Coronavirus Update

Without reliable information, we rely on fear or luck.

Coronavirus Update 7-9

Recent Developments & Information 

July 9, 2020

Reliable information is the best tool available to protect your family from the pandemic and its shockwaves

“By allowing yourself to get infected because of risky behavior, you are part of the propagation of the outbreak. There are so many other things that are very dangerous and bad about this virus. Don’t get yourself into false complacency.”   

Dr. Fauci

“None of us really anticipated the amount of community spread that began in really our 18-to-35-year-old age group. This is an age group that was so good and so disciplined through March and April. But when they saw people out and about on social media, they all went out and about.”  

Dr. Brix

Index

A. The Pandemic As Seen Through Headlines

B. Numbers & Trends

C. Airborne Transmission

  1. Airborne Coronavirus: What You Need to Know  
  2. WHO Says What?  WHO Admits Airborne Transmission Possible  

D. Assessing Risk

  1. How Risky Is Covid?  
  2. If you’re over 75, catching C19 can be like playing Russian roulette 

E. New Scientific Findings & Research

  1. Breathing Correctly Can Help the Body Fight Viral Infections   (!)
  2. Researchers create air filter that can catch and instantly kill the coronavirus – 99.8% Effective    (!)
  3. Study Is First to Identify Potential Therapeutic Targets for C19 Using Blood Samples From Critically Ill Patients 
  4. Italian Study Shows Lower ‘Viral Load,’ Milder Symptoms In C19 Patients 

F. Potential Treatments

  1. Researchers test COVID treatment that decreases mortality rates of patients on ventilators by 70%    (!) 
  2. Regeneron Advances Antibody Cocktail into Phase III Trials 

G. Reducing the Spread

  1. Can a $50 nasal spray thwart the spread of C19?!  

H. Concerns & Unknowns

  1. Popular Heartburn Drugs Linked to Heightened COVID-19 Risk  
  2. Warning of serious brain disorders in people with mild coronavirus symptoms    
  3. Can You Catch Covid-19 Twice? 
  4. T Cells, Antibodies, and Our Ignorance  

I. Projections & Our (Possible) Future

  1. Estimating the Spread of the Coronavirus  

J. The Road Back? 

  1. No one wants to go back to lockdown.  Is there a middle ground for containing C19?  

K. Practical Tips & Other Useful Information

  1. Why simple cloth masks without valves are better at fighting the spread of C19 
  2. EPA approves first surface disinfectant products tested on the coronavirus 

L. Johns Hopkins COVID-19 Update

M. Links to Other Stories

A. The Pandemic As Seen Through Headlines

(In no particular order)

B. Numbers & Trends

Note: Unless otherwise noted, (i) all cases/deaths are confirmed cases/deaths that have been reported, (ii) all numbers reported in this update are as of the end of the most recent reporting period, and (iii) all changes reflect changes since the preceding day.  Green highlights indicate a decrease or no change and yellow highlights indicate an increase. 

Sources: https://www.worldometers.info/coronavirus/ and https://covidtracking.com/

1. Cases & Tests

Worldwide Cases:  
  • Total Cases = 12,155,603 (+1.8%)
  • New Cases = 213,280 (+3,953)
  • Growth Rate of New Cases (7 day average) = 1.1% 
  • New Cases (7 day average) = 198,596 (+2,071)
Observations:
  • Second highest number of new cases 
  • Number of new cases has increased for 2 consecutive days
  • The number of new cases as been steadily increasing throughout the pandemic
  • 7 day average of new cases on 7/8 was a record high
  • 7 day average of new cases has increased every day since 5/26
US Cases & Testing: 
  • Total Cases = 3,158,932 (+1.9%)
  • New Cases = 61,848 (+5,597)
  • Percentage of New Global Cases = 29% 
  • Growth Rate of New Cases (7 day average) = 2.6% 
  • New Cases (7 day average) = 54,157 (+1,356)
  • Total Number of Tests = 39,479,437 
  • Percentage of positive tests (7 day average) = 7.9% 
Observations:
  • Number of new cases on 7/8 was a record high
  • Number of new cases have been rising rapidly since 6/10
  • 7 day average of new cases on 7/8 was a record high
  • 7 day average of new cases have increased every day since 6/9
  • Percentage of positive tests has been steadily increasing since 6/21

2. Deaths

Worldwide Deaths: 
  • Total Deaths = 551,192 (+1.0%) 
  • New Deaths = 5,540 (+25)
  • Growth Rate of New Deaths (7 day average) = 2.6% 
  • New Deaths (7 day average) = 4,728 (+100)
Observations:
  • Number of new deaths has increased for 2 consecutive days
  • Number of new deaths have been steadily increasing since 5/26
  • 7 day average of new deaths increased 8.2% during June
  • 7 day average of new deaths increased 4.6% so far in July
US Deaths: 
  • Total Deaths = 134,862 (+0.7%)
  • New Deaths = 890 (-103) 
  • Percentage of Global New Deaths = 16.1% 
  • Growth Rate of New Deaths (7 day average) = 5.5% 
  • New Deaths (7 day average) = 586 (+31)
Observations:
  • The number of new deaths have spiked during last 2 days
  • 3 day average of new deaths have increased by 250% since 7/6
  • 7 day average growth rate of new deaths is very high
  • 7 day average of new deaths has decreased 44.1% during June
  • 7 day average of new deaths has increased 5.4% so far during July

3. Top 5 States in Cases & Deaths (7/8)

ChartChart
ChartChart

C. Airborne Transmission

1. Airborne Coronavirus: What You Need to Know  

  • The coronavirus can stay aloft for hours in tiny droplets in stagnant air, infecting people as they inhale, mounting scientific evidence suggests.
  • This risk is highest in crowded indoor spaces with poor ventilation, and may help explain super-spreading events reported in meatpacking plants, churches and restaurants.
  • It’s unclear how often the virus is spread via these tiny droplets, or aerosols, compared with larger droplets that are expelled when a sick person coughs or sneezes, or transmitted through contact with contaminated surfaces, said Linsey Marr, an aerosol expert at Virginia Tech.
  • Aerosols are released even when a person without symptoms exhales, talks or sings, according to Dr. Marr and more than 200 other experts, who have outlined the evidence in an open letter to the World Health Organization.
  • What is clear, they said, is that people should consider minimizing time indoors with people outside their families. Schools, nursing homes and businesses should consider adding powerful new air filters and ultraviolet lights that can kill airborne viruses.
  • Here are answers to a few questions raised by the latest research.
What does it mean for a virus to be airborne?
  • For a virus to be airborne means that it can be carried through the air in a viable form. For most pathogens, this is a yes-no scenario. H.I.V., too delicate to survive outside the body, is not airborne. Measles is airborne, and dangerously so: It can survive in the air for up to two hours.
  • For the coronavirus, the definition has been more complicated. Experts agree that the virus does not travel long distances or remain viable outdoors. But evidence suggests it can traverse the length of a room and, in one set of experimental conditions, remain viable for perhaps three hours.
How are aerosols different from droplets?
  • Aerosols are droplets, droplets are aerosols — they do not differ except in size. Scientists sometimes refer to droplets less than five microns in diameter as aerosols. (By comparison, a red blood cell is about five microns in diameter; a human hair is about 50 microns wide.)
  • From the start of the pandemic, the WHO and other public health organizations have focused on the virus’s ability to spread through large droplets that are expelled when a symptomatic person coughs or sneezes.
  • These droplets are heavy, relatively speaking, and fall quickly to the floor or onto a surface that others might touch. This is why public health agencies have recommended maintaining a distance of at least six feet from others, and frequent hand washing.
  • But some experts have said for months that infected people also are releasing aerosols when they cough and sneeze. More important, they expel aerosols even when they breathe, talk or sing, especially with some exertion.
  • Scientists know now that people can spread the virus even in the absence of symptoms — without coughing or sneezing — and aerosols might explain that phenomenon.
  • Because aerosols are smaller, they contain much less virus than droplets do. But because they are lighter, they can linger in the air for hours, especially in the absence of fresh air. In a crowded indoor space, a single infected person can release enough aerosolized virus over time to infect many people, perhaps seeding a superspreader event.
  • For droplets to be responsible for that kind of spread, a single person would have to be within a few feet of all the other people, or to have contaminated an object that everyone else touched. All that seems unlikely to many experts: “I have to do too many mental gymnastics to explain those other routes of transmission compared to aerosol transmission, which is much simpler,” Dr. Marr said.
Can I stop worrying about physical distancing and washing my hands?
  • Physical distancing is still very important. The closer you are to an infected person, the more aerosols and droplets you may be exposed to. Washing your hands often is still a good idea.
  • What’s new is that those two things may not be enough. “We should be placing as much emphasis on masks and ventilation as we do with hand washing,” Dr. Marr said. “As far as we can tell, this is equally important, if not more important.”
Should I begin wearing a hospital-grade mask indoors? And how long is too long to stay indoors?
  • Health care workers may all need to wear N95 masks, which filter out most aerosols. At the moment, they are advised to do so only when engaged in certain medical procedures that are thought to produce aerosols.
  • For the rest of us, cloth face masks will still greatly reduce risk, as long as most people wear them. At home, when you’re with your own family or with roommates you know to be careful, masks are still not necessary. But it is a good idea to wear them in other indoor spaces, experts said.
  • As for how long is safe, that is frustratingly tough to answer. A lot depends on whether the room is too crowded to allow for a safe distance from others and whether there is fresh air circulating through the room.
What does airborne transmission mean for reopening schools and colleges?
  • This is a matter of intense debate. Many schools are poorly ventilated and are too poorly funded to invest in new filtration systems. “There is a huge vulnerability to infection transmission via aerosols in schools,” said Don Milton, an aerosol expert at the University of Maryland.
  • Most children younger than 12 seem to have only mild symptoms, if any, so elementary schools may get by. “So far, we don’t have evidence that elementary schools will be a problem, but the upper grades, I think, would be more likely to be a problem,” Dr. Milton said.
  • College dorms and classrooms are also cause for concern.
  • Dr. Milton said the government should think of long-term solutions for these problems. Having public schools closed “clogs up the whole economy, and it’s a major vulnerability,” he said.
  • “Until we understand how this is part of our national defense, and fund it appropriately, we’re going to remain extremely vulnerable to these kinds of biological threats.”
What are some things I can do to minimize the risks?
  • Do as much as you can outdoors. Despite the many photos of people at beaches, even a somewhat crowded beach, especially on a breezy day, is likely to be safer than a pub or an indoor restaurant with recycled air.
  • But even outdoors, wear a mask if you are likely to be close to others for an extended period.
  • When indoors, one simple thing people can do is to “open their windows and doors whenever possible,” Dr. Marr said. You can also upgrade the filters in your home air-conditioning systems, or adjust the settings to use more outdoor air rather than recirculated air.
  • Public buildings and businesses may want to invest in air purifiers and ultraviolet lights that can kill the virus. Despite their reputation, elevators may not be a big risk, Dr. Milton said, compared with public bathrooms or offices with stagnant air where you may spend a long time.
  • If none of those things are possible, try to minimize the time you spend in an indoor space, especially without a mask. The longer you spend inside, the greater the dose of virus you might inhale.

Source: Airborne Coronavirus: What You Should Do Now

2. WHO Says What?!  WHO Admits Airborne Transmission Possible  

  • After hundreds of experts urged the World Health Organization to review mounting scientific research, the agency acknowledged on Tuesday that airborne transmission of the coronavirus may be a threat in indoor spaces.
  • WHO expert committees are going over evidence on transmission of the virus and plan to release updated recommendations in a few days, agency scientists said in a news briefing.
  • The possibility of airborne transmission, especially in “crowded, closed, poorly ventilated settings, cannot be ruled out,” said Dr. Benedetta Allegranzi, who leads the WHO’s committee on infection prevention and control.
  • She said the agency recommends “appropriate and optimal ventilation” of indoor environments, as well as physical distancing.
  • Agency staff fielded several questions from reporters about transmission of the virus by air, prompted by an open letter from 239 experts calling on the agency to review its guidance. Many of the letter’s signatories have collaborated with the WHO and served on its committees.
  • “We are very glad that WHO has finally acknowledged the accumulating evidence, and will add aerosol transmission indoors to the likely modes of transmission” for the coronavirus, said Jose-Luis Jimenez, a professor of chemistry at the University of Colorado Boulder. “This will allow the world to better protect themselves and fight the pandemic.”
  • In their letter, Dr. Jimenez and other scientists called on the WHO to recommend that people avoid overcrowding, particularly on public transportation and in other confined spaces. Public buildings, businesses, schools, hospitals and care homes should also supply clean air, minimize recirculating air, and consider adding air filters and virus-killing ultraviolet lights, they said.
  • “Public health agencies around the world take their cues from WHO, and hopefully this will lead to greater emphasis on wearing of face coverings and avoiding the three Cs: close contact, closed and poorly ventilated spaces, and crowds,” said Linsey Marr, an aerosol expert at Virginia Tech. “These measures will help slow the pandemic and save lives.”
  • WHO scientists said that for the past few months, the infection prevention committee has been weighing the evidence on all the ways in which the coronavirus spreads, including by tiny droplets or aerosols.
  • “We acknowledge that there is emerging evidence in this field, as in all other fields,” Dr. Allegranzi said. “And therefore, we believe that we have to be open to this evidence and understand its implications regarding the modes of transmission and also regarding the precautions that need to be taken.”
  • It will also be important to understand the importance of transmission by aerosols compared with larger droplets, and the dose of the virus needed for infection from aerosols, she said.
  • “These are fields that are really growing and for which there is evidence emerging, but it is not definitive,” she said. “However, the evidence needs to be gathered and interpreted, and we continue to support this.”
  • Other experts said it has been clear for some time that airborne transmission of the virus is possible, but agreed that it’s not yet certain how big a role this route plays in spreading the virus.
  • “The question of how important it is for overall transmission remains an open one,” said Bill Hanage, an epidemiologist at the Harvard T.H. Chan School of Public Health.
  • Still, he and other experts have said that the WHO is too slow and cautious in adopting precautions based on emerging evidence.
  • WHO scientists offered an explanation for their seemingly slow pace. On average, they review 500 new papers a day, many of which turn out to be of dubious quality, said Dr. Soumya Swaminathan, the WHO’s chief scientist.
  • As such, the scientists have to review the quality of each paper before including it in their analysis, she said: “Any guidance we put out has implications for billions of people around the world. It has to be carefully done.”

Source: W.H.O. to Review Evidence of Airborne Transmission of Coronavirus

D. Assessing Risk 

1. How Risky Is Covid?  

By John Authers — Bloomberg

  • It is difficult not to think in circles about C19. There is a welter of research out there, very little of it yet subject to intensive peer review. Whatever your initial bias, someone somewhere has research to confirm it. 
  • To organize thinking, I would like to highlight just one piece of research — from Andrew Brigden, chief economist of Fathom Financial Consulting in London — that brought together the various strands better than anything I have read so far, or at least organized the problem for asset managers in a very useful way. 
  • After crunching through some statistical analysis, Brigden found that the crucial reproduction number, or “R” rate — the number of people infected by each person who has Covid — tends to diminish in line with reduced mobility. In other words, the more people stay at home, the less they infect others. 
  • But crucially, R also decreases in line with the number of people who have already been infected. This second variable is plainly very good news. The more any individual country has had the disease already, the slower it is likely to spread. To show the effect, Brigden offered this chart of how much reduced mobility can explain infection rates in the U.K. on its own, compared with the actual change in R that has happened:
  • The U.K.’s drastic lockdown in March and April plainly had everything to do with bringing spread under control. But we would have expected infection rates to drift upwards as the country began slowly to return to normal in the late spring; instead, the R rate has continued to fall and remains below 1.
  • Naturally, one of the greatest concerns at present centers on the U.S., and the way that Covid is now taking hold across the states of the “Sun Belt” that had largely been spared during the beginning of the outbreak in March. The failure of these states to clamp down on mobility doubtless has much to do with this. But when Brigden mapped R in each state (for these purposes, simply looking at the multiple of new cases this week compared to last), against the death rate that it had already suffered, there was a clear and strong relationship. States with minimal death rates so far are suffering serious levels of R well above 2. The states that have suffered the greatest death tolls to date, which are all now well into their reopenings, still have R rates comfortably below 1:
  • What is going on? Brigden very usefully breaks down the possibilities into five broad answers, which are not mutually exclusive. The first three, I would say, are unambiguously positive, both for us all as humans, and less importantly in terms of the prospects for risk assets. The fourth is somewhat negative, but still suggests that there is a clear if costly way to keep the damage wrought by the virus under control. The fifth would be a total nightmare:
    • Fear of dying from the disease provokes other changes in behavior, such as more frequent hand washing and the wearing of face masks, that prevent the spread of the disease but are not captured by measures of mobility
    • Heterogeneity across the population means that we all have a different ‘R’ number, with some people, including those with a large network of contacts, more likely both to acquire the disease and to pass it on. Once those people have been exposed, and are no longer susceptible, the average R will fall
    • The virus has spread far more rapidly than antibody testing suggests, which means the virus is running out of people to infect
    • Potential ‘super spreader’ events — such as nightclubs, and music concerts that involve a lot of people being close together indoors — are no longer happening
    • It is a seasonal phenomenon in the northern hemisphere, and it will return later this year in a ‘second wave’
  • Living in New York, I see a lot of truth in the first. It is unusual to see people walking down the street unmasked, and more or less every building requires you to wear a mask to enter. I have never yet seen anyone complain about this. As the disease takes hold in the Sun Belt, I suspect strong and understandable resistance to minor inconveniences like mask-wearing will begin to disappear.
  • I can believe that there is a fair amount of truth to the second hypothesis, and the authorities are busily testing the third. In New York in the early days, plenty of people with nasty cases of C19 who did not need to be hospitalized were never tested, and so do not appear in the figures. 
  • The fourth makes much sense, and bodes ill for cinemas, theaters, professional conference businesses and sports played indoors as well as nightclubs. It must be miserable news for single people in their twenties. Going without such “super spreading” events would inevitably have a negative ongoing impact on GDP, but it would be well short of a disaster.
  • A true second wave (what is happening in the Sun Belt is a continuation of the first wave that hit the Acela Corridor) would be a disaster. The second wave of the Spanish flu in the fall of 1918 proved far worse than the first wave that spring. As a second wave of C19 would overlap with seasonal flu, and would hit a population very reluctant to return to lockdown, it would be terrible for the world’s advanced economies, and quite possibly inflict even more economic damage than the first wave has done. Current events in the Sun Belt, India and Latin America do not disprove that the disease is seasonal. For the time being, it is most prevalent in the southern hemisphere, where it is winter.
  • We have few if any worthwhile precedents, so attempting to measure the risks with precision is futile. Very crudely, let’s give each of these five possibilities a 20% chance of being correct. So there’s roughly a 60% chance that the countries that have already had a serious outbreak truly have it under control now and that the U.S. will at last subdue it once the Sun Belt surge dies down; a 20% chance that there will be a continuing but manageable economic drag; and a 20% chance that the worst is yet to come. 
  • Anyone whose portfolio is substantially under-exposed to the chance of continuing growth in assets, or fails to hedge against the very significant tail risk that still exists, should probably make some changes.

Source: Covid-19: How to Weigh the Market Risks

2. If you’re over 75, catching C19 can be like playing Russian roulette 

By Antonio Regaladoa

  • Are you hiding from C19? I am. The reason is simple: the high chance of death from the virus. 
  • I was reminded of the risk last week by this report from the New York City health department and Columbia University which estimated that on average, between March and May, the chance of dying if you get infected by the coronavirus was 1.45%.
  • That’s higher than your lifetime chance of getting killed in a car wreck. That’s every driver cutting you off, every corner taken too fast, every time you nearly dozed off on the highway, all crammed into one. That’s not a disease I want to get. For someone my mother’s age, the chance of death came to 13.83% but ranged as high as 17%. That’s roughly 1 in 6, or the chance you’ll lose at Russian roulette. That’s not a game I want my mother to play.
  • The rate at which people are dying from the coronavirus has been estimated many times and is calculated in different ways. For example, if you become an official C19 “case” on the government’s books, your death chance is more like 5%, because you’re sick enough to have sought out help and to have been tested. 
  • But this study instead calculated the “infection fatality ratio,” or IFR. That’s the chance you die if infected at all. This is the real risk to keep in view. It includes people who are asymptomatic, get only a sniffle, or tough it out at home and never get tested. 
  • Because we don’t know who those people who never got tested are, IFR figures are always an estimate, and the 1.45% figure calculated for New York is higher than most others, many of which fluctuate around 1%. That could be due to higher rates of diabetes and heart disease in the city, or to estimates used in the study. [Note: Studies have estimated a much lower IFR, including the CDC which estimates an IFR of less than 0.3%]
  • It’s also true that your personal odds of dying from C19 will differ from the average. Location matters—cruise ship or city—and so do your sex, your age, and whether you have preexisting health conditions. If you’re in college, your death odds are probably lower by a factor of a hundred, though if you’re morbidly obese, they go back up. Poor health—cancer, clogged arteries—also steeply increase what scientists call the “odds ratio” of dying. 
  • The biggest factor, though, is age.  I looked at the actuarial tables, and the chance of death for a man in my age group (I’m 51) is around 0.4% per year from all causes. So if I get C19, my death chance is probably three times my annual all-cause annual risk (since I am a man, my C19 risk is higher than the average). Is that a chance I can live with? Maybe, but the problem is that I have to take that extra risk right now, all up front, not spread out over time where I can’t see or worry about it. 
  • On Twitter, some readers complained that average risks don’t tell them much about how to think or act. They have a point. What’s a real-life risk that’s similar to a 1.45% chance of dying? It wasn’t easy to think of one, since mathematically, you can’t encounter such a big risk very often. Skydiving, maybe?  According to the US Parachute Association, there’s just one fatality for every 220,301 jumps. It would take 3,200 jumps to equal the average risk of death from covid. 
  • Risk perceptions differ, but it’s the immense difference in IFR risk for the young (under 25) and the elderly (over 75) that really should complicate the reopening discussion. Judging from the New York data, Grandpa’s death chances from infection are 1,000 times that of Junior. So yes, we need schools to keep kids occupied, learning, and healthy. And for them, thank goodness, the chances of death are very low. But reopening schools and colleges has the ugly side effect that those with the lowest risk could be, in effect, putting a gun to the head of those with the highest (although there is still much we do not know about how transmissible the virus is among children).
Decent odds
  • The virus is now spreading fast again in the US, after the country failed to settle on a strong mitigation plan. At the current rate of spread—40,000 confirmed cases a day (and maybe 5 to 10 times that in reality)—it’s only two years until most people in the US have been infected. It means we’re pointed toward what, since the outset, has been seen as the worst-case scenario: a couple of hundred million infected and a quarter-million deaths. 
  • By now you might be wondering what your own death risk is. Online, you can find apps that will calculate it, like one at www.covid19survivalcalculator.com, which employs odds ratios from the World Health Organization.  I gave it my age, gender, body mass index, and underlying conditions and learned that my overall death risk was a bit higher than the average. But the site also wanted to account for my chance of getting infected in the first place. After I told it I was social distancing and mostly wearing a mask, and my rural zip code, the gadget thought I had only a 5% of getting infected. 
  • I clicked, the page paused, and the final answer appeared: “Survival Probability: 99.975%”. 
  • Those are odds I can live with. And that’s why I am not leaving the house.

Source: If you’re over 75, catching covid-19 can be like playing Russian roulette

E. New Scientific Findings & Research  

1. Breathing Correctly Can Help the Body Fight Viral Infections 

  • Inhale through your nose and exhale through your mouth. It’s not just something you do in yoga class – breathing this way actually provides a powerful medical benefit that can help the body fight viral infections.
  • The reason is that your nasal cavities produce the molecule nitric oxide, which chemists abbreviate NO, that increases blood flow through the lungs and boosts oxygen levels in the blood. 
  • Breathing in through the nose delivers NO directly into the lungs, where it helps fight coronavirus infection by blocking the replication of the coronavirus in the lungs. 
  • But many people who exercise or engage in yoga also receive the benefits of inhaling through the nose instead of the mouth. The higher oxygen saturation of the blood can make one feel more refreshed and provides greater endurance.
  • I am one of three pharmacologists who won the Nobel Prize in 1998 for discovering how nitric oxide is produced in the body and how it works.
The role of nitric oxide in the body
  • Nitric oxide is a widespread signaling molecule that triggers many different physiological effects. It is also used clinically as a gas to selectively dilate the pulmonary arteries in newborns with pulmonary hypertension. Unlike most signaling molecules, NO is a gas in its natural state.
  • NO is produced continuously by the 1 trillion cells that form the inner lining, or endothelium, of the 100,000 miles of arteries and veins in our bodies, especially the lungs. Endothelium-derived NO acts to relax the smooth muscle of the arteries to prevent high blood pressure and to promote blood flow to all organs. Another vital role of NO is to prevent blood clots in normal arteries.
  • In addition to relaxing vascular smooth muscle, NO also relaxes smooth muscle in the airways – trachea and bronchioles – making it easier to breathe. Another type of NO-mediated smooth muscle relaxation occurs in the erectile tissue (corpus cavernosum), which results in penile erection. In fact, NO is the principal mediator of penile erection and sexual arousal. This discovery led to the development and marketing of sildenafil, trade name Viagra, which works by enhancing the action of NO.
  • Other types of cells in the body, including circulating white blood cells and tissue macrophages, produce nitric oxide for antimicrobial purposes. The NO in these cells reacts with other molecules, also produced by the same cells, to form antimicrobial agents to destroy invading microorganisms including bacteria, parasites and viruses. As you can see, NO is quite an amazing molecule.
Nitric oxide gas as an inhaled therapy
  • Since NO is a gas, it can be administered with the aid of specialized devices as a therapy to patients by inhalation. Inhaled NO is used to treat infants born with persistent pulmonary hypertension, a condition in which constricted pulmonary arteries limit blood flow and oxygen harvesting.
  • Inhaled NO dilates the constricted pulmonary arteries and increases blood flow in the lungs. As a result, the red blood cell hemoglobin can extract more lifesaving oxygen and move it into the general circulation. Inhaled NO has literally turned blue babies pink and allowed them to be cured and to go home with mom and dad. Before the advent of inhaled NO, most of these babies died.
  • Inhaled NO is currently in clinical trials for the treatment of patients with C19. Researchers are hoping that three principal actions of NO may help fight covid: dilating the pulmonary arteries and increasing blood flow through the lungs, dilating the airways and increasing oxygen delivery to the lungs and blood, and directly killing and inhibiting the growth and spread of the coronavirus in the lungs.
How nitric oxide kills viruses
  • In an in vitro study done in 2004 during the last SARS outbreak, experimental compounds that release NO increased the survival rate of nucleus-containing mammalian cells infected with SARS-CoV. This suggested that NO had a direct antiviral effect. In this study, NO significantly inhibited the replication cycle of SARS-CoV by blocking production of viral proteins and its genetic material, RNA.
  • In a small clinical study in 2004, inhaled NO was effective against SARS-CoV in severely ill patients with pneumonia.
  • The SARS CoV, which caused the 2003/2004 outbreak, shares most of its genome with the coronavirus. This suggests that inhaled NO therapy may be effective for treating patients with C19. Indeed, several clinical trials of inhaled NO in patients with moderate to severe C19, who require ventilators, are currently ongoing in several institutions. The hope is that inhaled NO will prove to be an effective therapy and lessen the need for ventilators and beds in the ICU.
  • The sinuses in the nasal cavity, but not the mouth, continuously produce NO. The NO produced in the nasal cavity is chemically identical to the NO that is used clinically by inhalation. So by inhaling through the nose, you are delivering NO directly into your lungs, where it increases both airflow and blood flow and keeps microorganisms and virus particles in check.
  • While anxiously awaiting the results of the clinical trials with inhaled NO, and the development of an effective vaccine against C19, we should be on guard and practice breathing properly to maximize the inhalation of nitric oxide into our lungs. Remember to inhale through your nose; exhale through your mouth.

Source: Powerful Medical Benefit: The Right Way to Breathe During the Coronavirus Pandemic

2. Researchers create air filter that can catch and instantly kill the coronavirus – 99.8% Effective  

  • Researchers from the University of Houston, in collaboration with others, have designed a “catch and kill” air filter that can trap the virus responsible for C19, killing it instantly.
  • Zhifeng Ren, director of the Texas Center for Superconductivity at UH, collaborated with Monzer Hourani, CEO of Medistar, a Houston-based medical real estate development firm, and other researchers to design the filter, which is described in a paper published in Materials Today Physics.
  • The researchers reported that virus tests at the Galveston National Laboratory found 99.8% of the coronavirus was killed in a single pass through a filter made from commercially available nickel foam heated to 200 degrees Centigrade, or about 392 degrees Fahrenheit. It also killed 99.9% of the anthrax spores in testing at the national lab, which is run by the University of Texas Medical Branch.
  • “This filter could be useful in airports and in airplanes, in office buildings, schools and cruise ships to stop the spread of C19,” said Ren, MD Anderson Chair Professor of Physics at UH and co-corresponding author for the paper. “Its ability to help control the spread of the virus could be very useful for society.” Medistar executives are is also proposing a desk-top model, capable of purifying the air in an office worker’s immediate surroundings, he said.
  • Ren said the Texas Center for Superconductivity at the University of Houston (TcSUH) was approached by Medistar on March 31, as the pandemic was spreading throughout the United States, for help in developing the concept of a virus-trapping air filter.
  • Luo Yu of the UH Department of Physics and TcSUH along with Dr. Garrett K. Peel of Medistar and Dr. Faisal Cheema at the UH College of Medicine are co-first authors on the paper.
  • The researchers knew the virus can remain in the air for about three hours, meaning a filter that could remove it quickly was a viable plan. With businesses reopening, controlling the spread in air conditioned spaces was urgent.
  • And Medistar knew the virus can’t survive temperatures above 70 degrees Centigrade, about 158 degrees Fahrenheit, so the researchers decided to use a heated filter. By making the filter temperature far hotter – about 200 C – they were able to kill the virus almost instantly.
  • Ren suggested using nickel foam, saying it met several key requirements: It is porous, allowing the flow of air, and electrically conductive, which allowed it to be heated. It is also flexible.
  • But nickel foam has low resistivity, making it difficult to raise the temperature high enough to quickly kill the virus. The researchers solved that problem by folding the foam, connecting multiple compartments with electrical wires to increase the resistance high enough to raise the temperature as high as 250 degrees C.
  • By making the filter electrically heated, rather than heating it from an external source, the researchers said they minimized the amount of heat that escaped from the filter, allowing air conditioning to function with minimal strain.
  • A prototype was built by a local workshop and first tested at Ren’s lab for the relationship between voltage/current and temperature; it then went to the Galveston lab to be tested for its ability to kill the virus. Ren said it satisfies the requirements for conventional heating, ventilation and air conditioning (HVAC) systems.
  • “This novel biodefense indoor air protection technology offers the first-in-line prevention against environmentally mediated transmission of airborne coronavirus and will be on the forefront of technologies available to combat the current pandemic and any future airborne biothreats in indoor environments,”  Cheema said.
  • Hourani and Peel have called for a phased roll-out of the device, “beginning with high-priority venues, where essential workers are at elevated risk of exposure (particularly schools, hospitals and health care facilities, as well as public transit environs such as airplanes).”
  • That will both improve safety for frontline workers in essential industries and allow nonessential workers to return to public work spaces, they said.

Source: Researchers create air filter that can kill the coronavirus

3. Study Is First to Identify Potential Therapeutic Targets for C19 Using Blood Samples From Critically Ill Patients 

  • A team from Lawson Health Research Institute and Western University are the first in the world to profile the body’s immune response to C19. By studying blood samples from critically ill patients at London Health Sciences Centre (LHSC), the research team identified a unique pattern of six molecules that could be used as therapeutic targets to treat the virus. The study was recently published in Critical Care Explorations.
  • Since the pandemic’s start there have been reports that the immune system can overreact to the virus and cause a cytokine storm – elevated levels of inflammatory molecules that damage healthy cells.
  • “Clinicians have been trying to address this hyperinflammation but without evidence of what to target,” explains Dr. Douglas Fraser, lead researcher from Lawson and Western’s Schulich School of Medicine & Dentistry and Critical Care Physician at LHSC. “Our study takes away the guessing by identifying potential therapeutic targets for the first time.”
  • The study included 30 participants: 10 C19 patients and 10 patients with other infections admitted to LHSC’s intensive care unit (ICU), as well as 10 healthy control participants. Blood was drawn daily for the first seven days of ICU admission, processed in a lab and then analyzed using statistical methods and artificial intelligence (AI). 
  • The research team studied 57 inflammatory molecules. They found that six molecules were uniquely elevated in C19 ICU patients (tumor necrosis factor, granzyme B, heat shock protein 70, interleukin-18, interferon-gamma-inducible protein 10 and elastase 2). 
  • The team also used AI to validate their results. They found that inflammation profiling was able to predict the presence of C19 in critically ill patients with 98% accuracy. They also found that one of the molecules (heat shock protein 70) was strongly associated with an increased risk of death when measured in the blood early during the illness.
  • “Understanding the immune response is paramount to finding the best treatments,” says Dr. Fraser “Our next step is to test drugs that block the harmful effects of several of these molecules while still allowing the immune system to fight the virus.”

Source: Study Is First to Identify Potential Therapeutic Targets for Covid-19 Using Blood Samples From Critically Ill Patients

4. Italian Study Shows Lower ‘Viral Load,’ Milder Symptoms In C19 Patients 

  • C19 patients who were tested for the a virus at an Italian hospital in May had fewer virus particles than those tested a month before, a small study released last week found.
  • The researchers said the lower “viral load” could mean that the coronavirus is getting weaker. But the researchers also noted that it is unclear what is causing the lower viral load.
  • “The researchers analyzed 200 nasopharyngeal swabs taken at the San Raffaele hospital,” The Daily Mail reported. “Half were from patients treated in April – at the pandemic’s peak – and half were from patients treated in May.”
    • Based on the results, the researchers calculated that patients’ viral loads were higher in April. Patients swabbed in April also had more severe symptoms and were more likely to need hospitalization and intensive care, they found.
    • Viral loads were similar in men and women, but were higher in patients aged 60 and over, and in those with severe C19. Clementi’s team said that while it was theoretically possible that the new coronavirus had mutated, they did not have molecular data to prove it.
    • Theirs is not the only hospital to see falling viral loads.  Doctors at the University of Pittsburgh Medical Center in Pennsylvania have noted anecdotally that their patients don’t seem as sick, and that C19 tests show lower viral loads.
    • The most optimistic – and unproven – scenario is that, perhaps, the virus has mutated in such a way that it is less contagious than in the past several months. All viruses mutate, and usually the surviving viruses have mutated in ways that help them to make copies of themselves and spread more rapidly.
  • The new study follows another in which researchers found that the coronavirus that swept the world was losing its “potency,” according to a top Italian doctor.
  • “In reality, the virus clinically no longer exists in Italy,” Alberto Zangrillo, the head of the San Raffaele Hospital in Milan, said last month, according to Reuters. “The swabs that were performed over the last 10 days showed a viral load in quantitative terms that was absolutely infinitesimal compared to the ones carried out a month or two months ago,” he told RAI television.
  • C19 cases peaked in mid-April and while numbers continue to stay high, most experts attribute that to the surge in testing. “Italy, specifically, now averages fewer than 100 C19 deaths per day after becoming the global epicenter just two months ago,” Reuters reported.

Source: Italian Study Shows Lower ‘Viral Load,’ Milder Symptoms In COVID-19 Patients

F. Potential Treatments

1. Researchers test COVID treatment that decreases mortality rates of patients on ventilators by 70%  

  • A cellular therapy tested on 13 intubated patients with mechanical ventilation has been shown to be efficient for the clinical improvement of critical cases of C19.
  • The study, the broadest to date in these conditions, has been published in The Lancet’s EClinical Medicine, after proving that the advanced treatment decreases mortality rates of critical patients with coronavirus from 85% to 15%. These are the first results of the BALMYS-19 project, co-led by professor from the Miguel Hernández University (UMH) and researcher at the Health Research Institute of Alicante (ISABIAL) Bernat Soria, together with professor Damián García-Olmo from the Jiménez Díaz foundation (Autonomous University of Madrid). Another six Spanish universities and six hospitals have taken part in the study.
  • Professor Soria began his research on the use of cellular therapy at the UMH and, afterwards, at the National University Hospital of Singapore during the Asian epidemic of SARS-1 in 2003 where he observed the intense pulmonary infiltrates in the biopsies of these patients. Unlike SARS-1, in the infection by the coronavirus, the clinical picture shows a depression of the immune system (lymphopenia), a widespread extreme inflammatory response, tissue damage, hypercoagulability and intense pulmonary distress that requires admission in the ICU. 
  • This advanced therapy is based on stem cells with regenerative, anti-inflammatory and immunoregulating properties, and is the first cell therapy for C19 entirely developed and produced in Spain. During the pilot study, critical coronavirus patients were treated who did not respond to conventional cellular therapy treatment, composed of allogeneic mesenchymal stromal cells, in doses of one million cells per kilo of weight, in one or several doses. The results of its use in coronavirus patients admitted in ICUs were compared with the clinical evolution and mortality of similar cases.
  • According to the results obtained, the new cellular therapy does not cause adverse reactions, but does entail an overall clinical and radiological improvement. The mortality rate of patients decreased from 70-85% to 15%. 
  • A majority of people treated with the cellular therapy were extubated during the data collecting period. Their inflammation (C-reactive protein and ferritin), coagulation (D-dimer) and tissue damage (lactate dehydrogenase) markers decreased. Furthermore, it was verified that the drug did not decrease lymphocyte counts. In fact, the results show that the new treatment increases the presence of T lymphocytes (which directly attack the virus) and B lymphocytes (which synthesize antibodies).
  • The authors of the study explain that cellular therapies, unlike other treatments, are “live drugs” and must be used by qualified medical staff, and produced by departments accredited by the Spanish Agency for Medicines and Health Products. Knowledge on the biological scientific foundations of these treatments, as well as of the physiology of the interaction between the drug and the host, are essential for their appropriate handling.

Source: Researchers test COVID treatment that decreases mortality rates by 70%

2. Regeneron Advances Antibody Cocktail into Phase III Trials 

  • Regeneron Pharmaceuticals said today its double-antibody cocktail against C19 is advancing into Phase III studies, less than a month after the start of its first clinical trial, with preliminary data from one study expected to be reported later this summer.
  • Regeneron said it is proceeding with clinical development of the antibody cocktail after generating a positive review from the Independent Data Monitoring Committee overseeing the Phase I safety study, following an evaluation of data from an initial cohort of 30 hospitalized and non-hospitalized patients with C19. Regeneron launched the safety study in June.
  • The cocktail, REGN-COV2, consists of two antibodies—REGN10933 and REGN10987—that are designed to bind non-competitively to the receptor binding domain of the coronavirus’ spike protein. Regeneron says that such binding diminishes the ability of mutant viruses to escape treatment.
  • REGN-COV2 is among 18 “front runner” candidates among the more than 260 C19 therapeutics tracked by GEN’s updated “C19 DRUG & VACCINE TRACKER.”
  • Regeneron is partnering with the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) to conduct what is being planned as a 2,000-patient Phase III trial (NCT04452318) designed to assess REGN-COV2’s ability to prevent infection among uninfected people who have had close exposure to a C19 patient, such as a patient’s housemate.
  • The placebo-controlled trial, to be conducted at approximately 100 sites, had yet to begin recruiting patients as of June 30, the date of the study’s most recent update on ClinicalTrials.gov. According to that update, the trial’s estimated primary completion date is April 11, 2021, though Regeneron did not include a timeframe for reporting data from the NIAID study in its announcement today.
  • The trial will have three primary outcome measures:
    • Proportion of participants who have a positive SARS-CoV-2 quantitative reverse transcription polymerase chain reaction (RT-qPCR) based on central lab test and signs and symptoms of SARS-CoV-2 infection during an up to 1 month timeframe.
    • Proportion of participants who have a RT-qPCR confirmed SARS-CoV-2 infection (either symptomatic or asymptomatic) during the same efficacy assessment period.
    • Incidence and severity of treatment-emergent adverse events up to 8 months following treatment.
“Sooner than a vaccine”
  • “We are pleased to collaborate with NIAID to study REGN-COV2 in our quest to further prevent the spread of the virus with an antiviral antibody cocktail that could be available much sooner than a vaccine,” George D. Yancopoulos, MD, PhD, Regeneron co-founder, president, and chief scientific officer, said in a statement.
  • Regeneron has previously said that its antibody cocktail offers several advantages over a vaccine—including longer-term utility for elderly and immuno-compromised patients, who often do not respond well to vaccines.
  • In its statement today, Regeneron said it has advanced REGN-COV2 into the Phase II/III portion of two adaptive Phase I/II/III trials designed to evaluate the antibody cocktail’s ability to treat hospitalized and non-hospitalized patients with C19.
  • Regeneron said preliminary data from the Phase II/III trials is expected as soon as “later this summer,” though the study in ambulatory adults has an estimated primary completion date of November 21, and the study in hospitalized adults, March 3, 2021.
  • The two Phase II/III trials are set to be conducted at approximately 150 sites in the U.S., Brazil, Mexico and Chile.

Source: Regeneron Advances Antibody Cocktail into Phase III Trials

G. Reducing The Spread

1. Can a $50 nasal spray thwart the spread of C19?!  

  • You should practice social distancing and wear a mask to prevent the spread of C19. But even masks aren’t perfect. A high-end N95 mask can filter an estimated 99.8% of the virus from the air, while many cotton masks filter just 50% or less. Given that researchers now know the virus is airborne, you may wonder: Is there anything else you can do to prevent the spread of C19?
  • According to David Edwards, a Harvard professor and entrepreneur, there is. And it’s not much more complicated than sniffing a specialized saline solution. “It’s cleaning my bioaerosol footprint, if you will,” he says.
  • With his company Sensory Cloud (https://sensory-cloud.com/), Edwards has developed a $50 product that has two components: the Nimbus and FEND. The Nimbus is an aerosol squirter, capable of turning liquid into a cloud of vapor that you puff in front of your nose to inhale from the air. FEND is a solution that goes inside the squirter, composed of a mix of salts similar to seawater.
  • In a recent study on 10 subjects (PDF here), Edwards demonstrated that inhaling the solution can reduce potentially infected aerosols—droplets that fly from your nose and mouth while speaking or sneezing—by up to 99% for six hours. That means that if you have C19, you should be less contagious to others. Plus, Edwards believes it could help prevent the coronavirus from moving from your upper respiratory system (your nose) down to your lungs, too. 
  • While the Nimbus is a personal device, it can be shared between people (carefully) because it doesn’t go in your nose or body. Edwards imagines that an office, a restaurant, or a hospital could assign one person to pump it for each visitor who walks in, much like people do temperature checks or distribute hand sanitizer today. Each bottle costs $6 and can spray 250 doses, and while that cost is low, Edwards plans profits at scale, as he intends customers to buy subscription packages. “One hundred Nimbi could treat 50,000 people at a stadium,” he says.
How is this all possible?
  • As Edwards explains, your nose is “the body’s face mask.” Many viruses actually get caught inside your nose like a trap, thanks to mucus. From there, your entire respiratory tract is protected with airway lining fluid, a mix of mucus and fluid that protects the cells like a sticky raincoat. Cilia in those cells beat the liquid to clear it away and any infections stuck inside. But when you cough, tiny bits of that fluid, filled with viruses, can break away. They can fly out of your mouth to infect someone else. Or they can float deeper into your airway, infecting your lungs. Aerosols are a two-way street of infection, both out of your body and deeper therein.
  • In 2004, Edwards was researching how to protect people from anthrax, the quintessential airborne biological weapon. As part of that research, he looked at mucins, the protein building blocks inside mucus.
  • “It led to a paper . . . an observation that when you inhale simple saline—sodium chloride—there’s an effect that salt has on mucins and mucin-like proteins and . . . that leads to a calmness of surface in airways,” Edwards says. “It was a minor effect but an effect. For several years we dug into this.”
  • When you breathe in salt and water, the fluid in your trachea has a greater surface tension. So when you talk or cough, the equivalent of high winds blow across the liquid in your respiratory tract. The effect of saline is that tiny droplets are less likely to break away from the surface. The chemistry at work isn’t terribly complicated: Calcium chloride (a salt) has two positive charges. Mucus proteins are negatively charged. So the calcium in the liquid actually glues two mucus proteins together at the molecular level. (Four aerosol experts we reached out to in order to validate the product’s claims were unavailable for comment.) 
  • Edwards was only able to develop the device so quickly in response to C19 because he originally designed it for something else. It was a food product that Edwards had been working on for appetite control, and he had planned to release it this year. An earlier endeavor in inhalable food was called Le Whif, and it let you puff a few calories of chocolate powder instead of blowing your diet on a whole chocolate bar. This was followed up by Le Whaf, a device that used ultrasonic waves to vaporize cocktails. Le Whif is no longer in production; Le Whaf still makes international appearances at various events.
  • But as C19 spread across the globe earlier this year, Edwards back-burnered his food products and turned his attention to public health. The Nimbus is calibrated to mist the saline solution in 10 micron droplets. As he explains, if it misted in 50 micron droplets, they’d all end up in your nose. If it misted in 2 micron droplets, they would go straight to your lungs like an inhaler. At 10 microns, the aerosol lands inside the sweet spot of your trachea and bronchi.
  • Edwards currently has thousands of Nimbuses already produced. And he has licensed the FEND saline solution from the pharmaceutical company Pulmatrix. He is currently beginning pilot studies with the Beth Israel Hospital in Boston, while enlisting schools and offices to take part, too.
  • Right now, you can purchase a Nimbus system for yourself with two bottles of FEND solution for $49 shipping this September, and Edwards says it can mitigate the spread of not just C19, but any aerosol cold or flu, too.
  • Will the Nimbus prove effective in real-world testing? While the study showed promising results, it was small, and it didn’t replicate the conditions of millions of people worldwide battling a pandemic. Even if it does work as advertised, can people really be persuaded to inhale something, given the reluctance many of them have to wearing masks?
  • [Note: This product is not yet supported by sufficient research to know if it will mitigate the transmission of the coronavirus.  We are skeptical, but we’ll keep an eye on it.]

Source: Harvard professor develops a $50 nasal spray to thwart the spread of COVID-19

H. Concerns & Unknowns

1. Popular Heartburn Drugs Linked to Heightened C19 Risk  

  • A popular form of heartburn medication may increase a person’s risk of developing C19, according to a new study, lengthening the already long list of risk factors for the virus.
  • In the study, published Tuesday in pre-print form in the American Journal of Gastroenterology, scientists led by Cedars-Sinai Medical Center’s Dr. Brennan Spiegel conducted an online survey involving more than 86,000 people. Among them, more than 53,000 reported abdominal pain or discomfort, acid reflux, heartburn or regurgitation, and answered questions about the medications they took to relieve those symptoms. Of those, more than 3,300 tested positive for C19.
  • When the researchers analyzed the data, they found that respondents who said they used proton pump inhibitor (PPI) medications to treat their heartburn had anywhere from two to nearly four times the risk of testing positive for C19, compared to people not using such medications. PPI drugs, which are available by prescription and over the counter, work by turning off the pumps in cells that release acid into the stomach. They can be taken once or twice a day; people taking PPI medications twice a day had a higher risk of infection compared to those taking them once a day.
  • Spiegel, who is also editor-in-chief of the American Journal of Gastroenterology, says the results aren’t necessarily surprising. Previous studies have found that people taking PPI medications can be at higher risk of certain infections, including C.difficile (common in hospitals). That’s because the drugs reduce stomach acid, and acid is one way the body kills off potentially harmful bacteria and viruses. However, Spiegel was surprised at “just how large the effect seemed to be.”
  • “We found a biological gradient where the stronger the medicine, the higher the dose, the higher the effect for C19,” he says.
  • The gut, which includes the stomach and intestines, can be considered one of the body’s largest immune organs. If the gut’s normal environment is altered—as it can be when taking heartburn medications—that may turn it into fertile ground for viruses like SARS-CoV-2, which is responsible for C19.
  • “Viruses like SARS-CoV-2 are capable of hijacking the gastrointestinal tract quickly; we know that,” says Spiegel. “It can invade, replicate and multiply efficiently. There is even a theory that maybe it uses the intestines as a kind of home base where it entrenches itself and then spreads throughout the body.”
  • While people who take PPIs showed an increased risk of C19 infection compared to those who don’t, the absolute risk is still small. That means people taking PPIs shouldn’t immediately stop doing so for fear of contracting the virus without first consulting with their doctor. There are ways PPI users may be able to reduce their risk, too. Studies have shown, for example, that taking the drugs once a day is as effective as taking them twice a day. Since Spiegel’s study suggests that higher doses bring increased risk, people should discuss with their doctors whether reducing their daily dosage might make sense.
  • Meanwhile, other acid-controlling drugs don’t seem to have the same heightened risk of C19 infection. In Spiegel’s study, people taking H2 blockers, for example, did not show greater risk of infection (H2 blockers, which include Pepcid and Zantac, work by blocking receptors on stomach tissue cells that trigger acid production). However, the U.S. Food and Drug Administration in April requested that manufacturers remove prescription and over the counter H2 blockers containing ranitidine from the market after an investigation revealed that they contained a contaminant linked to cancer. The request applied to Zantac, but not Pepcid, which contains a different acid-blocking chemical called famotidine.
  • For people who need to take PPIs to control heartburn, Spiegel says their doctors should remind them of their heightened risk of infections of any kind, including C19. And his team’s findings also reinforce public health advice about taking proper precautions to protect against the virus.
  • “If you’re worried about getting C19, the best thing to do is to wash your hands, wear a mask, socially distance and do all the basic blocking and tackling public health measures,” says Spiegel. “They are way more important than immediately stopping PPIs.”
  • [Note: Common PPIs on the shelf include: Prilosec, Prevacid, Protonix, Aciphex, Nexium, and Dexilant]
  • Read the study here: Increased Risk of COVID-19 Among Users of Proton Pump Inhibitors 

Source: Popular Heartburn Drugs Linked to Heightened COVID-19 Risk

2. Warning of serious brain disorders in people with mild coronavirus symptoms  

  • Doctors may be missing signs of serious and potentially fatal brain disorders triggered by coronavirus, as they emerge in mildly affected or recovering patients, scientists have warned.
  • Neurologists are on Wednesday publishing details of more than 40 UK C19 patients whose complications ranged from brain inflammation and delirium to nerve damage and stroke. In some cases, the neurological problem was the patient’s first and main symptom.
  • The cases, published in the journal Brain, revealed a rise in a life-threatening condition called acute disseminated encephalomyelitis (Adem), as the first wave of infections swept through Britain. At UCL’s Institute of Neurology, Adem cases rose from one a month before the pandemic to two or three per week in April and May. One woman, who was 59, died of the complication.
  • Read the study here: https://academic.oup.com/brain/article/doi/10.1093/brain/awaa240/5868408 
  • A dozen patients had inflammation of the central nervous system, 10 had brain disease with delirium or psychosis, eight had strokes and a further eight had peripheral nerve problems, mostly diagnosed as Guillain-Barré syndrome, an immune reaction that attacks the nerves and causes paralysis. It is fatal in 5% of cases.
  • “We’re seeing things in the way C19 affects the brain that we haven’t seen before with other viruses,” said Michael Zandi, a senior author on the study and a consultant at the institute and University College London Hospitals NHS foundation trust.
  • “What we’ve seen with some of these Adem patients, and in other patients, is you can have severe neurology, you can be quite sick, but actually have trivial lung disease,” he added.
  • “Biologically, Adem has some similarities with multiple sclerosis, but it is more severe and usually happens as a one-off. Some patients are left with long-term disability, others can make a good recovery.”
  • The cases add to concerns over the long-term health effects of C19, which have left some patients breathless and fatigued long after they have cleared the virus, and others with numbness, weakness and memory problems.
  • One coronavirus patient described in the paper, a 55-year-old woman with no history of psychiatric illness, began to behave oddly the day after she was discharged from hospital.
  • She repeatedly put her coat on and took it off again and began to hallucinate, reporting that she saw monkeys and lions in her house. She was readmitted to hospital and gradually improved on antipsychotic medication.
  • Another woman, aged 47, was admitted to hospital with a headache and numbness in her right hand a week after a cough and fever came on. She later became drowsy and unresponsive and required an emergency operation to remove part of her skull to relieve pressure on her swollen brain.
  • “We want clinicians around the world to be alert to these complications of coronavirus,” Zandi said. He urged physicians, GPs and healthcare workers with patients with cognitive symptoms, memory problems, fatigue, numbness, or weakness, to discuss the case with neurologists.
  • “The message is not to put that all down to the recovery, and the psychological aspects of recovery,” he said. “The brain does appear to be involved in this illness.”
  • The full range of brain disorders caused by C19 may not have been picked up yet, because many patients in hospitals are too sick to examine in brain scanners or with other procedures. “What we really need now is better research to look at what’s really going on in the brain,” Zandi said.
  • One concern is that the virus could leave a minority of the population with subtle brain damage that only becomes apparent in years to come. This may have happened in the wake of the 1918 flu pandemic, when up to a million people appeared to develop brain disease.
  • “It’s a concern if some hidden epidemic could occur after Covid where you’re going to see delayed effects on the brain, because there could be subtle effects on the brain and slowly things happen over the coming years, but it’s far too early for us to judge now,” Zandi said.
  • “We hope, obviously, that that’s not going to happen, but when you’ve got such a big pandemic affecting such a vast proportion of the population it’s something we need to be alert to.”
  • David Strain, a senior clinical lecturer at the University of Exeter Medical School, said that only a small number of patients appeared to experience serious neurological complications and that more work was needed to understand their prevalence.
  • “This is very important as we start to prepare post-C19 rehabilitation programs,” he said. “We’ve already seen that some people with C19 may need a long rehabilitation period, both physical rehabilitation such as exercise, and brain rehabilitation. We need to understand more about the impact of this infection on the brain.” 

Source: Warning of serious brain disorders in people with mild coronavirus symptoms

3. Can You Catch Covid-19 Twice? 

  • Months into the pandemic, the scientific community’s understanding of C19, the illness caused by the new coronavirus, is rapidly evolving. New reports of patients testing positive, or appearing to suffer symptoms months after initial diagnosis, continues to generate concern that people who have had C19 are getting infected anew.
  • Here is the latest on what we know, and don’t know, about the possibility of becoming sick with the virus more than once.
I recently recovered from C19. Does that mean I can’t get it again?
  • Most scientists say that people who have had C19 gain some immunity to the virus that causes it. What they don’t know is whether that protection lasts a few months, a few years or a lifetime.
What factors affect immunity?
  • The immune system wards off infections by producing antibodies that fight invaders. A range of hereditary and environmental factors, including diet and sleep patterns, typically affect the strength and longevity of those defenses.
  • Immunity also depends on the pathogen. For example, infection by the virus that causes measles confers lifelong immunity. Others, like the influenza virus, can mutate so rapidly that protective antibodies might not recognize them during a reinfection.
  • The coronavirus mutates more slowly than the influenza virus. That gives researchers hope that any natural immunity, or vaccine, would offer more lasting protection. Even if someone gets sick again, researchers believe a second infection might be milder than the first.
How soon would my body produce antibodies to fight the novel coronavirus after an initial infection?
  • The CDC says antibodies develop within one to three weeks after infection.
  • A study involving 34 hospitalized cases in China found that two patients, both in their 80s, produced antibodies within three days of symptom onset. The rest produced them two weeks after symptoms first surfaced. The findings were vetted by other experts and published in an academic journal in March.
Is there any good news?
  • A group of Chinese researchers reported this month that they had infected six rhesus macaques, allowed them to recover and then reinfected four of them 28 days after the first infection. None became sick again, showing their immune system shielded them from a second infection.
  • The research, published in Science, says, however, that more studies are needed to understand whether the immune system can shield individuals from reinfection over longer periods of time.
Then why are some people testing positive again?
  • Roughly 450 South Koreans tested positive for the virus again after meeting the criteria for recovery and being discharged from isolation. The Korea Centers for Disease Control and Prevention re-tested more than half of those people and found no evidence of the live virus circulating.
  • Peer-reviewed research studies have shown that viral fragments can circulate even after an individual is symptom-free. That doesn’t mean that people are still sick or infectious.
How do I know I’ve fully recovered?
  • Clinicians have mixed views on what constitutes recovery because long-term data aren’t yet available. Guidelines vary across the globe.
  • For example, the CDC says that infected individuals are considered recovered if they test negative for the novel coronavirus twice, with tests approved by the FDA taken at least 24 hours apart.
  • Or, individuals must be fever-free for three consecutive days and show an improvement in their other symptoms, including reduced coughing and shortness of breath. At least 10 days should have passed since their symptoms first surfaced.
  • Some survivors testing negative for the virus say that certain symptoms, such as a loss of taste and smell, can linger for months after other symptoms are gone.

Source: Can You Catch Covid-19 Twice? – WSJ

4. T Cells, Antibodies, and Our Ignorance  

By Derek Lowe

  • I wrote here about the reports of rather short antibody persistence in recovering coronavirus patients, and what’s been coming out in the two weeks since then has only made this issue more important. In that post, I was emphasizing that although we can measure antibody levels, we don’t know how well that correlates with exposure to the virus nor to later immunity from it, and that T cells are surely a big part of this picture that we don’t have much insight into.
  • This Twitter thread by Eric Topol is exactly what I mean, and this article that he references is an important read. Its schematic, shown below (see also here), will help make clear that antibody levels are only one aspect of the immune response to the infection – it’s an important one, but we’re making it look even more important than it is because it’s by far the easiest part of the process to measure. The T-cell response (much harder to get good data on) is known to be a key player in viral infections, and is also known to be highly variable, both between different types of pathogens and among individuals themselves. The latter variations are also beginning to be characterized among patients in the current pandemic. We have to get more data on it across a broader population of patients in order to make sense of what we’re seeing.
  • Many readers will have seen, for example, this new paper from The Lancet on a large study in Spain. Testing tens of thousands of people across the country continues to show that (on average) only about 5% of the population is seropositive (that is, has antibodies to the virus). There are a lot of interesting findings – such as rather large differences in those positive testing rates in different regions of the country, as well as the realization that at least one-third of the people who now test positive never showed any symptoms at all. But we are still not sure if this means that 95% of the Spanish population has never been exposed to the virus, because we don’t know how many people might have cleared it without raising enough of an antibody response to still be detectable. This paper does show that seroprevalence was about 90% in people 14 days after a positive PCR test, which indicates that most people do raise some sort of antibody response, but we don’t know how many of these people will still show such antibodies at later testing dates. Remember the paper discussed in that link in the first paragraph above, which found that 40% of asymptomatic patients went completely seronegative during their convalescence.
  • In other words, the Spanish survey may appear to show that 95% of the country has not yet been exposed to the coronavirus, but that’s almost certainly not true. The authors do mention that cellular immunity is important and not something that they were able to address, but the combination of that factor plus the apparent dropoff in antibody levels with time makes these large IgG surveys almost impossible to interpret. But note that if there are indeed many people who have been exposed but do not read out in such surveys, that we also have no idea how immune they are to further infection. At a minimum, you’d want to know antibody levels over time, T-cell response over time, and (importantly) what a protective profile looks like for both of those. We barely have insight into any of this: the large-scale data are just a snapshot of antibody levels, and that’s not enough.
  • We have similar data here in the US: several surveys of IgG antibodies show single-digit seroconversion. You could conclude that we have large numbers of people who have never been exposed – and indeed, the recent upswing in infections in many regions argues that there are plenty of such people out there. But we need to know more. We could have people who look vulnerable but aren’t – perhaps they show no antibodies, but still have a protective T-cell response. Or we could have people who look like they might be protected, but aren’t – perhaps they showed an antibody response many weeks ago that has now declined, and they don’t have protective levels of T-cells to back them up. Across the population, you can use the limited data we have and our limited understanding of it to argue for a uselessly broad range of outcomes. Things could be better than we thought, or worse, getting better or deteriorating in front of our eyes. We just don’t know, and we have to do better at figuring it out.

Source: More on T Cells, Antibody Levels, and Our Ignorance 

I. Projections & Our (Possible) Future

1. Estimating the Spread of the Coronavirus  

  • Mathematicians and public-health experts watched through their fingers in May as British Prime Minister Boris Johnson unveiled a series of charts to explain how the government would guide Britain out of coronavirus lockdown. Perhaps most prominent was a colourful dial with a needle hovering near a single digit: 1.
  • The dial indicated R, a now-totemic figure in the COVID-19 pandemic. The nation, said Johnson, would set a COVID-19 alert level, to be “primarily determined” by the number of coronavirus cases, and by R, the reproduction number.
  • To infectious-disease experts, Johnson’s focus on the reproduction number as a guiding light for policy was worryingly myopic. They worry about placing too much weight on R, the average number of people each person with a disease goes on to infect.
  • In this pandemic, R has leapt from the pages of academic journals into regular discussions by politicians and newspapers, framed as a number that will shape everyone’s lives. As Germany’s chancellor, Angela Merkel, explained in a widely viewed video this April, an R above one means an outbreak is growing, and below one means that it is shrinking. In many countries, it is publicly reported every week. In June, epidemiologists at the Harvard T.H. Chan School of Public Health in Boston, Massachusetts, announced a website where anyone can look up the value for any country — and for many smaller regions — in the world.
  • But fascination might have turned into unhealthy political and media fixation, say disease experts. R is an imprecise estimate that rests on assumptions, says Jeremy Rossman, a virologist at the University of Kent, UK. It doesn’t capture the current status of an epidemic and can spike up and down when case numbers are low. It is also an average for a population and therefore can hide local variation. Too much attention to it could obscure the importance of other measures, such as trends in numbers of new infections, deaths and hospital admissions, and cohort surveys to see how many people in a population currently have the disease, or have already had it.
  • “Epidemiologists are quite keen on downplaying R, but the politicians seem to have embraced it with enthusiasm,” says Mark Woolhouse, an infectious-diseases expert at the University of Edinburgh in the United Kingdom, who is a member of a modelling group that advises the British government on the pandemic. “We’re concerned that we’ve created a monster. R does not tell us what we need to know to manage this.”
  • Researchers remain concerned that R is looming too large, and is being used for purposes for which it was never intended. “It’s not yet clear what actions they are or are not taking on the back of R. But we are concerned because they’re giving it such prominence,” says Woolhouse.
The origins of R
  • First used almost a century ago in demography, R originally measured the reproduction of people — whether a population was growing or not. In epidemiology, the same principle applies, but it measures the spread of infection in a population. If R is two, two infected people will, on average, infect four others, who will infect eight others, and so on. The measure allows modellers to work out the extent of the spread, but not the speed at which the infection grows.
  • Unless they regularly test an entire country’s population, epidemiologists can’t measure R directly. So it is usually estimated retrospectively: disease modellers look at current and previous numbers of cases and deaths, make some assumptions to find infection numbers that could have explained the trend and then derive R from these.
  • One variant of R, R0 [R-naught], assumes that everybody in a population is susceptible to infection. That usually isn’t true, but might be when a new virus, such as SARS-CoV-2, emerges. At the start of the epidemic, assessing R0 (and other metrics) was crucial for epidemiologists building models of how the disease might spread. But when politicians and scientists talk about R, they usually mean another variant called Rt (sometimes called Re, or ‘effective R’), which is calculated over time as an outbreak progresses and considers how some people might have gained immunity, perhaps because they have survived infection or been vaccinated.
  • Rt and R0 both vary with the social dynamics of a population: even an easily transmitted virus will have trouble spreading in a region where people rarely meet. In January, the COVID-19 R0 in Wuhan, China, was calculated to be between two and three; after lockdown, estimates put the Rt there at just over one.
A lagging indicator
  • Working out Rt involves trade-offs and compromise. Confirmed cases and mortality figures can be used to infer the total number of infections, but both come with a significant lag — which scientists estimate could be anything from a week to three weeks or more. “If you have your Rt estimate lagging by at least ten days, possibly two weeks, then it’s not going to be that useful as a real-time decision-making tool,” says Gabriel Leung, a public-health scientist at the University of Hong Kong.
  • With a mathematical trick called nowcasting, researchers can use the observed statistical distribution of reporting delays to predict how much higher the number of fresh infections will be in, for example, two weeks. Some estimates of Rt already rely on nowcasting infection data in this way: it is “the method with the least guesses”, says Lars Schaade, vice-president of the Robert Koch Institute in Berlin, Germany’s main public-health agency, which reports a daily and seven-day Rt value based on infections reported by state health authorities.
  • Nowcasting infections on the basis of trends in past COVID-19 cases is tricky enough, but mortality data typically come with a longer lag, because of the extra time someone has the disease before they succumb to it and because of the paperwork involved in registering deaths, which can take weeks or months to file. A group led by Sheila Bird at the University of Cambridge, UK, publishes nowcast data of COVID-19 deaths in English hospitals. But they cannot yet do the same with a separate data set of deaths compiled by the Office of National Statistics (ONS) because the researchers don’t have access to the necessary data on registration delays: the time difference between when a death occurred and when the ONS reported it.
Extra uncertainty
  • An issue with nowcasting is that it swaps one problem for another, says Sebastian Funk, a disease modeller at the London School of Hygiene and Tropical Medicine, who is also advising the British government on this pandemic. “You can try to do that, but for obvious reasons it always comes with uncertainty. There’s no way that you can know how many cases would still be observed that have already been infected,” he says.
  • Other data on the pandemic’s progress can feed into estimates of Rt by serving as proxies for infections and social behaviour. One is hospital and intensive-care admissions. Another is results from random testing of a population to see how many people currently have COVID-19, or have had it. Researchers also conduct contact surveys, which ask people who they mix with, and can be used to infer changes in R on the basis of estimates of how many others an infected person could meet, although these are time-consuming and could cover only small groups of people. Contact surveys in China showed daily contacts were reduced by seven- to eightfold during the COVID-19 social-distancing period, when most interactions were restricted to the household. Another way to observe trends in people’s movements is to use location data based on the signals from mobile phones, published by Facebook and Google.
  • “There’s a bit of a trade-off here,” says Funk. “There are some methods that are more immediate but not epidemiological, and there are others that are more directly epidemiological but at the same time more out of date.”
  • Groups of epidemiologists, Funk says, each have their own approach to combining and using these disparate sources of data to work out Rt, relying on their own statistical models to look at trends in presumed infections. To calculate the official Rt of the United Kingdom, about ten groups present the results of their models to a dedicated government committee, which reaches consensus on a possible range. The figures are presented in that range (currently 0.7—0.9), showing how uncertain the estimates are, but the individual models are not released.
Unofficial estimates
  • Those ‘official’ Rt numbers are not the only versions available. Academic researchers have taken advantage of infection and mortality figures collated by the World Health Organization and independent groups such as the Coronavirus Resource Centre at Johns Hopkins University in Baltimore, Maryland, to publish Rt figures for numerous countries and states. In late April, for example, public-health researchers in Colombia claimed that the Rt for the first ten days of the pandemic was above two in seven Latin American countries. The Harvard researchers’ website currently estimates that Rt is above one in more than 30 US states (see ‘Fall and rise: Rt in the United States’ below).
  • See the current Rt values: http://metrics.covid19-analysis.org 
  • Even non-experts can use plug-and-play formulas to create their own variants of R — which can sometimes lead to problems. In May, local newspapers across England ran stories claiming to reveal regional Rt values for specific towns and cities. The Swindon Advertiser claimed the town’s Rt was 0.35, perhaps “one of the lowest in the UK”. But officials at Brighton and Hove City Council (labelled with the fourth-highest Rt, at 1.7) issued a statement calling the figures misleading and potentially dangerous. “It is not possible to calculate meaningful R values at a very local level,” said Alistair Hill, a public-health official on the council.
  • The figures were not, it turned out, Rt values at all: they came from an index created by the founders of a London-based analytics start-up called deckzero.com. That index, termed RZ, was intended to show how fast local epidemics were growing on the basis of case data from local authorities; it is not an established variable in epidemiology, says Jenna Wang, a co-founder and director of the firm. On 7 June, the founders withdrew their page from public access and said it had been “interpreted out of the context and scope of its original intention”.
The drawbacks of an average
  • An important aspect of Rt is that it represents only an average across a region. This average can miss regional clusters of infection. Conversely, high incidences of infection among a spatially distinct smaller subsection of a population can sway a larger region’s Rt value. For instance, Germany’s national Rt value jumped from just over 1 to 2.88 in late June (later revised down to 2.17) largely because of an outbreak in a meat-processing plant at Gütersloh in North Rhine-Westphalia (see ‘Germany’s Regional Outbreaks’ below). The Robert Koch Institute noted that national infections overall were still low, which is why the local outbreak had such an effect on the country’s Rt, which had dropped below 1 again by the end of June. This makes it unlikely that Rt would be used to steer local lockdown policy in Germany, Schaade says. “If the rolling mean of R was at 1.2 for a few weeks, then that would show there was a problem that needed attention, even if case numbers were low.” But in practice, researchers find out about local outbreaks before that because of a reported spike in cases, not because of changes to Rt. Germany has ongoing surveillance and public reporting of transmission levels in 400 counties.
  • And most experts say that the Rt for the United Kingdom is kept artificially high by the very large numbers of infections and deaths in care homes for older people, and does not reliably represent the risk to the general population.
  • Regional Rt numbers have been touted as a way to guide the further easing of restrictions, because they could allow a place that showed a resurgence in cases to be sealed off. But regional Rt numbers become less accurate as they are applied to smaller populations, especially when absolute infections are low.
  • The Harvard site produces numbers for US counties — which can range from thousands to millions of inhabitants — but one of its creators, Xihong Lin, says that hyperlocal data come with big uncertainties. The researchers don’t calculate an Rt for a county unless there are ten cases, Lin says. And she stresses that policymakers should not use them in isolation, but only alongside other measures such as the total number of cases and whether it is increasing. “When making recommendations. it’s definitely important to look at the whole picture and not just rely on Rt,” she says. Used properly, the data could help public-health officials to identify hot spots of infection to prioritize resources such as testing, she says.
No accounting for superspreaders
  • Another subtlety not captured by Rt is that many people never infect others, but a few ‘superspreaders’ pass on the disease many more times than average, perhaps because they mingle in crowded, indoor events where the virus spreads more easily — church services, choir practices, nightclubs and birthday parties, for instance. As few as 10–20% of infected people seem to cause 80% of new COVID-19 cases, Leung says. (Epidemiologists describe this using a ‘dispersion’ parameter, k’, which depicts the variation in viral transmission among infected hosts). That means bans on certain crowded indoor activities could have more benefit than blanket restrictions introduced whenever the Rt value hits one.
  • When countries consider when to reopen schools and offices, a key question is not only Rt, but what the actual number of infected people walking around is. Denmark and the United Kingdom have similar Rt values for instance, but because the number of infected people walking around Denmark is ten times lower, it’s safer for their schools to be reopened.
  • “When infection numbers are low, maybe you don’t care so much about what the reproduction number is, or at least don’t care if there’s some uncertainty in it,” says Funk. A test for the United Kingdom, says Woolhouse, will be whether the country overreacts if case numbers are low but modellers estimate that R is above one.
  • All that demotes the usefulness of R in deciding policy, say Funk and others. For countries recovering from the first wave of the pandemic — such as the United Kingdom — researchers say it’s far more important to watch for clusters of cases and to set up comprehensive systems to test people, trace their contacts and isolate those infected, than to watch the needle swinging on a colourful dial.

Source: A guide to R — the pandemic’s misunderstood metric 

J. The Road Back?

1. No one wants to go back to lockdown.  Is there a middle ground for containing C19?  

  • Governors last month started to “press pause” on the next phases of their reopenings as C19 cases picked back up. Now, in certain hot spots, they are starting to roll back some of the allowances they’d granted.
  • These are measured retreats — a far cry from the lockdowns that much of the country burrowed into starting in March. But leaders are desperately hoping that the incremental approach can make a dent in the spread of the virus at a time when another round of lockdowns — and their accompanying disruptions to education, the economy, and the public psyche — seems beyond unpalatable, both politically and socially.
  • They come as Texas, Florida, and other states are seeing record highs in daily coronavirus infections and intensive care units are teetering toward capacity, further proof that the coronavirus will run loose when given the chance. They also raise a serious question: whether such half-measures are sufficiently intensive — and were put in place in time — to have the necessary impact.
  • “This is a good step to getting a handle on the epidemic,” said Ana Bento, a disease ecologist at Indiana University. “It still might not be enough.”
  • Even before states began to emerge from their lockdowns, experts were already trying to gauge which cocktail of interventions they could turn to should cases spiral again without having to rely on stay-at-home measures. They hoped more precise interventions — whether focused only on certain communities or business sectors or designed to protect the most vulnerable — could put out flare-ups of cases, a way to balance preventing the spread of C19 from swamping health systems while still sustaining some semblance of society and economic activity.
  • Now, states are going to find out if more targeted approaches can work. If they don’t, and if people don’t embrace other basic precautions like masking and distancing, it could require governors to reinstate even more restrictions. And if communities can’t contain their outbreaks, what might be left is another stay-at-home period — a sign, experts say, that economies won’t function until local epidemics are mitigated.
  • “Cutting a middle ground where people don’t change their behavior is probably not tenable,” said Barry Bloom, an infectious disease expert at Harvard’s T.H. Chan School of Public Health. “If people don’t do it voluntarily, then I think you have to start closing things so they don’t have the option of transmitting and being transmitted to.”
  • The challenge is, it can take some time to know if interventions are working. While new steps to keep people away from each other have an immediate effect on transmission, that won’t show up in case counts for some time, given that it can take a few days for a person to start feeling sick, then a few days more to get tested, then a few more to get results. That means infections that are reported a week and half from now have already occurred. And if the new measures aren’t sufficient to reduce transmission, spread will just continue to grow in the interim — though perhaps at a slower rate.
  • Public health experts sometimes liken various interventions to slices of Swiss cheese. One slice — say, suspending sporting events — prevents some transmission, but the virus still has lots of holes to pass through, meaning lots of opportunities to transmit. By layering slices — promoting masks, no theater or concerts, limiting group activities, dining only outside — the idea is to stack enough strategies to cover up the holes left by any one slice and to block the amount of virus that can get through.
  • Lockdowns, then, are like plopping a whole wheel of cheese on the problem. They’ve been shown around the world to dramatically cut rates of transmission, but they also introduce all sorts of economic, social, and health problems that communities want to avoid. Essentially, experts are trying to find the stack of cheese slices that can keep spread from overwhelming hospitals and minimize disease while creating the fewest disruptions to life.
  • The timing of imposing restrictions also matters greatly. An intervention that could have a big enough impact to bend the curve if instituted on a given day might no longer provide that drag if put into place weeks later. Once the spread balloons past a certain point, there would just be too much virus in the community for halfway measures to succeed.
  • “I would just urge people to remember if you put in milder interventions earlier on so that you do not build up this big powder keg of infections underneath you, which are then eventually going to start flowing into the ICUs, that’s a better outcome than allowing a large outbreak, which requires a shut down,” said Harvard epidemiologist William Hanage.
  • If states are being more targeted with their measures, experts are pushing them to be smarter as well. They say governors should be prioritizing which institutions need to be open, and then devising strategies to accomplish that. Schools — which foster not only education and development, but provide child care and, for many, meals — are top of mind. So, experts say, the question shouldn’t be will schools open in the fall, but rather, what can we do so that they can?
  • “We have this viewpoint that we will just reopen everything and go back to normal, but just do everything a bit more safely,” such as by wearing masks or capping capacity, said Helen Jenkins, an infectious disease epidemiologist at Boston University’s School of Public Health. But if everything that opens again contributes some amount to overall transmission, the approach might have to be keeping things like bars and casinos closed if you really want schools to have a chance this fall, she said.
  • Schools can open in areas with low levels of transmission, “but if everything reopens, we risk tipping things over the edge to high transmission,” Jenkins said. “And then everything has to close down, and that’s something that no one wants.”
  • As they try to limit restrictions, officials have zeroed in on a particular type of establishment: bars. There, people crowd together indoors for long periods of time — factors that encourage viral spread. Last month, Idaho health officials identified a cluster of 152 cases that originated from bars and clubs around Boise and shut down all venues in the area. Texas and Florida have similarly reimposed rules on bars.
  • People in their 20s and 30s are also accounting for greater proportions of new infections in Arizona, Texas, and Florida now than at other times and in other places during the U.S. epidemic, leading to speculation that young people are flouting distancing recommendations and packing unsafely into bars.
  • The Trump administration has pointed to the cases among young people, who generally experience milder infections, as well as a nationwide daily death count far below its level in April, to say that the country is not in the same crisis it was in months ago. Administration officials have not rolled out new strategies for mitigating the recent spikes in cases in the South and West.
  • “Younger Americans have been congregating in ways that may have disregarded the guidance that we gave on the federal level,” Vice President Mike Pence said Sunday on “Face the Nation.”
  • But experts have raised several critiques of the administration’s arguments. Whatever the explanation for the bulk of cases among young people — perhaps it’s changes in testing patterns, perhaps older people are taking precautions to protect themselves — cases building up in a certain population won’t stay in that population. The more virus that’s out there, the likelier it is to reach vulnerable populations, like older residents. Plus, even if younger people are generally less susceptible to severe C19, some will still get seriously ill, require medical care, and die.
  • As for deaths, clinicians have gotten better at caring for C19 patients over the months, and perhaps the concentration of cases among younger people is leading to better outcomes. But experts also caution that deaths are a lagging indicator; the time from when someone contracts the virus to when their death is recorded can be weeks. With hospitalizations rising in many states, it’s likely that deaths will follow in time.
  • “There is incredible stress on the system, and it appears that might be getting a whole lot worse over the next few weeks,” said Fred Campbell, an internist at UT Health San Antonio.
  • The situation in San Antonio, where Mayor Ron Nirenberg said cases are rising in “an exponential surge,” led the city to blast out an alert to residents’ phones over the weekend, urging them to stay home and wear masks on essential trips. It was one example of local officials begging for the public’s help, sometimes asking for more than what a state mandates. In Los Angeles County, Barbara Ferrer, the director of public health, said last week that officials “did not expect the increases to be this steep this quickly” about cases rising after reopening, and directed residents to “wear a face covering and keep your distance.” Utah state epidemiologist Angela Dunn on Friday called for “large-scale behavior change on the part of all Utahns to reverse” the record cases the state was seeing.
  • States where transmission is relatively low are also looking to what’s occurring elsewhere to guide their reopening decisions. New Jersey Gov. Phil Murphy cited “spikes in other states driven by, in part, the return of indoor dining” to push the return of that off “indefinitely.”
  • Not every state that reopened early is facing an outbreak on the scale of those in Arizona, Texas, and Florida. Colorado started to peek out from its shelter-in-place restrictions in late April, without a corresponding surge in cases.
  • It’s hard to pinpoint any one reason that explains the difference. Colorado had an initial wave of cases, so perhaps residents — who, as a whole, are among the country’s healthiest — take more precautions. The state also reopened as case counts were declining, whereas others lifted restrictions as cases were plateauing or even increasing. Its governor, Jared Polis, stressed mask-wearing starting in April.
  • But cases in recent days have started increasing.
  • “We are on the razor’s edge,” said epidemiologist Elizabeth Carlton of the Colorado School of Public Health. “We have seen this steady decline in hospitalizations since the beginning of April, and that’s great news. But we are starting to see an uptick in cases.”
  • Carlton noted that accelerating transmission in Arizona and Utah raises the possibility that cases could spill over into Colorado, where there’s not “some magic wand to protect us.” The reproduction number in the state — the average number of cases that come from each case — is about one, she said, which means that its epidemic, while not worsening, is not improving.
  • “Equilibrium can be good, but it can also be quite nerve-wracking,” Carlton said. “It doesn’t take much to restart the wildfire.”

Source: Is there a measured way to contain Covid-19, without full lockdowns? 

K. Practical Tips & Other Useful Information

1. Why simple cloth masks without valves are better at fighting the spread of C19 

  • Those face masks you see with coin-sized valves on the front may look intriguing but they are not as good at preventing the spread of the novel coronavirus as the seemingly lower-tech, non-valved masks.
  • Some masks designed for hot, dusty construction work — where the intent is to filter out dust before it hits the wearer’s lungs — have “exhaust” valves that allow the exhaled air to flow out more easily, to keep the mask-wearer cooler.
  • The 3M company, which makes valve masks for such occupations, illustrates on its website how they work: inhaled air is filtered through the fabric part of the mask, and hot, humid exhaled air goes out through the valve. The system may be what you want when tearing out a kitchen for remodeling, but the valve defeats the purpose when you’re trying to slow the spread of a virus.
  • Public health experts have been recommending mask-wearing to prevent respiratory droplets from spreading into the air when you exhale, speak, cough or sneeze, and the valves allow those droplets through.
  • Medical masks, you’ll notice, do not have valves.
  • In its guidelines for mask-wearing, San Francisco stipulates that masks with valves do not meet its standards.
  • “Any mask that incorporates a one-way valve (typically a raised plastic cylinder about the size of a quarter on the front or side of the mask) that is designed to facilitate easy exhaling allows droplets to be released from the mask, putting others nearby at risk,” the order says.
  • The CDC recommends simple cloth masks for the public to prevent the spread of C19. A few layers of cotton prevent most of the potentially infectious respiratory droplets from escaping into the air around you, and they are also much cooler than the form-fitting N95 masks.

Source: Why simple cloth masks without valves are better at fighting the spread of covid-19

2. EPA approves first surface disinfectant products tested on the coronavirus 

  • Throughout the C19 public health emergency, the U.S. Environmental Protection Agency (EPA) has worked to provide the American public with information about how to safely and effectively kill the coronavirus on surfaces. Last week, EPA approved two products, Lysol Disinfectant Spray (EPA Reg No. 777-99) and Lysol Disinfectant Max Cover Mist (EPA Reg No. 777-127), based on laboratory testing that shows the products are effective against the coronavirus.
  • “Before pesticide products can legally make claims that they can kill a particular pathogen such as the coronavirus, the claim must be authorized by EPA based on a review of data. Because novel viruses are typically not immediately available for laboratory testing, EPA established guidance for Emerging Viral Pathogens.
  • In January 2020, the agency activated the guidance for the first time in response to the coronavirus public health emergency. The guidance allows product manufacturers to provide EPA with data, even in advance of an outbreak, that shows their products are effective against harder-to-kill viruses than the coronavirus. Through this guidance and the agency’s review of newly registered products, EPA’s list of products that meet the agency’s criteria for use against the coronavirus (known as List N) includes more than 420 products. In many cases, the agency was able to approve claims in as little as 14 days.
  • This week, EPA updated the entries for two products on List N to show they have now been tested directly against the coronavirus. These are the first List N products for which the agency has reviewed laboratory testing data and approved label claims against the coronavirus. EPA expects to approve such claims for additional List N products in the coming weeks. 
  • All products on EPA’s List N meet the agency’s criteria for effectiveness against the coronavirus. When using an EPA-registered disinfectant, follow the label directions for safe, effective use. Make sure to follow the contact time, which is the amount of time the surface should be visibly wet. Read the agency’s infographic on how to use these products.

Source: EPA approves first surface disinfectant products tested on the SARS-CoV-2 virus | US EPA

L. Johns Hopkins COVID-19 Update

July 8, 2020

1. Cases & Trends

Overview
  • The WHO C19 Situation Report for July 7 reports 11.50 million cases (172,512 new) and 535,759 deaths (3,419 new). Prior to yesterday, the WHO reported more than 200,000 new cases for 3 consecutive days—July 4-6. The pandemic has been ongoing for more than 6 months and continues to accelerate. We have previously discussed the relative distribution of each continent to the total global daily incidence, but the data published by the WHO clearly illustrate similar trends across the WHO regions. Europe’s relative contribution has decreased steadily since early April, while other regions’ contributions are increasing. Most notably, the Americas continues to represent the most substantial proportion of global incidence, driven by multiple large and growing national epidemics, including in Argentina, Brazil, Bolivia, Chile, Colombia, Mexico, Panama, Peru, and the United States. Africa’s relative contribution continues to increase as well, owing largely to South Africa’s epidemic. The Eastern Mediterranean and Southeast Asia regions, which do not align directly with continents, are also representing a sizable fraction of the global daily incidence.
India, Pakistan & Bangladesh
  • India continues its overall trend in daily incidence, and we expect it to report increasing incidence as the week goes on, potentially with a new record high. India remains #3 globally in terms of daily incidence, and it surpassed Russia on July 6 as #3 globally in terms of cumulative incidence. Pakistan continues to report decreasing incidence since its peak in mid-June. Additionally, its total active cases continues to decline following a peak on July 1, dropping to 91,602 active cases (the lowest total since June 15). Pakistan remains #11 globally in terms of daily incidence. Bangladesh continues to report decreased daily incidence as well, with fewer than 3,500 new cases for 6 consecutive days. Bangladesh remains #12 globally in terms of daily incidence.
Central & South America
  • Brazil reported 45,305 new cases, its fifth highest daily incidence to date. Brazil remains #2 globally in terms of daily incidence, following only the US. Looking at bi-weekly incidence, it appears as though Brazil may have passed an inflection point on its way toward a peak. Mexico reported 6,258 new cases, its fifth highest daily incidence to date. If Mexico continues its reporting trend, we expect to see increased daily incidence as the week progresses, potentially including a new record high. Mexico remains #6 globally in terms of daily incidence. Broadly, the Central and South American regions are still a major C19 hotspot. Including Brazil and Mexico, the region represents 6 of the top 14 countries globally in terms of daily incidence—including Colombia (#8), Chile (#9), Peru (#10), and Argentina (#14). Additionally, Panama and Bolivia are reporting more than 1,000 new cases per day. Central and South America also represent 4 of the top 12 countries in terms of per capita daily incidence—Panama (#2), Chile (#5), Brazil (#10), and Peru (#12).
Israel
  • Israel has reported 7 of its 8 highest daily totals over the past 8 days, including its record high daily incidence on July 3 (1,285 new cases). Much like the US, Israel’s C19 epidemic peaked in early April, followed by decreasing daily incidence through late May before increasing again to a new, higher peak. In fact, Israel reported fewer than 10 new cases on several days between May 16 and May 24, including zero new cases twice. Since then, the daily incidence has increased to a new record level.
Eastern Mediterranean Region
South Africa
  • South Africa remains among the top countries globally in terms of both per capita (#7) and total daily incidence (#4). South Africa reported 10,134 new cases, its second highest daily total to date. South Africa’s daily incidence has more than doubled since June 24, and its epidemic continues to accelerate.
United States
  • The US CDC reported 2.93 million total cases (46,329 new) and 130,133 deaths (322 new). Following 4 consecutive days of more than 50,000 new cases, the US reported a slight decrease in daily incidence early this week. Low reported incidence early in the week is not unexpected due to delays in weekend reporting, particularly over a long holiday weekend; however, even these lower reports are greater than any day prior to June 27. In total, 21 states (no change) and New York City reported more than 40,000 total cases, including California with more than 250,000 cases; Florida, New York City, and Texas with more than 200,000 cases; and 5 additional states with more than 100,000. The current daily incidence in the US is more than 50% higher than the first peak in mid-April, and it has increased by more than 150% since June 9, up from 20,338 new cases per day to 51,711 yesterday (7-day average).
  • A number of US states are exhibiting per capita incidence on par with or greater than the peaks in states hit hardest by C19 early in the US epidemic. At its peak on April 10, New York state’s per capita daily incidence was 50.9 cases per 100,000 population (7-day average). Other notable states early in the epidemic include: New Jersey with 41.4 new cases per 100,000 population; Massachusetts with 38.1; Louisiana with 33.9; and Connecticut with 30.9. On July 6, Arizona reported 52.8 new cases per 100,000 population, higher than any state so far in the US epidemic. Similarly, Florida reported 40.8 new cases per 100,000 population on July 7, and South Carolina reported 32.6 on July 6. Louisiana’s per capita daily incidence decreased to 5.77 new cases per 100,000 population on May 29 before rebounding to 31.2 on July 7. California and Texas, the country’s two largest states by population, are reporting 20.0 and 25.9 new cases per 100,000 population, respectively, and a number of other states are reporting more than 25.

2. US C19 Resurgence 

  • A number of countries affected early in the C19 pandemic have gained control over their respective epidemics, and many others are combating their first wave of transmission. The US, on the other hand, began to turn the corner in its first wave before surging again several weeks later, following efforts to relax social distancing in many states. While the early stage of this first wave largely centered on the New York City area, including neighboring New Jersey and Connecticut, the current surge in transmission is spread across many states, particularly those that were not severely affected early in the epidemic. In addition to rapidly increasing C19 incidence, states are also experiencing increasing hospitalizations and, in some cases, deaths. Additionally, test positivity is increasing in many states, which indicates that existing capacity is not sufficient to meet the growing demand and suggests that reported incidence may be underestimating the scale of community transmission.
  • Florida’s C19 epidemic continues to accelerate. According to several reports, hospitals and health systems in multiple parts of the state are struggling to meet patient surge as C19 transmission increases. Unlike most states, Florida does not report current C19 hospitalizations (only cumulative), so other sources must be used to track this trend. Based on data from the state’s Agency for Health Care Administration, dozens of hospitals have reached their ICU capacity. While many of these are smaller hospitals with relatively few ICU beds, a substantial number are larger facilities with a capacity of 25 or more ICU beds. One local effort to track hospitalizations indicates that the state reported multiple record highs for daily C19 hospitalizations over the past week. Additionally, the recent surge in C19 incidence in Florida is complicating contact tracing efforts, as the volume of contacts exceeds available capacity. Potential exposures in public locations such as parties and nightclubs could result in dozens of contacts, many of which may not be identified. Despite the continued concerning C19 trends, Florida announced that schools will open for in-person instruction this fall. The emergency order, issued by the state’s Commissioner of Education, directs school boards to “open brick and mortar schools at least five days per week,” unless prohibited under future health department or executive orders. The order permits the use of alternative options for instruction, including remote classes, but schools must be open to offer in-person instruction for those who desire it. Some educators and organizations, including teachers unions, have opposed the order, emphasizing that decisions regarding in-person instruction should be directed by scientific evidence rather than economic priorities.
  • In addition to Florida, Arizona and Texas also remain major C19 hotspots in the US. Both states are reporting concerning trends in terms of incidence, testing, hospitalizations, and even deaths. In Arizona, state officials directed hospitals to implement crisis standards of care for C19 patients, if necessary, and there are reports that major health systems in some parts of Texas are quickly filling with C19 patients. In fact, more than 20 states have reported increased C19 hospitalizations over the past 2 weeks. There are concerns that existing supply of critical personal protective equipment (PPE)—including surgical masks, gowns, and gloves—could once again be in short supply as C19 hospitalizations continue to increase. Following initial shortages, particularly in the cities hit the hardest early in the US epidemic, PPE supplies have largely recovered, but a prolonged surge across multiple states could be a major challenge for national distribution systems.
  • The bi-weekly C19 incidence in the US is more than double that of every country except Brazil, and it does not show much of an indication that it is starting to slow. Notably, the current trend is a similar trajectory as the approach to the first US peak; however, it is spread across numerous states rather than largely concentrated on a single metropolitan area (New York City). Spreading these cases across more hospitals and health systems could factor into the continuing decrease in reported C19 deaths; however, if hospitals and health systems begin to reach or exceed capacity, it could exacerbate the disease severity and result in additional deaths. Additionally, decreasing mortality in some states could be masking increases in others when observed at the national level. With that in mind, several states that are exhibiting concerning C19 incidence trends are already reporting increasing C19 deaths. Arizona’s daily C19 death total never really exhibited a significant decline; however, it has increased from 12.4 deaths per day on May 27 to 40.3 on July 7 (225% increase; 7-day average). Several other states did report decreasing C19 mortality earlier in the epidemic, but are now increasing again. Texas’ C19 deaths are up from 18.6 deaths per day on June 12 to 43.3 on July 7 (133% increase), Florida increased from 30.4 deaths per day on June 18 to 47.9 (58% increase), and South Carolina increased from 4.71 deaths per day on June 18 to 15.3 (225% increase).

3. US Schools

  • The White House hosted an event yesterday to discuss plans for schools to reopen in the midst of the C19 pandemic. At the event, and on social media, US President Donald Trump indicated that he would put pressure on states to reopen schools this fall for in-person instruction, including K-12 as well as colleges and universities. In fact, multiple senior US government officials and advisors, including President Trump, emphasized that schools should strive to hold full-time, in-person classes this fall. US CDC Director Dr. Robert Redfield emphasized that the CDC never recommended school closures, and he noted that he hoped the agency’s guidance was not viewed by schools as a reason to remain closed.
  • Many, including health experts and officials, argue that attending school in person is important for childhood development, both from an educational and social perspective, and allowing children to return to school is critical for many families to return to work. Despite these benefits, many questions remain regarding how to safely resume in-person classes and mitigate transmission risk for students, teachers, and the community. Existing guidance emphasizes the importance of physical distancing, improved hygiene and sanitation, and utilizing outdoor spaces when possible, but these may be challenging for many schools. Maintaining 6-foot separation between students in classrooms could be particularly challenging for many schools, especially with full in-person attendance. Additionally, the risk of severe disease and death may be lower among children, but many teachers and other school staff are at high risk for C19.

4. College & University Toolkit

  • The Johns Hopkins Center for Health Security collaborated with Tuscany Strategy Consulting and the Council for Higher Education Accreditation to produce practical planning resources to help higher education institutions prepare for operations during the C19 pandemic. The team developed a comprehensive toolkit, OpenSmartEDU, that includes an operational guide and accompanying self-assessment calculator to help colleges and universities gauge how effectively they are addressing a range of C19 scenarios. The toolkit now includes a new planning template—the “Higher Education Return-to-Campus Planning Tool”—to aid schools in planning and monitoring the progress around essential health and safety factors as they work to bring students and instructors back to campus for in-person courses and other activities. Using Smartsheet—a free, customizable work management platform—school leadership can convert the C19 Planning Guide into an actionable plan, including through assigning workstreams, developing implementation timelines, and visualizing critical data via convenient dashboards.

5. US Higher Education VISAs

  • The US government, including US Immigration and Customs Enforcement (ICE), issued modifications to the federal Student and Exchange Visitor Program (SEVP) that would prevent immigrants on common types of student visas (F-1 and M-1) from remaining in the US if they take all of their courses online. Students attending universities that are fully transitioning to online coursework must either depart the US or transfer to a school that is holding in-person classes in order to fulfill their visa requirements. Earlier in the C19 pandemic, SEVP granted exceptions for F-1 and M-1 visa holders in order to accommodate students as universities transitioned to remote coursework.
  • The updated policy will pose numerous challenges for colleges and universities, as well as their students, as fall classes rapidly approach. Some schools plan to hold in-person classes, while others intend to hold all classes online. In the wake of the changes to SEVP, more schools may move toward hybrid models, which would involve a mixture of in-person and online courses. The impact of losing international students reaches far beyond academic institutions. International students generated more than $41 billion in revenue for the US economy during the 2018-19 academic year. Universities are now looking for stronger guidance regarding how to safely proceed with in-person courses in order to support their international students and protect students, faculty, and staff against C19.

6. Coronavirus Vaccine Candidates

  • The US is pushing ahead with “Operation Warp Speed” in an attempt to rapidly develop and deploy a SARS-CoV-2 vaccine. A commentary published in JAMA earlier this week outlined the 5 “core” vaccine candidates at the center of the federally organized effort. The US government has already invested considerable funding for vaccine research, including US$1.6 billion for the Novavax vaccine. The authors acknowledge that these 5 vaccine candidates are being developed using 3 unique technological platforms, exemplifying the diversity and innovation in SARS-CoV-2 vaccine development. Despite the current progress and the existence of multiple candidates, a number of questions still need to be answered regarding the efficacy of each vaccine candidate, and considerable work remains in terms of testing and production for all of the products. For example, US government officials have reportedly “squabbled” with Moderna over clinical trial design and implementation for its candidate vaccine, which has resulted in delays in initiating advanced clinical trials. The authors argue that the vaccine development landscape will be permanently altered by the C19 pandemic. 

7. Nursing Home Data

  • A report published by the Associated Press described incomplete C19 data for nursing homes available from the US Centers for Medicare and Medicaid Services (CMS). CMS publishes weekly reports on the impact of C19 in domestic nursing homes in order to provide additional transparency for residents, families, and the public during the country’s C19 response. According to the AP report, nursing homes are only required to share data dating back to May 8, several months after the start of the US epidemic. Notably, the data for multiple facilities with known C19 cases and deaths indicate none in the CMS reports, including from the first documented outbreak at a long-term care facility in Washington state. According to AP, the decision to provide data prior to May 8 is at the discretion of individual facilities. The incomplete data can be misleading, and there may be incentive for these facilities to limit reporting in order to present the appearance of fewer, or in some instances, no cases.  

8. Brazilian President Tests Positive for C19 

  • Numerous media outlets are reporting that Brazilian President Jair Bolsonaro tested positive for SARS-CoV-2 on Monday. President Bolsonaro reportedly developed symptoms, including a fever, on Sunday and was subsequently tested. He addressed his diagnosis in a TV interview yesterday and commented that he was feeling “very well.” President Bolsonaro is reportedly receiving hydroxychloroquine and azithromycin as a treatment. The Brazilian President has faced criticism over his response to the country’s C19 epidemic, including pressuring local governments to relax social distancing restrictions and downplaying the severity of the disease, even as Brazil’s epidemic accelerates. Brazil’s national epidemic is second only to the US in terms of cases.  

M. Links to Other Stories

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