the transition happened even in places without lockdown orders (see Iowa and Arkansas). And where there were lockdowns, the transitions tended to occur well before the lockdowns could have had any serious effect. The only possible exceptions are California, which on March 19 became the first state to officially lock down, and Connecticut, which followed four days later.
- Even in these places, though, the downward transitions probably started before the lockdowns could have altered the curves. The reason is that a one-day turnaround for C19 test results probably wasn’t met in either state. On March 30, the Los Angeles Times reported the turnaround time to be eight days. That would make the delay from infection to confirmation not the 10 we assumed, but more like 17 days (6 for symptoms to appear, 3 for them to develop, and 8 for test processing). In early April, the Hartford Courant reported similar problems with delayed test results in Connecticut.
- What’s more, there’s no decisive drop on the dates when lockdowns should have changed the course of the curves. Instead, the curves gradually bend downward for reasons that predate the lockdowns, with no clear changes ten days later.
- Lockdown partisans might say that the curves would have been higher after the ten-day mark without the lockdown. While we can’t redo history to prove them wrong, the point is that the sudden and dramatic changes we should see if they were right aren’t there. If we showed people these curves without any markings, they would not be able to discern when or even if lockdowns went into effect.
- The vertical lines mark the date when the number of deaths attributed to the coronavirus reached five per million people in the population. This is probably the best way to mark similar extents of viral progress in each state, since we don’t know how many total cases there were. The curves usually start to bend somewhere around the same death toll (roughly five per million people), which suggests that the approach of herd immunity caused the bends. In other words, we see in this data not only a lack of evidence that lockdowns caused the curves to bend, but also evidence of the very early stages of herd immunity.
- In fact, a May 18 column in the New York Times argued that coronavirus cases in New York City probably peaked before the state lockdown began on March 22. Though that newspaper is not known for taking a critical stance on lockdowns, this point implies that the spread was slowing before the mayor and governor even ordered the lockdown.
- Something caused this overall decline. It couldn’t have been lockdowns, which weren’t maintained (or heeded) in full force through June. At the moment, we can only speculate. But if this virus is like others, its decline is likely attributable to some mix of changing seasons and the gradual onset of herd immunity. Another factor, of course, could be the widespread use of masks as the year progressed.
- The evidence suggests, then, that the sweeping, mandated lockdowns that followed voluntary responses exacted a great cost, with little effect on transmission. We can’t change the past, but we should avoid making the same mistake again.
K. Practical Tips & Other Useful Information
1. Read This Before You Even Consider Dining Indoors
- Linsey Marr has not dined indoors at a restaurant since the pandemic began, and she won’t until it’s over. Because she knows the risk, better than just about anyone. Marr, PhD, is a scientist at Virginia Tech and an expert on the transmission of the coronavirus through the air. She and several of her colleagues agree that the riskiest environments for catching C19 are crowded indoor spaces, including restaurants.
- “Restaurants are among the higher-risk activities because you’re indoors with other people without masks for some of the time at least,” Marr tells Elemental.
- The coronavirus spreads in three known ways: from infected surfaces, by large respiratory droplets that typically fall to the ground within a few feet, and in smaller droplets called aerosols that can stay suspended for minutes or hours — a particular risk in poorly ventilated buildings where the aerosol concentration can build up.
- The risk of airborne transmission increases with several factors related to dose and duration.
- The louder a person talks, the more aerosols are released.
- If you’re closer to someone or more than one person in a room is sick (even if they don’t know it), the risk rises.
- If you stay in an infected space for, say, an hour, your odds of getting sick are higher than if you spend less than 15 minutes there, but there are no firm thresholds given the many other variables.
- The relative extent of each transmission mode is not known, so Marr, and other scientists and health experts encourage hand-washing as well as physical distancing, mask-wearing, and avoiding large crowds as the keys to slowing the spread.
- The risk, they say, is much greater in a crowded, poorly ventilated restaurant than an uncrowded, well-ventilated one and much greater when people don’t wear masks. In an FAQ on the topic, 10 aerosol-transmission experts point out that many outbreaks have been documented in crowded indoor spaces where people spend a lot of time together and especially when there is a lot of loud talking, shouting, or singing — as in bars or choir practices — but there have been no documented outbreaks in movie theaters where there is little talking and good ventilation.
Measuring the risk
- A limited case study of coronavirus infections that occurred in a restaurant in China found one infected person spread the virus to five people who were seated at other tables, each in the path of air-conditioning vents. Doors and windows were closed, and the restaurant was not filtering the conditioned air, a substandard ventilation scenario by modern U.S. building health standards.
- Richard Corsi, PhD, dean of the College of Engineering and Computer Science at Portland State University, studies indoor air quality. He recently ran computer simulations using the data from the case study in China. Corsi’s hypothetical U.S. restaurant was relatively full, with a similar number of people per square feet as the restaurant in China. The main difference: The simulated restaurant meets ventilation standards set by the American Society of Heating, Refrigerating, and Air-Conditioning Engineers.
- The results of his unpublished findings: The amount of coronavirus potentially reaching the lungs of some patrons from a single infected person in the hypothetical U.S. restaurant would be about 20% of what occurred in the restaurant in China, Corsi says.
- If a restaurant was running at 50% capacity, that not only allows for better physical distancing than a packed house but also cuts in half the probability that an infected person might be there, Corsi explains in a phone interview. Likewise, restaurants at 25% capacity, as planned for New York City starting September 30, further reduces risk. The risk could be lower still in restaurants that have upgraded air filters or have installed air purifiers, but short of asking the owner about precautions taken, there’s no way to guess or even measure how safe the air might be. (Though if an owner is baffled by your questions, that would be a clue.)
- Corsi says he totally understands the emotional drain of the pandemic — what other experts are calling “Covid fatigue” — and why people want to get back to living normally, but under none of these conditions would he go to a restaurant right now. “I think there’s still too much of a risk there of getting sick,” he says. “I’m not going to a restaurant because I know they’re not safe.”
- Weather permitting, restaurants can take one very useful and visible prevention step: Open doors or windows and create cross-ventilation so that fresh outdoor air dilutes the air in the shared space, says Shelly Miller, PhD, an environmental engineer at the University of Colorado, Boulder, who studies the indoor transmission of infectious diseases.
- Miller just made reservations for dinner indoors at a fancy restaurant for her son’s 18th birthday — her first dining-in experience during the pandemic. She didn’t make the decision lightly. The restaurant has high ceilings, lots of space, and the owners have upgraded their ventilation. Still, she’ll be packing a carbon dioxide detector. It won’t reveal whether there’s coronavirus in the air, but it will measure how much fresh air is being mixed into the building, diluting any virus that might be wafting about.
- Don’t have $100-plus for a CO2 detector? “If you walk into a place and it feels hot and stuffy to you, and there’s a lot of people in there, you should walk back out,” Miller says.
- “If you have 100 people in a restaurant, there’s going to be infected people there in most parts of the country right now.”
What to look for before you sit down
- All three of these scientists are sensitive to the economic consequences of avoiding restaurants, and they’re eager to support their favorite local establishments by doing takeout or delivery where available. They also recognize that as states and cities relax regulations on indoor dining, some people won’t be able to resist the craving to eat out. Here, then, are their collective suggestions on what to look for to suggest a restaurant is taking the pandemic risk seriously:
- Masks on all employees
- Tables spaced to keep several feet between groups
- Respectful distancing and minimal talking from wait staff and hosts
- Good ventilation from open doors or windows if practical weather-wise
- Frequent and serious cleaning of tables and menus
- A quiet atmosphere
- “I’d be looking for a place where it’s uncrowded, there’s no music or TVs in the background, at least not audio, no sound, so that people don’t have to talk over it,” Marr says. Also consider whether your state, city, or community is experiencing strong outbreaks or not, the experts say. And do a headcount.
- “If you have 100 people in a restaurant, there’s going to be infected people there in most parts of the country right now,” Corsi says. “If you have a third as many there, you can cut the probability that there’s an infected person there by two-thirds.”
- Importantly, the guideline you’ve heard for six feet of separation is just that: a guideline. It’s a useful distance to separate you from most large respiratory droplets but not from aerosols, experts agree. Corsi does not think it’s sufficient distance for indoor dining given the length of time people could be exposed to others who won’t be wearing masks throughout a meal.
What you can do to lower risk
- As with any activity that goes against the advice to avoid crowded indoor spaces, lowering risk in a restaurant involves layered measures, starting with mask-wearing.
- “I would suggest that, ideally, people would be wearing their masks anytime they’re not eating or drinking,” Marr says. While face masks are effective primarily at protecting others, Marr’s research lab is finding, in ongoing research on mannequins that’s not yet published, that good-quality, properly fitted homemade masks can protect the wearer from infection more than has been suggested. “If it fits well with no gaps and you have at least a couple of layers of densely woven material, then it probably protects you against at least half if not 80% or more of the droplets and aerosols that we think are most important for transmission.”
- Effectiveness also presumes a person avoids touching the mask, their face, or their eyes.
- The scientists cite other simple ways to cut down intensity and duration of exposure, all of which, admittedly, veer from some of the attractions of eating out:
- Go during off-hours or on slow days
- Ask for the bill early and eliminate the wait to pay
- Take a walk outside while waiting to order or waiting for your food
- Experts also suggest sitting only with people you live with, unless you’ve created a small social “quaranteaming bubble” agreeing to prevention rules while dining and in other activities.
- Of course, any activity done outside, including dining, is safer than the same activity indoors in terms of Covid-19 prevention. But even outdoor dining has risks. The experts say tables should still be well-spaced-apart outdoors, servers should still wear masks, and diners should don masks if seated close to others, especially if downwind.
- Even with all these precautions, eating in restaurants runs the risk of increasing coronavirus infections in any community. Health experts urge policymakers and individuals to consider which aspects of “returning to normal” are most important.
- “I still think that restaurants and bars are nonessential, and opening them for indoor service now puts a lot at risk, including the opening of schools if infection rates increase,” Corsi says. “We need to have priorities as a nation if we are going to get past this without three times as many deaths and a destroyed economy.”
2. This scientist made a Google Doc to educate the public about airborne coronavirus transmission (click here to see the doc)
- The evidence that the coronavirus spreads through the air has been mounting for months. However, the official guidance from the World Health Organization and Centers for Disease Control is still that droplets are the main route of transmission. In fact, the CDC changed its website last month to acknowledge airborne transmission as a route for C19 infections but removed the new guidance just days later, saying it had been posted in error. An official told CNN that it “wasn’t ready to be posted.” All clear?
- Back in July, a group of 239 experts sent an open letter to the WHO imploring it to acknowledge airborne transmission. Three months later, the WHO’s guidance has changed subtly but still only suggests airborne transmission plays a limited role. Rather than wait for officialdom to catch up, one of those signatories, Jose-Luis Jimenez, a chemistry professor at the University of Colorado, Boulder, who has studied aerosols for 20 years, decided to go straight to the public with the latest advice on how people can protect themselves and those around them. He convened a group of nine other experts in the field to create this open-access Google Doc offering comprehensive advice on what you need to know about aerosol transmission, from best practices for masks to whether it’s safe to travel by airplane.
- We spoke to him about why he created the document, and the response he’s had so far. The conversation has been condensed and lightly edited for clarity.
Why did you create this document?
- A lot of people were asking questions, so I thought it made sense to put them in one place. It means you don’t have to keep repeating yourself, and you can tweak the document and improve it over time. We [aerosol transmission experts] were answering so many questions on Twitter and via email. I’ve had several thousand emails and Twitter questions. But the answer is so often the same. Some of the coauthors I found through the WHO open letter, others I found via Twitter, and I proposed to them, “What do you think about putting our research together, so we don’t have to keep repeating ourselves so much?” A few of them said yes, so I set it up, put in some questions, and then others starting adding theirs in too. When we saw it was useful, we made it public. We update the document all the time. We’re effectively having to be a little WHO or CDC. We’re saying the things that they should be saying. This is frustrating, but it’s the situation we find ourselves in. These organizations have been flat-out refusing to consider if aerosol transmission is important, which leaves people unprotected. So we feel it’s our duty to communicate directly with the public.
How are people using it?
- We’ve advertised the document as much as possible through Twitter, emails, and asking journalists to help. That’s how most members of the public see it. There are always more than 100 people looking at it whenever I check, so we know a lot of people are reading it. And people have said it’s very useful. A lot of doctors have said it’s a good resource. And Google Translate means it can be automatically translated it into any language. Every time I give an interview in a new country, people are shocked transmission is mostly through aerosols.
Why did you make this document instead of going down the traditional science publishing route?
- Science publishing is very slow. For the scale of the pandemic, people need information today. And publishers can be cryptic. They all have their own rules. In reality, you can only publish things that have not been published before, so it’s not a good way to answer questions from the public. And crucially, it needed to be updateable so we can answer people’s questions as they come. In a journal, it would be frozen.
What have been your main frustrations with the response to the evidence around airborne transmission?
- Ever since we wrote that letter, signed by 239 scientists, I have been waiting for the landslide. The evidence is now simply overwhelming that the virus is spread through aerosols. The idea it’s mainly droplets is a myth. It’s an error from 1910 made by Charles Chapin, who wrote a book called The Sources and Modes of Infection. In that book, he associated the risk of infection with droplets. He said, admitting later it had been without evidence, that aerosol transmission is almost impossible, and anyone who says otherwise has to prove it. And that has become dogma ever since. It’s almost a superstition. To this day it’s still what the CDC says.
- I’m still waiting for that landslide, where suddenly everyone moves and there’s a huge change. But it hasn’t happened yet. Germany has started saying that good ventilation is the cheapest and best method to reduce the spread of the virus—and that only makes sense if you think it’s mostly spread by aerosols, not droplets or surfaces. The CDC published some guidelines which were confusing, which said inhalation is the main way it spreads—and that means aerosols, as only they can be inhaled—so they were admitting aerosols were the main mode of transmission. Then they took it down. We don’t know if it’s because of politics or dogmatic scientists who refuse to let go of droplets.
- Aerosol transmission is the main way this virus spreads: the only question if it’s 70%, 80%, or 90%. Ballistic droplets are a negligible way to spread the virus. They only spread if someone coughs or sneezes on you. They drop to the ground, whereas aerosols linger. If you look at superspreading events, for example the Washington choir case, it is impossible they are being spread by droplets. For 52 people to get infected, it has to be by aerosols. If droplets were important, it would matter less if you are inside or outside, and you’d expect transmission to happen a lot more outdoors. But if you go outside, transmission drops tremendously. The evidence is clear. It’s scandalous and absurd these agencies refuse to give correct guidance.
What are the most important parts of the document to understand for personal safety?
- The thing people need to understand is aerosol transmission is like everyone breathing out cigarette smoke, and you want to breathe in as little of others’ as possible. Everyone you are around, imagine they are breathing smoke, and try to avoid it. It’s not good enough to just give people guidelines; you need to explain the actual science behind it, too.
- The second most important thing is the recommendations section—how to interpret the science for any given situation. Avoid anything that involves breathing in a lot of other people’s breath. Do things outdoors. But the most important things are free. Wear the mask you already have when you are inside public spaces, and open a window. If we did those, transmission would go down dramatically. Things like ventilation and air filtering matter, but the main things we can do cost nothing.
- And finally, perhaps not for the general public but for people who want to understand how we got here—look at the history, in section 1.3 and 1.4 of the document. It is critical, and it explains why the WHO and CDC are not budging. I wonder what percentage of the global population we could reach with our advice. We’ve reached millions, but it’s still a tiny fraction. And if the CDC, WHO, and local health agencies don’t change their guidance, it really defeats the purpose. It makes me so angry.
3. Identify the Different Symptoms of the Flu and C19
- As influenza season approaches, some Americans, and especially parents, are worried that, if they or their children should become ill, it may not be easy to know which disease they have — the flu or C19.
- They are correct. Most symptoms of the two diseases are so similar that, short of a test — or two or three tests — it won’t be possible to know for sure. But there are some clues. (And it is possible to have both infections at the same time; some patients in China this year were found to have both.)
- But first: get a flu shot.
- It is not yet clear whether the United States will have much of a flu season this year. Flu activity in the Southern Hemisphere, which is often predictive of activity in the United States, was 99 percent below normal during its winter. Epidemiologists believe that is because Australians, New Zealanders, South Africans, Chileans and other residents of the southern half of the globe were wearing masks, staying several feet apart and washing their hands to prevent transmission of the coronavirus. Those same precautions also prevent flu transmission.
- Because there are very few flights between the Southern Hemisphere and the United States right now, there may be no opportunity for the usual four seasonal influenza strains to “reseed” themselves among Americans. If they do, masks and social distancing should limit their spread.
- Nonetheless, experts urge all Americans to get flu shots. Before it ended abruptly during lockdown, last year’s flu season was on track to be one of the worst in recent memory. The number of children who died was equal to that in the 2017-18 season, which was the worst since the Centers for Disease Control and Prevention began tracking flu-season deaths in 1976.
- If you catch the flu, experts say, having had the shot makes it much less likely that you will be hospitalized or die.
- Because of the fears of a “twindemic,” flu shots were made in large numbers this year and distributed to pharmacies and doctors’ offices beginning in August, which is early. As of late last month, some doctors reported difficulty ordering as many as they want, but pharmacy chains say they are getting steady supplies. To find a flu shot, try vaccinefinder.org or one of the chain pharmacy websites, such as CVS.com/immunizations/flu.
- Assessing the difference between a cold and the flu.
- There are at least 100 viruses that can cause the common cold, but only four that cause seasonal flu. Many people who catch colds assume they have the flu, but experts consistently say the same thing about how to tell the difference: “Flu makes you feel as if you were hit by a truck.” The fever, aches and headaches of a bad case of influenza are generally worse than a case of respiratory syncytial virus, rhinovirus or other common cold viruses.
- Everyone knows the symptoms of the flu: fever, headaches, body aches, sore throat, runny nose, stuffed sinuses, coughing and sneezing — and, for infants, ear infections. Some victims, especially children, get diarrhea or vomiting too.
- In severe cases, the most common complication is pneumonia. The typical signs of a flu pneumonia are shortness of breath, especially when you exert yourself, and unusually rapid breathing — doctors typically look for that in children — and sometimes pain in the chest or back.
- Identifying C19 by its flulike and ‘wacky’ symptoms.
- Knowing whether you have C19 is much more complicated because there are so many different — and sometimes pretty wacky — symptoms, many of which echo those of the flu.
- The most common symptoms are high fever, sometimes with chills, a dry cough and fatigue.
- The one sign that really distinguishes the two infections is that many C19 victims suddenly lose their sense of smell — not because they have a stuffy nose, but because they don’t register even strong odors like onions or coffee. Not all virus victims get anosmia, the formal name for loss of smell, but one study found that 87 percent did.
- Less common symptoms include a sore throat, congestion, runny nose, vomiting, diarrhea, stomach pain and feeling somewhat out of breath when exerting yourself. Some victims have red or itchy eyes, and some get redness or blisters on their fingers or toes — so-called Covid toes, which resemble chilblains.
- More dangerous symptoms — which mean you should get immediate medical attention — include serious breathing difficulty; pain or pressure in the chest; blue lips or blue face; confusion or incoherent answers to simple questions; and collapsing or losing consciousness.
- Adding to the disease’s fearsome nature is that it can cause blood clots that lead to heart damage, brain damage and lung damage. And even some cases that appear mild or asymptomatic create signs of what doctors believe may be long-lasting heart damage.
- Another unusual aspect of Covid is that people sometimes develop pneumonia without realizing how sick they are. Doctors are unsure why; one theory is that the air sacs in the lungs are damaged in a way that does not cause the buildup of carbon dioxide, which creates that “desperate for air” feeling.
- Many doctors recommend buying a pulse oximeter, a fingertip device that measures oxygen levels in the blood. Multiple readings below 92 percent should trigger a call to a doctor. The earlier pneumonia is caught, the better the outcome.
- Understand that C19 symptoms in children are similar to those in adults.
- Children generally get through C19 with few problems; for the youngest ages, it is thought to be less dangerous than the flu.
- Children have the same constellation of symptoms that adults do, although parents may be more likely to notice it when their youngsters have runny noses, red eyes and the exhausted crankiness that comes from just feeling terrible.
- Dangerous symptoms include difficulty breathing, bluish lips, confusion or inability to wake up, and intense abdominal pains or inability to keep down any liquids. If there are any sign of these, it is important to get a child to a doctor or hospital quickly.
- In very rare cases, children can get multisystem inflammatory syndrome, which is thought to be caused by an overactive immune response and can cause shock and organ failure.
- But doctors emphasize that it is rare and that parents should realize it is highly unlikely their sick child has it.
- Expect potential difficulties with testing.
- For C19, symptoms can begin two to 14 days after exposure, but most begin five to seven days after it.
- However, as with diseases like measles, you can start spreading the virus two days before you begin to feel sick. So if you think you might have been exposed, it is very important to warn others and isolate yourself from them as soon as you can, especially if they are older or medically fragile.
- It is an axiom of general medicine that when one disease is sweeping through an area and a patient has its symptoms, it is usually safe to assume that’s what the patient has and begin treating it, rather than waiting for test results. So unless both the flu and the coronavirus begin circulating heavily at the same time in your city, do not be surprised if your doctor does not recommend a test.
- And getting tested for the coronavirus can be tricky, especially with so many test delays. The PCR type is more accurate than 15-minute “rapid antigen tests,” but it can take hours or even days to return results, depending on whether it has to be sent away to a central lab.
- One positive test probably means you are infected, but one negative test should not be trusted; too many things can go wrong. Two negative PCR tests taken at least 24 hours apart are a better indication of whether or not you are infection-free.
- If your insurance company will pay for only one test, you might consider paying for the second one yourself for the peace of mind.
L. Johns Hopkins COVID-19 Update
October 2, 2020
1. Cases & Trends
- The WHO C19 Dashboard reports 34.16 million cases and 1.02 million deaths as of 11:00am EDT on October 2.
- Early in the pandemic, there was concern that C19 could have devastating effects on countries in Africa, due to a variety of factors, including importation risk, inadequate public health and healthcare infrastructure, ongoing armed conflict and outbreaks of other diseases, food security challenges, and political and economic instability. When severe C19 epidemics did not emerge, there was concern that testing capacity and surveillance and reporting systems in Africa were not able to fully capture the scale of countries’ epidemics and that large-scale transmission was occurring undetected. However, over the past several months, most African countries have continued to report encouragingly low C19 incidence. Notably, Africa as a whole is reporting daily per capita C19 incidence similar to Oceania. To put that in the global context, the global per capita average is currently more than 6 times the incidence in Africa, and Europe, North America, and South America are reporting 14.5, 16.5, and 23 times the current rate in Africa, respectively.
- For much of the pandemic, Africa’s C19 incidence was largely driven by the epidemic in South Africa, which passed its first peak (more than 12,500 new cases per day) in mid-to-late June and steadily decreased since then. Currently, only 5 countries in Africa are reporting more than 500 new cases per day: Morocco, South Africa, Tunisia, Libya, and Ethiopia. These 5 countries represent more than 75% of Africa’s daily total. All other African countries are reporting fewer than 250 new cases per day. In terms of per capita incidence, Cape Verde/Cabo Verde** is reporting the highest daily total, with 157 daily cases per million population. This would rank #14 globally, and it is slightly higher than the US (#16; 129 per million population). No other African countries are reporting more than 100 daily cases per million population, and only 3 more are reporting more than 50: Libya, Tunisia, and Morocco. All remaining African countries are reporting per capita daily incidence below the global average (37.5 daily cases per million), and all but 8 are reporting fewer than 10 daily cases per million population. Other indicators not immediately available, including test positivity and excess mortality, may shed additional light on the pandemic’s effects.
- The US CDC reported 7.21 million total cases and 206,402 deaths. The US is averaging 42,446 new cases and 713 deaths per day. In total, 22 states (no change) are reporting more than 100,000 cases, including California with more than 800,000 cases; Texas with more than 700,000; Florida with more than 600,000; New York with more than 400,000; Georgia with more than 300,000; and Arizona, Illinois, New Jersey, and North Carolina with more than 200,000.
- Florida’s C19 website has reported more than 700,000 total cases since at least the beginning of this week, but it is not yet reflected in the US CDC data. Notably, Florida’s C19 dashboard reports both “total cases” and “positive residents.” The “positive residents” total just surpassed 700,000 cases, whereas the “total cases” is nearly 710,000—more than 10,000 more cases than are reported in the CDC data. It is unclear which data Florida is reporting to the CDC, but the CDC data appear to align more closely with Florida’s “positive residents” data.
- Minnesota’s COVID website is reporting more than 100,000 cases, and we expect that to be reflected soon in the CDC data. We also expect Illinois to surpass 300,000 cases; Tennessee to surpass 200,000 cases; and Mississippi to surpass 100,000 cases over the next several days.
- The Johns Hopkins CSSE dashboard reported 7.29 million US cases and 208,068 deaths as of 12:30pm EDT on September 28.
2. PRESIDENT TRUMP TESTS POSITIVE
- Late last night, US President Donald Trump announced that he and First Lady Melania Trump tested positive for SARS-CoV-2. The announcement follows a report that Hope Hicks, one of President Trump’s closest advisers, tested positive earlier this week; however, the exact timing of the infections and potential sources of transmission remain uncertain. According to a timeline published by the Associated Press, Ms. Hicks felt unwell on Wednesday while onboard Air Force One, and she then she later tested positive. President Trump and his staff are tested regularly. In recent days, President Trump has traveled to participate in the first presidential debate, campaign rallies, and fundraiser events.
- The Israeli Knesset, its national legislative body, passed several measures this week to combat the impacts of C19. Israeli legislators passed the Special Powers for Dealing with the Novel Coronavirus Bill, which authorizes the government to declare a “special state of emergency” during a period of “national lockdown” that can be renewed weekly for up to 21 days. Under the state of emergency, the government can impose additional restrictions to mitigate SARS-CoV-2 transmission risk. In particular, the measures prohibit individuals from traveling more than 1 kilometer from their homes. Exceptions include seeking medical care. The government can also place additional restrictions on large gatherings, including religious services and demonstrations, but the events are not banned entirely. Some members of the Knesset have expressed concern that the additional restrictions are unconstitutional, arguing that the lockdown is political in nature. The Knesset also approved an economic aid package to support businesses impacted by social distancing and other restrictions and maintain unemployment benefits for affected individuals. The bill will allow businesses to apply for grants if they “sustained a 25% drop in volume compared to the corresponding period last year.”
4. UNITED KINGDOM
- In recent weeks, the UK has reported a sharp increase in daily C19 incidence, and the UK government is implementing new restrictions to reduce inter-household interactions and reduce community transmission. The most recent restrictions will be implemented in the port city of Liverpool, as local case numbers continue to rise. The UK announced similar measures on September 28 for 7 areas in the northeastern part of the country. The announcement notes that 6 of the 7 areas are reporting more than 1,000 daily cases per million population. Schools and businesses designated as “COVID-safe” are not impacted by the new restrictions. The enhanced restrictions advise individuals to avoid contact with people outside of their household or “bubble” when indoors, including restaurants and pubs.
- A recent large-scale study found that the trajectory of the UK’s C19 epidemic is beginning to slow, providing evidence that the UK’s current approach is helping to reduce SARS-CoV-2 transmission. The study, conducted by researchers at Imperial College London, involved diagnostic testing for more than 84,000 individuals, and the researchers estimate that 0.55% of the entire population is actively infected with SARS-CoV-2, up from 0.13% in a previous study. Notably, however, the researchers estimate that transmission is slowing—with an estimated reproductive number of 1.1, compared to 1.7 in the previous study. The ongoing study aims to test 150,000 randomly selected individuals each month.
5. INDIA EPIDEMIOLOGY
- A study published in Science analyzed surveillance and contact tracing data from two South Indian states, Tamil Nadu and Andhra Pradesh, collected through August 1. This is one of the few studies that captures the epidemiology of C19 in low- or middle-income countries on a large scale. Together, these states account for approximately 10% (127.8 million) of India’s national population, and they contain the most robust healthcare workforces and public health infrastructure in the country. The study provides a detailed look at the timeline and growth of the C19 epidemics in these states, including incidence and mortality.
- The researchers found that the majority of cases (71%) did not result in secondary transmission to any of their contacts identified through contact tracing efforts. Based on data collected from more than 600,000 cases and contacts, the researchers estimate that 8% of the detected C19 cases accounted for 60% of the transmission, providing further evidence that super-spreading events play a major role in the C19 pandemic. The researchers also identified that transmission among individuals of approximately the same age was highest among children under 15 years old and adults 65 years and older. While the researchers were not able to determine the degree of transmission from children to adults, the study results support that pediatric cases do play a role in the ongoing pandemic. Overall, the case fatality ratio was 2.06%, and generally increased with age; however, unlike the US, mortality tended to plateau rather than increase in individuals 75 years and older. The reasons for this trend are uncertain. Additionally, the median hospital admission time before death was 6 days.
6. IMPACTS ON CHILDREN
- The far-reaching economic and societal impacts of the C19 pandemic have raised concerns in recent months about the rise of child labor in many countries. Due to a combination of interrupted schooling and household financial instability, children are going to work in grueling and dangerous jobs to support their families. While many schools have implemented some level of virtual learning, UNICEF has warned that approximately 463 million children cannot access remote learning due to a range of factors, lack of access to computers, reliable internet access, or other technology. Additionally, approximately 24 million children are projected to drop out of school entirely as a result of the pandemic. These challenges are affecting students in countries and communities at all income levels; however, low-income countries and communities living in poverty are the most severely impacted.
7. LONG COVID
- A commentary published in The BMJ: Opinion highlights the increasing importance of long-term effects of C19. The article, authored by researchers across several UK universities, makes the case for using the term “Long COVID” to describe this condition, which can persist in some C19 patients for weeks or months after recovery from the acute stage of the disease or infection. A number of terms have been used to address this condition—including “long haulers,” as we have covered previously. The authors argue that the term “Long COVID” is sufficiently non-specific to account for the many outstanding unknowns associated with the condition—including the timeline and duration, clinical presentation, severity, and cause—and it highlights morbidity as a major concern for C19 patients, as opposed to just mortality. As the authors note, clinicians, researchers, and policymakers need to acknowledge “Long COVID” as a condition, and further study is necessary to better characterize the longer-term effects of C19, which will enhance our understanding of the full impact of the ongoing pandemic.
8. GLOBAL RAPID TESTING
- The WHO announced a plan to increase testing capacity across low- and middle-income countries. The plan will distribute 120 million SARS-CoV-2 tests to 133 countries. The low-cost rapid tests, which can provide results in as little as 15-30 minutes and do not require advanced laboratory equipment to process, have garnered considerable attention in recent weeks as they are implemented in a variety of settings. These tests aim to provide critical testing capacity for low- and middle-income countries, particularly in areas without the necessary equipment or trained personnel to perform more traditional diagnostic tests. Initial funding for the program to support the scale-up of production capacity was provided by the Bill and Melinda Gates Foundation, and WHO Director-General Dr. Tedros Adhanom Ghebreyesus called on countries to provide the funding necessary to purchase the tests. The tests are scheduled to be provided over the next 6 months.
9. SOCIAL & PHYSICAL DISTANCING
- A study published in The Lancet explores lessons identified as countries began to ease social distancing measures implemented in response to C19. The researchers evaluated efforts to scale back social distancing measures in 9 high-income countries—5 in the Asia Pacific region, and 4 in Europe. They documented and categorized the approaches used in each country’s recovery plan, including key metrics used in determining when to proceed to the next step. The authors conclude that effective transition from C19 restrictions did not rush to return to pre-pandemic practices, but rather, worked to establish a “new normal.” Effective policies incorporated the principle of physical distancing into recovery phases and supported individuals and businesses in effectively modifying behaviors to reduce risk while resuming some level of normal activity. Additionally, countries must be able to recognize when it is necessary to increase restrictions in response to unacceptable levels of community transmission.
- As countries continue to ease social distancing restrictions and increase social and economic activity, the age distribution of C19 cases is shifting toward younger portions of the population. This shift has led a number of experts, elected officials, and pundits to blame associated resurgences in community transmission on younger individuals. Younger individuals are perceived to be responsible due to increased activity at restaurants and cafes, pubs and bars, parties, and other social gatherings as well as a perceived aversion to maintaining appropriate physical distancing. Recent survey data published by the Life with Corona network suggests that young adults are undertaking recommended protective actions to mitigate transmission risk. While the researchers identified an association between increased age and increased participation in protective measures, the actual difference in the degree of participation between age groups was small.