COVID-19 Research Roundup 3: 9/19/20–9/25/20

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Greenlight

32 min readNov 10, 2020

Summaries from new articles and research papers exploring COVID-19, disparities, schools, novel treatments, and prevention strategies for 9/19/20–9/25/20.

Greenlight’s weekly deep dives our brought to you through our partnership with the Pandemic Response Network.

Executive Summary

Johnson & Johnson and Novavax have begun Phase 3 clinical trials on their vaccine candidates. There are still no clinical trials of COVID-19 vaccine candidates in children. Auto-antibodies to type I interferons were shown to partially explain severe COVID-19 and some of the gender disparity in severe disease course. Risk for X-linked recessive traits in males over females may explain such differences. Statins were found to potentially reduce risk for severe COVID-19, indicating that they may confer therapeutic benefit. COVID-19 has been shown to damage heart cells and some patients experience prolonged symptoms including shortness of breath, chest pain, and heart palpitations. However, it is still unclear if SARS-CoV-2 impacts the heart to a greater extent than other viruses. Red blood cell distribution width was identified as a potential important biomarker that could be used by hospitals for patient risk stratification. Reagent shortage continues to act as a bottleneck in COVID-19 diagnostic testing in the United States.

School districts are still trying to reach lost students and understand the best methods for teaching kids during a pandemic. Kindergarten enrollment has dropped exponentially and students in poverty remain largely unconnected. Furthermore, while transmission rates are lower than expected within K-12 classrooms, schools are bracing for an outbreak, as college campuses continue to get hit with a rising number of COVID-19 cases.

The CDC continues to confuse the public as it retracts its guidelines on airborne transmission, claiming that it was an accidental, early release. While the CDC cleans up its PR, some scientists in Houston have found that the virus may be mutating. This comes as terrifying news with N-95 masks still heavily depleted in the United States and one study highlighting that contact-tracing methods may not be as representative or effective as it may seem. A call for more routine screening strategies seems appropriate and necessary at this time with the number of COVID-related deaths climbing over 200,000 this week.

The shift among school districts across the United States towards distance learning has caused severe challenges to school districts serving low-income children. Reports indicate there is wide variability in access to quality educational instruction, digital technology, and internet access. While school districts are engaging in distance learning, many students are also losing access to programs that provide necessary resources for health care and nutrition. In order to help alleviate these consequences, future COVID-19 legislation must target child health and well-being.

Important Statistics/Quotes

According to a survey last month by the American Association for Clinical Chemistry, which represents commercial, hospital and public health laboratories, 67% of labs are having issues getting both reagents and test kits-the highest level since the group started querying labs in May. In late June and early July, 58% of labs struggled to get enough test kits and 46% enough reagents, according to an earlier survey.
In a study of 100 COVID-19 patients two months after their illness, researchers found heart muscle inflammation in the magnetic resonance imaging of 60 patients.
“Everyone had a fear there would be explosive outbreaks of transmission in the schools. In colleges, there have been. We have to say that, to date, we have not seen those in the younger kids, and that is a really important observation,” said Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota.
“Although we don’t know yet, it is well within the realm of possibility that this coronavirus, when our population-level immunity gets high enough, this coronavirus will find a way to get around our immunity,” David Morens, a virologist at the National Institute of Allergy and Infectious Diseases said. “If that happened, we’d be in the same situation as with flu. We’ll have to chase the virus and, as it mutates, we’ll have to tinker with our vaccine.”
“Latinos have been hospitalized four times as much as people who are white,” said American Federation of Teachers President Randi Weingarten, who participated in the event hosted by SOMOS, a New York-based nonprofit network of health care providers. “What we’re seeing, in terms of the start of school, is the kind of neglect from the top down that is unconscionable: the lack of resources to schools to reopen them safely. All of this could have been solved. This kind of work should have started in April.”

Headlines from this Week

Type I Interferon Auto-Antibodies Partially Explain Severe COVID-19. Science 1, 2, 3.

Two recent studies have elucidated potential mechanisms underlying severe COVID-19. Many patients who underwent severe COVID-19 were shown to have auto-antibodies to type I inferferon. A subset of these patients had extremely low or undetectable levels of type I interferon. Type I interferons are extremely important in the initial immune response, as they cause infected cells to synthesize proteins that attack the virus, summon immune cells to mediate the response, and alert neighboring, uninfected cells of the situation. These patients with high levels of type I interferon auto-antibodies were overwhelming male, potentially explaining some of the gender disparities in risk for severe disease course. No individuals in the control groups with mild or asymptomatic COVID-19 had these antibodies, and such antibodies show up at very low rates in the general population. Another study found evidence for increased risk of severe COVID-19 in patients with genetic mutations which impaired type I interferon production. Such traits are proposed to be X-linked recessive, which again would help to further explain the gender differences in risk for severe disease. These findings have potential therapeutic implications: convalescent plasma aliquots should be screened for these type I interferon auto-antibodies, as administration of such plasma would likely be counterproductive. Administration of synthetic type I interferons is an additional area of therapeutic interest; however, such a treatment strategy would likely not be effective in patients with auto-antibodies.

Getting Back to School: An Update on Plans from Across the Country. Center on Reinventing Public Education. The 74.

Most states were unable to provide guidance to school districts until late into the summer, forcing many schools to push out their decisions to restart. Reactions and methods for returning to the classroom have greatly varied between rural and urban school districts as well as among areas of high or low poverty rates. Students in rural areas are more likely to attend in-person classes while those in larger cities will most likely attend virtual lectures. Among the schools surveyed in this report, 49% are planning to restart in-person, 26% will start fully remote, and 12% attend a hybrid model. Further, 85% of the schools surveyed will offer the option of fully remote instruction. When comparing these numbers between rural and urban school districts, it can be seen in the figure that 65% of rural districts will be starting fully in-person, while only 24% of suburban and 9% of urban districts plan to do so.

Interestingly, districts with the highest rates of poverty are more likely to go remote, with 41% of low-income schools choosing to do so. This comes as a huge concern with students in poverty generally needing more support socially, emotionally, and academically in the classroom. It is hard to say if these students are receiving the support and care they need to learn; virtual learning makes it much more difficult for teachers to form critical relationships with students in poverty. Furthermore, students from low-income families may not have ideal working and studying environments. Parents from these families are more likely to work and less likely to be able to spend time guiding their children through virtual school.

Most importantly, it is concerning that families in poverty are choosing remote instruction over in-person classes as they are less likely to have internet connectivity required to give their children access to virtual learning platforms. In cities, such as Cleveland, nearly 31% of all households have no internet access at home at all. As household income decreases, the percentage of households that have no broadband of any type increases. This means that those in poverty may have even less access to learning opportunities.

As school districts continue to figure out the best methods for reaching and teaching kids during a pandemic, it can be seen that the approaches are quite divisive and regional, with little unity among school districts and the education system as a whole.

The Consequences of Distance Learning and Necessary Solutions. JAMA Pediatrics. The 74.

The restrictions imposed by COVID-19 have caused severe challenges to school districts serving low-income children. While school districts are engaging in distance learning across the U.S., reports indicate there is wide variability in access to quality educational instruction, digital technology, and internet access. In some urban areas, as many as one-third of students are not participating in online classes. These consequences are compounded by the challenge of accessing school resources, including nutrition and health care programs. More than 30 million children rely on school nutrition programs, and, with schools closed, emergency food assistance is reaching only a fraction of the children previously served. School-based health centers, nursing services, and mental health programs also help alleviate disparities in access to health care services.

Among those affected, the Latino community was hard hit. The Latino Decisions survey results show that 59 percent of Latino households in New York and New Jersey have experienced job loss or a pay cut or have closed a business due to the pandemic, and just over half of respondents there said they are considering not sending their child back to school this fall. Respondents expressed concerns about the possibility of their children falling behind this fall. More than a third said they didn’t have anyone to stay home with their child, 34 percent said they didn’t have Wi-Fi, and 38 percent said they didn’t have enough devices at home.

With the shift towards distance learning affecting these consequences, it becomes imperative that future legislation targets child health and well-being. Congress should expand critical programs for low-income children, including additional funding for Medicaid to cover rising demand. The Supplemental Nutrition Assistance Program and the Special Supplemental Nutrition Program for Women, Infants, and Children need an expansion of benefits to reach the rising number of families experiencing food insecurity and income loss.

Other immediate needs include funds to address the digital learning divide, including access to high-speed internet and versatile electronic devices so all children can participate in distance learning. State social service agencies should receive additional funds to support outreach to families during and after the pandemic. Finally, investments are needed in innovative delivery mechanisms of health, education, and social services, particularly in a new paradigm in which social interaction is limited.

COVID-19 and the Education System

Another pandemic shift: In many school districts, 1 in 10 kindergartners didn’t show up. Chalkbeat.

School districts are seeing double-digit declines in Kindergarten enrollment across the country
Kindergarten enrollment is down 15% in Hawaii’s schools
In LA, t’s down 14%.
In Gwinnett County, Georgia, it’s down 10% since last fall
The pattern was similar for high-poverty and more affluent school districts
The enrollment declines may mean that more young students will go without the academic and other benefits of kindergarten, which could deepen existing educational inequities.
“It all has to do with the quality of that care setting,” said Elizabeth Votruba-Drzal, a University of Pittsburgh professor who studies child care and early education. “Affluent parents can buy their way into high-quality settings, regardless of the constraints that they face, whereas families that have fewer resources have fewer choices and face very tough decisions.”
Virtual classrooms have proved to be poor learning environments for younger students. Younger children have a hard time paying attention to the screen for long periods, require help navigating educational apps or websites, and need supervision. This type of learning environment can be frustrating and unsustainable for working parents.
Enrollment data fails to make clear whether or not these “lost children” are enrolled in private school programs or charter schools as most states do not track it.

Feared coronavirus outbreaks in schools yet to arrive, early data shows. Washington Post.

Public health experts have found little evidence that the virus is being transmitted in schools
The rates of infection in school buildings are far below what is found in the surrounding communities.
Children and adolescents are at a “much lower risk” for the coronavirus
Assumptions that children play a key role in the transmission chain are “most likely” wrong
14 active teachers, principals and counselors have died of COVID-19 since the school year started, according to the American Federation of Teachers

Study: Less than 1 percent of teachers, students infected since schools reopened. The Hill.

Brown University researchers collaborated with school administrators and created a new COVID-19 Response in schools dashboard (the tracker will be linked in our newsletter starting this week!)
The dashboard shows a relatively small degree of spread among staff and students.
The data was collected from more than 550 schools across 46 states over a two-week period starting Aug. 31,
More than 300 schools are maintaining some level of in-person classes.
0.23% of students had confirmed or suspected cases of the virus, while educators had 0.51% of cases

Schools Briefing: Coronavirus Dorms and Super Spreaders. New York Times.

Coronavirus cases are spiking on college campuses, leaving many administrators with two unappealing options: quarantine students in dorms or send them home.
Many universities are employing different methods to enforce self-isolation and quarantines:
The University of Alabama posted university police officers at its quarantine dorms
Notre Dame hired guards to monitor students in quarantine in hotels and off-campus apartments
Many schools are experiencing difficulties running these “disease containment units”
Susan Dynarski, a University of Michigan economist, wrote on Twitter, that “unloading students onto home communities” was “deeply unethical.”

Infection Rates and Disease Course in Children

Frequency of Children vs Adults Carrying Severe Acute Respiratory Syndrome Coronavirus 2 Asymptomatically. JAMA Pediatrics.

A retrospective cohort study of children and adults admitted to Fondazione Ca’ Granda Ospedale Maggiore Policlinico in Milan, Italy, to the pediatric and adult emergency department, respectively, found that fewer children than adults tested positive for SARS-CoV-2 infection.
83 children and 131 adults were included in the study.
One child (1.2%) and 12 adults (9.2%) tested positive for SARS-CoV-2.
These findings suggest that previous hypotheses that children are especially important asymptomatic spreaders of COVID-19 may be incorrect.
However, this study does have significant limitations, as it only includes one hospital and only includes individuals who were admitted for other reasons.

Severe COVID-19 Infections — Knowledge Gained and Remaining Questions. JAMA Internal Medicine.

The current knowledge base of management of patients with acute respiratory distress syndrome (ARDS) due to severe SARS-CoV-2 infection includes typical supportive care of ARDS and dexamethasone.
Remdesivir has only been shown to reduce time to recovery in hospitalized patients; it has not been shown to be of therapeutic benefit in patients on mechanical ventilation.
Criteria for ARDS include bilateral radiographic opacities and a sufficient degree of hypoxemia.
ARDS supportive care includes lung protective ventilation, symptom-targeted sedation and analgesia, consideration of neuromuscular blockade for ventilator dyssynchrony or severe hypoxemia, prone positioning for moderate to severe ARDS, and consideration of extracorporeal membrane oxygenation for patients with very severe ARDS.
While there has been considerable use of hydroxychloroquine, lopinavir/ritonavir, and IL-6 inhibitors such a tocilizumab in patients with severe COVID-19, none of these have been shown to improve outcomes in rigorous, randomized clinical trials.
Further research into the pathogenesis of COVID-19 and its association with the pathophysiology of ARDS are vital to developing improved guidelines for modulating the deleterious aspects of the host immune response while preserving beneficial aspects.

COVID-19 in children and young people. Science.

This Science article argues for reconsideration of school closures in the face of evidence for school settings, and children in general, playing a much less significant role in COVID-19 transmission than other respiratory viruses, and evidence for notable deleterious effects of school closures on child health.
Multiple studies have shown minimal outward transmission of COVID-19 from primary and secondary schools into homes and other areas, assuaging to some extent the fears of schools creating an ongoing pool of viral circulation that is then diffused into the surrounding community.
However, reports of community outbreaks beginning in schools do exist.
Other studies have shown great deleterious effects of school closures on mental health of children, increased suicide rates, increased accidents, and delays in hospitalization due to COVID-19.
The authors suggest that such a body of evidence indicates that school closures should only be enacted if they are shown to help mitigate the pandemic, as they concomitantly do significant harm.

Infant Outcomes Following Maternal Infection with SARS-CoV-2: First Report from the PRIORITY Study. Clinical Infectious Diseases.

Maternal viral infection during pregnancy, peripartum, and postpartum periods can adversely affect infant outcomes.
Maternal to infant vertical transmission of SARS-CoV-2 has been shown to occur but risk has not been well characterized.
This study sought to address this knowledge gap via a prospective analysis of 263 infants and mothers enrolled in the Pregnancy Coronavirus Outcomes Registry (PRIORITY).
The authors found that SARS-CoV-2 status was not associated with birth weight, difficulty breathing, apnea or upper or lower respiratory infection through 8 weeks of age.

The Core Lesson of the COVID-19 Heart Debate. The Atlantic.

While the myocardial effects of COVID-19 have received a lot of attention recently in the news, it remains to be seen if such issues are specific and enhanced in COVID-19 or characteristic of a wide swath of viral infections.
For example, myocarditis has been found in respiratory syncytial virus (RSV) patients that have experienced a mild disease course.
It is uncertain if our knowledge of the deleterious effects of COVID-19 on the heart is simply due to the vast amount of research that has been and continues to be conducted on the virus.
Nevertheless, cardiac and neurologic symptoms of COVID 19 continue to be of great concern and further research will elucidate the true effects of such disease mechanisms.

Some Covid-19 Patients Show Signs of Heart Damage Months Later. The Wall Street Journal.

A confluence of studies, both clinical and lab in nature, have been conducted in order to elucidate the impact of COVID-19 on the heart.
Lab grown heart cells were shown to seemingly be diced up after exposure to SARS-CoV-2 and some showed missing portions of DNA within their nuclei.
Autopsy studies on the hearts of COVID-19 patients detected SARS-CoV-2 in 24 of 39 hearts, suggesting that the virus directly infects the heart to an extent, rather than heart damage solely resulting from aggressive immune responses to virus present in other areas of the body.
Some patients recovering from COVID-19 experience continued symptoms of shortness of breath, chest pain, and heart palpitations months after their illness.
In a study of 100 COVID-19 patients two months after their illness, researchers found heart muscle inflammation in the magnetic resonance imaging of 60 patients.
Much remains to be sorted out concerning the impact of COVID-19 on the heart, but there is worry that the pandemic could result in an uptick of heart related disease and death years down the line.

A Covid-19 Vaccine for Children May Not Arrive Before Fall 2021. The New York Times.

While there are Phase 3 vaccine clinical trials ongoing in adult populations from Astrazeneca, Pfizer, and Moderna, no trials for pediatric COVID-19 vaccines have begun.
Some experts argue that such trials should be started at once, as vaccination of children will be able to prevent infection, disease, hospitalization, and death from the virus.
Vaccination of children will also likely lead to schools being able to reopen in greater capacities, with reduction in the risk of development of transmission hotspots in school settings.
Others maintain that an adult vaccine is much more important currently, as children experience a much lower risk of severe disease course.
While adult vaccines may be available by the spring or summer of 2021, pediatric vaccines likely will not be available until the fall.
Completely separate pediatric clinical trials of vaccine candidates must be conducted because children have very different underlying biology than adults and will therefore need adequate doses of such vaccines to maximize protection and minimize risks of side effects.

Early Experience of COVID-19 in a US Children’s Hospital. Pediatrics.

A retrospective cohort study was conduced at Steven and Alexandra Cohen Children’s Medical Center at Northwell Health to determine the demographics, clinical presentation, hospital course, and severity of COVID-19 in 65 pediatric patients.
Most hospitalized patients were either younger that 60 days or older than 12 years of age.
35% of patients required admission to the intensive care unit (ICU).
Respiratory support was required in 34% of patients.
Elevated white blood cell counts and C-reactive protein levels were associated with greater severity of COVID-19.

Susceptibility to SARS-CoV-2 Infection Among Children and Adolescents Compared With Adults. JAMA.

A meta analysis of 13,926 total studies pertaining to SARS-CoV-2 prevalence, transmission, seroprevalence, and secondary infection in children versus adults found that children and adolescents have lower susceptibility to SARS-CoV-2 infection, with a 0.56 odds ratio for being an infected contact compared with adults.
Most studies indicated lower seroprevalence in children compared with adults, and similar seroprevalence in adolescents versus adults.
The study was not able to make any definitive conclusions about transmission and infectivity in children in comparison with adults.

Virus Cases Surged in Young Adults. The Elderly Were Hit Next. The New York Times.

A New York Times COVID-19 database indicates nearly 88,000 cases of COVID-19 on 1,200 college campuses as of early September.
Centers for Disease Control and Prevention (CDC) data suggest SARS-CoV-2 infection trends that begin with waves in young adults that are thereafter sequentially passed on to older age groups that are more susceptible to severe disease.
Scientists argue that these data demonstrate the invalidity of pandemic management strategies in which the elderly are contained and the virus is allowed to more readily pass through younger populations that are less susceptible to severe disease.
COVID-19 transmission in younger populations inherently impacts older populations.
Finally, spikes in COVID-19 transmission in counties in which colleges are located only tended to occur in cases in which colleges opened up primarily in-person courses.
Spikes were not seen in cases in which students moved to the counties in which their college was located but did not participate in primarily in-person courses.

Emerging Prevention & Treatment Strategies

Not trusting the FDA, Black doctors’ group creates panel to vet Covid-19 vaccines. STAT.

A group of Black physicians has been working to create their own committee to vet the scientific validity of vaccine decisions made by the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC).
The committee has been organized through the National Medical Association (NMA), which was founded in 1895 in response to racist professional societies excluding Black doctors.
The committee hopes to be able to review vaccine clinical trial protocols and data concomitantly with the FDA and CDC in order to make their own vaccine recommendation.
Such decisions by this committee are likely to have significant impact on vaccine uptake by the African American community.
Decisions and recommendations coming from the committee are fraught with potential, as they could serve to dramatically increase or decrease vaccine uptake at the time of vaccine FDA approval.

World Health Organization unveils plan for distributing coronavirus vaccine, urges cooperation. The Washington Post.

Currently, more than 150 countries, representing 64% of the world’s population, have signed on to the COVID-19 Vaccines Global Access Facility (Covax), which aims to distribute $2 billion in vaccine doses by the end of the year.
64 high income countries have signed on, with 38 additional expected; however, notably, the U.S. and China have not, with the U.S. specifically stating that they will not, in part because the Trump Administration does not want to work with the World Health Organization (WHO), whereas China simply has not yet made a statement in either direction.
Covax aims to promote equitable vaccine distribution across countries, and to those at highest risk of infection and severe disease.
Therein lies two phases, during the first of which vaccine doses will be distributed to countries proportional to their total population, beginning at 3% and moving up to a 20% threshold, at which Phase 2 will be enacted.
In Phase 2, vaccine doses will be distributed to countries and populations depending on their risk level.
Some experts have critiqued the biphasic plan for its politically oriented first phase: promising population proportional distribution to countries ensures that more countries will sign on.
They argue against the country based approach and hold that vaccine doses should be distributed solely based on risk level of individuals.
The U.S., in not signing on to Covax, is betting on its own advance purchase agreements.

Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients. Science.

Previous studies as well as this study show that pediatric COVID-19 patients have milder disease than adults, even when considering multisystem inflammatory syndrome in children (MIS-C) in which mortality is rare.
This study hypothesized difference in antiviral immune response based on age dependent factors.
Findings included that serum concentrations of IL-17A and IFN-gamma, but not TNF-alpha or IL-6, were inversely related to age.
Interestingly, adults mounted more robust T cell responses to the viral spike protein, had greater serum levels of neutralizing antibodies, and had higher levels of antibody-dependent cellular phagocytosis compared with pediatric COVID-19 patients.
Thus, the authors propose that poor outcomes in hospitalized adults with COVID-19 compared to children may not be attributable to a failure to generate adaptive immune responses.

FDA to announce tougher standards for a coronavirus vaccine that make it unlikely one will be cleared by Election Day. The Washington Post.

The Food and Drug Administration (FDA) plans to announce more stringent requirements for emergency authorization of a COVID-19 vaccine candidate.
In doing this, the agency hopes to alleviate vaccine hesitancy and rejection, both of which currently exist at high levels within the U.S. population.
Concerns abound over politicization of the vaccine approval process by the Trump administration, which has continued to echo that a vaccine candidate may be approved by election day.
The FDA will require participants in Phase 3 clinical trials to be followed for 2 months after their second vaccine dose.
The agency will also necessitate that minimum numbers of individuals in the placebo group develop severe COVID-19 and cases of disease in elderly populations in order to validate the efficacy of Phase 3 vaccine candidates.
Finally, debate has been ripe surrounding the benefits and perils of emergency use authorization (EUA) of the COVID-19 vaccines.
One view is that, with vaccine confidence at an extreme low point, a full approval process should take place top assuage the concerns of many individuals.
Another view is that regardless of vaccine confidence levels, EUA is absolutely necessary when thousands of Americans continue to die every day from the virus.

Covid-19 Testing Is Hampered by Shortages of Critical Ingredient. The Wall Street Journal.

Shortages in reagents and test kits continues to be a bottleneck issue in COVID-19 rapid diagnostic testing across the United States.
Companies such as Roche and Abbott are having difficulty keeping up with high testing demands.
Resources are being diverted away from community testing programs back into hospitals, in which only patients who are admitted or referred with COVID-19 symptoms are tested.
This reduction in community testing has led to decreased knowledge of how SARS-CoV-2 is spreading.
According to a survey last month by the American Association for Clinical Chemistry, which represents commercial, hospital and public health laboratories, 67% of labs are having issues getting both reagents and test kits-the highest level since the group started querying labs in May.
In late June and early July, 58% of labs struggled to get enough test kits and 46% enough reagents, according to an earlier survey.

Johnson & Johnson Begins Final-Stage Testing of Covid-19 Vaccine. The Wall Street Journal.

Johnson & Johnson (J&J) has begun a Phase 3 trial that aims to enroll 60,000 participants in the U.S., Brazil, and South Africa.
Participants will either receive a one dose regimen of the vaccine, which is composed of a modified adenovirus that has been engineered to carry the SARS-CoV-2 spike protein as an antigen to induce an immune response, or placebo, and participants will be tracked to determine if those vaccinated experience lower rates of COVID-19.
J&J is additionally collaborating with the United Kingdom to conduct another Phase 3 trial in which participants will receive a two dose regimen of the vaccine candidate.
J&J is the fourth company to conduct COVID-19 vaccine Phase 3 clinical trials, after Moderna and Pfizer, which began trials in July, and Astrazeneca, which began trials in August.
J&J stated that they expect to have decisive results of the trials by early next year.

Association of Red Blood Cell Distribution Width With Mortality Risk in Hospitalized Adults With SARS-CoV-2 Infection. JAMA Network Open.

Red blood cell distribution width (RDW) was identified as a potential important biomarker that could be used by hospitals for patient risk stratification.
RDW is a measure of the variance in red blood cell (RBC) volume, with a definition of the standard deviation of RBC volume divided by the mean.
Although the exact mechanism of increasing RDW is not known, the hypothesis is that in a state in which leukocytes and platelets are being produced at a high rate, as in inflammation, RBC production slows and older RBCs concomitantly persist, avoiding degradation.
RBC volume generally decreases across the lifetime of the cells, and thus an increasing amount of older RBCs would lead to greater variance in RBC volume and thereby a greater RDW.
This study investigated RDW of 1641 COVID-19 patients in Boston, Massachusetts at hospital admission and during hospitalization and its association with mortality risk.
The relative risk of mortality for the entire cohort was 2.73, with a mortality rate of 11% in patients with normal RDW and 31% in those with an elevated RDW.
The patients whose RDW increased during hospitalization had higher mortality compared with those whose RDW did not change; for those with normal RDW, mortality increased from 6% to 24%, and for those with an elevated RDW at admission, mortality increased from 22% to 40%.

Statins reduce COVID-19 severity, likely by removing cholesterol that virus uses to infect. Science Daily. The American Journal of Cardiology. The EMBO Journal.

Researchers at UC San Diego Health and UC San Diego School of Medicine have uncovered that statins, a drug that is FDA approved to lower cholesterol, is associated with lower risk for severe COVID-19 and that part of the mechanism through which this occurs may be lowering of cholesterol in cell membranes, which inhibits viral entry into host cells.
After it was discovered that SARS-CoV-2 enters into host cells via angiotensin converting enzyme 2 (ACE2) receptor, drug that tend to increase ACE2 expression, including ACE inhibitors, angiotensin II recepto blockers (ARBs), and statins received a lot of research attention.
None of these drugs has been shown to increase risk for COVID-19 infection or severe disease.
Researchers studying the mechanisms of SARS-CoV-2 infection of human lung cells found that the CH25H gene was highly upregulated.
This gene encodes an enzyme that modifies cholesterol, producing 25-hydroxycholesterol (25HC) within cells, which then activates another enzyme called ACAT which is found within the endoplasmic reticulum.
ACAT depletes cholesterol in the plasma membrane, which inhibits viral entry into these cells.
Statins work to remove cholesterol from the vasculature, but additionally remove cholesterol from plasma membranes, a potential explanation for their conferring of reduced risk for severe COVID-19.
Such studies suggest the need for clinical trials to determine the therapeutic benefit of statins in COVID-19.
Researchers continue to study 25HC as a potential antiviral agent, as its mechanism of action is likely more specific and targeted than that of statins.

Treatment of COVID-19 Patients with Prolonged Post-Symptomatic Viral Shedding with Leflunomide — a Single-Center, Randomized, Controlled Clinical Trial. Clinical Infectious Diseases.

A subset of COVID-19 patients experience prolonged viral shedding, with PCR positivity for viral RNA long after their symptoms subsided and abnormal computed tomography (CT) imaging improved significantly.
These patients necessitate more medical resources, longer hospital stays, and experience high rates of psychological disorders.
This study examined the effect of the drug leflunomide, an approved dihydroorotate dehydrogenase (DHODH) antagonist, on the duration of viral shedding in patients experiencing prolonged PCR positivity.
Dihydroorotate dehydrogenase catalyzes the fourth enzymatic step in the pyrimidine biosynthesis pathway, and therefore leflunomide, an inhibitor of this step, works mechanistically to inhibit viral replication within infected host cells.
The authors found no difference in the duration of viral shedding in patient treated with a combination of leflunomide and interferon-alpha-2a compared with patients treated solely with interferon-alpha-2a.

Covid-19 Vaccine From Novavax Begins Phase 3 Trial in U.K. The Wall Street Journal.

Novavax has begun a Phase 3 clinical trial of its vaccine candidate in the United Kingdom and plans to fully enroll a participant body of 10,000 individuals within four to six weeks.
The trials will begin in the UK, a country in which there has been a recent surge of infection that have led to new lockdown restrictions.
Such a wave of infections may be beneficial to the clinical trial, as it will provide more data that will be used to determine whether the vaccine candidate decreases risk for symptomatic COVID-19.
Novavax also plans to begin a Phase 3 clinical trial in the United States that will eventually enroll 60,000 participants, but such a trial will likely not begin until some time in October.

Methods & Effectiveness of Risk Mitigation & Transmission Prevention

Clinical Impact, Costs, and Cost-Effectiveness of Expanded SARS-CoV-2 Testing in Massachusetts (Accepted Manuscript). Clinical Infectious Diseases.

A team of researchers used a microsimulation model to understand the impact of four different testing strategies under slowing, intermediate, and surging epidemic growth scenarios from May 1, 2020 to November 1, 2020.
Estimated that if PCR testing had been widely available in MA from April 1, 2020 to May 1, 2020, 103,000 to 176,900 infections and around 90–260 deaths could have been averted during that time.
Monthly routine testing averted 58%-64% of infections whereas daily testing averted 75%-91% of infections
All expanded screening strategies would decrease key hospital resource use and equate to fewer days spent self-isolating
Resources redirected for COVID-related cases may reduce the ability to care for other diseases
Policies that enforce isolation practices for positive cases are essential; therefore, federal and setting-specific incentives for infected individuals to self-isolate should be considered
Scaling technology innovations may not be possible in all regions, therefore, pooled-, rapid antigen-, and home self-testing options should continue to be developed.
Testing individuals with any COVID-19 consistent symptoms would ultimately be more cost-effective than testing only those who have symptoms which warrant hospital care
Allowing asymptomatic individuals to test for COVID-19 would decrease the number of infections, deaths, and hospital resource use.
Low-cost, repeat screenings of all individuals in a community would be cost-effective in all epidemic settings

The N95 Shortage America can’t seem to fix. The Washington Post.

N95s were designed to be thrown away after every patient
6 months later, the shortage still persists:
Health-care workers are exposed
Patients are at risk
Public health experts are asking: “Why is the world’s richest country still struggling to meet the demand for an item that once cost around $1 apiece?”
But for N95s and other respirators, Trump has used his authority far less for N95s and other respirators in comparison to ventilators. This has led some manufacturers to take advantage of the situation while leaving potential manufacturers behind.
The organizations that represent healthcare professionals and systems are asking for additional federal intervention; the administration maintains that the government has already done enough
Hospitals and health departments are left to compete for N95s and other PPE
68% of 21,500 nurses surveyed are required to reuse respirators, many for more than the five times recommended by the CDC
The DPA has a provision that would allow manufacturers to work together without being subject to antitrust laws, but it has yet to be applied for N95s.
Healthcare professionals are indicating increased sleeplessness, anxiety, depression and post-traumatic stress due to the lack of resources and constant exposure to death

COVID-19 Contact Tracing in Two Counties — North Carolina, June–July 2020. MMWR.

During June 1–July 12, 2020, the number of COVID-19 cases increased 183% (7 to 19 per 100,000 persons per day) in North Carolina
Data from two counties in North Carolina were analyzed during a period of high incidence to understand the effectiveness of contact tracing measures
Individuals with COVID-19 often did not report contacts and many contacts were not reached.
Improved timeliness of contact tracing, community engagement, and increased use of community-wide mitigation are needed
Contact tracing was performed for persons identified as close contacts. This included inquiry about COVID-19–compatible symptoms and instructions to self-quarantine for 14 days since last exposure
Contacts were classified as lost to follow-up if they did not respond after 3 failed attempts to contact them at different times on consecutive days
In Mecklenberg County, 5,514 (77%) persons with positive test results were reached for case investigation and elicitation of contacts
2,624 (48%) reported no contacts
13,401 contacts were named among positive individuals
In Randolph County, 589 (83%) were confirmed as new COVID-19 cases among county residents and 584 (99%) were reached for case investigation and elicitation of contacts
Five (1%) contacts were lost to follow-up
35% (Randolph County) to 48% (Mecklenburg County) of patients with COVID-19 did not report contacts
A high proportion of individuals with COVID-19 did not report contacts, many contacts could not be reached, and the time needed to reach contacts reduced the impact of contact tracing

Advice on Airborne Virus Transmission Vanishes From C.D.C. Website. New York Times. Washington Post.

The C.D.C. withdrew guidance on airborne transmission, claiming it was posted in error
The new document had acknowledged that the virus spreads mainly by air, which had huge implications for indoor ventilation and interactions
The incident seems to be a genuine mistake in the agency’s scientific review process; Officials will post revised guidance soon
The C.D.C. has suffered a series of blows to its reputation since the pandemic began
In August, the C.D.C. released guidance that claimed people who have close contact with an infected person but no symptoms didn’t need to get tested for the infection
Last week, it was uncovered that the guidance was dictated by officials in the administration rather than by scientists; the C.D.C. quickly reversed its position
The latest guidelines are concerned with the spread of the virus by air through droplets and aerosols, which would include floating particlees, expelled by talking, breathing or even singing
Experts who reviewed the CDC’s Friday post said that the language change had the power to shift policy and public behavior

Massive genetic study shows coronavirus mutating and potentially evolving amid rapid U.S. spread. Washington Post.

Scientists in Houston released a study of more than 5,000 genetic sequences of COVID-19; it revealed the virus’s mutations may have made it more contagious
The mutations have mot made the virus deadlier or changed clinical outcomes, however
Most viral mutations are insignificant
David Morens, a virologist at the National Institute of Allergy and Infectious Diseases, concluded that, as the virus moved through the population, it became more transmissible
These repeated mutations show that as the virus interacts with our bodies and our immune systems, it is learning new tricks to infiltrate the host

Disparities Among Race, Ethnicity, & Geography

Racial and/or Ethnic and Socioeconomic Disparities of SARS-CoV-2 Infection Among Children. Pediatrics.

In this cross-sectional study, where a large cohort of children were tested in the United States for SARS-CoV-2, rates of SARS-CoV-2 infection were disproportionately higher among minority and socioeconomically disadvantaged youth.
Specifically, minority and socioeconomically disadvantaged children had a higher likelihood of SARS-CoV-2 infection. These observed racial and/or ethnic disparities in infection rates only slightly attenuated after adjustment for socioeconomic status.
Rates of SARS-CoV-2 infection were higher among Hispanic children than Non Hispanic Black or Non Hispanic white children. Hispanic children may have experienced the most pronounced burden of infection because of compounding additional factors, such as immigration status and language barriers. Furthermore, symptomatic adults may avoid testing because of fears of deportation.

Medicare Wouldn’t Cover Costs of Administering Coronavirus Vaccine Approved Under Emergency-Use Authorization. Wall Street Journal.

Lawmakers in March passed the Coronavirus Aid, Relief, and Economic Security Act, or Cares Act, which ensures free coronavirus vaccine coverage, including no out-of-pocket costs for people on Medicare.
However, Medicare doesn’t cover costs for drugs approved under emergency-use designations. The Food and Drug Administration authorizes certain drugs for emergency use to provide speedy access to treatments for serious diseases during a health crisis, and the standards for emergency-use authorization are not as high as they are for its typical drug approvals.
Medicare’s exclusion of emergency-use drug costs could leave millions of people paying out-of-pocket for vaccines the government intends to make free. About 62 million people, or about 19% of the U.S. population, are covered by Medicare.
While the White House pushes to get an emergency-use vaccine approved as early as next month, the White House and the Department of Health and Human Services are exploring solutions to include Medicare coverage. These include:
Pressing Congress to change the language in the Cares Act
Looking at whether any creative interpretation of existing regulations could allow for Medicare coverage
Officials are especially concerned about the Medicare restriction because seniors who are at risk of severe disease from Covid-19 are among the highest priority groups for getting a vaccine.

COVID-19 and Human Trafficking — the Amplified Impact on Vulnerable Populations. JAMA Pediatrics.

The COVID-19 pandemic has created circumstances that may increase the risk of trafficking, inhibit identification of those who are trafficked and those who survive trafficking, and make it harder to deliver comprehensive services to support survivors’ recovery.
Homelessness and a history of child maltreatment are 2 significant risk factors for trafficking of young people. The economic impact of COVID-19, including widespread job loss, has left many people unable to pay rent. Despite moratoriums on evictions for some, others have been left unprotected.
Also, there is widespread agreement among child advocates that COVID-19 has spurred an increase in child maltreatment. Although reporting is down (primarily because mandatory reporters, including teachers and pediatricians, are not seeing some children), hospital reports of child abuse injuries have increased.
With school closures, children and adolescents are spending more time online, increasing risks that could lead to trafficking situations. The National Center for Missing and Exploited Children noted an increase from 2 million to 4.2 million reports of online exploitation from March to April 2020.
When survivors are identified, COVID-19 can affect services. Because of the breadth of harms inflicted on trafficking survivors, they typically need a range of services — physical and mental health care, education and job training, legal services, and more.1 Shutdowns associated with the pandemic have constrained the ability to deliver the comprehensive, integrated care that survivors need.

The Impact of Sociodemographic Factors, Comorbidities and Physiologic Response on 30-day Mortality in COVID-19 Patients in Metropolitan Detroit. Clinical Infectious Diseases.

In this study, the relationship between health disparities and comorbidities in COVID-19 related outcomes are explored, assessing risk factors associated with mortality in patients presenting with Covid-19 infection and healthcare disparities.
In this large cohort of COVID-19 patients, those with comorbidities, advanced age, and physiological abnormalities on presentation had higher odds of death. Disparities in income or source of health insurance were not associated with outcomes.
Black women had a lower risk of dying. During the first two weeks of the pandemic, black patients had higher rates of death, but lower rates compared to whites for the remaining weeks. This finding may reflect random variability, given the lower number of patients treated in the first weeks, or the evolution of clinical management, including the initiation of corticosteroids as part of routine care, which may have contributed to this change.

Location Matters: Geographic Disparities and Impact of Coronavirus Disease 2019 (COVID-19). The Journal of Infectious Diseases.

The COVID-19 pandemic in the United States has revealed major disparities in the access to testing and messaging about the pandemic based on the geographic location of individuals, particularly in communities of color, rural areas, and areas of low income.
There is a wide disparity in COVID-19 testing by geographic area, stemming from a lack of:
hospitals and health care facilities
walk-in testing sites
access to transportation to drive-up testing sites
lack of information regarding availability of testing
Although urban sites may have public transportation and walk-in testing facilities, communities in rural areas or low income settings are challenged by limited access to individual/private transportation or walk-in testing locations.
Some of these limitations may be unique to communities in specific geographic areas, including areas with a large Amish or Mennonite population (where access to healthcare facilities is limited), Native American communities, and other socially isolated communities.
Testing for novel diseases and information regarding how to access testing needs to be made widely available with resources tailored to the needs of the persons residing in the community, to avoid stigma associated with a new disease.
In many areas of the country, prioritization for testing has been limited to persons who are symptomatic
In general, many studies report that persons ≤ 18 years of age are more likely to be asymptomatic or have milder symptoms.
Therefore, they may not meet the testing criteria even if there has been significant exposure, leading to limited number of tests provided to children relative to the 22% of the population that they comprise.
Although the risk of severe illness from COVID-19 is lower in the pediatric population, severe disease such as multisystem inflammatory syndrome in children (MIS-C) is occurring in an increasing number of children and studies have shown an increased burden of MIS-C among children of color.

Racial Disparities in Incidence and Outcomes Among Patients With COVID-19. JAMA.

This study used information from the largest academic health system in Wisconsin, located in Milwaukee County, aiming to describe the patterns and outcomes of COVID-19 by race while controlling for age, sex, SES, and comorbidity conditions.
African American patients testing positive for COVID-19, compared with patients who belonged to other racial groups, were more likely to be younger, to have no insurance or receive Medicaid, to have 3 or more comorbidities, to have higher mean BMI, and to present with shortness of breath and gastrointestinal symptoms at testing.
Both Black race and poverty were significantly associated with increased likelihood of hospitalization among the 369 individuals with COVID-19. Among those admitted, poverty, but not race, was significantly associated with ICU admission. Poverty increased by more than 3-fold the odds of ICU admission.
Results for mechanical ventilation and death indicated that neither race nor poverty were significantly associated with these outcomes. Smoking history and higher BMI were associated with mechanical ventilation. Older age, having 3 or more comorbidities, and having shortness of breath or less prevalent, atypical symptoms at presentation significantly increased the likelihood of death. Higher BMI was also significantly associated with death, with each BMI unit increasing the odds of mortality by 19%.