Coronavirus Weekend Update 4-26

Note: This Special Edition is a limited update that includes stories of interest from last week that were not included an update during the week.

Today’s Features

Additional Symptoms Identified by CDC
New Concerns
Long-Term Effects of Coronavirus
Potential Treatments
Updates
Cytokine Storms
The Road Back?
How is the Coronavirus Transmitted?

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Available Resource: Having put together almost 60 daily updates, our team has compiled and distributed a tremendous amount of information about the coronavirus and COVID-19 and we are happy to share what we know. So, if you have any questions regarding the virus or disease, please feel free to contact either pwduval@gmail.com or brian.sivy@gmail.com. We’d be happy to respond by email or arrange a call with you or anyone you know as soon as we can.

A. Additional Symptoms Identified by CDC

1. CDC Triples Number of Coronavirus Symptoms

The Centers for Disease Control and Prevention has added six new symptoms for the novel strain of coronavirus (COVID-19)
The symptoms that had been listed by the CDC are:
- fever
- cough
- shortness of breath
Now, the CDC has tripled that number, saying people “have had a wide range of symptoms reported.”
The new symptoms for the disease are:
- chills
- repeated shaking with chills
- muscle pain
- headache
- sore throat
- new loss of taste or smell
Some patients have also reported other symptoms, including a runny nose, red eyes, skin rash, diarrhea and fatigue.
The CDC said those who have “trouble breathing, persistent pain or pressure in their chest, new confusion or inability to arouse or have bluish lips or face” should seek immediate medical attention.
You can view all of the symptoms of COVID-19 at: Symptoms of Coronavirus

Source: COVID-19: CDC Triples Number Of Novel Coronavirus Symptoms

B. New Concerns

1. WHO Warns You May Catch Coronavirus More Than Once

Catching Covid-19 once may not protect you from getting it again, according to the World Health Organization, a finding that could jeopardize efforts to allow people to return to work after recovering from the virus.
“There is currently no evidence that people who have recovered from Covid-19 and have antibodies are protected from a second infection,” the United Nations agency said in an April 24 statement.
The WHO guidance came after some governments suggested that people who have antibodies to the coronavirus could be issued an “immunity passport” or “risk-free certificate” that would allow them to travel or return to work, based on the assumption that they were safe from re-infection, according to the statement. People issued such a certificate could ignore public-health guidance, increasing the risk of the disease spreading further.
Chile was the first country to announce plans to issue immunity cards based partly on antibody tests. This has raised concerns because the tests have proven unreliable elsewhere, and some people may get deliberately ill in order to obtain the card. The U.S. and others have nonetheless said they’re looking into the option.
While there’s a consensus that the key to ending the coronavirus pandemic is establishing co-called herd immunity, there are many unknowns. One is whether researchers can develop a safe and effective vaccine. Another is how long people who’ve recovered have immunity; reinfection after months or years is common with other human coronaviruses. Finally, it’s not clear what percentage of people must be immune to protect the “herd.” That depends on the contagiousness of the virus.
The WHO said it’s reviewing the scientific evidence on antibody responses to coronavirus, but as yet no study has evaluated whether the presence of antibodies “confers immunity to subsequent infection by this virus in humans.” And while many countries are currently testing for antibodies, these studies aren’t designed to determine whether people recovered from the disease acquire immunity, the agency said.

Source: Can You Catch Covid-19, Coronavirus Twice?: WHO Says Yes

2. Scientists probing whether blood-pressure drugs accelerate coronavirus

Scientists are urgently investigating whether life-saving blood-pressure drugs may be a crucial factor behind many of those who die from the coronavirus.
A disproportionate number of patients hospitalized during the pandemic are known to have high blood pressure, and the main drugs for the condition — known as ACE inhibitors and ARBs — affect the same pathways that the bug takes to enter the lungs and heart.
America’s top infectious disease expert, Dr. Anthony Fauci, is among those who have called for urgent research into whether the drugs could be acting as an accelerant for COVID-19.
“There are millions of Americans that take an ACE inhibitor or AR daily,” said Dr. Caleb Alexander, co-director of the Johns Hopkins Center for Drug Safety and Effectiveness in Baltimore.
“This is one of the most important clinical questions,” he said, saying there are “dozens of scientific teams working feverishly to put this question to bed.”
Fauci also recently said that “we really need to get data and we need to get data fast.”
“What is possible is that people who are on ACE inhibitor … may be, without knowing it, increasing the expression of receptors for the virus, itself,” he told the Journal of the American Medical Association.
Fauci said a “red flag” was news that 75% of the pandemic deaths in Italy were people with hypertension — a developed country where he assumes they must have been treated for the condition.
“Why should someone who has hypertension that’s well controlled have a much greater chance of dying than somebody else with any other kind of underlying condition?” he asked.
An estimated 100 million Americans suffer from high blood pressure, with about four-fifths needing prescription drugs to control it. The drugs include Vasotec, Valsartan, Irbesartan, as well as their generic versions.
Researchers generally agree that it is too risky for people with severe hypertension or heart failure to stop taking the drugs. Many are divided, however, when it comes to helping those with milder cases.
Health Watch USA recommends that doctors temporarily avoid putting new patients on the drugs and warn those currently on them to take extreme precautions to avoid virus exposure.
However, Dr. Scott David Solomon, director of noninvasive cardiology at Brigham and Women’s Hospital in Boston, is one of many who suggest it is too early to reach potentially dangerous decisions.
“Not only is there no compelling evidence that we should be discontinuing those medications, but there’s reason to think that doing so might actually cause harm,” Solomon said.
Novartis International AG and Sanofi SA are among the major drugmakers selling ACE inhibitors and ARBs.
Sanofi spokesman Nicolas Kressmann said patients should consult their doctors on whether to continue taking the drugs but that the company has found insufficient evidence that they worsen COVID-19 through its own assessment of available scientific data.
Novartis has not issued any guidance to clinicians or patients and defers to scientists studying the issue, said spokesman Eric Althoff.

[Note: While the effect of blood pressure medicine on the virus is being studied, it is important to note that there is no proven link between blood pressure medicines and the virus (good or bad) and, therefore, no one should discontinue their blood pressure medicine in connection with the virus unless recommended by a physician.]

Source: Scientists probe whether ACE inhibitors, ARBs accelerate COVID-19

3. Doctors warn coronavirus might cause sudden strokes in young adults

New York doctors are warning that the coronavirus may cause sudden strokes in adults in their 30s and 40s who are not severely sick.
The doctors at Mount Sinai Health System believe there is growing evidence that COVID-19 can cause the blood to clot in unusual ways, resulting in an uptick in strokes among patients who don’t typically suffer from them.
“The virus seems to be causing increased clotting in the large arteries, leading to severe stroke,” neurosurgeon Dr. Thomas Oxley told CNN.
Oxley and his colleagues said they typically record fewer than two strokes per month in people under the age of 50, but in a two-week period during the pandemic, they treated five. Their findings are to be published in a letter in the New England Journal of Medicine.
“Our report shows a seven-fold increase in incidence of sudden stroke in young patients during the past two weeks. Most of these patients have no past medical history and were at home with either mild symptoms (or in two cases, no symptoms) of Covid.”
“All tested positive. Two of them delayed calling an ambulance,” he went on.
The report could be particularly troubling in New York, where officials have advised against calling 911 unless they come down with severe symptoms, like difficulty breathing, in order to not further overwhelm already inundated EMS.
Some, meanwhile, have been reluctant to visit a hospital for fear they might catch the virus there.
Oxley said his team urged people to watch themselves for symptoms of coronavirus and to call 911 if they believe they’ve suffered a stroke.
He referred to the mnemonic device to remember warning signs for strokes, FAST: F for face drooping; A for arm weakness; S for speech difficulty, and T for time to call 911.

Source: Doctors warn coronavirus might cause sudden strokes in young adults

4. Are Antibody Tests Reliable?

Antibody tests are crucial to reopening the economy, but public health experts have raised urgent concerns about their quality. New research, completed just days ago and posted online Friday, confirmed some of those fears: Of the 14 tests currently on the market, only three delivered consistently reliable results. Even the best had some flaws.
The research has not been peer-reviewed and is subject to revision. But the results are raising difficult questions about the course of the epidemic that could greatly complicate plans to reopen the economy.
Already Americans are scrambling to take antibody tests to see if they might escape lockdowns. Public health experts are wondering if those with positive results might be allowed to return to work. But these tactics mean nothing if the test results can’t be trusted.
In the new research, researchers found that only one of the tests never delivered a so-called false positive — that is, it never mistakenly signaled antibodies in people who did not have them. Two other tests did not deliver false-positive results 99 percent of the time.
But the converse was not true. Even these three tests detected antibodies in infected people only 90 percent of the time, at best. (In other words, the 3 best tests had at least a 10% false negative rate.)
The false-positive metric is particularly important. The result may lead people to believe themselves immune to the virus when they are not, and to put themselves in danger by abandoning social distancing and other protective measures. It is also the result on which scientists are most divided.
“There are multiple tests that look reasonable and promising,” said Dr. Alexander Marson, an immunologist at the University of California, San Francisco, and one of the project’s leaders. “That’s some reason for optimism.”
Other scientists were less sanguine than Dr. Marson. Four of the tests produced false-positive rates ranging from 11 percent to 16 percent; many of the rest hovered around 5 percent.
The proportion of people in the United States who have been exposed to the coronavirus is likely to be 5 percent or less, Dr. Hensley said. “If your kit has a 3 percent false-positive, how do you interpret that? It’s basically impossible,” he said. “If your kit has 14 percent false positive, it’s useless.”
In all, the investigators analyzed 10 rapid tests that deliver a yes-no signal for antibodies, and two tests using a lab technique known as Elisa that indicate the amount of antibodies present and are generally considered to be more reliable.
Tests made by Sure Biotech and Wondfo Biotech, along with an in-house Elisa test, produced the fewest false positives.
A test made by Bioperfectus detected antibodies in 100 percent of the infected samples, but only after three weeks of infection. None of the tests did better than 80 percent until that time period, which was longer than expected, Dr. Hsu said.
The lesson is that the tests are less likely to produce false negatives the longer ago the initial infection occurred, he said.
The tests were particularly variable when looking for a transient antibody that comes up soon after infection, called IgM, and more consistent in identifying a subsequent antibody, called IgG, that may signal longer-term immunity.
“You can see that antibody levels rise at different points for every patient,” Dr. Hsu said. The tests performed best when the researchers assessed both types of antibodies together. None of the tests could say whether the presence of these antibodies means a person is protected from reinfection, however.
The results overall are promising, Dr. Marson added. “There are multiple tests that have specificities greater than 95 percent.”
Rapid antibody tests are generally used to get a simple yes-no result, but the team assigned the positive results — which appear as bands on a test strip — a score from zero to six. They trained readers to interpret those results, and found their decisions often agreed and were supported by the more quantitative Elisa tests.
“If you train the readers well, they can start to be reliable,” Dr. Marson said of rapid tests. “That is critical to understand if these tests could ever be deployed.”
The team at Mass General set a higher bar for specificity; they considered a score of one for the intensity of a band to be a negative result, rather than a score of zero.
Perhaps because they eliminated the fainter bands — the ones most likely to be erroneous — their estimate of specificity for BioMedomics, the one test that was evaluated by both teams, was more than 99 percent, compared with the San Francisco team’s estimate of 87 percent.
Other experts were skeptical of the scoring approach, however. “That’s not really a method that would give you a real quantitation,” said Florian Krammer of the Icahn School of Medicine at Mount Sinai in New York.
Dr. Krammer has developed a two-step Elisa test that he said has 100 percent specificity and delivers a measure of the quantity of IgM and IgG antibodies a person has. Scoring a rapid test’s bands might offer some data for a scientific study, he said, “but I would not make any decisions based on that.”
Dr. Krammer said false positives are less of an issue for assessing how widely the virus has spread in the population. If a test has a known false-positive rate, scientists can factor that into their calculations, he said.
But false positives become dangerous when making policy and personal decisions about who can go back to work.
Scanwell Health, a Los Angeles-based start-up, has ordered millions of test kits from Innovita, a Chinese manufacturer, and has applied to the Food and Drug Administration to market the tests for at-home use.
In the new study, the Innovita test detected antibodies in 83 percent of infected people and yielded a false-positive rate of 4 percent.
Dr. Jack Jeng, chief medical officer of Scanwell Health, said the study looked at an earlier version of Innovita’s test and not the “newer, improved version” his company had ordered. “It will be interesting to see how it performs,” he said.
Dr. Marson and his colleagues have acquired tests from nearly 100 manufacturers, and plan to continue comparing them. The scientists also hope to expand their sample set to include people who were mildly ill or did not feel ill at all, and to stratify their data by age and the presence of chronic conditions.
“This is just the beginning,” Dr. Marson said. “Our goal would be to keep going till we feel there’s adequate supply in the market.”

Source: Coronavirus Antibody Tests: Can You Trust the Results?

C. Potential Long-Term Effects of Coronavirus

1. Coronavirus Ravages the Lungs. It Also Affects the Brain

As the number of confirmed Covid-19 cases worldwide reaches 2 million, clinicians are realizing the disease doesn’t just ravage the lungs and hurt the heart. Covid-29 also can, in a significant proportion of cases, affect the nervous system in myriad little-understood ways.
Through a growing number of papers, doctors around the globe are chronicling Covid-19’s lesser-known neurological manifestations including brain inflammation, hallucinations, seizures, cognitive deficits and loss of smell and taste. It is unknown whether these are caused directly by the virus infiltrating the nervous system, or by the body’s immune response to infection.
The hope is these reports could speed up diagnosis. Some patients say they were going out in public, potentially exposing others, due to lack of awareness of these symptoms. The reports could also open avenues of research that elucidate whether the virus gets into the brain, how long neurological symptoms might persist, and whether a full recovery can be expected.
The range of effects could take decades to play out. Some epidemiological studies and lab experiments with other viruses suggest severe infections could set in motion molecular events that might increase the risk of developing neurodegenerative disorders, like Alzheimer’s or Parkinson’s, many years later. The links are a matter of debate among neurologists and neuroscientists.
Last Friday, Chinese doctors published a study of 214 hospitalized patients in Wuhan showing that more than a third had neurologic symptoms. The most common included dizziness, headaches, impaired consciousness, skeletal-muscle injury and loss of smell and taste. The paper— published in the Journal of the American Medical Association and the largest to date on the disease’s impact on normal nervoussystem function—also documented rare, but more serious, effects including seizures and stroke, which occurs when a blood clot hits the brain.
“When this virus first came out, the general feeling was that there wasn’t much in the way of neurological manifestations. This was a pulmonary process,” said S. Andrew Josephson, chair of neurology at the University of California, San Francisco. “This article should open up everyone’s eyes that this disorder affects the brain as well.”
Some neurologists hypothesize, based on results from animal studies, that the sometimes fatal breathing problems seen in severe Covid-19 cases might be in part due to direct infection and subsequent malfunction of the brainstem, which is involved in coordinating breathing.
Symptoms like confusion, trouble speaking or numbness on one side of the body should also be red flags. Those symptoms can signal an impending stroke, which, if not treated within a certain time window, can lead to permanent brain damage, they said. Covid-19 patients are at higher risk of stroke due to the virus’s impact on blood clotting.
Northwell Health, a health-care system in New York, plans to soon start using portable MRIs to monitor the brains of very sick patients, some of whom are sedated and on ventilators, according to Richard Temes, Northwell’s director of neurocritical care.
The hospital system is also using another type of brain-monitoring test, known as an electroencephalogram, to ensure patients aren’t having silent seizures, he said. Catching problems early increases the chances that patients’ brains can fully recover.

Source: Coronavirus Ravages the Lungs. It Also Affects the Brain.

2. Coronavirus may cause lasting damage throughout body

For the sickest patients, infection with the new coronavirus is proving to be a full-body assault, causing damage well beyond the lungs. And even after patients who become severely ill have recovered and cleared the virus, physicians have begun seeing evidence of the infection’s lingering effects.
In a study posted this week, scientists in China examined the blood test results of 34 COVID-19 patients over the course of their hospitalization. In those who survived mild and severe disease alike, the researchers found that many of the biological measures had “failed to return to normal.”
Chief among the worrisome test results were readings that suggested these apparently recovered patients continued to have impaired liver function. That was the case even after two tests for the live virus had come back negative and the patients were cleared to be discharged.
At the same time, as cardiologists are contending with the immediate effects of COVID-19 on the heart, they’re asking how much of the damage could be long-lasting. In an early study of COVID-19 patients in China, heart failure was seen in nearly 12% of those who survived, including in some who had shown no signs of respiratory distress.
When lungs do a poor job of delivering oxygen to the body, the heart can come under severe stress and may emerge weaker. That’s concerning enough in an illness that typically causes breathing problems. But when even those without respiratory distress sustain injury to the heart, doctors have to wonder whether they have underestimated COVID-19’s ability to wreak lasting havoc.
“COVID-19 is not just a respiratory disorder,” said Dr. Harlan Krumholtz, a cardiologist at Yale University. “It can affect the heart, the liver, the kidneys, the brain, the endocrine system and the blood system.”
There are no long-term survivors of this wholly new disease. Even its first victims in China are little more than three months removed from their ordeal. And physicians have been too busy treating the acutely ill to closely monitor the progress of the people worldwide known to have recovered from COVID-19.
Still, doctors are worried that in its wake, some organs whose function has been knocked off kilter will not recover quickly, or completely. That could leave patients more vulnerable for months or years to come.
“I think there will be long-term sequelae,” said Yale cardiologist Dr. Joseph Brennan, using the medical term for a disease’s downstream effects.
“I don’t know that for real,” he cautioned. “But this disease is so overwhelming” that some of the recovered are likely to face ongoing health concerns, he said.
Another question that could take years to answer is whether the SARS-CoV-2 virus that causes COVID-19 may lie dormant in the body for years and spring back later in different form.
It wouldn’t be the first virus to behave that way. After a chicken pox infection, for instance, the herpes virus that causes the illness hides quietly for decades and often emerges as the painful affliction shingles. The virus that causes hepatitis B can sow the seeds of liver cancer years later. And in the months after the West African Ebola epidemic subsided in 2016, the virus responsible for that illness was found to have taken up residence in the vitreous fluid of some of its victims’ eyes, causing blindness or vision impairment in 40% of those affected.
GIVEN SARS-CoV-2’s affinity for lung tissue, doctors quickly suspected that some recovered COVID-19 patients would sustain lasting damage to their lungs. In infections involving the coronavirus that cause severe acute respiratory syndrome, or SARS, about one-third of recovered patients had lung impairment after three years, but those symptoms had largely cleared 15 years later. And researchers found that one-third of patients who suffered Middle East respiratory syndrome, or MERS, had scarring of the lungs – fibrosis – that was probably permanent.
In a mid-March review of a dozen COVID-19 patients discharged from a hospital in Hong Kong, two or three were described as having difficulty with activities they had done in the past.
Dr. Owen Tsang Tak-yin, director of infectious diseases at Princess Margaret Hospital in Hong Kong, told reporters that some patients “might have around a drop of 20% to 30% in lung function” after their recovery.
Citing the history of lasting lung damage in SARS and MERS patients, a team led by University of California, Los Angeles radiologist Melina Hosseiny is recommending that patients who have recovered from COVID-19 get follow-up lung scans “to evaluate long-term or permanent lung damage including fibrosis.”
As doctors try to assess organ damage after COVID-19 recovery, there’s a key complication: Patients with disorders that affect the heart, liver, blood and lungs face a higher risk of becoming very sick with COVID-19 in the first place. That makes it difficult to distinguish COVID-19 after-effects from the problems that made patients vulnerable to begin with – especially so early in the game.
Right now, “we’re all in the middle of it,” said Dr. Kim Williams, a cardiovascular disease specialist at Rush University Medical Center in Chicago. “We have much more information about what happens acutely, and we’re trying to manage that.”
What they do know is that when COVID-19 patients show symptoms of infection, the function of many organs is knocked off course. And when one organ begins to fail, others often follow.
Add to that chaos the force of inflammation, which flares in those with severe COVID-19. The result can do damage throughout the body, prying plaques and clots from the walls of blood vessels and causing strokes, heart attacks and venous embolisms.
Krumholtz, who organized a meeting of cardiologists to discuss COVID-19 this week, said the infection can cause damage to the heart and the sac that encases it. Some patients develop heart failure and/or arrhythmias during the disease’s acute phase.
Heart failure weakens the organ, though it can regain much of its strength with medications and lifestyle changes. Still, former COVID-19 patients can become lifelong cardiology patients.
Muddying this picture is another potential after-effect: blood abnormalities that make clots of all sorts more likely to form.
In a case report published this week in the New England Journal of Medicine, Chinese doctors described a patient with severe COVID-19, clots evident in several parts of his body, and immune proteins called antiphospholipid antibodies.
A hallmark of an autoimmune disease called antiphospholipid syndrome, these antibodies sometimes occur as a passing response to an infection. But sometimes they linger, causing dangerous blood clots in the legs, kidneys, lungs and brain. In pregnant women, antiphospholipid syndrome also can result in miscarriage and stillbirth.
Brennan said that in a new disease like COVID-19, the signposts that usually guide physicians in assessing a patient’s long-term prognosis are just not there yet. “Coagulopathy,” for instance, “usually rights itself,” he said. “But this isn’t usual.”

Source: Coronavirus may cause lasting damage throughout body, doctors fear

3. Coronavirus crisis: What are the potential long-term health impacts?

When one is struck by the coronavirus, symptoms can range from none to fatal. But for the many million in between who are infected by the novel pathogen and then recover, just how damaging are the lingering effects?
Medical researchers are on the quest to find out.
“Anytime you get really sick, it is possible that it affects your different organ systems, leaving varying degrees of compromise, or you may have none at all,” Dr. Eric Carter, physician and co-CEO of medical app DocClocker, told Fox News. “We still don’t fully understand the immune response and if recovery and immunity development offer any level of protection against reinfection and disease severity.”
Thus, while the prognostic symptoms of coronavirus, formally called COVID-19, have been well-documented – ranging from fevers and a loss of taste to breathing problems and pneumonia – scientists are trying to piece together what may happen to those who contract the illness and recover.
Studies to date have shown that the vast majority of those who are infected are on the mild scale and should recover with no lasting effects. But for more serious cases, especially those who require a ventilator and/or ICU treatment which is around 20 percent of those hospitalized, the possibility of lasting lung damage or severe respiratory affliction is a very real threat.
“For more than 80 percent of patients infected with the coronavirus, recovery is likely to be complete. However according to a recent study from Hong Kong, about 20-30 percent of hospitalized patients will have decreased lung capacity due to pneumonia and inflammation caused by the disease or by the ventilator treatment itself,” explained Dr. Steven Berk, executive vice president and dean of Texas Tech Health Sciences Center School of Medicine.
He also noted that patients who develop acute respiratory distress syndrome and require long-term mechanical ventilation, sometimes a week or more, are most likely to have persistent shortness of breath, and evidence of scarring or pulmonary fibrosis.
A report published earlier this month in the medical publication journal Cellular & Molecular Immunology from researchers at Fudan University in Shanghai and the New York Blood Center noted that when researchers instituted contact between coronavirus and lab-grown T lymphocytes – referred to as T cells – the virus paralyzed these critical cells, which help identify and expel pathogens in the body. The researchers also found that SARS, a related coronavirus, could not infect T cells.
Disturbingly, the study also indicated that damage to the T lymphocytes paralleled that caused by HIV.
Moreover, preliminary studies out of China have also underscored that around 12 percent of survivors of severe cases endured protracted heart issues, and some showed signs of impaired liver function.
Given that the virus itself is only a few months old, having originated out of China at some point late last year, experts have only small-scale, immediate term studies to go on, and are mainly looking at data from related viruses SARS and MERS to gauge a more in-depth understanding.
“Those with SARS pneumonia had shortness of breath and evidence of pulmonary fibrosis one month after infection. Most patients improved over time,” Berk continued. “Patients with SARS continued to excrete the virus, sometimes for more than 20 days. Those who had developed acute respiratory distress syndrome (ARDS) remained short of breath for months or for a lifetime.”
Texas and Arizona-based hormone specialist Dr. Elizabeth Lee Vliet also pointed out that, in examining the long-term adverse effects of a variety of viral illnesses, problems include lungs illnesses, as well as issues with neurological systems showing cognitive and nerve dysfunction, heart damage – viral cardiomyopathy that can lead to congestive heart failure – as well as kidney impairment that in astringent cases can lead to progressive kidney failure.
“We have known that severe viral illnesses can lead to severe fatigue that can become debilitating,” she said. “Those are the major organ systems we already know can be damaged by severe viral illnesses with known viruses, so I plan to be monitoring my patients for the emergence of such problems as we go forward.”
From Vliet’s purview, long-term consequences will more commonly be seen in older patients who have pre-existing conditions such as heart disease, kidney disease and pulmonary fibrosis.
And for those just weeks or months in recovery with now negative test results, it is not only the enduring physical ramifications – such as reported breathlessness, lung pain, or fatigue – that plague, but the psychological distress, isolation and fear of a relapse that medical professionals are monitoring.
“From the original SARS outbreak in 2003, we see that psychiatric illness is the most notable long-term outcome,” said Dr. Melissa Nolan, an infectious disease expert, and professor at the University of South Carolina. “Including post-traumatic stress disorder and depression.”
Berk concurred that “anxiety, depression, and muscle weakness were also common.”
But if the novel pathogen has proven anything to date, it is that uncertainty and outliers are its hallmarks.
“It will also be very important to determine the level of antibody developed to coronavirus, as investigators also determine the level of antibody that guarantees protection against a second infection,” Berk added.

Source: Coronavirus crisis: What are the potential long-term health impacts?

D. Potential Treatments

1. Possible coronavirus vaccine enters human testing trial at ‘unprecedented speed’

Progress is being made toward a viable vaccine for the coronavirus, say researchers at a Philadelphia-based pharmaceutical company.
Inovio Pharmaceuticals, along with the University of Pennsylvania’s research facility and the Wistar Institute, had been working on the vaccine as early as this past January. The vaccine was fast-tracked into development after the Chinese government made the genome sequencing of COVID-19 public.
Nearly three months later, a crucial first phase of testing has begun. Researchers with Inovio say they were able to design their vaccine in just three hours after receiving a sequence for the virus.
“We immediately started testing the vaccine in the laboratory. And we’re quite confident about the results that we’ve seen,” Dr. Kate Broderick, senior vice president, R&D at Inovio Pharmaceuticals, adds that trials on human subjects began just last week. “We treated three people last week. But getting our vaccine into human beings is a huge step. But we did that in 83 days, which certainly in my career is absolutely an unprecedented level of speed.”
While testing has begun, Broderick says there are still too many unknown variables associated with the virus and how it may affect the vaccine.
“In some patients, it looks like people who had the disease but now recovered have kind of these sort of low antibody levels, but we don’t know if that’s a consistent result across everybody that’s contracted the virus so far,” she says. “So, we need to learn more about how the virus affects people and how people are affected by that infection before we can see too much about how that impacts vaccine design.”
“What we don’t know is that they contract the virus for a second time, which obviously would be very unlucky, but possible. Or is it just that they haven’t fully recovered the first time around? So that’s really what we’re learning as we speak and as we move forward. And that’s what kind of makes treating this virus very difficult because there’s still so much we don’t understand about it.”
Approximately 40 people will be tested during the initial phase at locations in Kansas City and the University of Pennsylvania. Final results from the tests are expected by the summer.
“Phase one is supposed to be normal, healthy people. And in this case, they have not, as far as we know, they have not been infected with COVID-19,” Dr. David Weiner, of the Wistar Institute, and one of the lead researchers working on the coronavirus vaccine, told Fox News. “The first study is really just safety and tolerability in relatively low-risk people just to make sure the vaccine by itself, how well it’s tolerated by people. You’re watching that very closely, so you can figure how many people you can give it to and whether there’s going to be issues.”
This part of the study would be followed by phase two, in which the at-risk population is tested.
“Phase two is really where you start to test out larger numbers and efficacy. And Inovio has already produced enough dosing for that several thousand doses in there because that process is so robust to get through that study as well. So, that’s clearly on their radar.”
Inovio recently received a $9 million grant from the Coalition for Epidemic Preparedness Innovations for the express purpose of speeding up the process of getting a vaccine to market. The process is tedious as researchers often have to start from scratch when there’s a new outbreak. But the pharmaceutical company, along with Weiner’s team, has been using proprietary tech from past vaccination developments in which they used digital mapping of DNA sequences. Back in 2016, Inovio was able to get a Zika virus vaccine to market in seven months.
However, getting a corona vaccine to market may take longer.
Scientists in Weiner’s lab were testing synthetic DNA technology to fine-tune synthetic vaccine candidates, prior to the COVID-19 pandemic.
“When it goes to expanded efficacy studies, which are called phase three, normally take a very, very long time,” Weiner says. “That’s why with vaccine development, all the proceeds normally take years to decades.”
“So to get to a licensed vaccine, a vaccine that would be available like that, we’re talking about a year and a half to two years. Well, that would be all the way through.”
The doctor points out, however, that doesn’t necessarily mean we won’t see the vaccine being used much sooner. Wiener references the response to the Ebola outbreak.
“Ebola in West Africa was basically tested through phase one,” he says. “They did a very, very exceptionally clever trial design and were able to get to advocacy in a relatively small number of people in very quick time to get through their phase two. And it surprised everybody, quite honestly, in a positive way, how fast they’re able to do that. It took certainly less than a year.”
Weiner says he believes that high-risk areas of the outbreak could see the vaccine much sooner and, if needed, an emergency use authorization could be enacted.
“An emergency use authorization is not usually used, and that is where you get through early studies and show it’s safe and you’re given permission to start distributing it more widely,” he says. “And there has been a lot of discussion from that from a group in Oxford, which is going to start their vaccine trial sometime in the summer. That has the positive in the sense that if the vaccine is safe, you’re sort of using it already on lots of people.
“And that’s really completely up to the authorities to decide those kinds of things. And I’m sure there’d be a lot of discussions. So that’s something you’re likely to hear about a lot. The idea of emergency authorization.”

Source: Coronavirus vaccine enters human testing trial

2. Portable ‘cold plasma’ wand prototype could destroy germs in seconds

A team of engineering professors from the University of Michigan have created a plasma jet wand that they believe could quickly and easily disinfect hospital rooms. The ion-emitting device looks something like a Ghostbusters’ proton packs, and its plasma beam can destroy bacteria and viruses in just seconds.
The device produces plasma by running a gas, like air, through a high electric field, which rips electrons off of atoms to tear molecules apart. That creates what the University of Michigan team describes as a soup of charged atoms and molecule fragments. The oxygen-based ions in the plasma then destroy bacteria and viruses by pulling carbon out of their cell walls or protein casings.
Because the wand can sanitize both hard and soft surfaces, it could be a game changer for hospitals and healthcare facilities. While it’s safe to clean most solid surfaces (including your iPhone) with disinfectant wipes, sanitizing fabric and other soft materials isn’t as straightforward. In hospitals, those usually get locked in specialized cabinets that pump in poisonous gases, like hydrogen peroxide. Instead, this handheld device could, for instance, shine over floors and chair cushions, quickly disinfecting both.
The project has already received a rapid response grant from the National Science Foundation. The professors — John Foster, Mirko Gamba and Mark Kushner — hope to use that funding to test and build a portable prototype. They believe that by adding chemicals to the gas used, they might be able to target particular viruses or bacteria.
Unfortunately, the product probably won’t be ready for at least a year. The goal is to deploy it toward the end of the current coronavirus pandemic or to have it ready for future epidemics. When it’s ready, it might also find a use outside of hospitals, like in air planes or buses.

Source: Portable ‘cold plasma’ wand prototype could destroy germs in seconds

3. Doctors experiment with unproven stem cell therapy on COVID-19 patients

Doctors are hoping stem cell therapy could be a weapon in the fight against coronavirus. On Friday, regenerative medicine company Mesoblast announced a 300-person trial to determine whether stem cell treatments will work in COVID-19 patients suffering from severe lung inflammation.
One hospital in New York tried it as an experiment with 12 patients, 10 of whom were able to come off of ventilators.
“What we saw in the very first patient was that within four hours of getting the cells, a lot of her parameters started to get better,” Dr. Karen Osman, who led the team at Mount Sinai, told CBS News’ Adriana Diaz.
The doctor said she was encouraged by the results, though she was hesitant to link the stem cell procedure to her patients’ recovery.
“We don’t know” if the 10 people removed from ventilators would not have gotten had they not gotten the stem cells, she said. “And we would never dare to claim that it was related to the cells.”
She explained that only a “randomized controlled trial” would be the only way “to make a true comparison.”
Luis Naranjo, a 60-year-old COVID-19 survivor, was one of Mount Sinai’s stem cell trial success stories. He told Diaz in Spanish that he was feeling “much better.”
Naranjo’s daughter, Paola, brought him to the emergency room, fearful she would not see her father again. Like so many families struck by the coronavirus, she was not allowed inside with him.
“I forgot to tell him that I love him,” she said. “All I said was go inside, I hope you feel better.”
During his hospital stay, Naranjo was unconscious and on a ventilator for 14 days.
Doctors proposed giving him stem cells from bone marrow in hopes it would suppress the severe lung inflammation caused by the virus.
Now, Naranjo credits the doctors who treated him for his survival. Though income from his family’s jewelry business has been cut off and they found themselves falling behind on rent, Naranjo said he is focused primarily on his recovery and regaining the 25 pounds he lost at the hospital.
Although stem cell treatment, usually reserved for other diseases like rheumatoid arthritis, might end up being another step toward helping coronavirus patients recover, Dr. Osman was quick to say it would not be a “miracle treatment.”
“The miracle treatment will be a vaccine,” she said.

Source: Doctors experiment with unproven stem cell therapy on COVID-19 patients

4. ‘Science will come through’: Doctor who pioneered HIV treatment discusses potential Covid-19 drugs

Dr. David Ho has more experience than most with viruses.
As director of the Aaron Diamond AIDS Research Center in New York City in the early 1990s, Ho’s lab pioneered treatment approaches to HIV and he was TIME’s Man of the Year for that work in 1996. He still leads the center.
Now, his focus is Covid-19, or more specifically, SARS-CoV-2, the virus that causes Covid-19.
He and a team of about 15 people are working on two different approaches to stopping the virus: isolating antibodies from people who’ve recovered from Covid-19, and developing new drugs called protease inhibitors that interfere with the virus’s ability to replicate.
He’s also watching the rest of the field closely. “There’s been a huge mobilization of the scientific community, and to me it’s unprecedented,” Ho said in a telephone interview Friday. “Even greater than what we witnessed for HIV.”
He shared his thoughts on some of the most prominent drugs and approaches under consideration for Covid-19 right now.

Gilead’s remdesivir

“Personally, I think remdesivir is up there for a promising drug,” Ho said. Though he noted the data “up to this point, are just case series or anecdotal reports of it being somewhat helpful. I think everyone in the field is waiting for the controlled trials, which will tell us exactly whether it’s working or not.”
And, he notes, “given our case load, we’re going to have a readout on those very, very soon.”
Gilead noted Thursday that, despite a negative headline from a suspended Chinese study, “trends in the data suggest a potential benefit for remdesivir, particularly among patients treated early in disease.”
Ho agreed it would make sense that treating earlier could increase the odds of success.
“For a lot of viral infections, the earlier you treat, the better the outcome,” he explained. “With influenza, with oseltamivir [Tamiflu] it’s only effective in the first 48 hours of developing symptoms. Thereafter the antiviral doesn’t do very much.”
The first trial data from Gilead is due within a week, though that study didn’t include a control group receiving a placebo. Another Gilead study is due to read out results in May, and an NIH trial that did include a placebo control is expected to have results next month as well.

Hydroxychloroquine and chloroquine

“The case series so far are unimpressive or negative,” Ho said of the re-purposed malaria drugs. “The only impact was that, the French continue to say, it may have some role in decreasing the period of viral persistence, but if you look at those studies, they’re unconvincing.”
Ho noted hydroxychloroquine “was largely ignored by the scientific community” before it was “promulgated by our president.”
And he said, “if you look at the compound in the lab against the virus, it’s unimpressive and it’s clearly not doing [anything] to the virus; it’s doing something to the cell.”
That’s concerning from a safety perspective, he said, because “it’s not likely to harm the virus unless you’re harming the cell also, which is not something we want to do lightly.”
Indeed, the FDA warned Friday against using hydroxychloroquine or chloroquine for Covid-19 outside of the hospital setting or a clinical trial because of the risk of heart rhythm problems. “Close supervision is strongly recommended,” the regulator said.

Regeneron and Roche’s rheumatoid arthritis drugs

The approach of using certain medicines already approved for rheumatoid arthritis to treat the lung inflammation in patients with severe Covid-19 “makes sense,” Ho said.
“The IL6-receptor antibodies,” Ho said, “block one limb of the inflammation pathway… the question is, are you intervening soon enough?”
Regeneron and partner Sanofi, and separately Roche, are testing their drugs Kevzara and Actemra in hospitalized patients with Covid-19, after some promising data from a clinical trial of Roche’s drug in China.
The problem, Ho noted, is the trial in China didn’t have a placebo control.
“I think the mistake is not doing controlled trials,” he said. “That’s the only way you’re going to be able to tell [if a drug is working], given most patients do recover.”
Initial results from Regeneron and Sanofi’s U.S. trial of Kevzara, which includes approximately 1,000 patients, are imminent, Sanofi spokeswoman Ashleigh Koss said Friday. Regeneron spokeswoman Hala Mirza noted about 450 patients are included in the phase 2 portion of the trial, which is what will be reported soon.
Roche, which started a trial in early April with plans to enroll 330 patients, expects results in early summer, said Shirley Dang, a spokeswoman for Roche’s genentech unit.
“If there is a dramatic effect, it should be evident very, very rapidly given the number of subjects” in the trials, Ho said. “I suspect we’re going to hear about all of them fairly soon.”

Ho’s coronavirus research

What about his own work? Ho expects his team’s hunt for monoclonal antibodies in the blood of people who’ve recovered from Covid-19 will yield some findings next month.
“I don’t know whether we will find good ones or not,” Ho said. “We’re very hopeful, but time will tell.”
It’s a similar approach to ones being taken by Vir Biotechnology, Eli Lilly and its partner AbCellera, Regeneron, and Amgen and partner Adaptive Biotechnologies. Ho also noted a group in China “has already isolated a couple pretty good antibodies.”
His group is searching for antibodies that bind to the entire spike protein on the coronavirus rather than ones that home in on one area, the receptor binding domain of the spike, aiming to “find something that will complement what others are doing,” he said.
Meanwhile, the protease inhibitor search is reminiscent of approaches to HIV. Ho warned “this is not a fast process. This is going to take months and months to go through iterative improvements” to find the best drug candidates.
But ultimately, if he or others are successful, Ho said these medicines could be used “at the very onset of symptoms” with Covid-19.
“You could take a pill and hopefully halt replication of the virus, and then prevent the cascade of events that occurs in some of the sicker patients,” Ho said.
He also drew a parallel to HIV in the ability to use antiviral medicines to prevent disease.
“Here you could say health-care workers or certain household contacts of an index case could consider taking a pill as prophylaxis,” Ho said. “There are multiple ways of using drugs if an effective one is found.”
And Ho said he does believe the question is when, not if.
“I think society needs to buy time for the scientists,” Ho said. It’s “maybe not in the time frame of less than a year, but from a year to two years, I think a lot of potential solutions will emerge… I’m quite confident that science will come through.”

Source: Coronavirus: AIDS researcher David Ho discusses Covid-19 treatments

E. Updates

1. Hydroxychloroquine had no effect on seriously ill coronavirus patients in New York

Preliminary results of a study on hydroxychloroquine in New York showed that the anti-malaria drug had no effect on critically ill coronavirus patients, Gov. Andrew Cuomo said Thursday.
The study, sponsored by the Department of Health, looked at about 600 patients at 22 hospitals in the greater New York City area.
“I think from the review that I heard basically it was not seen as a positive, not seen as a negative,” Cuomo said.
Some seriously ill COVID-19 patients in the state began to be treated with the drug, at times in combination with the antibiotic Zithromax, or azithromycin, earlier this month.
Those who took the medicine, with or without the antibiotic, weren’t any more likely to survive than those who didn’t, the lead researcher on the New York study told CNN.
“We don’t see a statistically significant difference between patients who took the drugs and those who did not,” said David Holtgrave, dean of the University at Albany School of Public Health.
The drug also proved to be no better than standard care in a smaller study of 300 male patients at Veterans Health Administration medical centers across the nation.

Source: Hydroxychloroquine had no effect on seriously ill in New York: study

F. Cytokine Storms

1. If your immune system is killing you, then you need to do something

As COVID-19 cases fill the hospitals, among the sickest and most likely to die are those whose bodies react in a signature, catastrophic way. Immune cells flood and attack the lungs they should be protecting. Blood vessels leak; the blood itself clots. Blood pressure plummets and organs start to fail.
Such cases, doctors and scientists increasingly believe, are due to an immune system gone overboard — so that it harms instead of helps.
Normally, when the human body encounters a germ, the immune system attacks the invader and then stands down. But sometimes, that orderly army of cells wielding molecular weapons gets out of control, morphing from obedient soldiers into an unruly, torch- and pitchfork-bearing mob. Though there are tests and treatments that could help to identify and tamp down this insurrection, it’s too early to be sure of the best course of therapy for those who are suffering a storm due to COVID-19.
Variants on this hyperactive immune reaction occur in an array of conditions, triggered by infection, faulty genes, or autoimmune disorders in which the body thinks its own tissues are invaders. All fall under the umbrella term “cytokine storm,” named because substances called cytokines rampage through the bloodstream. These small proteins — there are dozens — are the immune army’s messengers, transiting between cells with a variety of effects: Some ask for more immune activity; some request less.

Rising storm

When the cytokines that raise immune activity become too abundant, the immune system may not be able to stop itself. Immune cells spread beyond infected body parts and start attacking healthy tissues, gobbling up red and white blood cells and damaging the liver. Blood vessel walls open up to let immune cells into surrounding tissues, but the vessels get so leaky that the lungs may fill with fluid, and blood pressure drops. Blood clots throughout the body, further choking blood flow. When organs don’t get enough blood, a person can go into shock, risking permanent organ damage or death.
Most patients experiencing a storm will have a fever, and about half will have some sort of nervous system symptoms, such as headache, seizures, or even coma, says Randy Cron, a pediatric rheumatologist and immunologist at the University of Alabama at Birmingham and co-editor of the 2019 textbook Cytokine Storm Syndrome. “They tend to be sicker than you expect,” he says.
Doctors are only now coming to understand cytokine storms and how to treat them, he adds. Though there’s no fail-safe diagnostic test, there are signs that a storm may be underway. For example, blood levels of the protein ferritin may rise, as may blood concentrations of the inflammation indicator C-reactive protein, which is made by the liver.

Cytokine storm in COVID-19

The first hints that severe COVID-19 cases included a cytokine storm came out of Chinese hospitals near the outbreak’s epicenter. Physicians in Wuhan, in a study of 29 patients, reported that higher levels of the cytokines IL-2R and IL-6 were found in more severe COVID-19 infections.
IL-6 was also an early indicator of a cytokine storm-like condition in an 11-patient analysis by physicians in Guangdong. Another team, analyzing 150 cases in Wuhan, found that an array of molecular indicators for a cytokine storm — including IL-6, CRP, and ferritin — were higher in those who died than in those who survived.
And immunologists in Hefei reported similar results among patients who died, as well as high levels of active, damaging immune cells spewing dangerous cytokines in the blood of COVID-19 patients who required intensive care.
Cytokine storms are also raging among U.S. patients. “I’ve seen plenty of it,” says Roberto Caricchio, chief of rheumatology at Temple University in Philadelphia. Precise data aren’t in yet, but he says that a “sizable fraction” — perhaps 20 to 30 percent — of patients with severe cases and lung symptoms have signs of a cytokine storm.
The picture is still coming together. “COVID is — maybe — a relatively unique cytokine storm,” Cron says. Blood-clotting rates seem to go beyond those often seen in other storm conditions, but ferritin levels don’t rise to quite the same sky-high levels. In COVID-19, doctors may observe immune cells attacking the lungs so early, and so harshly, that a sort of scar tissue called fibrosis forms. “It seems to happen quickly with this virus.”
This is not the first time a cytokine storm has been linked to a pandemic. Scientists suspect that cytokine storms caused many of the fatalities in the 1918 flu pandemic and the 2003 outbreak of SARS, a virus related to the one that causes COVID-19.
More recently, Cron and colleagues analyzed 16 fatal cases, from between 2009 and 2014, of the pandemic H1N1 “swine” flu — a novel influenza virus that emerged in 2009 and has since become a fixture during flu season. Up to four-fifths of those patients met standard criteria for a cytokine storm. In addition, several had genetic variants that might have made their immune systems more likely to overreact.
Two patients, for example, had mutations in the PRF1 gene, which makes a protein called perforin. Made by certain immune cells, perforin pokes holes in other, infected cells to destroy them. Mutations in the perforin gene impede the process, but these immune cells — known as natural killer cells — don’t stop trying. “They just keep banging their heads against this, secreting all these cytokines, and you get a cytokine storm,” says study collaborator Grant Schulert, a pediatric rheumatologist at Cincinnati Children’s Hospital Center, who co-wrote an overview of one kind of storm and potential treatments in the Annual Review of Medicine.
And five of the patients looked at by Cron and colleagues carried mutations in a gene called LYST, which causes defects in trafficking of cellular garbage. This disrupts the activity of perforin and prevents immune cells from responding properly to invaders. A handful of others had mutations that the scientists suspect might also influence immune function.
It’s possible, Cron says, that these or similar mutations might explain why about 20 percent of people get a severe or critical version of COVID-19, while others have milder symptoms or even no symptoms at all. Those whose genomes carry such a mutation might, unknowingly, possess an immune system primed to get out of control, so they’d get sicker than everyone else.
“It’s hard to fight off infections when your immune system is being trashed,” Cron says.

Taming the storm

The solution, then, might be to quiet the rampaging immune response. Steroids are often the first choice of treatment. They act broadly to dampen the immune system — but, of course, that system is needed at a lower intensity to fight invaders. In the case of COVID-19, it’s not yet clear if steroids are beneficial or harmful, Cron says.
There are also medications that interfere with specific cytokines. If steroids are an atom bomb, these drugs are targeted missile strikes. The idea is that they’ll leave the good immune response intact.
For example, anakinra (Kineret) is a modified version of a natural human protein that blocks receptors for the cytokine IL-1. It’s FDA-approved for rheumatoid arthritis and a multisystem inflammatory disease in infants. And emapalumab (Gamifant), an antibody that stifles the cytokine interferon-gamma, is approved for people who are genetically predisposed to a cytokine storm.
Early evidence, again from China, indicates that the antibody tocilizumab (Actemra) may be beneficial in COVID-19. This antibody clogs the IL-6 receptor, preventing cells from receiving the IL-6 message. Tocilizumab is normally used to treat arthritis and to alleviate cytokine storms in cancer patients receiving immunotherapy. In early February, doctors from two hospitals in the province of Anhui tried it in 21 patients with severe or critical COVID-19. Fevers and other symptoms were substantially reduced within a few days. Levels of C-reactive protein dropped in the majority of patients. Nineteen patients were discharged within about two weeks.
Researchers are initiating several clinical trials of cytokine blockers for COVID-19. Tocilizumab is under further study in Italy and China; tocilizumab and sarilumab (Kevzara), another antibody to the IL-6 receptor used for rheumatoid arthritis, are both being tested in Denmark; and emapalumab and anakinra are undergoing trial in Italy.
In Philadelphia, Caricchio’s hospital is participating in a trial of sarilumab. If patients don’t want to risk being in the placebo arm, doctors are also prescribing tocilizumab, other anti-cytokine treatments or steroids. One patient who had lung disease and a cytokine storm improved quite a bit on tocilizumab, Caricchio says. It’s important that physicians develop a treatment plan to attack both the raging cytokine storm and the viral infection that caused it, he adds.
But for any treatment to work, doctors must catch the storm happening. “The biggest trick in cytokine storm is just recognizing it,” Schulert says. He, Caricchio, and Cron recommend that everyone sick enough to be hospitalized with COVID-19 get an inexpensive test for ferritin in their blood. All three of their hospitals have instituted such testing, as have many other academic medical centers, they say.
Interim guidelines from the CDC, updated April 3, mention that high CRP and ferritin levels may be correlated with more severe illness; World Health Organization guidelines make no mention of markers for a cytokine storm.
The sooner doctors can treat the raging storm, the better the results, Cron says. “If it’s your immune system killing you, then you need to do something.”

Source: What is a cytokine storm?

G. The Road Back?

1. Innovations we need to reopen the economy [Opinion – Bill Gates]

Bill Gates is a co-chair of the Bill & Melinda Gates Foundation. This article is adapted from his blog post “Pandemic I: the First Modern Pandemic,” available at gatesnotes.com.
It’s entirely understandable that the national conversation has turned to a single question: “When can we get back to normal?” The shutdown has caused immeasurable pain in jobs lost, people isolated and worsening inequity. People are ready to get going again.
Unfortunately, although we have the will, we don’t have the way — not yet. Before the United States and other countries can return to business and life as usual, we will need some innovative new tools that help us detect, treat and prevent covid-19.
It begins with testing. We can’t defeat an enemy if we don’t know where it is. To reopen the economy, we need to be testing enough people that we can quickly detect emerging hotspots and intervene early. We don’t want to wait until the hospitals start to fill up and more people die.
Innovation can help us get the numbers up. The current coronavirus tests require that health-care workers perform nasal swabs, which means they have to change their protective gear before every test. But our foundation supported research showing that having patients do the swab themselves produces results that are just as accurate. This self-swab approach is faster and safer, since regulators should be able to approve swabbing at home or in other locations rather than having people risk additional contact.
Another diagnostic test under development would work much like an at-home pregnancy test. You would swab your nose, but instead of sending it into a processing center, you’d put it in a liquid and then pour that liquid onto a strip of paper, which would change color if the virus was present. This test may be available in a few months.
We need one other advance in testing, but it’s social, not technical: consistent standards about who can get tested. If the country doesn’t test the right people — essential workers, people who are symptomatic and those who have been in contact with someone who tested positive — then we’re wasting a precious resource and potentially missing big reserves of the virus. Asymptomatic people who aren’t in one of those three groups should not be tested until there are enough for everyone else.
The second area where we need innovation is contact tracing. Once someone tests positive, public-health officials need to know who else that person might have infected.
For now, the United States can follow Germany’s example: interview everyone who tests positive and use a database to make sure someone follows up with all their contacts. This approach is far from perfect, because it relies on the infected person to report their contacts accurately and requires a lot of staff to follow up with everyone in person. But it would be an improvement over the sporadic way that contact tracing is being done across the United States now.
An even better solution would be the broad, voluntary adoption of digital tools. For example, there are apps that will help you remember where you have been; if you ever test positive, you can review the history or choose to share it with whoever comes to interview you about your contacts. And some people have proposed allowing phones to detect other phones that are near them by using Bluetooth and emitting sounds that humans can’t hear. If someone tested positive, their phone would send a message to the other phones, and their owners could get tested. If most people chose to install this kind of application, it would probably help some.
Naturally, anyone who tests positive will immediately want to know about treatment options. Yet, right now, there is no treatment for covid-19. Hydroxychloroquine, which works by changing the way the human body reacts to a virus, has received a lot of attention. Our foundation is funding a clinical trial that will give an indication whether it works on covid-19 by the end of May, and it appears the benefits will be modest at best.
But several more-promising candidates are on the horizon. One involves drawing blood from patients who have recovered from covid-19, making sure it is free of the coronavirus and other infections, and giving the plasma (and the antibodies it contains) to sick people. Several major companies are working together to see whether this succeeds.
Another type of drug candidate involves identifying the antibodies that are most effective against the novel coronavirus, and then manufacturing them in a lab. If this works, it is not yet clear how many doses could be produced; it depends on how much antibody material is needed per dose. In 2021, manufacturers may be able to make as few as 100,000 treatments or many millions.
If, a year from now, people are going to big public events — such as games or concerts in a stadium — it will be because researchers have discovered an extremely effective treatment that makes everyone feel safe to go out again. Unfortunately, based on the evidence I’ve seen, they’ll likely find a good treatment, but not one that virtually guarantees you’ll recover.
That’s why we need to invest in a fourth area of innovation: making a vaccine. Every additional month that it takes to produce a vaccine is a month in which the economy cannot completely return to normal.
The new approach I’m most excited about is known as an RNA vaccine. (The first covid-19 vaccine to start human trials is an RNA vaccine.) Unlike a flu shot, which contains fragments of the influenza virus so your immune system can learn to attack them, an RNA vaccine gives your body the genetic code needed to produce viral fragments on its own. When the immune system sees these fragments, it learns how to attack them. An RNA vaccine essentially turns your body into its own vaccine manufacturing unit.
There are at least five other efforts that look promising. But because no one knows which approach will work, a number of them need to be funded so they can all advance at full speed simultaneously.
Even before there’s a safe, effective vaccine, governments need to work out how to distribute it. The countries that provide the funding, the countries where the trials are run, and the ones that are hardest-hit will all have a good case that they should receive priority. Ideally, there would be global agreement about who should get the vaccine first, but given how many competing interests there are, this is unlikely to happen. Whoever solves this problem equitably will have made a major breakthrough.
World War II was the defining moment of my parents’ generation. Similarly, the coronavirus pandemic — the first in a century — will define this era. But there is one big difference between a world war and a pandemic: All of humanity can work together to learn about the disease and develop the capacity to fight it. With the right tools in hand, and smart implementation, we will eventually be able to declare an end to this pandemic — and turn our attention to how to prevent and contain the next one.

Source: Opinion | Bill Gates: Here are the innovations we need to reopen the economy

H. How is the Coronavirus Transmitted?

1. Transmission and Superspreader Events

In 1899, a German bacteriologist named Carl Flügge proved that microbes can be transmitted ballistically through large droplets that emit at high velocity from the mouth and nose. His method for proving the existence of these “Flügge droplets” (as they came to be known) was to painstakingly count the microbe colonies growing on culture plates hit with the expelled secretions of infected lab subjects. It couldn’t have been pleasant work. But his discoveries saved countless lives. And more than 12 decades later, these large respiratory droplets have been identified as a transmission mode for COVID-19.
Very few, if any… droplets are produced during quiet breathing, but [instead, they] are expelled during activities such as talking, coughing, blowing and sneezing. A single heavy cough, it is now known, can expel as much as a quarter teaspoon of fluid in the form of Flügge droplets. And the higher the exit velocity of the cough, the larger the globules that can be expelled.
Yet if Flügge were with us today, he might be surprised by how little his science has been usefully advanced over the last few generations. As Lydia Bourouiba of the MIT Fluid Dynamics of Disease Transmission Laboratory recently noted in JAMA Insights, the basic framework used to represent human-to-human transmission of respiratory diseases such as COVID-19 remain rooted in the tuberculosis era. According to the binary model established in the 1930s, droplets typically are classified as either (1) large globules of the Flüggian variety—arcing through the air like a tennis ball until gravity brings them down to Earth; or (2) smaller particles, less than five to 10 micrometers in diameter (roughly a 10th the width of a human hair), which drift lazily through the air as fine aerosols.
In a fascinating paper published on March 26th, Turbulent Gas Clouds and Respiratory Pathogen Emissions: Potential Implications for Reducing Transmission of COVID-19, Bourouiba shows that analyzing a human sneeze is unusually difficult, even by the standards of fluid dynamics. That’s because those mucosalivary droplets we emit are cocooned within a warm, moist enveloping gas cloud—Bourouiba calls it a “puff”—that protects the droplets from evaporation and allows even small globules to travel much farther than one might otherwise predict. The binary distinction between large and small droplets remains fundamental: Eventually, the big particles fall while the smaller ones don’t. But during those first fractions of a second when a sneeze (or cough, or shout) is expelled, Bourouiba shows, the enveloping gas sheath allows smaller particles to act, ballistically speaking, as if they were larger.
The science here is mind-bogglingly complex, because modeling the puff’s behaviour requires that Bourouiba and her team model not only the dynamics of the puff as it travels and dissipates, but also the biophysical and thermodynamic processes unfolding within the gas cloud. But the overall upshot is that such a puff “and its payload of pathogen-bearing droplets of all sizes” can travel seven to eight meters—about four times the length of the six-foot social-distancing buffer zone we’ve all been taught to enforce since mid-March.
Bourouiba’s research hits squarely on a blind spot in our knowledge of COVID-19. On one hand, scientists have an intimate molecule-by-molecule knowledge of the virus’s structure, its full genome having been sequenced months ago. On the other hand, the scientific and lay literature is bursting with epidemiological reports from just about every corner of the planet. But the actual nitty-gritty mechanics of actual disease transmission doesn’t take place on the microscopic scale of nucleic acids or on the gargantuan scale of whole nations. It takes place on the everyday face-to-face scale of inches and feet, as Flügge showed 121 years ago.
And it is on this crucial scale that our knowledge is thinnest. Despite the passage of four months since the first known human cases of COVID-19, our public-health officials remain committed to policies that reflect no clear understanding as to whether it is one-off ballistic droplet payloads or clouds of fine aerosols that pose the greatest risk—or even how these two modes compare to the possibility of indirect infection through contaminated surfaces (known as “fomites”).
Gaining such an understanding is absolutely critical to the task of tailoring emerging public-health measures and workplace policies, because the process of policy optimization depends entirely on which mechanism (if any) is dominant:
If large droplets are found to be a dominant mode of transmission, then the expanded use of masks and social distancing is critical, because the threat will be understood as emerging from the ballistic droplet flight connected to sneezing, coughing, and laboured breathing. We would also be urged to speak softly, avoid “coughing, blowing and sneezing,” or exhibiting any kind of agitated respiratory state in public, and angle their mouths downward when speaking.
If lingering clouds of tiny aerosol droplets are found to be a dominant mode of transmission, on the other hand, then the focus on sneeze ballistics and the precise geometric delineation of social distancing protocols become somewhat less important—since particles that remain indefinitely suspended in an airborne state can travel over large distances through the normal processes of natural convection and gas diffusion. In this case, we would need to prioritize the use of outdoor spaces (where aerosols are more quickly swept away) and improve the ventilation of indoor spaces.
If contaminated surfaces are found to be a dominant mode of transmission, then we would need to continue, and even expand, our current practice of fastidiously washing hands following contact with store-bought items and other outside surfaces; as well as wiping down delivered items with bleach solution or other disinfectants.
Unfortunately, the available international data hasn’t been particularly helpful in addressing this inquiry. Every nation is reporting its data in a different way. And to my knowledge, no one has produced a comprehensive international database of large COVID-19 infection clusters—or “superspreading events” (SSEs), as they are sometimes referred to in the scientific literature—which would facilitate a systematic study of the forms of behaviour that spread the disease most rapidly. As SSE expert Richard Stein put it in a definitive 2011 article, roughly “20% of the individuals within any given population are thought to contribute at least 80% to the transmission potential” of typical pathogens.
In the absence of any comprehensive database of COVID-19 superspreading events, I built my own, cataloguing 58 SSEs in 28 different countries (plus ships at sea). As there is no formal scientific definition of SSE at play, nor any World Health Organization-established protocol for cataloguing them, I simply spent several weeks scanning the scientific and lay press for any information I could find, using search terms such as “superspreader,” “cluster,” “hot spot”; or non-English variants, such as superpropagadore. I also made abundant inquiries to personal and professional contacts through email and social media, seeking to unearth examples that hadn’t been reported in the mass media or scientific journals. That process will continue, and I am appreciative of readers who send me information I may have missed.
I am not an epidemiologist, let alone a virologist. And the data I am working with is substandard anyway, as there are all sorts of obvious selection biases at play, including the editorial biases of the journalists on whom I rely for local reports. In some countries, such as South Korea, COVID-19 contact tracing is meticulous. In other places, it’s virtually non-existent. Some relatively small SSEs—such as the Chicago cluster surrounding the superspreader designated by the US Centers for Disease Control as A1.1—are documented by dozens of different sources. Yet many much larger SSEs, which have infected hundreds or even thousands of people, remain only vaguely described in the literature.
In some cases, I found it hard to get even the most basic information—such as the number of individuals believed to have been infected or killed by an SSE. This is one reason why I didn’t impose a hard cut-off in regard to either index, and instead based my inclusion on whether credible local sources presented the cluster as epidemiologically noteworthy.
There are no doubt hundreds, or even thousands, of SSEs that simply have never been reported, and never will be. And so it is impossible to determine what overall share of global COVID-19 cases are attributable to SSEs. To cite one example: Was Liverpool’s March 11 football match against Atletico Madrid an SSE, as many believe? Possibly. But no one knows, because the study of COVID-19 SSEs is bedevilled by the same sloppy contact-tracing practices and inadequate testing resources as has hampered the public-health response to the disease more generally.
Another research frustration lies with the fact that even countries that employ competent contact-tracing methods—such as Australia and New Zealand—withhold important information from publication for privacy reasons. (There is a “hospitality worker” in Victoria, for instance, whose case seems particularly interesting. But I have been unable to find detailed information about the events and venues at which he infected others.) In other cases, I’ve received private correspondence whose contents I’ve chosen to exclude from my database—involving Purim parties in Israel, for instance, and a Swedish party at which a whistle apparently was passed around—because the information can’t be corroborated through public sources.
I also chose to exclude examples from some countries that have blocked or distorted information about SSEs. It is widely known, for instance, that large officially-sanctioned religious gatherings in the Iranian city of Qom led to massive outbreaks in February. But no adequately reliable data or public reporting exists as to the extent. The same is true of the outbreaks that reportedly have broken out amongst the political leadership in Afghanistan. The Chinese literature is full of fascinating examples (including one from a restaurant in Guangdong Province that I discuss in some detail later on). But China’s policy of selective disclosure and, in some cases, outright dishonesty, has made me skeptical of many reported details.
Finally, I have chosen to exclude SSEs that center on hospitals and old-age homes, despite the fact that in many countries (including Canada, where I live), these comprise the main spawning ground for COVID-19. This is because the purpose of this exercise is to gain information about the relative effects of three broad modes of COVID-19 transmission—large droplets transmitted ballistically, persistent concentrations of tiny airborne droplets, and contaminated surfaces. In hospitals and old-age homes, all three of these mechanisms are almost invariably at play—as these tend to be shared spaces full of commonly touched surfaces and close interpersonal contact among residents and staff. And so such SSEs serve to inflate the size of the database without providing assistance in isolating variables. The same principle is true of COVID-19 transmission within households, which is why I have excluded intra-household clusters as well.
Only 38 of the 58 SSEs that I recorded were documented in a way that permitted me to determine their date with any specificity. (And even in these cases, I sometimes had to make educated estimates because of the vague nature of the reporting.) In the case of multi-day SSEs, such as religious festivals, I picked a day corresponding to the middle of the event. Unfortunately, some of the largest SSEs, such as those at North American meat processing plants, can’t be usefully pinpointed at all because the infections span multiple weeks (or even months), and the employers haven’t released detailed date-tagged data.
Of the 38 SSEs for which dates could be usefully identified, about 75 percent (29/38) took place in the 26-day span between February 25th and March 21st, roughly corresponding to the period when thousands of infected COVID-19 individuals were already traveling around the world, but before social distancing and event-cancelation policies had been uniformly implemented in many of the affected countries. (A notable early outlier is Steve Walsh, who spread COVID-19 from a Singapore corporate meeting to a French ski resort to his native UK in late January and early February.) No doubt, a vast number of SSEs occurred in January and February without being reported as such, because public-health officials and journalists weren’t alive to the nature or scale of the coming pandemic. But it is reassuring that, so far, April has been almost entirely bereft of publicly reported SSEs.
I was struck by how few of the SSEs originated in conditions stereotypically associated with the underclass (though a March outbreak at a Qatari migrant workers camp in the industrial area north of Doha offers one such example). Many of the early SSEs, in fact, centered on weddings, birthday parties, and other events that were described in local media as glamorous or populated by “socialites.” Examples here include a March 7th engagement party at a Rio de Janeiro “mansion” that attracted “high society” fly-ins from around the world, and a similarly described birthday party in Westport, CT.
It is theoretically possible that socioeconomically privileged individuals really do lack some immune-response mechanism that protects individuals who have been exposed to a wider array of infectious pathogens. (A recent report on COVID-19 surveillance testing at a Boston homeless shelter contained the stunning disclosure that 36 percent of 408 screened individuals tested positive for COVID-19. Yet the vast majority were asymptomatic, and even the few who were symptomatic did not diverge statistically from the 64 percent of tested individuals who were COVID-19-negative.) But absent more data, the more obvious explanation is that these early SSEs are linked to the intercontinental travel practices of the guests. (In the case of the Connecticut event, reports the New York Times, “a visitor from Johannesburg—a 43-year-old businessman—fell ill on his flight home.” And the Rio party was attended by guests who’d traveled recently from, or through New York, Belgium and Italy.) Moreover, COVID-19 outbreaks in poor communities are simply less likely to be reported, because the victims have less access to testing, high-end medical care, or media contacts.
In fact, the truly remarkable trend that jumped off my spreadsheet has nothing to do with the sort of people involved in these SSEs, but rather the extraordinarily narrow range of underlying activities. And I believe it is on this point that a close study of SSEs, even one based on such a biased and incomplete data set as the one I’ve assembled in my lay capacity, can help us:
Of the 54 SSEs on my list for which the underlying activities were identified, no fewer than nine were linked to religious services or missionary work. This includes massive gatherings such as February’s weeklong Christian Open Door prayer meeting in Mulhouse, France, which has been linked to an astounding 2,500 cases; and a massive Tablighi Jamaat Islamic event in Lahore that attracted a quarter-million people. But it also includes much smaller-scale religious activities, such as proselytizing in rural Punjabi villages and a religious meeting in a Calgary home.
Nineteen of the SSEs—about one-third—involved parties or liquor-fueled mass attendance festivals of one kind or another, including (as with the examples cited above) celebrations of weddings, engagements and birthdays.
Five of the SSEs involved funerals.
Six of the SSEs involved face-to-face business networking. This includes large-scale events such as Biogen’s notorious Boston leadership meeting in February, as well as one-on-one business meetings—from the unidentified “traveling salesperson” who spread COVID-19 in Maine to Hisham Hamdan, a powerful sovereign-wealth fund official who spread the disease in Malaysia.
All told, 38 of the 54 SSEs for which activities were known involved one or more of these four activities—about 70 percent. Indeed, the categories sometimes overlap, as with patient A1.1 in Chicago, who attended both a party and a funeral in the space of a few days; or the New Rochelle, NY man who covered the SSE trifecta of Bar Mitzvah party, synagogue services, and local funeral, all the while going to his day job as a lawyer in New York City.
But even that 70 percent figure underestimates the prevalence of these activities in COVID-19 SSEs, because my database also includes five SSEs involving two warships and three cruise ships—the USS Roosevelt, Charles de Gaulle, Diamond Princess, Grand Princess and Ruby Princess—at least three of which (and probably all five) featured onboard parties.
These parties, funerals, religious meet-ups and business networking sessions all seem to have involved the same type of behaviour: extended, close-range, face-to-face conversation—typically in crowded, socially animated spaces. This includes the many people infected by a bartender while being served at a raucous après ski venue in Austria, and party guests in Brazil greeting “each other with two kisses on the cheek [a local custom], hugs and handshakes.” The funerals in question are generally described as highly intimate and congested scenes of grieving among close friends and relatives. In the case of the SSE funeral in Albany, Georgia that devastated the local population, “people wiped tears away, and embraced, and blew their noses, and belted out hymns. They laughed, remembering. It was a big gathering, with upward of 200 mourners overflowing the memorial chapel, so people had to stand outside.”
With few exceptions, almost all of the SSEs took place indoors, where people tend to pack closer together in social situations, and where ventilation is poorer. (It is notable, for instance, that the notorious outbreak at an Austrian ski resort is connected to a bartender and not, say, a lift operator.) But generalizations in this area are complicated by the fact that some of the religious festivals described herein were mixed indoor/outdoor affairs. Moreover, the February 19 SSE at San Siro stadium in Milan is also ambiguous, since that stadium has a roof over the seating area, but not over the field.
The media accounts of these SSEs are full of descriptions in this vein. At a February 15 festival in Gangelt, a town in Germany’s tiny Heinsberg district, “beer and wine flowed aplenty as approximately 350 adults in fancy dress locked arms on long wooden benches and swayed to the rhythm of music provided by a live band. During an interval in the programme, guests got up to mingle with friends and relatives at other tables, greeting each other as Rhineland tradition commands, with a bützchen, or peck on the cheek.” Since that time, more than 40 Germans from the Heinsberg district have died. It’s been called “Germany’s Wuhan.”
In the case of religious SSEs, Sikhs, Christians, Jews and Muslims are all represented in the database. The virus makes no distinction according to creed, but does seem to prey on physically intimate congregations that feature some combination of mass participation, folk proselytizing and spontaneous, emotionally charged expressions of devotion. In the case of Islam, it is notable that the same movement, Tablighi Jamaat, has been responsible for massive outbreaks at completely separate events in Lahore (noted above), Delhi and Kuala Lampur. At Mulhouse, the week’s schedule included Christian “choir performances, collective prayer, singing, sermons from preachers, workshops, and testimony from people who said God had cured their illnesses… Many people came day after day, and spent hours there.” And in Punjab, dozens of Sikhs died thanks to the itinerant rural preaching of a single (now deceased) infamous septuagenarian named Baldev Singh (whose deadly travels inspired a hit Punjabi song by Sidhu Moose Wala, linked immediately below).
Of the 54 SSEs for which underlying activities could be identified, only 11 did not involve either religious activity, a party, a funeral, a cruise or extended face-to-face professional networking. But even in this minority of cases, one can observe almost identical interpersonal dynamics. Three of the SSEs—in Japan, Skagit County, WA, and Singapore—involved concert-goers and singing groups belting out tunes together over a period of hours. (The Skagit example is particularly interesting, because the organizers were aware of the COVID-19 risk beforehand, and took the precaution of spacing out the participants by several feet. If they had been merely chatting, instead of singing, no one might have gotten sick.)
Another SSE involved a group of Canadian doctors engaged in a day of recreational curling. This is a sport that involves hyperventilating participants frenetically sweeping the ice with brooms while their faces are positioned inches apart, sometimes changing partners—an ideal climate for Flüggian infection. Indeed, this partner-swapping aspect of the activity seems to be a common feature of many suspected SSEs, such as square-dancing parties.
Four of the SSEs were outbreaks at meat-processing plants, in which “gut snatchers” and other densely packed workers must communicate with one another amidst the ear-piercing shriek of industrial machinery. I lack the expertise to determine how the refrigerated nature of some meat-processing facilities may affect the dynamics of droplet transmission—though I would also note that at least four of the SSEs on my list unfolded at European ski resorts. But high levels of noise do seem to be a common feature of SSEs, as such environments force conversationalists to speak at extremely close range. (Related factors may be at play in old-age homes. These tend to be quiet places. But the reduced speaking volume and hearing functions of some elderly residents lend themselves to conversations held at much closer range than is socially typical in the general population.)
Finally, three of the SSEs involved mass sports spectacles, during which fans regularly rain saliva in all directions as they communally celebrate or commiserate in response to each turn of fortune. (Advance to the 8:30 mark of this video, showing euphoric hometown fan reaction during the infamous February 19th football match between Atlanata and Valencia, and you will see exactly what I mean.) As we now know, the danger starts even before the action begins: One of the most dangerous things you can do at a sports event in the COVID-19 era is sing the national anthem.
When do COVID-19 SSEs happen? Based on the list I’ve assembled, the short answer is: Wherever and whenever people are up in each other’s faces, laughing, shouting, cheering, sobbing, singing, greeting, and praying. You don’t have to be a 19th-century German bacteriologist or MIT expert in mucosalivary ballistics to understand what this tells us about the most likely mode of transmission.
It’s worth scanning all the myriad forms of common human activity that aren’t represented among these listed SSEs: watching movies in a theater, being on a train or bus, attending theater, opera, or symphony (these latter activities may seem like rarified examples, but they are important once you take stock of all those wealthy infectees who got sick in March, and consider that New York City is a major COVID-19 hot spot). These are activities where people often find themselves surrounded by strangers in densely packed rooms—as with all those above-described SSEs—but, crucially, where attendees also are expected to sit still and talk in hushed tones.
The world’s untold thousands of white-collar cubicle farms don’t seem to be generating abundant COVID-19 SSEs—despite the uneven quality of ventilation one finds in global workplaces. This category includes call centers (many of which are still operating), places where millions of people around the world literally talk for a living. (Addendum: there are at least two examples of call-centre-based clusters, both of which were indicated to me by readers after the original version of this article appeared—one in South Korea, which overlaps with the massive Shincheonji Church of Jesus cluster; and the other in Jamaica.)
In New Zealand, one SSE centered on students at a girls’ school. Given the exuberant and socially intimate way in which children laugh, argue and gossip, I am surprised there are not more schools on my list. Moreover, I had trouble finding any SSEs that originated in university classrooms, which one would expect to be massive engines of infection if COVID-19 could be transmitted easily through airborne small-droplet diffusion.
In the United States, the two university-based examples that have received the most media attention are Liberty University in Lynchburg, Va. and the University of Texas. But in neither case was there any apparent connection to classroom activity. At Liberty, where several employees got sick, the one student known to be infected isn’t even currently enrolled in classes. And the UT outbreak, which has caused more than 40 students to be infected, actually took place on a Spring Break trip to Mexico. It’s possible, I suppose, that these students spent the week holed up in a conference room with a stack of books. But my instincts indicate otherwise.
It’s similarly notable that airplanes don’t seem to be common sites for known SSEs, notwithstanding the sardine-like manner in which airlines transport us and the ample opportunity that the industry’s bureaucracy offers for contact tracing. Yes, New Zealand has one cluster that’s based around an infected but asymptomatic flight attendant. But the many known infections he caused took place at a wedding reception, not in an airplane. This flight attendant was running what was, in effect, an unintended experiment, with the passengers on board his aircraft playing the role of control group. And the results offer a microcosm of the nature of SSEs as a whole.
I’ve already cataloged the limitations of my approach at some length. And I will emphasize again that I am not an epidemiologist, virologist, or infectious-diseases expert (though I like to think I’ve made myself a somewhat educated reader of the most recently published scientific literature in these fields). But even a layperson can see that there is a fairly clear pattern in the most notorious, destructive, and widely reported cases of mass COVID-19 infection—virtually all of which feature forms of human behaviour that permit the direct ballistic delivery of a large-droplet Flüggian payload from face A to face B. If fomites were a major pathway for COVID-19 infection outside of hospitals, old-age residences, and homes, one would expect restaurant cooks, mass-transit ticket handlers, and FedEx delivery workers to be at the center of major clusters. They’re not. If small-droplet airborne concentrations in unventilated spaces were a common vector for COVID-19 transmission (as with measles, for instance), one would expect whole office buildings to become mass-infection hot spots. That doesn’t seem to have happened.
One critical factor in all this is that we still have no idea what the minimal infectious dose (MID) is for COVID-19—the number of viral particles required “to start the pathogenesis cascade that causes a clinical disease”—even if we do have some idea about what regions of our respiratory system the virus can use as a point of entry. Knowing the MID for COVID-19 would be invaluable, because it may well turn out that it is significantly higher than the viral load capacity of small droplets, not to mention the even smaller viral load typically delivered by glancing contact with an infected surface. This would mean that many of our current COVID-19-avoidance protocols, however well-intentioned, would be guarding against modes of transmission that aren’t really significant contributors to the overall pandemic.
In some cases, public-health rules that guard against non-existent threats may actually make the problem worse. Consider, for instance, the spread of COVID-19 among diners at a Guangzhou restaurant on January 24th, an episode that I have not included in my database, but which has become the subject of a fascinating forthcoming article in Emerging Infectious Diseases.
As the authors note, the restaurant in question was air-conditioned on the date in question. Using video footage, they were able to chart the position of every diner in the restaurant, and then map their subsequent infection status in relation to both the single infected individual known to be present at the time and the air conditioning system’s outgoing and intake streams. If the primary transmission mode of COVID-19 were by small, sub-Flüggian airborne particles, the presence of the forced air convection might have made the environment safer (especially since “smear samples from the air conditioner [itself] were all [COVID-19] nucleotide negative”). But the researchers instead found evidence for the opposite: “The key factor for infection was the direction of the airflow,” with downstream individuals being most at risk—a result consistent with the thesis that COVID-19 is transmitted primarily through the ballistic transmission of large respiratory droplets.
None of the suggested causality patterns I have described have been proven definitively, of course—let alone by any layperson’s journalistic analysis of a few dozen SSEs. But if the principal modes of COVID-19 transmission can be narrowed down in this way, it would provide an enormous boon to the policymakers who are now starting to think about restarting our economies. Fighting this disease will always be hard. But it will be harder still if we fail to develop a proper understanding of the precise way it attacks us.

Source: COVID-19 Superspreader Events in 28 Countries: Critical Patterns and Lessons