Recent Developments & Information
August 20, 2020
Without reliable information, we rely on fear or luck.
“The frats are being frats — they are having their parties.”Lamar Richards, a sophomore at the University of North Carolina, told The New York Times regarding an outbreak of new cases
“Evidence of the effectiveness of face mask use is astonishingly weak. Countries with widespread mask compliance, such as Belgium and Spain, were still seeing rising virus rates. With numbers diminishing very quickly in Sweden, we see no point in wearing a face mask in Sweden, not even on public transport.”Anders Tegnell, chief epidemiologist at Sweden’s Public Health Agency
A. The Pandemic as Seen Through Headlines
B. Numbers & Trends
1. Cases & Tests
3. Top 5 States in Cases, Deaths, Hospitalizations, and Positivity
C. New Scientific Findings & Research
D. Improved & Potential Treatments
E. Vaccines & Testing
F. Concerns & Unknowns
G. Do Lockdowns Work?
H. Back To School!?
I. The Road Back?
J. Projections & Our (Possible) Future
K. Practical Tips & Other Useful Information
L. Johns Hopkins COVID-19 Update (8/19)
M. Links to Other Stories
- UCI develops low-cost, accurate C19 antibody detection platform A robust, low-cost imaging platform utilizing lab-on-a-chip technology created by University of California, Irvine scientists may be available for rapid coronavirus diagnostic and antibody testing throughout the nation by the end of the year.
- LSU Health New Orleans team creates better tool to aid COVID diagnosis An LSU Health New Orleans radiologist and evolutionary anatomist have teamed up to show the same techniques used for research on reptile and bird lungs can be used to help confirm the diagnosis of C19 in patients. Their paper published in BMJ Case Reports demonstrates that 3D models are a strikingly clearer method for visually evaluating the distribution of C19-related infection in the respiratory system.
- Clinical and sociodemographic features of early C19 patients Data from the first C19 patients treated at three large Massachusetts hospitals reveal important trends, including disproportionate representation of vulnerable populations, high rates of disease-related complications, and the need for post-discharge, post-acute care and monitoring.
- Is C19 transmitted through breast milk? Study suggests not likely A study by UC San Diego School of Medicine suggest breast milk itself is not likely a source of infection for infants.
- New Research Finds Hydroxychloroquine Is Not a Possible Defense Against C19 Researchers at Case Western Reserve University have added to the growing body of understanding about how hydroxychloroquine (HCQ) is not a possible defense against C19.
- Researchers Find Early Spread of C19 Was Far Greater Than Reported Patients with undiagnosed flu symptoms who actually had C19 last winter were among thousands of undetected early cases of the disease at the beginning of this year. In a new paper in The Lancet’s open-access journal EClinicalMedicine, epidemiological researchers from The University of Texas at Austin estimated C19 to be far more widespread in Wuhan, China, and Seattle, Washington, weeks ahead of lockdown measures in each city.
- How Computer Science and AI Can Help Fight C19 — “We Have the Potential to Alter the Course of This Global Pandemic” At the University of Chicago, public health experts, computer scientists, economists and policy analysts have launched projects using computational tools to better detect, diagnose, treat and prevent the spread of the deadly virus.
- Food Security: Satellites Provide Crucial Data on Crops During C19 A recent report from the World Food Program forecasts that the C19 pandemic could push over 130 million additional people into chronic hunger by the end of 2020.
- Pepperoni shortage 2020: The new C19 shortage item is meaty Move over, national coin and Clorox wipes shortages. There’s a new coronavirus pandemic shortage of the nation’s most popular pizza topping. Small pizza shops across the nation are reporting higher prices for pepperoni, according to Bloomberg, which found a South Dakota shop is paying $4.12 a pound compared to $2.87 in January 2019.
- College towns brace for a new wave of C19 Ann Arbor residents are worried about students’ return to the University of Michigan.
- The Race to Investigate a Coronavirus Outbreak at a Georgia Prep School Graduating seniors at the Lovett School celebrated at parties large and small. Then came the positive C19 tests, the media coverage, and the refusals to speak to contact tracers.
- Will C19 vaccines be safe for children and pregnant women? As potential C19 vaccines speed their way through development, manufacturers and U.S. regulators have largely delayed testing in children and women who are pregnant, raising the possibility that experts will lack critical safety and efficacy data in those populations when there’s a pressing need to inoculate them.
- Analysis of C19 Public Health Information Indicates the Material is Too Dense Major health organizations recommend that any medical information for the public be written at an 8th grade reading level, but a new analysis of 18 government websites with C19 information finds the material on them often exceeds a 6th to 8th grade level. Making public health information too dense to understand could worsen the impacts of the pandemic, the authors warn.
- The Physicians Foundation 2020 Physician Survey Nearly half of physicians believe that the C19 pandemic won’t be under control until after June 2021, according to a new survey of 3,500 doctors. The majority of those surveyed also said that pandemic-related delays in care will lead to serious health consequences and that opening schools and other public places presents a greater danger to patients than prolonged lockdowns.
- Costa Rica Readies Horse Antibodies for Trials as an Inexpensive C19 Therapy After neutralizing coronavirus in cell culture, scientists at the University of Costa Rica are proceeding with human testing.
- Researchers Show Mathematically How to Best Reopen Your Business After C19 Lockdown
A. The Pandemic As Seen Through Headlines
(In no particular order)
- Emergency use of Covid-19 blood plasma in the U.S. is on hold, after top federal health officials, including Dr. Fauci, warned that the data on the treatment is still too weak
- An additional 135 million people globally will face acute hunger by the end of the year because of the pandemic
- WHO says coronavirus pandemic is now driven by younger adults
- ‘Swedish Dr. Fauci’ makes a strong case against masks
- A U.S. report found that officials in Wuhan and Hubei Province tried to hide information about the outbreak from China’s central leadership
- Australia Prime Minister Puts Citizens On Notice: All Will Likely Undergo Mandatory Covid-19 Vaccinations
- Oxford Covid-19 vaccine phase 3 trials begin in India
- Chinese Regulator Says COVID-19 Vaccines Must Be At Least 50% Effective, Last For 6 Months
- Coronavirus outbreak on Seattle fishing boat suggests antibodies may provide immunity
- U.S. health officials announce nationwide sewage testing for the virus
- Pool testing was once hailed as a solution to US testing problems, but the virus is too pervasive in many areas for it to be effective
- A new report published by the CDC points to economic sectors in which workers are at high risk of infection, including factories, warehouses and building sites
- COVID-19 is third leading cause of death in the US
- A new study determined that a rare immune syndrome that strikes some children with the virus — known as multisystem inflammatory syndrome — is distinct from both Kawasaki disease and Covid-19 in adults
- ‘Survival does not mean that individuals fully recovered’: Another warning from 1918 flu
- States are testing a new way to combat the spread of the virus in nursing homes: “Strike teams” that apply an emergency response model traditionally used in natural disasters
- Harvard researchers developed a formula to determine how many daily tests a state should be conducting in order to slow the spread of the virus
- Walgreens coding error causes underreporting of 59,000 COVID-19 tests
- Germany to extend coronavirus furlough to 24 months
- California sees cases slow
- Pope Francis warns against “vaccine nationalism”
- NYC teachers union demands all students get tested before reopening
- Italy, Spain see most cases since May, April
- NYC sees positivity rate hit pandemic low
- Hawaii delays tourism reopening
- Toulouse adds facemask requirements
- Greece locked down two facilities for migrants linked to an outbreak of new infections; another overcrowded reception center was put under lockdown last week
- France, which has been experiencing a surge in virus cases, will make mask-wearing mandatory in enclosed office spaces by the end of August
- Venezuela is treating the infected like criminals in its virus crackdown
- Iran, a country hit early and hard by the virus, is in the midst of a second wave
- South Korea reports 297 new cases, biggest since March
- In response to new cases, South Korea shut down high-risk facilities such as nightclubs, karaoke rooms and buffet restaurants in the Seoul metropolitan area
- North Korea admits that the pandemic hurt its economic plans
- South Africa’s virus response is floundering amid allegations of corruption and fraud
- Finland, which has some of the most severe travel restrictions in Europe, announced that it would tighten restrictions on incoming travelers starting on Monday
- Nepal plans to reimpose a strict lockdown and curfew in the Kathmandu Valley for a week, when all movement except essential services will be restricted
- Coronavirus brings a wave of early retirements
- Mayor Bill de Blasio of New York City is facing mounting pressure to delay the start of in-person K-12 schoool
- Economies of college towns slammed by online learning
- University of North Carolina-Chapel Hill told faculty that most cases of the virus could be traced to the “social sphere of campus life”
- Notre Dame moves classes online after COVID-19 case spike linked to parties
- UNC students rip school for creating COVID-19 ‘clusterf–k’ after outbreaks
- UConn students evicted from dorm after packed campus party amid COVID-19
- Teachers Say School Isn’t Safe—So They’re Calling in Sick
- LA schools to test nearly 700,000 students, staff for COVID-19
- Tennessee teachers who have been exposed to COVID-19 allowed to return to class
- Utah teachers are resigning in droves — or retiring early — as some districts plan to return to in-person classes amid the coronavirus pandemic
- Only one in five U.S. families will have any sort of in-person help at home this school year
- The Mariinsky Ballet, one of the most renowned companies in Russia, returned to the stage last month but was abruptly ordered to quarantine last week after about 30 members contracted the virus
- High-Frequency Data Suggests Europe’s Recovery Is Stalling
- S&P 500 hits all-time high despite COVID-19 devastation
- Oil Piracy Has Spiked During COVID Pandemic
- Pope Francis said that a vaccine should be made universally available, especially to the poor
- Millions of women have lost access to contraceptives, abortions amid COVID-19
- Coronavirus outbreak linked to Maine wedding reception
- Kim Jong-Un Reportedly Orders North Koreans To Hand Over Pet Dogs So They Can Be Eaten
- Russia races to develop world’s first COVID-19 vaccine for cats
- Whether it’s illicit raves or pool parties, partying on a large scale has returned to many areas of the world
- LA cuts power to TikTok star Bryce Hall’s home after massive parties
- You won’t see any NFL cheerleaders this season
- Movie theaters could be next on NY Gov. Andrew Cuomo’s reopening list
- St. Regis Punta Mita offers luxe ‘work-from-home’ accommodations
- Sorry, Mayor de Blasio: NYC desperately needs its billionaires
- US Open bubble filling with players and optimism
- Namibia warns against using elephant dung as coronavirus cure
- Pest-seller: Cuomo wants you to read his book on pandemic leadership
- Italy wants tourists back, but only if they behave themselves
- Zoom boom boom: Couple caught having sex during conference call
B. Numbers & Trends
Note: Unless otherwise noted, (i) all cases/deaths are confirmed cases/deaths that have been reported, (ii) all numbers reported in this update are as of the end of the most recent reporting period, and (iii) all changes reflect changes since the preceding day.
1. Cases & Tests
- Total Cases = 22,569,248 (+1.2%)
- New Cases = 271,795 (+17,852) (+7.0%)
- New Cases (7 day average) = 254,936 (-2,343) (-0.9%)
- 7 day average of new cases has been declining since 8/14
- 1,000,000+ cases every 4 days (based on 7 day average)
US Cases & Testing:
- Total Cases = 5,700,931 (+0.8%)
- New Cases = 44,956 (+956) (+2.2%)
- Percentage of New Global Cases = 16.5%
- New Cases (7 day average) = 47,936 (-348) (-0.7%)
- Total Number of Tests = 73,115,709
- Percentage of positive tests (7 day average) = 7.4%
- Number of new cases has been under 50,000 for 4 consecutive days, which is the first time since 7/4
- 7 day average of new cases has declined from 69,328 on 7/25 to 47,936 on 8/19, a decrease of 30.9%
- Number of new cases is 7,112 less than one week ago
- Number of new cases in US fall to 3rd highest, behind India & Brazil
- 7 day average of the percentage of positive tests continues to decline
- Total Deaths = 790,195 (+0.9%)
- New Deaths = 6,676 (+373) (+5.9%)
- New Deaths (7 day average) = 5,689 (-16) (-0.3%)
- 7 day average of new deaths has been declining since 8/14
- Total Deaths = 176,337 (+0.7%)
- New Deaths = 1,263 (-95) (-7.0%)
- Percentage of Global New Deaths = 18.9%
- New Deaths (7 day average) = 1,030 (-17) (-1.6%)
- Number of new deaths is 123 less than last week
- 7 day average of new deaths declined for 4 consecutive days, which likely indicates that we are past the second peak
3. Top 5 States in Cases, Deaths, Hospitalizations & Positivity (8/19)
Source: Worldometer and The Covid Tracking Project
C. New Scientific Findings & Research
1. New study finds very weak asymptomatic coronavirus transmission
- For the first time in history, governments across the globe have quarantined the healthy with the sick for fear that asymptomatic carriers are spreading the virus and killing people in droves. But after months of crushed liberty and destroyed livelihoods, is there any proof that asymptomatic carriers are indeed super-spreaders? Shouldn’t we first investigate this theory before we force universal shutdowns and universal muzzle-wearing?
- A recently published contact tracing study of 3,410 close contacts of 391 coronavirus cases in a Chinese province near Wuhan during the peak months of the virus found that transmissibility seems to increase commensurately with the severity of symptoms presented by the infected individual. Of the 127 secondary infections that were traced to the original 3,410 cases, just eight were from individuals confirmed as asymptomatic.
- All asymptomatic individuals were followed up with 14 days later by study administrators to confirm that they had not presented symptoms. The study was published on August 13 in the Annals of Internal Medicine journal.
- The study’s authors conclude not only that asymptomatic transmitters compose only a tiny slice of the spread, but that the rate of transmission increases with the severity of the illness, further validating the strategy of focusing on the sick, not the healthy:
- The secondary attack rate increased with the severity of index cases, from 0.3% (CI, 0.0 to 1.0%) for asymptomatic to 3.3% (CI, 1.8% to 4.8%) for mild, 5.6% (CI, 4.4% to 6.8%) for moderate, and 6.2% (CI, 3.2% to 9.1%) for severe or critical cases (P for trend < 0.001). Manifestation of certain symptoms, such as fever (6.7% [CI, 5.3 to 8.0] vs. 3.3% [CI, 1.6 to 4.9]) and expectoration (13.6% [CI, 10.6 to 16.7] vs. 3.0% [CI, 2.1 to 3.9]), in the index cases was associated with an increased risk for infection in their close contacts.
- Researchers also found, as other studies have already concluded, that most of the secondary infections occurred among household members. Thus, putting together the low rate of asymptomatic transmission with the fact that most cases (of all severity levels) are spread in the home, why should we destroy our civilization over the concern of asymptomatic spread? Where is the evidence that a non-symptomatic individual merely passing someone for a few seconds in a store will transmit the virus?
- One might dismiss this study because it was conducted by Chinese researchers, but if there is a political bias in Chinese research, wouldn’t it be skewed to the side that says asymptomatic people spread the virus?
- Let’s not forget that the World Health Organization said in May that asymptomatic spread was “very rare.” Then, like any time a major scientific figure reveals the truth, the WHO suddenly recanted that position when the media raised a howl. But the “experts” never explained where the evidence exists to show major community spread through asymptomatic individuals.
- A U.S.-based study from the University of Florida, Gainesville Department of Biostatistics, observed similar low rates of transmission among the asymptomatic. They found symptomatic individuals transmitted the virus at rate 28 times higher than asymptomatic individuals. Another Chinese study from May found very weak transmission capability among asymptomatic infections.
- From lockdowns and school closures to mask-wearing and quarantining people without symptoms, our government continues to violate the Constitution and destroy our civilization without providing evidence for the premises they assert as scientific law.
- It would be one thing if just 10% of people are asymptomatic and the other 90% of those infected get fatal cases. But given that some estimates show more than two-thirds of those infected are asymptomatic, and we know most of the remaining individuals are not at risk of dying unless they have certain conditions, the asymptomatic quirkiness of this virus is actually something to celebrate, not a pretext for fear and panic.
- Add to that the fact that nearly all these studies conclude that most transmission of any kind occurs at home (not passing someone for three seconds in Walmart) and the current restrictions, indiscriminate quarantine, and mask-wearing are completely indefensible.
2. Airborne Viruses Can Spread on Dust, Nonrespiratory Particles
- Influenza viruses can spread through the air on dust, fibers and other microscopic particles, according to new research from the University of California, Davis, and the Icahn School of Medicine at Mount Sinai. The findings, with obvious implications for coronavirus transmission as well as influenza, are published Aug. 18 in Nature Communications.
- “It’s really shocking to most virologists and epidemiologists that airborne dust, rather than expiratory droplets, can carry influenza virus capable of infecting animals,” said Professor William Ristenpart of the UC Davis Department of Chemical Engineering, who helped lead the research. “The implicit assumption is always that airborne transmission occurs because of respiratory droplets emitted by coughing, sneezing or talking. Transmission via dust opens up whole new areas of investigation and has profound implications for how we interpret laboratory experiments as well as epidemiological investigations of outbreaks.”
Fomites and influenza virus
- Influenza virus is thought to spread by several different routes, including in droplets exhaled from the respiratory tract or on secondary objects such as door handles or used tissues. These secondary objects are called fomites. Yet little is known about which routes are the most important. The answer may be different for different strains of influenza virus or for other respiratory viruses, including the coronavirus.
- In the new study, UC Davis engineering graduate student Sima Asadi and Ristenpart teamed up with virologists led by Dr. Nicole Bouvier at Mount Sinai to look at whether tiny, nonrespiratory particles they call “aerosolized fomites” could carry influenza virus between guinea pigs.
- Using an automated particle sizer to count airborne particles, they found that uninfected guinea pigs give off spikes of up to 1,000 particles per second as they move around the cage. Particles given off by the animals’ breathing were at a constant, much lower rate.
- Immune guinea pigs with influenza virus painted on their fur could transmit the virus through the air to other, susceptible guinea pigs, showing that the virus did not have to come directly from the respiratory tract to be infectious.
- Finally, the researchers tested whether microscopic fibers from an inanimate object could carry infectious viruses. They treated paper facial tissues with influenza virus, let them dry out, then crumpled them in front of the automated particle sizer. Crumpling the tissues released up to 900 particles per second in a size range that could be inhaled, they found. They were also able to infect cells from these particles released from the virus-contaminated paper tissues.
- Additional co-authors on the paper are Anthony Wexler at UC Davis, and Nassima Gaaloul ben Hnia and Ramya S. Barre at the Icahn School of Medicine at Mount Sinai, New York.
- The work was supported by a grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.
3. Lasting immunity to coronavirus reported in early studies
- Scientists say they are seeing signs of lasting immunity to the coronavirus, even in those who only experience mild symptoms of C19.
- A slew of studies show that disease-fighting antibodies, as well as B-cells and T-cells that can recognize the virus, appear to persist months after infections have run their course, The New York Times reported.
- “This is exactly what you would hope for. All the pieces are there to have a totally protective immune response,” said Marion Pepper, an immunologist at the University of Washington and an author of one of the new studies, which is now undergoing review by the journal Nature.
- “This is very promising,” said Smita Iyer, an immunologist at the University of California, Davis, who is studying immune responses to the coronavirus in rhesus macaques, told the Times. “This calls for some optimism about herd immunity, and potentially a vaccine.”
- Although researchers cannot predict how long these immune responses will last, experts consider the data to be the first proof that the body has a good chance of fending off the coronavirus if exposed to it again.
- “Things are really working as they’re supposed to,” Deepta Bhattacharya, an immunologist at the University of Arizona, told the Times. Bhattacharya is an author on one of the new studies, which was published on medRxiv, a pre-print server for health research that has not yet been peer-reviewed.
4. Study finds no race difference in C19 hospital deaths
- After adjusting for sociodemographic factors and underlying conditions, black C19 patients were no more likely than white patients to die of any cause in hospitals, a retrospective study published today in JAMA Network Open has found.
- Researchers at Ascension Health in St. Louis analyzed data from 11,210 adults with C19 in 92 hospitals in 12 states from Feb 19 to May 31.
- The death rate from any cause was 23.1% in white patients and 19.2% in black patients. After adjusting for age, sex, insurance, underlying conditions, neighborhood deprivation, and site of care, the risk of death was not significantly different between blacks and whites (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.80 to 1.09).
Underlying illnesses, sociodemographics
- Compared with whites, blacks had higher rates of asthma (8.8% vs 4.7%), cancer (3.6% vs 3.2%), chronic kidney disease (20.5% vs 12.9%), congestive heart failure (12.5% vs 10.8%), diabetes (32.0% vs 23%), high blood pressure (30.3% vs 25.0%), obesity (32.2% vs 18.2%), and organ transplantation (0.5% vs 0.3%).
- Compared with hospitalized whites, black patients were more likely to have been admitted to the hospital with a fever of 38°C (100.4°F) or higher (32.1% vs 22.1%) and a respiratory rate of at least 24 breaths per minute (34.1% vs 29.6%), while they were less likely to have an oxygen saturation less than 94% (34.9% vs 40.9%).
- Black and white patients required hospitalization in an intensive care unit (ICU) and invasive mechanical ventilation at similar rates (31.2% vs 34.0%).
- All-cause death rates were 20.3% overall, 34.7% among ICU patients, and 38.1% among those receiving mechanical ventilation. The death rate among white patients was 23.1%, while it was 19.2% among black patients.
- Of ICU patients, 36.4% of white patients and 35.2% of black patients died. Of those receiving mechanical ventilation, 39.0% of white patients and 38.2% of black patients died.
- Patients with Medicare insurance (HR, 1.47; 95% CI, 1.08 to 2.00) and those without insurance coverage data (HR, 2.17; 95% CI, 1.32 to 3.57) were at higher risk for death than those with commercial insurance.
- Of the 11, 210 patients, 4,180 (37.3%) were black. Black patients were younger than white patients (median age, 61 vs 66 years), more likely to have Medicaid insurance (24.7% vs 13.3%), and had higher median scores on the Neighborhood Deprivation Index (0.82 vs -0.11) and the Elixhauser Comorbidity Index (22 vs 21).
- Hospitals included in the study were located in Alabama (6 hospitals), Florida (5), Illinois (8), Indiana (14), Kansas (4), Maryland (1), Michigan (13), New York (2), Oklahoma (6), Tennessee (4), Texas (11), and Wisconsin (18).
Overall risks, those for hospitalized patients
- While current reports suggest that blacks shoulder a disproportionate burden of C19 infections and deaths (21% vs 13%), the authors noted that local, state, and territorial reports to the Centers for Disease Control and Prevention are missing about 55% of race data.
- They said that living conditions, workplace differences, and underlying medical conditions may help explain why ethnic minorities appear to bear a disproportionate burden of C19 illness and death overall. But their findings, they added, confirm those of previous studies in Louisiana and Georgia that found no difference in death rates by race in hospitalized C19 patients.
- “Taken together, these findings suggest that while Black US residents may be at higher risk of contracting C19 and represent a disproportionate share of C19 death, mortality for those able to access hospital care does not differ from White patients,” the authors wrote.
D. Improved & Potential Treatments
1. The Treatment That Could Crush Covid
- More than 500 clinical trials are under way world-wide in the race to find an effective treatment for C19. Everybody wants it; nobody has it—yet. But one of the most promising therapies for C19 patients uses “medicinal signaling cells,” or MSCs, which are found on blood vessels throughout the body.
- In preliminary studies, these cells cut the death rate significantly, particularly in the sickest patients. With a powerful 1-2-3 punch, these cells eliminate the virus, calm the immune overreaction known as a cytokine storm, and repair damaged lung tissue—a combination offered by no other drug. This type of regenerative medicine could be as revolutionary as Jonas Salk’s polio vaccine.
- In one pilot study in March, doctors at Mount Sinai Hospital in New York treated a dozen severely ill C19 patients on ventilators with MSCs. Two infusions modulated their hyperactive immune systems, and 83% of those patients survived. With such promising results, the team at Mount Sinai and the supplier of the cells, Mesoblast Ltd., won FDA clearance and NIH funding to conduct a randomized trial on 300 patients. The first patients in the trial received the treatment in early May.
- A July 10 article in the Lancet reported on 13 critically ill C19 patients also treated with MSCs. Eleven of the 13 patients lived—an 85% survival rate, which mirrors the results from Mount Sinai. The number of virus-fighting T-cells rose even as inflammation fell, suggesting that these cells can control the immune response as needed. In addition, chest X-rays showed that the drug repaired lung tissue, in some cases within 48 hours.
- Healing tissue is essential because the cytokine battle with the C19 virus is so vicious that it punches holes in the delicate lung membranes, allowing the virus to flood into the bloodstream and body cavities. These holes must be repaired, as virus leaks create some of the complications not usually associated with respiratory infections—blood clotting, heart attacks, stroke and multiple organ failure, which cause about 40% of C19-related deaths. Blood-vessel density, and thereby the number of MSCs, decreases as we age, gain weight or develop diseases, which may explain why the elderly and those with chronic health conditions are faring worst.
- In other words, this disease appears to be both a respiratory and a vascular infection. That is why the ability to fight infection, control the immune response and repair damaged tissue is such a valuable combination.
- How can one drug do all this? MSCs were first identified and named by Prof. Arnold Caplan and colleagues at Case Western Reserve University in Ohio nearly 30 years ago. To translate this discovery into therapies, Mr. Caplan and I in 1993 launched Osiris Therapeutics, Inc. which developed this MSC into the world’s first approved systemically delivered cell therapy. During early years of scientific inquiry, Mr. Caplan and colleagues discovered that MSCs monitor and protect virtually every vessel in our bodies—the 60,000 miles of vessels that transport oxygen, nutrition and waste to and from every one of our cells.
- When a MSC detects an infection or an injury to those vessels, it transforms into a factory to recruit and pump out immune-modulating and vessel-repair agents. These cells ameliorate crippling and deadly conditions when traditional chemical or biochemical drugs fail. The number of potential uses is enormous. MSCs are being tested on more than 900 different human ailments. Mr. Caplan describes these cells not as a “wonder drug,” but as a wonder drugstore.
- Consider the results from trials conducted by Mesoblast on graft-versus-host Disease. Children with this horrible affliction suffer such a violent immune reaction that the skin and the lining of their intestines peel off. Up to 80% of children die if steroids don’t stop the inflammation. But in one trial, 160 of 239 patients (67%) who didn’t respond to steroids and other treatments survived after infusion with MSCs. Their cytokine storm disappeared. Injured tissues normalized. Based on these results, the FDA agreed to expedite its review and grant a decision by Sept. 30.
- This is exactly the type of cell being tested for C19 in the May trial. If the cells perform as they did at Mount Sinai in March and elsewhere, the results should be available before the end of September. A positive finding could help those most at risk of the disease’s worst effects. But the medical community and wider public are largely unaware of the potential for using MSCs to treat Covid.
- Amid so much darkness, MSCs are a ray of hope—not only for the most desperate coronavirus patients, but all of us ready to end the pandemic and discover new ways to fix the body’s broken systems.
- Mr. Kimberlin is chairman of Spencer Trask & Co. and a co-founder of Osiris Therapeutics, Myriad Genetics and Ciena Corp.
2. Hypoxia in hospitalized C19 patients may be treatable
- C19 patients with hypoxia respond positively to icatibant treatment, Radboud university medical center researchers wrote in JAMA Network Open. These findings have led to a follow-up study at ten Dutch hospitals into a drug that may be even more effective. The current study has been funded by ZonMw.
- Rapid fluid overload of the lungs – pulmonary edema – is a hallmark of severe infection with the coronavirus. In a previous article, Nijmegen researchers suggested that this involves the ACE2 receptor. The coronavirus enters the cells via this receptor, after which it can multiply. However, the ACE2 receptor not only provides a gateway for the coronavirus, but it also keeps vasodilatory kinins under control. The infection causes most of the ACE2 receptors of the lung cells to dysfunction. Without ACE2, these kinins have free rein and – by binding to bradykinin receptors – can make the blood vessels leaky. Internist Frank van de Veerdonk, hospital pharmacist Roger Brüggemann and colleagues hypothesized that this process plays an important role in severe C19 infection.
- After consultation with the Central Committee on Research Involving Human Subjects (CMO) and the Health Care and Youth Inspectorate (IGJ), and with the informed consent of the participating patients, the researchers tested their hypothesis with the drug icatibant. Van de Veerdonk: “This drug is used in patients with the rare condition: hereditary angioedema.
- These patients sometimes develop acute subcutaneous fluid deposits due to local leakage of blood vessels. Icatibant blocks the bradykinin receptor B2R, which quickly stops the leakage. To determine whether the drug is also suitable for the specific group of C19 patients with fluid in their lungs, earlier this year we administered this drug to nine patients in the Internal Medicine Department and one patient in the Intensive Care Unit.”
- The results of this study have now been published in JAMA Network Open. All the patients, which were in need for oxygen treatment due to fluid in their lungs, were given three doses of icatibant by subcutaneous injection at six-hour intervals. The patient in the ICU recovered sufficiently within 24 hours to be moved to the ward and was discharged after 7 days. Eight of the remaining nine patients needed less oxygen supplementation within 24 hours and the ninth after 38 hours. In 18 comparable patients who served as controls, substantially higher levels of oxygen supplementation were needed over time.
Support for the hypothesis
- Brüggemann: “Although this was not a randomized trial, the results support our hypothesis. In an early phase of the infection with severe oxygen deficit, we see that icatibant improves the situation. A disadvantage is the short-term effect of the drug. Half of the drug is broken down in two hours, so the effect diminishes quickly. After the treatment, three patients had to be given oxygen again because the drug had worn off.”
- The research published in JAMA Network Open was actually a proof of concept, which the researchers have already built upon. Improved understanding of the role of the kinin-kallikrein system (KKS) in C19 means that the researchers expect even better results from another drug. Brüggemann: “The drug lanadelumab remains active for much longer than icatibant, so you will probably only need to administer it only once or twice”. Van de Veerdonk: “Lanadelumab also has a much broader effect. It inhibits the activation of the whole system that causes leakage of the blood vessels. It is therefore not only active for longer but might also be more effective.”
Research in hospitals
- Based on the initial results published in JAMA Network Open and these more recent insights, Van de Veerdonk and Brüggemann have been awarded a grant from ZonMw for a phase 2 clinical trial with lanadelumab for this specific group of C19 patients. Several Dutch hospitals are participating in the study. If this approach works, Brüggemann and van de Veerdonk expect that the research can immediately be rolled out on a large scale internationally.
- This is not only important for rapid recovery of patients with hypoxia admitted to the hospital but can also reduce the pressure on IC capacity. Global organizations such as the WHO and REMAP-CAP are directly involved in this research, and the strategy is currently being considered by several others. With this strategy Van de Veerdonk and Brüggemann aim to help patients presenting with hypoxia to recover quickly and thus avoid ICU admission.
2. Coronavirus outcomes improved by heartburn drug famotidine (Pepcid)
- Another observational study was released supporting the notion that a heartburn drug helps improve clinical outcomes in coronavirus patients.
- Famotidine, which is used to treat heartburn and is commonly sold as Pepcid AC, was associated with improved clinical outcomes in C19 patients according to a recent study by Hartford Hospital that has been accepted in the American Journal of Gastroenterology.
- “The main finding of our single-center, retrospective study of hospitalized C19 patients is that use of famotidine is associated with improved clinical outcome including lower in-hospital mortality and a lower composite endpoint of death and/or intubation,” study author, Jeffrey F. Mather, from the division of research administration at Hartford Hospital, said in one report.
- Researchers developed a database for all C19 patients and their clinical information to answer questions about the medical outcomes in their coronavirus treatment. The database allowed the researchers to observe the effect of experiments in patients with other conditions and the effect of medications on the course of the disease, Rocco Orlando, chief of academic affairs at Hartford Healthcare, told Fox News.
- Famotidine in Pepcid, which is an acid-reducing drug, used in hospitalized patients with C19 was associated with a lower risk of death, lower risk of combined-outcome of death and intubation, and lower levels of severe disease effects in the blood of hospitalized patients with C19, he said.
- The research team discovered that treating patients with famotidine was associated with certain markers that are potential signs for severe forms of the virus, according to health experts.
- According to reports about the study, another analysis found that famotidine worked well in coronavirus patients who had the highest national early warning scores, a measure healthcare professionals use to determine the degree of illness of a patient and critical care treatment intervention, health experts state. It is still being investigated as to how this drug affects the coronavirus, the scientific name for the new coronavirus that causes C19, according to the reports.
- “There have been a few small observational studies and retrospective reviews that raise the potential benefit of Pepcid in early COVID disease.” Dr. Ira Schmelkin, chief of the division of gastroenterology at Baystate Health in Springfield, Mass., told Fox News. “Early on, doctors in China noticed that elderly patients with lower socioeconomic status seem to be dying at a lower rate. It was noticed that these patients were taking the less expensive famotidine than the more expensive Proton pump inhibitors,” Schmelkin said to Fox News.
- The next step in the research would be a randomized placebo-controlled prospective study to see if famotidine is of clinical benefit, the chief of gastroenterology said.
- The Hartford researchers said in reports that their findings should be interpreted cautiously since it is a retrospective, observational, single-center study. Like Schmelkin, they suggested further research is needed regarding the use and dosage of famotidine in the treatment of novel coronavirus.
E. Vaccines & Testing
1. CUNY med school, TechnoVax report C19 vaccine breakthrough
- The CUNY School of Medicine at The City College of New York and TechnoVax, Inc., a biotechnology developer of novel vaccines, announce a breakthrough in their collaborative effort to develop a vaccine for C19. Scientists from the two organizations have generated and characterized coronavirus-like particles (VLPs) which are structural mimics of the native virus in size, morphology and surface composition but devoid of viral, infection causing, genetic material. These features of the VLP platform make it an ideal candidate for C19 vaccine development.
- This technology has a proven track record as evidenced by the success of vaccines directed against human papillomavirus virus (HPV) and hepatitis B virus (HepB) which have been proven both highly effective and exceedingly safe in stimulating immune responses. The CV-19 VLPs were assembled in a suspension culture of mammalian cells from both the coronavirus structural elements as well as uniquely modified surface spike molecules specifically designed to ensure stability, abundance, and most importantly the immunogenic properties known to be essential for creation of a highly effective vaccine.
- Electron microscopy studies of purified VLPs reveal that there is not only a high frequency of spikes projecting from the surface of the particles, but that the morphology of the structure also resembles that of the native coronavirus. CCNY researchers Paul Gottlieb and Reza Khayat noted that the stabilized surface spikes are expected to be highly immunogenic.
- “This innovation is most likely to accelerate the development of a C19 vaccine in that it utilizes a proven technology that is distinct from current C19 vaccine candidates,” said Jose Galarza, CEO, TechnoVax.
- “The CUNY School of Medicine, the newest addition to City College, continues, with this avenue of research, the College’s established tradition of directing our research efforts where they are most needed by society,” said CCNY President Vince Boudreau. “The search for a C19 vaccine is among the most important research efforts of our day and we are proud that researchers working on our campus have turned up such a promising avenue of advancement.”
- Overall, CCNY and TechnoVax are committed to the advancement of the development of a safe and effective VLP based C19 vaccine and are entertaining inquiries from potential partners to collaborate on these efforts in order to expedite this work and bring to fruition a successful alternative vaccine solution with great potential for stemming this destructive pandemic.
2. Toward a coronavirus breathalyzer test
- Few people who have undergone nasopharyngeal swabs for coronavirus testing would describe it as a pleasant experience. The procedure involves sticking a long swab up the nose to collect a sample from the back of the nose and throat, which is then analyzed for coronavirus RNA by the reverse-transcription polymerase chain reaction (RT-PCR).
- Now, researchers reporting in ACS Nano have developed a prototype device that non-invasively detected C19 in the exhaled breath of infected patients.
- In addition to being uncomfortable, the current gold standard for C19 testing requires RT-PCR, a time-consuming laboratory procedure. Because of backlogs, obtaining a result can take several days. To reduce transmission and mortality rates, healthcare systems need quick, inexpensive and easy-to-use tests.
- Hossam Haick, Hu Liu, Yueyin Pan and colleagues wanted to develop a nanomaterial-based sensor that could detect C19 in exhaled breath, similar to a breathalyzer test for alcohol intoxication. Previous studies have shown that viruses and the cells they infect emit volatile organic compounds (VOCs) that can be exhaled in the breath.
- The researchers made an array of gold nanoparticles linked to molecules that are sensitive to various VOCs. When VOCs interact with the molecules on a nanoparticle, the electrical resistance changes. The researchers trained the sensor to detect C19 by using machine learning to compare the pattern of electrical resistance signals obtained from the breath of 49 confirmed C19 patients with those from 58 healthy controls and 33 non-COVID lung infection patients in Wuhan, China.
- Each study participant blew into the device for 2-3 seconds from a distance of 1¬-2 cm. Once machine learning identified a potential C19 signature, the team tested the accuracy of the device on a subset of participants. In the test set, the device showed 76% accuracy in distinguishing C19 cases from controls and 95% accuracy in discriminating C19 cases from lung infections. The sensor could also distinguish, with 88% accuracy, between sick and recovered C19 patients. Although the test needs to be validated in more patients, it could be useful for screening large populations to determine which individuals need further testing, the researchers say.
3. Innovative Approaches to C19 Vaccine Taken by Molecular Engineers
- As scientists around the world rush to learn more about C19, several labs at the University of Chicago’s Pritzker School of Molecular Engineering are taking an innovative approach to vaccine development.
- While some companies are already beginning to test vaccine formulations in small trials, there are a lot of potential hurdles to the finish line. It’s important to be exploring approaches from multiple angles, scientists say.
- “The reality of vaccine work is that a lot of vaccine candidates won’t turn out, so it’s better to have a deep bench,” said Aaron Esser-Kahn, an associate professor of molecular engineering whose lab has rapidly shifted to address the coronavirus pandemic.
- His lab is one of several at PME that is taking a slightly different tack in exploring vaccine development than most commercial labs. Melody Swartz, the William B. Ogden Professor of Molecular Engineering, and Jeff Hubbell, the Eugene Bell Professor in Tissue Engineering, are two others.
‘Turbocharging’ vaccine performance
- Esser-Kahn researches the immune system and vaccines, but he previously worked on other diseases including influenza. Because the flu virus mutates so fast, one of their approaches has been to find molecules that boost any vaccine they are added to. C19 doesn’t mutate as fast as the flu, but the same approach is useful, as scientists are exploring many different vaccine avenues for a vaccine in parallel—and these could be added to any promising candidate.
- “The idea is that you can add these molecules to many vaccines, and it will improve the response you get,” said Esser-Kahn.
- There are two parts to virtually all vaccines. One part is some version of the virus in question, usually with some essential parts lopped off to make it tamer, so that the immune system can learn to recognize it. Then there’s an ‘adjuvant,’ which is the wake-up call for the immune system.
- One of Esser-Kahn’s approaches is to adjust the adjuvant to activate immune cell called CD4+ cells. These cells protect the lungs in flu, SARS and Zika infections; and since C19 tends to attack the lungs, it’s possible that marshalling a strong CD4+ response could offer better protection. “We tried this recently with smallpox, and saw good response,” Esser-Kahn said.
- “Another angle is to add a third component to the vaccine, made up of molecules that control how the body responds to the vaccine. These would tweak cells’ signaling processes to help the body better respond to C19 with less chance of side effects.”
- Finally, Esser-Kahn is also interested in an approach called “trained immunity.” “This one’s in a very early stage, but we think it has a lot of potential,” he said.
- It’s been observed that getting vaccines sometimes reduces a person’s overall likelihood of getting sick—even with diseases that the vaccine wasn’t treating directly. For example, people who get vaccinated for tuberculosis are less likely to get the flu that winter.
- “We think this is because the immune system is on extra alert,” Esser-Kahn said. They’ve zeroed in a particular molecule called beta-glucan, which is a nontoxic sugar molecule. “We wondered, if we just inject beta-glucan without the rest of the vaccine, it could boost the overall immune response against any pathogen,” he said.
- Instead of a true vaccine, this would instead boost a person’s initial immune response if they were infected, buying time while the immune system makes specific antibodies to C19. A slow-release formulation would allow the system to mount a measured response over many days.
- If it works, it could be used for any pandemic, Esser-Kahn said—given as a preventative to people who are most at risk, such as healthcare workers. But because it’s a new idea, they have to do fairly extensive testing first.
A novel delivery system
- Another approach is to work on the delivery system of the vaccine. Swartz and Hubbell, both molecular engineers, have previously developed nanoparticle vaccines.
- Nanoparticles are easy to make, and they form naturally into little capsules that can be easily customized with any of the viral proteins identified as good for vaccines. “We know from previous work that you can get better responses if you incorporate the viral protein and the adjuvant within the nanoparticles,” Swartz said.
- For example, researchers can attach molecules that serve as a kind of “mailing address” to get the vaccine to the specific areas or kinds of cells they want to activate, which can enhance the effectiveness of the vaccine. “How you target the nanoparticle to the right cell populations, and how you induce the cells to then uptake them and become activated, is critical,” Swartz said.
- In this case, they want to target lymph nodes, the organs in the body that are one of the frontlines for the immune system. Within the node, there are specific cells that trigger different types of responses; Swartz and Hubbell want to induce production of a particular kind of antibody called “broadly neutralizing antibodies.” These are antibodies that seem to act on a variety of virus strains, and thus may be able to clear several strains of the virus.
- “We’ll start by making various variants of the vaccine and testing them in mice to see which drives the best response, in terms of the breadth and potentency of virus-specific antibodies,” Swartz said. They’re also developing a way to test small amounts of human immune cells in microdevices on the benchtop, to complement the results from mice.
- They have previously seen good success with the approach in malaria vaccines as well as tuberculosis and Lassa fever, so they hope to adapt it quickly to C19.
- “We’ve just started testing in mice,” Swartz said. “If all goes well, we could be ready for advanced animal studies in the early fall.”
4. What the immune response to the coronavirus says about the prospects for a vaccine
- In the late 1980s, 15 healthy people moved into new apartments in Salisbury, UK. On their third day, each was asked to snort a nostrilful of solution containing a coronavirus — one of several viruses that causes the common cold. Then the volunteers spent three weeks quarantined at the Common Cold Unit, part of the Medical Research Council, where researchers monitored a range of symptoms. Some study participants likened stays at the Common Cold Unit to a vacation — if so, it was a holiday complete with blood draws and nasal washes.
- About a year later, 14 of the volunteers came back to do it again. This time, researchers were keen to know if the participants’ exposure to the virus had made them immune. The answer: sort of. Although they showed no symptoms, analyses revealed that nearly all of them became infected before their immune systems could launch an effective defence.
- It was an early hint to the answer for a question that now keeps researchers, physicians and politicians alike awake at night: can the human immune system mount a lasting defence against the pandemic coronavirus? The answer is crucial to understanding whether a vaccine will provide adequate protection, whether those who have recovered from C19 can return to pre-pandemic behaviours, and how readily the world can reduce the threat posed by the disease.
- Researchers have been rummaging through results from the Common Cold Study and others like it, while scrambling to understand the human immune response to the coronavirus using animals and cell cultures, along with the latest molecular techniques. They have catalogued antibody and immune-cell responses with uncommon speed, determined which are likely to be the most effective, and designed vaccines and therapies that, in animal studies and small human studies, provoke at least short-term immune responses. But there is no quick and simple experiment that can firmly determine whether immunity will be effective or lasting. It is just too soon to know.
- “Only the future can tell us,” says Reinhold Förster, an immunologist at the Hanover Medical School in Germany.
- Sporadic accounts of reinfection — people recovering from C19, only to fall ill and test positive for the disease again — have stoked fears that immunity might be short-lived. Media outlets have latched on to such reports, and have offered gloomy predictions about the prospects for a vaccine. But scientists are more circumspect.
- “We’re all hearing anecdotes, but I don’t know if any of us know what to think about them,” says John Wherry, an immunologist at the University of Pennsylvania in Philadelphia. So far, reports of reinfection have lacked sufficient information about the person’s immune responses to rule out other possibilities, he says.
- For the scientists digging deeply into the details of the immune response to the coronavirus, the data are so far unsurprising — and that bodes well. “We’re seeing great immune responses and fantastic-looking antibodies. We just don’t know the longevity of that response yet,” says Mehul Suthar, a viral immunologist at Emory University in Atlanta, Georgia. “Unfortunately, that will take time.”
Antibodies are immunity pros
- The immune system has myriad ways to fend off viral invaders and keep them from returning. It selects for the B cells that produce antibodies capable of binding to the virus. It also squirrels away a store of long-lived memory B cells that produce those antibodies and that jump into action if the virus comes back. Another defence enlists T cells, which patrol the body seeking out and destroying infected cells, to disrupt the virus’s ability to replicate. These immune cells can also endure for years.
- Long-term immunity can vary by type and also by degree of response. Vaccine developers often hope to elicit what’s known as sterilizing immunity, a response, typically mediated by antibodies, that can rapidly prevent a returning virus from gaining ground in the body. But not all vaccines or infections elicit the neutralizing antibodies required for sterilizing immunity. HIV, for example, rarely induces neutralizing antibodies, a fact that has complicated efforts to develop vaccines against it.
- The signs so far for the coronavirus are encouraging. Several teams of researchers were quick to isolate neutralizing antibodies from people infected with the virus; most could mount such an antibody response within days of testing positive. And several vaccine candidates against the coronavirus provoke a strong antibody response, a positive sign that the vaccines might generate immunity.
- But some scientists have caveats about the preliminary data. Antibody responses tended to be highest in people with the most severe infection. Those with mild infections — which is to say most people who have had C19 — sometimes produced small amounts of neutralizing antibody. This pattern is often seen with viruses: the longer, more severe infections are more likely to produce strong, durable responses. This is one reason that common-cold coronaviruses sometimes don’t yield long-lasting immunity, says Shane Crotty, a virologist at the La Jolla Institute for Immunology in California.
- Then there’s the question of how long antibodies last. When researchers tracked C19 patients over time, they found that the amount of antibody peaked in the days following the onset of symptoms, then began to decline. In some study participants, the antibodies were practically undetectable within about three months. Several major media outlets reported this as a loss of immunity, saying that it would complicate vaccine efforts.
- Many immunologists found that declaration a bit premature, however. The data showed a perfectly normal response to a viral infection, says Luis Barreiro at the University of Chicago in Illinois, who studies the evolution of immune responses to pathogens. When a virus attacks, it spurs the proliferation of B cells that produce antibodies capable of recognizing pieces of the virus. But once the infection is gone, antibody levels typically wane. “There is a lot of fear out there,” says Miles Carroll, an infectious-disease specialist with Public Health England in Porton Down, UK. “But I think, on the whole, that it’s a fairly robust immune response.”
- To determine how significant that waning could be, researchers still need to know how much antibody it takes to successfully fend off the coronavirus. “Even small amounts of antibodies can potentially still be protective,” says Mala Maini, a viral immunologist at University College London.
- They also need to track antibody levels for longer, to find out whether they eventually hold at a low concentration — as is common in viral infections — or continue to rapidly decline. Given these unknowns, virologist Katie Doores of King’s College London, lead author of one of the antibody studies, says that the negative press coverage of her work caught her off guard. “Everyone seems to have gone ‘Argh!’,” she says. “But we don’t know what level of antibodies are needed for protection.”
Plans B and T
- Even if antibody levels dip to vanishingly low levels, the immune system often has a backup plan. Memory B cells linger in the bone marrow until a virus returns, when they take on a new identity as antibody-producing plasma cells. The data on memory B cells’ role in fending off C19 are incomplete — the cells are more difficult to locate and count than antibodies — but thus far, the evidence suggests that they proliferate, says Marcus Buggert, an immunologist at the Karolinska Institute in Stockholm. One recent study, which has not yet been peer reviewed, found memory B cells capable of producing neutralizing antibodies that recognize the coronavirus in people who had recovered from mild C19.
- Furthermore, immunity does not rely entirely on antibodies. T cells might be able to recognize virally infected cells and destroy them, limiting the virus’s spread in the body. Like memory B cells, T cells are more complicated to probe than antibodies, but studies so far suggest that they are called into action during coronavirus infection. One recent study surveyed immune responses in 36 people recovering from C19, and found T cells that recognize the coronavirus in all of them. “It looks like a virus that’s very stimulatory to T cells,” says immunologist Danny Altmann at Imperial College London. “Most people have very good T-cell responses to it.”
- T-cell studies are also converging on the possibility of cross-reactivity, in which T cells that recognize other coronaviruses also recognize the coronavirus. Several studies have found T cells that react to the coronavirus in blood samples from people who had not been exposed to the virus. And one team recently reported that some of these T cells react not only to the coroavirus, but also to some common-cold coronaviruses. The results suggest that there may be some lasting cross-immunity between these cold coronaviruses and the coronavirus, leading to speculation that this could be responsible, in part, for the wild differences in severity of C19 symptoms between individuals.
- Lessons learnt from other viruses also give reasons to be optimistic that immunity to the coronavirus will be lasting. T cells against the virus responsible for severe acute respiratory syndrome (SARS) have been found 17 years after infection. Also, the coronavirus does not seem to mutate as rapidly as the influenza viruses, notes Barreiro, which change so frequently that fresh vaccination is needed each year.
- The Common Cold Unit study found little sign of hope for sterilizing immunity for its common-cold coronavirus, but the results also suggested that immunity could be strong enough to reduce or even eliminate symptoms. Sterilizing immunity for C19 would be ideal, because it would reduce the risk of people with minimal symptoms spreading the infection widely. But at this point, a vaccine that could reduce mortality would likely still be helpful, says Alessandro Sette, an immunologist also at the La Jolla Institute for Immunology.
- Altogether, the diverse and sometimes devastating effects of the coronavirus on the body and its ease of spread have made it an unusual foe. But the immune system’s response to the virus, so far, has held few surprises, says Barreiro. In this case, he adds, ‘boring’ bodes well for long-lasting immunity. “There are still a lot of things that we don’t know, but so far, there’s nothing really unique.”
F. Concerns & Unknowns
1. C19 cytokine storms may prevent a durable immune response
- Shiv Pillai, MD, PhD, investigator in the Ragon Institute of MGH, MIT and Harvard and professor at Harvard Medical School (HMS), recently published a paper in Cell showing that that high levels of some cytokines seen in C19 patients, as part of a cytokine storm, may prevent the development of long-term immunity to the coronavirus.
- “We’ve seen a lot of studies suggesting that immunity in C19 may not be durable because the antibodies decline over time,” says Pillai. “More telling for us was that in patients with both mild as well as severe disease, antibodies lacked a key structural feature that is a hallmark of the ‘highest quality’ antibodies in a normal immune response. By using our understanding of how two different types of immune cells normally collaborate to make the best antibodies, we were able to find a mechanism that could explain this lower-quality immune response in C19 patients.”
- Pillai’s group, working with Robert Padera, MD, PhD, associate professor at HMS, examined the spleens and lymph nodes of deceased C19 patients and found a lack of germinal centers, an essential part of a durable immune response.
- Germinal centers are structures induced within the lymph nodes and spleens during infection or vaccination. In them, B cells, the immune cells that produce antibodies, mature to become long-lived “memory” cells.
- This process, along with controlled mutations in antibody genes, allows the immune system to select for and immortalize B cells that make the best antibodies against a particular pathogen. This creates a life-long “memory” of a pathogen which allows the body to quickly and effectively identify and attack the pathogen in the case of re-infection. Without germinal centers, there aren’t enough B cells that can create a high-quality antibody response to produce long-term immunity. To form germinal centers, B cells depend on key support from another specialized type of cell called a helper T cell. Pillai’s group showed that in C19 patients the specialized type of helper T cell does not develop, and as a consequence B cells are not helped in the right way. The study found no germinal centers in acutely ill patients.
- Previous studies with infectious disease in mice have shown that high levels of cytokines, small signaling molecules unique to the immune system, can prevent the formation of these helper T cells and therefore of germinal centers. Large amounts of a cytokine called TNF, in particular, prevented germinal center formation. Severe C19 cases were found to have massive amounts of TNF in the location where germinal centers would normally form.
- Lack of germinal centers has been observed in other diseases, including SARS, and does not mean there is no immune response. “There is an immune response in C19,” Padera says. “It’s just not coming from a germinal center.” However, the lack of germinal centers could have major implications for development of herd immunity.
- “Without the formation of germinal centers, there is unlikely to be long-term memory to this virus developing from natural infections, meaning that while antibodies may protect people for a relatively short time, a single person who recovers from the disease could get infected again, perhaps six months later, or even multiple times with the coronavirus. This suggests that developing herd immunity may be difficult,” adds Pillai.
- This finding would likely not affect vaccine-induced immunity, as vaccines do not induce cytokine storms. A vaccine-induced immune response would likely include the development of a germinal center, and the ensuing creation and immortalization of high-quality antibodies that would provide long-lasting protecting against C19.
2. C19 Is Creating a Wave of Heart Disease
Emerging data show that some of the coronavirus’s most potent damage is inflicted on the heart.
- The coronavirus was initially thought to primarily impact the lungs — SARS stands for “severe acute respiratory syndrome.” Now we know there is barely a part of the body this infection spares. And emerging data show that some of the virus’s most potent damage is inflicted on the heart.
- Eduardo Rodriguez was poised to start as the No. 1 pitcher for the Boston Red Sox this season. But in July the 27-year-old tested positive for C19. Feeling “100 years old,” he told reporters: “I’ve never been that sick in my life, and I don’t want to get that sick again.” His symptoms abated, but a few weeks later he felt so tired after throwing about 20 pitches during practice that his team told him to stop and rest.
- Further investigation revealed that he had a condition many are still struggling to understand: C19-associated myocarditis. Mr. Rodriguez won’t be playing baseball this season.
- Myocarditis means inflammation of the heart muscle. Some patients are never bothered by it, but for others it can have serious implications. And Mr. Rodriguez isn’t the only athlete to suffer from it: Multiple college football players have possibly developed myocarditis from C19, putting the entire college football landscape in jeopardy.
- I recently treated one C19 patient in his early 50s. He had been in perfect shape with no history of serious illness. When the fevers and body aches started, he locked himself in his room. But instead of getting better, his condition deteriorated and he eventually accumulated gallons of fluid in his legs. When he came to the hospital unable to catch a breath, it wasn’t his lungs that had pushed him to the brink — it was his heart. Now we are evaluating him to see if he needs a heart transplant.
- An intriguing new study from Germany offers a glimpse into how the coronavirus affects the heart. Researchers studied 100 individuals, with a median age of just 49, who had recovered from C19. Most were asymptomatic or had mild symptoms.
- An average of two months after they received the diagnosis, the researchers performed M.R.I. scans of their hearts and made some alarming discoveries: Nearly 80 percent had persistent abnormalities and 60 percent had evidence of myocarditis. The degree of myocarditis was not explained by the severity of the initial illness.
- Though the study has some flaws, and the generalizability and significance of its findings not fully known, it makes clear that in young patients who had seemingly overcome the coronavirus it’s fairly common for the heart to be affected. We may be seeing only the beginning of the damage.
- Researchers are still figuring out how the coronavirus causes myocarditis — whether it’s through the virus directly injuring the heart or whether it’s from the virulent immune reaction that it stimulates. It’s possible that part of the success of immunosuppressant medications such as the steroid dexamethasone in treating sick C19 patients comes from their preventing inflammatory damage to the heart. Such steroids are commonly used to treat cases of myocarditis. Despite treatment, more severe forms of C19-associated myocarditis can lead to permanent damage of the heart — which, in turn, can lead to heart failure.
- But myocarditis is not the only way C19 can cause more people to die of heart disease. When I analyzed data from the Centers for Disease Control and Prevention, I found that since February nearly 25,000 more Americans have died of heart disease compared with the same period in previous years. Some of these deaths could be put down to C19, but the majority are likely to be because patients deferred care for their hearts. That could lead to a wave of untreated heart disease in the wake of the pandemic.
- Many patients are understandably apprehensive about coming back to the clinic or hospital. The American Heart Association has started a campaign called “Don’t Die of Doubt” to address the alarming reduction in people calling 911 or seeking medical care after a heart attack or stroke.
- Since the beginning of the pandemic, it’s been clear that people with heart disease or related conditions such as diabetes or high blood pressure are at increased risk for severe C19 illness. The C.D.C. recommends that the more than 30 million Americans living with heart disease practice extra precautions to avoid infection. Hospitals and clinics should work overtime both to ensure they are safe for patients and to bolster telemedicine services so that patients can be cared for without having to leave their homes.
- Doctors and researchers should no longer think of C19 as a disease of the lungs but as one that can affect any part of the body, especially the heart. The only way to prevent more people dying of heart disease, both from damage caused by the virus as well as from deferred care of heart disease, is to control the pandemic.
- Haider Warraich (@haiderwarraich), the author of “State of the Heart: Exploring the History, Science, and Future of Cardiac Disease,” is a cardiologist and researcher at the Veterans Affairs Boston Healthcare System, Brigham and Women’s Hospital and Harvard Medical School.
3. Urinals and toilets may spread C19, adding fuel to the mask debate
- Here’s one more thing to worry about: Flushing that toilet—or urinal—could spread C19.
- A study from Chinese researchers at Yangzhou University on Wednesday found that the flushing action from both toilets and urinals can release clouds of virus-teeming aerosols, making public restrooms a potentially risky place for transmission. The researchers’ advice: If you’re going to use a public restroom, wear a mask.
- “Wearing a mask should be mandatory within public restrooms during the pandemic, and anti-diffusion improvements are urgently needed to prevent the spread of C19,” the researchers warned.
- Flushing a toilet or urinal has always posed some kind of hygiene risk, as the action creates an interaction between gas and air. In the paper, titled Virus Transmission from Urinals, published in the journal Physics of Fluids, the researchers found that a urinal was potentially even more risky. The research used a model to track aerosol particles released during flushing, and found that in a urinal, those particles could spread up to a typical man’s thigh level in about five and a half seconds, versus around half a minute for a flushing toilet.
- As a result, flushing from urinals produces a “more violent climbing tendency,” the researchers said, adding it’s something they had noticed outside of their research.
- This latest study builds on previous evidence that C19 can spread through restrooms. As early as February, Chinese researchers flagged that the virus could spread through feces, and one of the virus routes of transmission could be via the “fecal-oral” route—a particular worry on cruise ships.
- Queasiness aside, the research highlights just how difficult it is to track and understand the many sources of virus transmission—a struggle that is frustrating even the most diligent governments the world over, including New Zealand, which previously announced it had contained the virus.
- And it appears to underscore a simple message to life in the C19 era: If you must use a public toilet, bring your mask.
4. Study finds possible link between C19 and rise in childhood type 1 diabetes
- Cases of type 1 diabetes among children in a small UK study almost doubled during the peak of Britain’s C19 epidemic, suggesting a possible link between the two diseases that needs more investigation, scientists said on Tuesday.
- While the study is based on only a handful of cases, it is the first to link C19 and new-onset type 1 diabetes in children, and doctors should be on the look-out, the Imperial College London researchers said.
- “Our analysis shows that during the peak of the pandemic the number of new cases of type 1 diabetes in children was unusually high in two of the hospitals (we studied) compared to previous years,” said Karen Logan, who co-led the study.
- “When we investigated further, some of these children had active coronavirus or had previously been exposed to the virus.”
- Logan said previous reports from China and Italy had noted that children were being diagnosed in hospitals with new-onset type 1 diabetes during the pandemic.
- This study, published in the Diabetes Care journal, analysed data from 30 children in London hospitals diagnosed with new-onset type 1 diabetes during the first peak of the pandemic — around double the cases seen in this period in previous years.
- Twenty-one of the children were tested for C19 or had antibody tests to see whether they had been exposed to the virus — and five tested positive for novel coronavirus infection.
- Type 1 diabetes causes insulin-producing cells in the pancreas to be destroyed, preventing the body from producing enough insulin to regulate blood sugar levels. The Imperial team said one possible explanation might be that the novel coronavirus’ spike protein might attack insulin-making cells in the pancreas.
- “More research is needed to establish whether there is a definitive link, … but in the meantime we hope clinicians will be mindful of this,” Logan said.
G. Do Lockdowns Work?
1. Lockdown Becomes an Australian Nightmare
- Australia’s coronavirus response was, until recently, the envy of the world. Like its economy, which had gone nearly 30 years without a recession, Australia seemed to have cracked the Covid code. Community transmission had been all but eliminated, deaths kept low—a little over 100—and life in the population centers of Sydney and Melbourne was getting back to normal. At the same time, economists and business leaders had their fingers crossed for a V-shaped recovery, with hopes that the federal government would wind up its expensive stimulus and support programs before the end of the year.
- No longer. Australia is discovering what much of the world has already learned: Like holding a beach ball underwater, you can keep your infection rate down only for so long before it pops up again. And there’s only so much you can do to stop a virus from spreading without resort to petty totalitarianism.
- The details of how the Australian state of Victoria got caught in a second wave, wrecking its hopes for a quick recovery while enlisting the citizenry as an army of snitches, tell a tawdry tale of political incompetence. The trouble began in Melbourne, where far-left Labor Premier Daniel Andrews leads the state government.
- Early in the pandemic, the center-right national government of Liberal Prime Minister Scott Morrison made the decision to quarantine returning international travelers in hotels for 14 days. While this was managed well in most of the country, the Andrews government put private security contractors in charge of the hotels in Victoria. Scandal erupted when the hotels became infection hot spots. Australian media reported that the private contractors had recruited inexperienced guards via WhatsApp chat groups. Some were caught sleeping on the job and may have had sex with the returned travelers they were supposed to be guarding. Authorities have opened a judicial inquiry into the debacle.
- Victoria, with roughly the same population as Indiana, was soon recording several hundred infections a day. The state government placed Melbourne under one of the strictest lockdowns in the world. Residents are allowed out of their homes for only an hour each day. Travel is limited to a 3-mile radius. The only permitted activities are shopping and exercise.
- Commercial life in Melbourne has plunged into a deep freeze. Mr. Andrews ordered Victoria’s meat-processing plants to cut capacity and began flagging the potential for shortages. “You may not necessarily be able to get exactly the cut of meat that you want,” he said. “But you will get what you need, and you will get all the products that are basically, fundamentally important to you.”
- Countless Melbourne businesses—particularly the cafes and restaurants that once gave the city its charm—are shutting down for good. The earlier nationwide lockdown measures, which were based on the most lethal assumptions about the virus, had put the nation into technical recession. Victoria’s harsh new restrictions could spark an economic cataclysm.
- This couldn’t come at a worse time for Australia’s overburdened social safety net. The federal government is now responsible for supporting more Australians than at any other time in the nation’s history. In June 6.8 million people, or 52% of the workforce, were either employed by the government or receiving unemployment payments or wage-support measures.
- The devastation will grow. Australian colleges and universities have long built their business models around selling degrees to foreign (mostly Chinese) students. Because of the lockdown, these schools will take a potentially fatal hit to their cash flow. According to the Australian Bureau of Statistics, international education brought 32.4 billion Australian dollars (about US$23.3 billion) into the economy in 2017-18. If the pandemic keeps foreign students from returning to study in Australia, some schools may not survive.
- It’s the same story with tourism. The 9.5 million international tourists who usually visit Australia every year aren’t coming in 2020. It’s winter in the Southern Hemisphere. With most Australians now confined to their home states, resorts in sunny Queensland can’t even count on domestic travelers to offset lost income.
- While some countries have focused on “flattening the curve” and may be approaching limited herd immunity, Australia’s politicians have pushed a strategy of de facto elimination, figuring the country can stay cut off from the world until a vaccine arrives or a treatment is developed. Any discussion of the economic costs of the lockdown strategy is regarded as immoral ghoulishness. As those costs mount, this squeamishness will need to end.
2. After Nearly 150 Days Of Lockdown, Argentina’s C19 Outbreak Is Deadlier Than Ever
- With the reform-minded business-friendly conservatives out, and the Peronistas back in power in Argentina, one of South America’s biggest and most troubled economies is struggling to get back on its feet, bolstered by the promise of more rope from the IMF and the country’s other creditors, despite arriving at its 3rd default in 20 years, and its 9th in history – the most of any country.
- This unfortunate reputation has led some to joke that only three things in life are certain: death, taxes and another Argentinian sovereign default.
- But as the country prepares for yet another refinancing thanks to the IMF, the government has revealed that the country’s already damaged economy has been absolutely hammered by one of the world’s longest, and strictest, lockdowns.
- And even as new COVID cases have tapered off somewhat, Argentina’s death toll is quickly climbing the ranks of the deadliest outbreaks in the world.
- According to Bloomberg, in the past seven days, Argentina has reported 22.5 deaths per million people compared with 28.1 in Brazil and 23.4 in the US, the homes of the deadliest outbreaks in the world.
- Total deaths in Argentina have now surpassed 5,000 since the pandemic began.
- The deaths, and the weariness of the Argentina quarantine, which has crushed the country’s economy while doing little to stanch the virus’s spread, have spurred more protests in the country.
- Even worse, concerns are mounting that Argentina is undercounting cases and deaths. The positivity rate across the country has been hovering around 40% for the past week, similar levels to Mexico, which suggests that testing levels are insufficient.
- But after 146 days of lockdowns, the government is facing pressure to reopen immediately.
- Buenos Aires remains the epicenter of the virus. The city had 64% of all cases, though it is Argentina’s most populous province.
H. Back to School!?
1. How schools can reopen safely during the pandemic
- At schools across South Korea, children eat their lunches in silence, facing plastic screens that separate them from their friends. They wear masks, except when practising social distancing in the playground. And their temperatures are checked twice every morning — first at home and again at the school gates.
- This could be the new reality for the millions of children around the world. Summer holidays are drawing to an end in the Northern Hemisphere, and in places such as the United States, the United Kingdom and some European countries that closed schools during the coronavirus pandemic, governments are debating when and how to open schools. A growing number of studies show that there are ways to do this safely. The key is vigilance on hygiene and physical distancing, a swift public-health response to halt the spread of any infections and, most crucially, low levels of viral spread in the community.
- “Some countries in Asia, particularly South Korea, provide a good model for how schools can provide face-to-face teaching during the pandemic,” says Zoë Hyde, an epidemiologist at the University of Western Australia in Perth.
- But researchers say that if schools are opened before community transmission reaches low levels, cases will surge.
- Schools can be high-risk places, says Young June Choe, a paediatrician and epidemiologist at Hallym University in Chuncheon, South Korea. Children are often crammed into poorly ventilated rooms for eight hours or more, he says. And there’s a lot of mixing, because children come from across the neighbourhood, some on public transport, and often with their parents in tow.
- Earlier in the pandemic, it appeared that the virus might affect children differently from adults. Because children had milder symptoms, it was assumed they might be less infectious. But now there is evidence that children can spread the virus to other people, especially those living in the same household. Several studies show that once children are infected, they are no less infectious than adults.
- “If schools are reopened in areas with high levels of community transmission, major outbreaks are inevitable and deaths will occur in the community as a result,” says Hyde. Evidence of this can be seen in the sporadic outbreaks and spill-overs that have already occurred, including those at a high school in Israel and a camp in the United States.
Low community spread
- Studies in South Korea, Europe and Australia show that schools can open safely when community transmission is low. Children in South Korea returned to their classrooms in mid-May, when daily confirmed cases dropped to below 50 — equivalent to around one case per million people. Even with such low transmission rates, the government introduced measures to control viral spread, such as staged opening of schools, starting with high schools and then junior schools. At larger schools, or those in areas where cases were rising, only a portion of students attended. When someone tested positive, teaching went back online.
- An analysis by researchers in Seoul that has not yet been peer reviewed found no sudden increase in cases of C19 among children aged 19 and below in the 2 months after schools reopened. And government data report that only 1 of the 111 school-aged children who tested positive between May and July got the infection at school. Most were infected by family members, or at other locations. “The takeaway message is that with the right policies, we can control transmission in schools in a setting of low community transmission,” says Choe. “There is no special recipe that makes Korea unique.”
- A survey by the European Centre for Disease Prevention and Control also found that the reopening of schools from mid-May onwards in several European countries has so far not been associated with a significant increase in community transmission.
- The state of New South Wales (NSW) in Australia partially closed schools at the peak of the state’s epidemic in March, but kept day-care centres open. Kristine Macartney, director of Australia’s National Centre for Immunisation Research and Surveillance in Sydney, and her colleagues analysed data from schools and day-care centres from between late January and early April. Schools remained open for the children of health-care workers or those with no alternatives.
- During the study period, the state averaged 193 cases a day — 24 per million people — but 58% of the cases were in travellers returning from overseas. Macartney and her co-workers found that only 25 of the 7,700 schools or day-care centres reported a primary infection during the study period5. Of those cases, only four facilities had onward transmission.
- Macartney points out that the results must be viewed in the context of the state’s strong public-health response. NSW maintained high levels of testing in the population, rapidly identified cases and implemented contact tracing, and its borders were closed, with strict enforcement of quarantines. “If transmission would be occurring unchecked in the community, we are sure it would spill over into schools,” says Macartney, noting that in a recent surge in cases in the neighbouring state of Victoria, hotspots have been identified at schools. “This virus will take advantage of any chink in the armour,” she says.
- In places where there is ongoing community spread, schools and camps have become sites of major outbreaks. The virus swept through an overnight camp in the US state of Georgia in mid-June. On the first day of camp, Georgia reported 993 new cases of C19. Campers slept in cabins in groups of up to 26, did not need to wear masks, and sang and cheered every day. A staggering three-quarters of the 344 tested participants were positive for the coronavirus.
- Another large outbreak was detected in a high school in Jerusalem, Israel, 10 days after all schools re-opened in mid-May. There were around 127 reported cases a day in the country in early May when some children began returning to school — equivalent to 15 cases per million people.
- As temperatures exceeded 40°C, teenagers sat in air-conditioned rooms with more than 30 other classmates without masks. The outbreak affected 153 students and 25 staff members, as well as 87 siblings, parents and friends of those affected.
- The school environment can also increase the risk of further community spread. In mid-March, a large school in Santiago, Chile, had a sizeable outbreak just nine days after the country detected its first case of C19. The school had more than 30 children in a class, and had been busy holding parent–teacher meetings. Researchers detected coronavirus antibodies in 10% of students and 17% of staff when they were tested about two months later.
- The school outbreaks in Israel and Chile suggest that large class sizes could play a part in transmission in schools, says Edward Goldstein, an infectious-disease epidemiologist at the Harvard T.H. Chan School of Public Health in Boston, Massachusetts.
- Schools should implement measures for reasonable distancing, by splitting the day into morning and afternoon shifts to reduce the number of children in a classroom, for example, and by preventing parents and teachers from gathering at school entrances and exits, says Miguel O’Ryan, a paediatric infectious-disease researcher at the University of Chile in Santiago who led the Santiago school study.
- If schools reopen in areas with a high rate of community transmission, being diligent about masking, class sizes, hand washing, and testing and tracing will be particularly important, says Katherine Auger, a paediatric researcher at Cincinnati Children’s Hospital Medical Center in Ohio.
- “If we go back to schools the way they used to be, then we are going to be in trouble,” she says.
- [NOTE: Noticeably absent from this article are comments about Sweden. Schools did not close during the spring, and the “major outbreaks” noted earlier never occurred.]
2. How to Help Kids Manage Back-to-School Anxiety in the Covid Era
- For many children in the U.S., the usual back-to-school jitters are likely to be a lot more intense this year amid the coronavirus pandemic.
- Among students slated to attend school in person, “there are worries about illness and germs and am I going to be able to see my grandparents if I go back to school,” says Muniya Khanna, a clinical psychologist and research instructor at the Children’s Hospital of Philadelphia. Children may worry about forgetting masks or running afoul of social-distancing rules. And many students—whether they’ll be learning in-person or online—may be anxious about missing milestones and special events, such as dances and band concerts, like they did in the spring.
- We talked to psychologists about how to ease children’s back-to-school anxiety. Here’s their advice:
Keep calm and listen
- First, parents need to cope with their own anxieties, says Dr. Khanna. It is especially important for parents of younger children to “demonstrate a sense of calm and confidence, demonstrating that the world is OK, that we are OK, even if I’m having doubts flying around,” she says. Moods are contagious, and a calm parent is more likely to mean a calm child, she notes.
- Dr. Khanna also advises parents to listen closely to their children’s actual fears. “Stay as small as possible. Start where their concerns are as opposed to starting with where your concerns are,” she says. Then pause—Dr. Khanna calls it the 10-second rule—and ask questions before “jumping in to correct or soothe,” she says. You’ll get more information that way. And you’ll give children the opportunity to solve problems—like what to do if a friend gets too close—themselves. “It is putting the control back in their hands and conveying they are capable of a lot of this,” Dr. Khanna says.
- Dr. Khanna advises parents to home in on practical safety measures like wearing masks, washing hands and keeping distance from other people.
- If children are worried about getting sick or loved ones getting sick, highlight “how people are staying safe in the family,” says Anne Marie Albano, a professor of medical psychology in psychiatry at Columbia University Irving Medical Center in New York.
- And when it comes to anxiety about potential disappointments, like a canceled baseball season or Halloween parade, Dr. Albano suggests that parents first empathize and validate their children’s feelings: “Yes, that really would stink.” And then help them strategize ways to adapt. For a canceled baseball game, for example, “what are some ways of getting your crew together” safely, she says.
Enforce good routines
- Now is the time to get back on a regular sleep schedule, says Jill Ehrenreich-May, a psychology professor at the University of Miami. Going to sleep late and not getting enough sleep has been linked to anxiety in children. Good nutrition and regular physical activity are also key, she says.
- This school year is likely to throw so much uncertainty at kids. So take time to prepare for as much as you can, says Dr. Ehrenreich-May. She suggests taking your child and a friend to a school-like setting, such as the local library where “you would wear your mask and maybe sit down and read a book or use the computer and wash your hands afterward,” she says. “Kids are going to have to learn to be next to each other while maintaining a safe distance.” Dr. Ehrenreich-May notes that exposing yourself to the very things you’re afraid of is a critical component of cognitive behavioral therapy, the most evidence-based nondrug treatment for anxiety disorders.
- Susan White, a professor of psychology at the University of Alabama, encourages parents to get children together in small groups so kids can practice wearing masks and maintaining distance while parents are there to give direction and reminders. “What scares a lot of parents is knowing they are going to go back to school and you won’t be able to coach them,” says Dr. White. She also suggests that children practice “advocacy and protection” by navigating pandemic-era social situations that may arise like “what do you say if somebody takes their mask off?”
- Christopher A. Kearney, chair of the department of psychology at the University of Nevada, Las Vegas, advises parents to have their children start practicing the morning routine at least a week before school begins: Get up on time, get dressed and put your backpack together (including masks and hand sanitizer). Take a tour of the school in advance if you can. “A lot of classrooms are going to look different and feel different,” says Dr. Kearney.
- Psychologists are particularly concerned about how children who already struggled with anxiety about school pre-pandemic or had difficulty making and keeping friends will fare in the new school year. These students may have been relieved when school went virtual and now may be out of practice when it comes to navigating social situations and feel intense anxiety. Practice is especially important for these children.
Prepare for things to change
- Already, several schools that started the year in person have shifted to remote learning after students and staff tested positive for C19. Columbia’s Dr. Albano suggests that parents create backup plans in advance, like “learning pods in someone’s backyard,” so they are prepared if school moves online. Also, keep some activities virtual, whether it be a music lesson or a math tutoring session, she says. That way, if in-person school and extracurriculars shut down, “it doesn’t feel like everything is being pulled out from under you again.”
3. What to Do If Your Child May Have Been Exposed to C19
- My child has been sent home from school after becoming sick following possible exposure to coronavirus. What should I do?
The bottom line
- Children attending school in person this year are likely to face new protocols when tracking illness, lowering the threshold for who gets sent home. In many instances, children with a runny nose, cough or fever will be asked to leave until symptoms subside. Those who are within 6 feet of someone positive for C19 and have at least 15 minutes of exposure will need to stay home for two weeks, according to federal guidelines. Many symptoms for the coronavirus overlap with the flu and common cold, so parents should consult their pediatrician to assess whether to take their child to get tested.
- Call your pediatrician to share the details of potential exposure. They will help determine how long testing results for C19 take in your area and whether to combine it with rapid tests for the flu or strep throat, says Nathaniel Beers, pediatrician at Children’s National Hospital in Washington, D.C., who co-authored the guidance on school re-entry drafted by the American Academy of Pediatrics. It’s best to test at least two days after exposure to C19 to avoid false negatives. If they do test positive, most children are healthy enough to come back to school 10 days after the onset of symptoms. Children who test negative and have a known exposure still need to quarantine; doctors caution against sending children with a pending test back to school.
- Known exposure doesn’t always warrant testing, Dr. Beers says. Conduct daily temperature and symptoms checks during the at-home isolation period. Anything over 100.4 degrees Fahrenheit is considered a fever. “It could be 14 days of isolation and monitoring for symptoms, not necessarily testing of every child,” Dr. Beers says. While parents can’t isolate from their children, hand-washing, avoiding sharing utensils, wiping down high-touch surfaces and wearing masks can help reduce risk of exposure.
- Children sent home with symptoms who don’t have known coronavirus exposure can return to school two days after their symptoms subside and at least 24 hours of no fever without medications, says Dane Snyder, chief of primary care pediatrics at Nationwide Children’s hospital. Children usually have a milder form of the virus with symptoms including cough, runny noses, congestion, sore throat, gastrointestinal problems and loss of smell. “The chances of Covid go down if it’s just a fever and they don’t have cough and congestion, but a stuffy nose could still be Covid,” says Dr. Snyder.
- To avoid additional confusion, children with asthma, allergies or other pre-existing conditions should bring in a note from their pediatrician at the start of the school year that explains associated symptoms.
- A bit of good news: Mask-wearing at school may help lower the spread of influenza and colds, making it a lighter season for other illnesses, says Jason Wang, director of the Center for Policy, Outcomes and Prevention at the Stanford University School of Medicine, who cited evidence from schools in the Southern hemisphere where flu season is underway.
I. The Road Back?
1. We Need Better Risk Communication to Combat the Coronavirus
- Pictures of crowded bars and restaurants could lead one to conclude that people are terrible at understanding risk. After everything we’ve been confronted with over the last six months — images of overflowing hospitals, dozens of stories in newspapers of young healthy people who either died or came near death from C19 — it’s easy to throw up one’s hands, feeling that the majority simply aren’t capable of making good decisions about risk.
- It is true that managing health risk is difficult. A new danger sows fear and uncertainty, and it has been generations since most Americans have experienced a public-health crisis (the AIDS epidemic a notable exception). We must also grapple with what economists call externalities: Risk assessment involves estimating not only the likelihood that you will get infected, but also the likelihood that you will infect loved ones or others in your community.
- Yet evidence suggests people can make good decisions about risk. Acting with incomplete information is part of everyday life. There is only one requirement: To make good decisions, we need information to be conveyed in a way that aligns with how we naturally experience and think about risk.
- But government agencies and the media have centered their communications on anecdotes and abstruse statistics, leaving Americans poorly equipped to rationally adapt to the public-health situation. We are told vivid stories of tail cases, without much context as to how rare they are, that reinforce our tendency to put too much weight on anecdotal evidence. We are given probabilities of hospitalization and deaths without adjustments for risk factors and without analogies to risks that we do understand. For example, we know eating at an outdoor restaurant is riskier than leaving home, but is it less risky than riding a bike in city traffic? The failure to express risk in terms we can understand is dangerous: There is clear evidence that people’s perceptions of the magnitude of a risk can vary significantly depending on whether that risk is described in abstract terms or in a way they can relate to more naturally.
- The lack of good risk communication during the pandemic is a major policy failure, comparable to the more tangible shortcomings on test capacity and PPE provision. Until we have a treatment or vaccine, rational behavioral adjustments are our best hope of managing the virus.
- One simple strategy to help the public understand probabilities is to frame them as frequencies. The fatality rate, for instance, is the number of people you would expect to succumb to C19 out of a group of 100 infected individuals. When framed as a percentage, though, it seems abstract and remote. Imagine that instead of being told that you had a 0.5 percent chance of death from C19, you were told that of your 400 Facebook friends, you should expect two to die if they all contracted the virus.
- Another way to explain a risk is to compare it to other risks with which people have more experience. Risk analogies can be quite powerful in helping us make decisions with a higher degree of confidence. For example, the odds of dying while walking down the street are about 1 in 541, roughly the same as the risk of death from C19 infection for someone aged 20 to 44. Such comparisons equip us to separate personal risks from the risks to others.
- One reason we may not hear much about relative risks is that, due to the externalities involved, comparing coronavirus deaths to things like car accidents is considered taboo. If we catch the disease, we can spread it, and, as we know, with C19 the rates of infection can be exponential. But even these risks can be explained using analogies. To get across the key component of exponential growth, we can make analogies to other quickly multiplying phenomena, such as forest fires, the growth of invasive species, or the way that one rotten apple can spoil the bunch. In fact, powerful analogies can make the consequences of our choices more vivid and meaningful; for example, by visualizing how the choice to work from home can affect many more people than just those with whom we work or commute.
- To be fair, the risks around C19 have presented a unique challenge. In March, little was known about the virus, but we are now more than six months into the pandemic. There is a history of super-spreader events. There are more reliable data on mortality and individual risk factors, as well as on behaviors to mitigate risks, such as wearing masks. And even if we don’t fully understand how the virus is transmitted, we know more than we used to.
- And yet, the CDC website does not offer meaningful risk communication; it merely lists risk factors, without data as to the severity of those factors. High-profile public-health officials offer ominous warnings but little in the way of sustainable ways to live with C19 risks. News reports still tend to highlight stories about individuals experiencing complications without explaining the likelihoods of such complications. It is nearly impossible to find meaningful risk assessments of different activities — say, going to the grocery store or getting your haircut. Even public-health officials won’t take a clear stand on whether a crowded beach is riskier than a large protest.
- This leaves non-experts to figure it out based on what they hear from their favored news sources or social-media platforms. It is no wonder some Americans are afraid to leave their homes entirely, while others flock to crowded indoor spaces. Much of the current reporting on C19 requires guesswork to fill in the holes.
- It’s not realistic to leave it to the government to manage all our risks. Government has a responsibility to regulate or ban the riskiest activities, but it can’t eliminate all C19 risk. America is too large, diverse, and interconnected. We also can’t all stay at home until there’s a vaccine, unless we want to ignore the heavy emotional toll of social isolation and the inevitable destruction of our economy. Instead, we must rely on our fellow citizens to make smart risk decisions. Some will make reckless choices and others will be overly cautious, no matter how much information they are given. But we can at the very least reduce some of C19’s spread if those who want to act responsibly are given the tools to do so. For that to happen, they need better information.
2. Covid Spit Tests are Faster, Cheaper and Don’t Use Chemicals in Short Supply
- The FDA this weekend authorized a saliva-based diagnostic test for C19 that costs less than $5, is faster than current laboratory tests, and may dodge supply shortages plaguing the country—without losing much in accuracy, according to early data.
- The test, called SalivaDirect, was developed by researchers at Yale University, who have no plans to commercialize the test and have made the test’s protocol completely open and available.
- If the protocol becomes widely adopted, it could help improve the country’s C19 testing, which is currently dismal. Some patients face weeks-long waits to get results. With such long delays, contact tracers have no chance of reaching out to those exposed before they have the chance to pass on the infection. The delays stem from the sheer volume of tests coming in, as well as shortages of critical supplies, such as nose swabs and chemical reagents necessary to run the tests. SalivaDirect tries to address both of those problems.
How standard testing works
- The new test is basically a streamlined version of the current standard for C19 diagnostic testing. Generally, these tests determine if a person is currently infected with the coronavirus by detecting its genetic material, which is in the form of RNA rather than DNA.
- The basic steps of the test start with sticking a long swab far into a person’s nose until it hits the back—a nasopharyngeal swap—to try to scrape up any coronavirus that may be present. The swab picks up all sorts of things, of course, including snot, bits of human cells from the nose, whole viral particles, and any other germs that may be present. To clean up the starting material, most test protocols then call for performing an assay that extracts out just the genetic material, clearing away all the debris and inconsequential bits. This requires time and specific reagents, which can be in short supply.
- Then, the isolated genetic material heads to a second assay called an RT-qPCR, or a quantitative reverse transcription polymerase chain reaction. In it, bits of RNA are converted into DNA, which is then probed for sequences present only in coronavirus. If those sequences are present, tiny fragments of synthetic DNA—called primers—latch onto the coronavirus code and direct enzymes to make copies of that stretch of DNA. The copies are cleverly designed to fluoresce when they’re formed. Then, the assay repeats this step to make another set of glowing copies, and another, and another, and another in an exponential process, until enough copies of the coronavirus DNA are present to detect a fluorescent signal above background.
- The faster that signal is detected—that is, the fewer cycles it takes to get it—the more coronavirus RNA was there to begin with, hence the “quantitative” part of the name. Researchers refer to this as the “Cycle threshold,” or Ct. If the Ct is low, say below 30 cycles, it suggests there was a good amount of RNA to begin with, perhaps from a raging infection. If it’s above, say 37, it means there was little coronavirus RNA in the sample, perhaps from a fading infection or genetic remnants of a recently ended infection.
- For diagnostic tests, the Ct value isn’t necessarily useful—if you have any amount of coronavirus RNA in your nose, you are or were very recently infected. The test doesn’t indicate infectiousness or past exposure to the virus. But comparing the Ct values between different tests for coronavirus is helpful for comparing how sensitive any given test is.
- For the SalivaDirect test, Yale researchers cut some corners without losing much in accuracy or sensitivity. First, with the global shortage of swabs, they skipped the stick and went just to spit. They verified that coronavirus is present in saliva as it is in the nose. They took saliva and nasal swabs from 37 known-positive patients and ran a standard lab test for coronavirus on all the samples. Between the paired nasal swabs and saliva samples, there was 83 percent agreement. Nearly all were positive, but three nasal swabs and three different saliva samples came back negative, invalid, or inconclusive. They also found that in collected saliva, the virus was stable for up to seven days at 4°C, room temperature, or 30°C without the addition of preservatives.
- The researchers then skipped the RNA extraction step entirely. Instead, they warmed up the saliva samples along with an enzyme called proteinase K that hacks away at any protein debris in the sample—human cells, whole viral particles, etc—leaving the coronavirus RNA standing. This is useful since the extraction step takes extra time and the reagents used in the assay are currently in short supply. Last, the researchers streamlined the RT-qPCR by combining a few steps and still saw similar Ct values.
- In a head-to-head comparison with dozens of positive samples from infected people, SalivaDirect results were the same as standard nasal test results 94 percent of the time. Comparing SalivaDirect to standard lab tests on saliva, the tests agreed 97 percent of the time for positive samples and 100 percent on negative samples. The researchers didn’t see any false positive results in any of their experiments.
- To do some of their validation work, Yale partnered with the National Basketball Association to test players and staff in the NBA’s bubble. The NBA partly funded the research.
- Based on list prices of materials used, the researchers estimate SalivaDirect costs anywhere from $1.29 to $4.37 per sample, depending on if a lab chooses to use a saliva collection device. This is cheaper than the current standard tests, which experts estimate in the range of $15 to $50 per sample for materials. The Yale researchers suggest that labs charge $10 for a SalivaDirect test.
- “Widespread testing is critical for our control efforts,” Nathan Grubaugh, one of the test developers and professor at Yale School of Public health said in a news release. “We simplified the test so that it only costs a couple of dollars for reagents, and we expect that labs will only charge about $10 per sample. If cheap alternatives like SalivaDirect can be implemented across the country, we may finally get a handle on this pandemic, even before a vaccine,” he said.
Step in the right direction
- On Saturday, August 15, the FDA granted SalivaDirect at an Emergency Use Authorization. “The SalivaDirect test for rapid detection of coronavirus is yet another testing innovation game changer that will reduce the demand for scarce testing resources,” Assistant Secretary for Health and C19 Testing Coordinator Admiral Brett Giroir said in a statement. Though the FDA noted that it has approved four other C19 tests that use saliva, those tests had “variable performance.”
- While there has been much fanfare around the authorization of SalivaDirect, it’s important to note that it is not a rapid, at-home test that some have suggested using on a daily basis to control the pandemic. Those cheaper, less accurate tests are more akin to home pregnancy tests—though with saliva instead of pee. SalivaDirect still requires testing in a laboratory involving a specialized machine to run the RT-qPCR.
J. Projections & Our (Possible) Future
1. Flu Season Will Be a Test Run for the U.S.’s Biggest-Ever Vaccine Campaign
Mobile vans, vaccine strike teams and drive-throughs will take the place of traditional tactics to get shots to the public
- This fall, the U.S. will need to vaccinate huge numbers of Americans in the middle of a public-health crisis. It will also be a valuable dry run should a coronavirus shot arrive months later.
- The annual U.S. flu vaccine campaign has been cast into disarray by C19, with people staying away from pharmacies, schools, offices, hospitals and other places where they typically get their shots. But with fears of a flu surge colliding with the coronavirus pandemic, health authorities are looking at how one vaccine effort can inform the other.
- In Denver, public-health officials are trying to increase the number of adults who get the flu vaccine this year to 65% from 45%. To do it, they’re setting up “strike teams” that can go from school to school giving vaccines, vans that can stop at construction sites and inoculate workers, and doing outreach to hard-to-reach communities.
- “This whole model that we’re building can then be moved into Covid,” said Judith Shlay a physician and associate director at Denver Public Health.
- In Baltimore, the city has several vans it sends out to conduct C19 testing, targeting high-risk residents. It will likely use those vehicles for flu vaccines and then C19, City Health Commissioner Letitia Dzirasa said in an interview.
- “Our flu vaccine distribution will inform a Covid vaccine distribution,” Dzirasa said.
- The federal government has helped lead development of a vaccine, issuing more than $4 billion in contracts to drugmakers. The money is meant to speed production and cut financial risk for the most promising of the dozens of inoculations in development. President Donald Trump has said a shot could be ready by November, though other experts inside his government predict it will be well into 2021 before most Americans have access to one.
- So far, federal health authorities have offered little detail about their plans for administering vaccines. The U.S. has said that it will likely rely on the private sector to distribute the shots, and last week extended a contract to health-care supplier McKesson Corp potentially worth more than $300 million. But the government has said almost nothing about who will get the shots first, where they’ll be given, and how to make sure they get to hard-to-reach and vulnerable communities.
- This week, the CDC plans a call with health-care providers to discuss flu vaccination, along with guidance for delivering vaccines during the pandemic and operating “large vaccination clinics held in satellite, temporary, or off-site locations.”
- In the meantime, local authorities are still awaiting clarity. “We have not heard anything yet,” Baltimore’s Dzirasa said.
- The U.S. has been consulting with experts and medical ethicists on C19 vaccine allocation plans. The government plans to work with the existing medical-distribution network to get shots to the public, said a senior Trump administration official, with possible help from the Defense Department.
Never Done Before
- There is no single national U.S. flu vaccination campaign, per se. American and global health authorities pick the flu strains to target, drugmakers manufacture the shots, and they’re given by workplaces, schools, drugstores, local public-health departments, physicians and hospitals.
- The federal government typically plays a role in financing and promoting the vaccines, but not in physically distributing them. This year, the Centers for Disease Control and Prevention has purchased 9 million doses of the adult flu vaccine, compared with 500,000 in a normal year.
- The scale of the vaccination campaign needed for C19 will be a daunting logistical challenge, said Howard Markel, a physician and historian of medicine at the University of Michigan School of Public Health. Past efforts to vaccinate against pandemic threats have fallen short.
- “We’ve never vaccinated an entire American population,” he said in an interview.
- In 1976, after an outbreak of swine flu at Fort Dix in New Jersey, the Gerald Ford administration planned a mass vaccination program to prevent a pandemic. “They were held in large gymnasiums and public meeting places,” said Markel, who recalled getting the shot when he was 16. “It was really very much an assembly line.”
- The vaccination drive was dismantled after several cases of Guillen-Barre syndrome were identified in people who got the shots. A U.S. review of the campaign in 2003 confirmed the increase in cases of the disease, which can cause a form of muscle weakness or temporary paralysis, though the exact biological link between the vaccine and the condition wasn’t established.
- In 2009, the H1N1 flu pandemic prompted another effort to quickly produce vaccines. Ultimately, only about 20% of the population got the shot, Markel said.
- “It is an enormous task, no question about it,” Markel said.
- Public-health officials will also have to overcome reluctance by some Americans to get a shot. An Aug. 7 Gallup poll found that one-third of people would not get a C19 vaccine when it’s ready, even if it was free. And some Americans have rejected basic public health measures like wearing masks or social distancing, raising more questions about how willing they are to participate in a vaccine campaign.
- Some vaccine infrastructure already exists. A surge in demand for C19 tests had drugstore chains, states and cities set up sites where people could line up or drive through. And the H1N1 flu pandemic also provided a roadmap for mass vaccination, said CVS Health Corp. Chief Executive Officer Larry Merlo.
- “That was really the spark plug,” Merlo said in an interview this month. The company is in planning sessions with officials for an eventual coronavirus vaccine, Merlo said.
- A spokesperson for Walgreens, the next-largest U.S. pharmacy chain behind CVS, said both existing testing and immunization infrastructure will support the future delivery of Covid vaccines.
- Sanofi, the French drugmaker that’s working with GlaxoSmithKline Plc on a coronavirus vaccine, said it’s been in touch with CVS and other drugstores about vaccination plans.
- “I would suspect that some of the blueprint that we’ve developed for flu immunization will also hopefully be a blueprint for C19 vaccination,” said Elaine O’Hara, Sanofi’s head of vaccines for North America.
- At Denver’s public health department, Shlay said she began thinking about how to deliver C19 vaccines back in June.
- She knew childhood immunizations had dropped sharply since March, when Covid shut things down, and she thought her agency could build a model to get a C19 vaccine to people who need it.
- Under a $1 million grant from the CARES Act, the federal stimulus law to respond to the pandemic, her team has begun working on alternative flu vaccination strategies. The strike teams they are developing will be targeted at 84 schools where vaccination rates have slipped. And the agency is working with leaders from the Black, Hispanic, Asian and Native American communities to bring flu-shot sites into neighborhoods.
- Particular outreach will focus on uninsured and unemployed adults — some of the same people are more likely to be hospitalized if they get sick — along with essential workers and people who are homeless.
- “We are going to try to reach that group that people don’t always think about,” Shlay said.
- There will be challenges making the switch to C19. Early vaccines are expected to require two shots weeks apart, compared with a single flu dose. Health officials will have to keep careful registries of who has received which shots when, and make sure to reach people when their second doses are due. They’ll also have to handle the logistics of keeping vaccines refrigerated at the proper temperature.
- “A two-dose Covid vaccine will be much more complicated,” Shlay said. That’s part of the reason Denver health officials are planning now. “Covid has made us do things quicker than we’ve ever done before, and so we figure it out and we do it.”
K. Practical Tips & Other Useful Information
1. Plastic face shields do masks one better
- One of the biggest challenges of the C19 pandemic is that we simply don’t know what works against the coronavirus. Most of the scientific studies on controlling pandemics have been focused on the influenza virus, which is distinct from the coronavirus in a lot of ways. The coronaviruses we do know something about—SARS, MERS, and two cold viruses—are quite different from each other.
- We’re left without hard data on what works. Do we need two meters of social distancing or three? What types of face masks are most effective? We’re trying to gather data on these issues at the same time that we’re implementing them. So in a small bit of good news, we now have some data indicating something that’s effective: plastic face shields.
- The work was done in India and takes advantage of a public health program initiated as the pandemic spread through that country. Workers in a research network in Chennai agreed to voluntarily go into isolation, then visit with the families of those who had tested positive for the coronavirus in order to explain things like quarantining, mask use, social distancing, and so on.
- Before going into what happened to these workers, we should step back to admire these people. They agreed to leave their families behind in order to live in hotel rooms. They were kept completely isolated from their friends and peers—meals were delivered to their rooms, and even their transport was a van with a steel divider installed to keep them isolated from their driver. All of their direct contact with humans was with people who were likely to have been infected. While the families they visited were asked to wear masks and stay at least six feet away from health workers, compliance was erratic.
- And while they were given gloves, surgical masks, and alcohol hand sanitizer, it took only two weeks for the first workers to develop symptoms. The program was suspended, and all the workers were tested for the virus. Of the 62 involved, a dozen had been infected. Collectively, they had visited 5,880 homes and come in contact with a total of 222 people who ultimately tested positive for the virus. Fortunately, the partitions in their transport worked, and none of their drivers ended up infected.
- When the program was restarted, an additional form of protection was put in place: a clear plastic face shield. The health workers were also given ethanol to clean their masks between home visits. With those measures in place, the workers visited an additional 18,228 homes, in which 2,682 people eventually tested positive for the virus.
- There were zero infections among the healthcare workers.
- It’s entirely possible that the initial infection heightened the sense of caution the workers took when the program restarted. But it’s not clear whether any behavioral changes could be maintained over the course of 18,000 home visits. Thus, the face shields are likely what provided the critical difference.
- The authors of the paper describing the results aren’t sure what the critical contribution was. The shield could have diverted air around the face or prevented the face mask from getting contaminated. It would also provide some protection for the eyes, which are a known route of infection. So there’s still more we could learn here. But the results seem to be enough to indicate that high-risk individuals could benefit from using face shields.
- Read the study here: SARS-CoV-2 Infection Before and After Face Shields
L. Johns Hopkins COVID-19 Update
August 19, 2020
1. Cases & Trends
- The WHO COVID-19 Dashboard reports 21.99 million cases (213,391 new) and 775,893 deaths (4,644 new) as of 10:00am EDT on August 19.
- The US CDC reported 5.42 million total cases (40,117 new) and 169,870 deaths (520 new). In total, 19 states (no change) are reporting more than 100,000 cases, including California with more than 600,000 cases; Florida and Texas more than 500,000 cases; New York more than 400,000; and Georgia and Illinois more than 200,000. For nearly 3 weeks, the US has averaged more than 1,000 deaths per day.
- The US epidemic passed its second peak around July 24, and since then, the national C19 incidence has decreased steadily. While many states are exhibiting similar trends, case counts in some states continue to climb. Hawai’i, which largely maintained low C19 incidence for the first several months of the pandemic, has reported increasing incidence since mid-July, now up to more than 200 new cases per day. Illinois has reported steadily increasing daily incidence for the past 2 months, up to nearly 75% of its first peak. While it is only reporting approximately 100 new cases per day, South Dakota’s daily incidence has been slowly increasing since mid-to-late July, and it does not appear to be exhibiting any indication of slowing. Kansas appeared to reach a second peak in late July; however, incidence rebounded after approximately a week, and it set a new high daily incidence yesterday of nearly 500 new cases per day. Missouri and Wyoming exhibited a similar trend, peaking in late July before rebounding. The increase in daily incidence in Kentucky and North Dakota has tapered off to some degree, but it is still increasing in both states, potentially approaching a peak or plateau. A number of other states have largely plateaued over the past 2 weeks and continued to report elevated daily incidence.
- The COVID Exit Strategy website still classifies 18 states as having “Uncontrolled Spread,” although the US as a whole recently improved from “Uncontrolled Spread” to “Trending Poorly.” Additionally, the site reports 16 states with increasing test positivity, including 2 with test positivity greater than 10%.* An additional 7 states are reporting test positivity greater than 10% percent and exhibiting a flat or decreasing trend.
- *In addition to the 2 states reporting both increasing test positivity and test positivity greater than 10%, the data for Washington indicates 100% test positivity, which may not accurately reflect the current state of testing.
- With the peak in national daily incidence occurring approximately 3 weeks ago, we expect to see an associated decrease in daily mortality in the near future. Mortality tends to lag several weeks behind incidence, as it takes time for C19 patients to progress through the course of disease. Nationally, the US continues to average more than 1,000 new deaths per day. Multiple states are reporting overall increases in daily mortality, including several states that were severely affected during the summer resurgence.
- Notably, Georgia reported its record high mortality (133 deaths) on August 11, and it continues to report more than 60 deaths per day. The Tennessee Department of Health does not report or display average daily mortality, but the weekly average reported by STAT News shows the state remaining at its record high of 22 deaths per day. California’s C19 mortality has plateaued over the past week or so, remaining relatively steady at approximately 130 deaths per day. Florida’s average mortality has fluctuated over the past 2 weeks, but it remains elevated at approximately 170 deaths per day. Texas reported a peak in mortality in early August (largely driven by a spike of more than 1,000 deaths reported on August 6), and mortality decreased substantially since then; however, Texas continues to report 170-200 deaths per day.
- The Johns Hopkins CSSE dashboard reported 5.50 million US cases and 172,109 deaths as of 1:30pm EDT on August 19.
2. US Schools
- The challenge of resuming classes continues across the US, at all levels of education. As more schools resume classes, particularly those using in-person or hybrid models, school districts and states are reporting more C19 cases linked to schools. One teacher in Kansas started compiling reports of C19 cases in K-12 schools as a local resource for her school, but when the document circulated more widely, she received hundreds of reports from across the country. Today, 35 people are supporting the effort to document reports of C19 among US students, teachers, and other school staff, and the Google Sheet includes data from all 50 states, plus Washington, DC, and Guam.
- A school district outside Phoenix, Arizona, was forced to cancel plans to resume in-person classes this week due to a “sickout” organized by teachers and staff. The school district’s Governing Board recently voted to start the school year with in-person classes, which prompted “a high volume of staff absences for Monday citing health and safety concerns.” Facing the prospect of “insufficient staffing levels” when classes were scheduled to resume this week, the school district elected to postpone in-person classes. Notably, no school districts in Arizona have met the benchmarks established by the Arizona Department of Health Services in order to resume in-person or hybrid classes (as of August 13).
- The Los Angeles Unified School District (California), the country’s second-largest school district, announced its own SARS-CoV-2 testing program to support in-person classes this fall. The program reportedly aims to administer nearly 800,000 tests to students and staff over a period of weeks or months, in advance of schools resuming in-person instruction. The school district will implement its own testing program in order to ensure sufficient testing capacity, which might not be available under existing local public health testing efforts. The program is expected to cost US$150 million, the equivalent of $300 per student across the entire school district. The school system views widespread and routine testing as a key to eventually being able to resume in-person classes.
- By this point, K-12 school systems nationwide have largely determined how they intend to resume instruction in the fall, and we are starting to see the early impact of those decisions. Tomorrow—Thursday, August 20—at 12:15pm EDT, the Johns Hopkins University Bloomberg Schools of Public Health will host a webcast to address the various scenarios that community and elected leaders, teachers, parents, and students may face in the coming months, depending on the US epidemic’s trajectory. The webcast will include experts from both the Bloomberg School of Public Health—including Center for Health Security Senior Scholar Dr. Jennifer Nuzzo—and the Johns Hopkins School of Education. The discussion will include a broad scope of topics, such as how to react to cases in schools offering in-person classes, manage stress and concern among students amid uncertainty during the coming school year, and plan ahead for potential changes.
Colleges & Universities
- Numerous colleges and universities are also facing challenges as students return to campus. In the short time since many schools started their school year, numerous colleges and universities have reported cases, clusters, and larger outbreaks of C19. At the University of North Carolina (UNC), the Chapel Hill campus was forced to abruptly cancel in-person classes after identifying at least 135 cases since the start of fall classes, including multiple clusters, and an associated increase in test positivity from 2.8% to 13.6%. While classes transitioned to online only, some space at on-campus residential facilities will remain open to support students, including international students, who may not have other options available to them. The University of Notre Dame (Indiana) also suspended in-person classes, following 147 cases detected since August 3.
- In order to support resuming in-person classes, colleges and universities have implemented a variety of risk mitigation measures, including testing programs; however, most schools do not have the ability to enforce school policies off campus. For example, videos and photos of off-campus parties and local bars—including at schools in Alabama, Georgia, and Oklahoma—show dozens or hundreds of students present, the majority of whom do not appear to be practicing appropriate physical distancing or wearing masks. Elected and university officials have been quick to admonish students for not adhering to public health recommendations; however, none appeared to take any responsibility for the decision to resume in-person classes in the first place, as noted by the Editorial Board of UNC student newspaper, The Daily Tar Heel.
- In addition to traditional colleges and universities, the US services academies—the US Military (West Point), Naval, Air Force, Coast Guard, and Merchant Marine Academies—resumed activity in time for fall classes, including the traditional summer orientation period for new Cadets and Midshipmen. The service academies implemented a variety of strict measures, including mandatory mask use and physical distancing, routine testing, and staggered arrival times for students (complete with quarantine periods). These student populations and environments are much different than a traditional campus setting (e.g., students are used to wearing prescribed uniforms and following orders); however, there may be lessons that other schools can draw for their own students.
3. US Election & Voting Safety
- As the US approaches the 2020 election, in the midst of the C19 pandemic, traditional voting practices are raising concerns about increased transmission risk, particularly for in-person voting. A report published by the RAND Corporation assessed state voting processes in preparation for the upcoming election. The researchers identified flexible voter registration policies, remote voting, and early voting among the key tools in mitigating exposure risk for voters and election workers. In particular, the researchers highlighted options for remote or automatic registration and no-excuse mail-in voting as particularly important in terms of reducing in-person contact that can facilitate SARS-CoV-2 transmission. Twelve (12) states and Washington, DC, have implemented automatic registration, early voting, and no-excuse mail-in voting for this year’s election, while 9 states have implemented none of these options. In a companion report, RAND outlines key factors that policymakers and election officials must balance in order to promote voter safety and election integrity, including protecting the health of election workers and ensuring equitable access for all eligible voters. In particular, the report highlights the increased risk that in-person voting can pose for higher-risk individuals (eg, older individuals and those with underlying health conditions), but also that increased absentee or mail-in voting can pose logistical challenges compared to previous elections.
- Similarly, the Brennan Center and the Infectious Diseases Society of America issued guidance for mitigating C19 risk for voters for in-person voting. Physical distancing and associated signage, selection of well-ventilated polling locations, mask use, and limiting unnecessary persons in the facility can help reduce contact at polling locations that can facilitate transmission. Compared to previous elections, these efforts may require additional resources in order to implement, so advance planning is recommended.
4. US Testing Volume & Delays
- Even as the US moves further away from its second peak in daily C19 incidence, the country struggles to conduct SARS-CoV-2 testing. The peak in daily testing occurred in late July, around the same time as the peak daily incidence, and both have decreased, in relative tandem, since then. Some health officials have expressed concern about the decrease in testing volume, particularly in states with increasing test positivity. Notably, national test positivity remains elevated (ie, greater than 5%), but it has been decreasing since late July as well. This indicates that testing volume is beginning to catch up with community transmission, at least at the national level. The situation varies considerably at the state level, however, and multiple states are reporting increasing test positivity, including 13 that already exceed 5%. Notably, Mississippi is currently reporting test positivity greater than 20% and increasing. While the test positivity trend appears encouraging at the national level, testing volume needs to increase in multiple states in order to better capture the scale of community transmission.
- In addition to testing volume, there are growing concerns about delays in obtaining test results. A survey conducted by CNBC and Dynata, conducted July 30-August 10, found that nearly 40% of C19 tests took more than 3 days to process. By the time these test results are returned, affected individuals may be past their infectious period, which largely negates the value of the test in terms of limiting transmission risk. The turnaround time varies widely by state, ranging from 2 to 5.5 days on average, but there are reports of some individuals waiting a week or longer. The situation has improved dramatically since mid-July, when the national average was greater than 7 days; however, rapid results (or at least timely results) are critical to containing the epidemic. Additionally, individuals who get tested are recommended to keep themselves isolated until they receive their test results in order to mitigate transmission risk for those who are positive, and longer wait times may make it difficult for individuals to comply with this guidance or less likely that they will choose to do so.
- Beyond scaling up testing capacity, which has been an ongoing struggle since the onset of the US epidemic, there are other options to increase testing volume. Some states, health systems, and laboratory networks have attempted to implement pooled testing strategies as a way to increase testing capacity, but these efforts have largely been ineffective due, in part, to increasing prevalence of SARS-CoV-2 infection in the community. As the proportion of infected specimens increases, pooled strategies are less effective at decreasing the number of tests required. New York is a notable exception, as it has maintained low levels of transmission since it contained the “first wave” of C19. Additionally, a group of professional organizations, headlined by the American Medical Association, called for prioritizing some specimens for testing, including patients exhibiting symptoms and those with known exposure to a C19 case. While this could decrease turnaround time for the priority specimens, it could potentially increase wait times for others. The groups argue that increased testing demand has been driven by asymptomatic individuals with no known exposure and that existing capacity should be directed toward “those with a medically-indicated need.” Additionally, as we covered previously, the US FDA recently issued an Emergency Use Authorization for a saliva-based test that could be a useful tool for screening purposes, which could potentially be directed at individuals without “medically-indicated need,” including those who are returning to work or school, and free up more traditional diagnostic test capacity.
5. Democratic National Convention
- The Democratic National Convention, which traditionally nominates the Democratic Party’s candidate for the US presidential election, is taking place remotely/virtually this year. The Democratic and Republican National Conventions typically take place in person and draw tens of thousands of attendees to the host city for several days; however, both conventions are largely forgoing in-person events for the first time in modern history. In addition to a series of video or live-streamed speeches, the Democratic National Convention utilized remote voting by delegates, who nominated Joe Biden as the presidential candidate. The Republican National Convention is expected to use a similar virtual format for speakers, or possibly multiple smaller satellite events, when it convenes next week, but it intends to host delegates in Charlotte, North Carolina, in order to vote in person for the Republican presidential candidate, presumably President Donald Trump.
6. Vaccine Allocation
- In support of planning efforts for future vaccination campaigns, the Johns Hopkins Center for Health Security published a framework for vaccine allocation and distribution in the US. The report, published today, focuses on challenges early in the vaccination campaign that stem from limited availability as production capacity increases. There will inevitably be initial vaccine shortages, so it will be critical to identify who will be eligible for the first available doses in advance of the start of a vaccination campaign. The researchers included a variety of relevant factors in the development of this framework, including “medical risk, public health, ethics and equity, economic impact, and logistics” with the dual aim of mitigating harm and maintaining societal function. This is a complex challenge with no single correct answer, and other organizations may reach different conclusions, even with the same considerations.
- The report outlines numerous “candidate groups that should be given serious consideration” for priority access, with the highest priority groups divided between 2 tiers. In Tier 1, the highest priority, the researchers included 3 groups of individuals: (1) those who are “most essential” to implementing the C19 response, including frontline healthcare workers caring for C19 patients and “vaccine manufacturing and supply chain personnel”; (2) “those at the greatest risk of severe disease and death,” such as individuals aged 65 and older and those with certain underlying health conditions; and (3) those “most essential to maintaining core societal functions,” including public transportation and food supply personnel and teachers. Tier 2 includes other individuals who support the provision of health care and maintenance of core societal functions, those who may have difficulty accessing healthcare in the event they are infected, and others who may be at elevated risk of infection (eg, due to living or working conditions). The report also addresses historical efforts to develop and implement priority groups for vaccination programs as well as important considerations with respect to obtaining input and support from the public, developing culturally competent prioritization protocols, and communicating the plan to the community.
7. Convalescent Plasma
- The use of convalescent plasma to treat C19 patients has been discussed and evaluated since the onset of the pandemic, but it has been difficult to fully assess evidence of its efficacy. Antibodies found in convalescent plasma obtained from C19 survivors could provide a meaningful boost to the immune systems of hospitalized patients, but the extent to which this occurs remains uncertain. To examine this possibility, the Mayo Clinic enrolled more than 35,000 C19 patients in an observational study, the results of which are beginning to be published. The study (preprint) found that patients who received convalescent plasma transfusions within 3 days of diagnosis exhibited improved mortality after 7 days over those who received the treatment 4 days or more after diagnosis—8.7% compared to 11.9%. The results were statistically significant, but there was no control group against which to compare the results. The researchers also observed that patients who received plasma with higher antibody concentrations exhibited a statistically significant improvement in 7-day mortality over patients receiving plasma with lower antibody concentrations—8.9% for high antibody levels, compared to 11.6% for medium and 13.7% for low levels.
- While these results are promising, the lack of a control group significantly limits the strength of conclusions that can be drawn from this study. Unlike in a randomized control trial, which is designed to evaluate the direct impact of a certain treatment on patient outcomes, this observational study had several uncontrolled factors, including differences in clinical care and disease severity. The use of convalescent plasma under “expanded access” protocols has made the treatment more widely available and provided increased data; however, it has made the development and enrollment for randomized control trials more difficult. While there are some randomized control trials ongoing for C19 convalescent plasma, some researchers maintain that it is too soon for the US FDA to determine whether to grant an EUA to the treatment based on the Mayo Clinic’s study data alone. According to a report by The New York Times, the FDA was “preparing to issue and emergency use authorization” for convalescent plasma, but the decision was postponed while regulatory officials evaluate data from the Mayo Clinic study.