Coronavirus COVID-19 Update for September 3, 2021

Clinical Reports

Unvaccinated COVID-19 hospitalizations cost the U.S. health system billions of dollars
Despite the availability of safe and effective COVID-19 vaccines, vaccination rates have lagged, particularly in some states and among younger people. As of early August 2021, 28% of adults over the age of 18 in the U.S. remain unvaccinated for COVID-19. As a result of lagging vaccinations and the more infectious delta variant, COVID-19 cases, hospitalizations, and deaths are on the rise again. These COVID-19 hospitalizations are devastating for patients, their families, and health care providers. The hospitalizations are also costing taxpayer-funded public insurance programs and the workers and businesses paying health insurance premiums. Analysis of CDC data indicates there were 37,000 preventable COVID-19 hospitalizations in June and another 76,000 preventable COVID-19 hospitalizations in July, among unvaccinated adults in the U.S. If each of these preventable hospitalizations cost roughly $20,000, on average, that would mean these largely avoidable hospitalizations have already cost the U.S. health system billions of dollars since the beginning of June.

Antiviral Therapeutics and Vaccines

Comirnaty and Pfizer-BioNTech COVID-19 Vaccine
On August 23, 2021, the FDA approved the first COVID-19 vaccine. The vaccine has been known as the Pfizer-BioNTech COVID-19 Vaccine, and will now be marketed as Comirnaty, for the prevention of COVID-19 disease in individuals 16 years of age and older. The vaccine also continues to be available under emergency use authorization (EUA), including for individuals 12 through 15 years of age and for the administration of a third dose in certain immunocompromised individuals.

SARS-CoV-2 Infections and Hospitalizations Among Persons Aged ≥16 Years, by Vaccination Status — Los Angeles County, California, May 1–July 25, 2021
Although COVID-19 vaccines are highly effective, some fully vaccinated persons will be infected with SARS-CoV-2. During May 1–July 25, 2021, among 43,127 SARS-CoV-2 infections in residents of Los Angeles County, California, 10,895 (25.3%) were in fully vaccinated persons, 1,431 (3.3%) were in partially vaccinated persons, and 30,801 (71.4%) were in unvaccinated persons. On July 25, infection and hospitalization rates among unvaccinated persons were 4.9 and 29.2 times, respectively, those in fully vaccinated persons. In July, when the Delta variant was predominant, cycle threshold values were similar for unvaccinated, partially vaccinated, and vaccinated persons. Efforts to enhance COVID-19 vaccination coverage, in coordination with other prevention strategies, are critical to preventing COVID-19–related hospitalizations and deaths.

A third COVID-19 vaccine shot markedly boosts neutralizing antibody potency and breadth
COVID-19 (coronavirus disease 2019) vaccines have been rapidly developed and deployed globally as a measure to combat the disease. These vaccines have been demonstrated to confer significant protection, but there have been reports of temporal decay in antibody titer. Furthermore, several variants have been identified with variable degrees of antibody resistance. These two factors suggest that a booster vaccination may be worthy of consideration. While such a booster dose has been studied as a series of three homologous vaccines in healthy individuals, to our knowledge, information on a heterologous regimen remains unreported, despite the practical benefits of such a scheme. This observational study investigated the serological profile of four healthy individuals who received two doses of the BNT162b2 vaccine, followed by a third booster dose with the Ad26.COV2.S vaccine. While all individuals had spike-binding antibodies at each of the timepoints tested, there was an appreciable drop in titer by four months following the second vaccination. The third vaccine dose increased titers beyond that of two vaccinations, and these elicited antibodies had neutralizing capability against all SARS-CoV-2 strains tested in both a recombinant vesicular stomatitis virus-based pseudovirus assay and an authentic SARS-CoV-2 assay, except for one individual against B.1.351 in the latter assay. Thus, a third COVID-19 vaccine dose in healthy individuals promoted not just neutralizing antibody potency, but also induced breadth against dominant SARS-CoV-2 variants.

Durability of antibody responses elicited by a single dose of Ad26.COV2.S and substantial increase following late boosting
The durability of SARS-CoV-2 antibody levels elicited by the single dose Janssen COVID-19 vaccine, Ad26.COV2.S, and the impact on antibody responses of boosting with Ad26.COV2.S after 6 months was evaluated in clinical trial participants. Spike-binding antibody and SARS-CoV-2 neutralizing antibody levels elicited by a single-dose Ad26.COV2.S (5×10¹⁰ viral particles [vp]) primary regimen and booster doses (5×10¹⁰ vp and 1.25×10¹⁰ vp) were assessed by ELISA and wild-type VNA in sera from participants in a Phase 1/2a clinical trial (Cohort 1a, 18–55 years old, N=25; Cohort 2a, 18–55 years old boosted at 6 months, N=17; Cohort 3, ≥65 years old, N=22) and a Phase 2 clinical trial (18–55 and ≥65-year old participants boosted at 6 months, total N=73). Neutralizing antibody levels were determined approximately 8 months after the primary vaccination in participants aged 18–55 years and approximately 9 months in participants aged ≥65 years. Binding antibody levels were evaluated 6 months after primary vaccination and 7- and 28-days after booster doses in both age groups. A single dose of Ad26.COV2.S elicited neutralizing antibodies that remained largely stable for approximately 8–9 months and binding antibodies that remained stable for at least 6 months irrespective of age group. A 5×10¹⁰ vp booster dose at 6 months post prime vaccination in 18–55-year-old adults elicited a steep and robust 9-fold increase at Day 7 post boost compared to Day 29 levels following the initial immunization. A lower booster dose of 1.25×10¹⁰ vp at 6 months in adults 18–55 and ≥65 years of age also elicited a rapid and high increase of 6–7.7 fold at Day 28 post boost compared to Day 29 levels following the initial immunization, with similar magnitude of post-boost responses in both age groups. A single dose of Ad26.COV2.S, which demonstrated protection in a Phase 3 efficacy trial, elicited durable neutralizing and binding antibodies for at least 8 and 6 months, respectively, in adults >18 years of age at levels similar to Day 29 responses. A 5×10¹⁰ vp or 1.25×10¹⁰ vp booster dose at 6 months elicited rapid and robust increases in spike binding antibody levels. The anamnestic responses after booster immunization imply robust immune memory elicited by single-dose Ad26.COV2.S.

Epidemiology

Virological characteristics of SARS-CoV-2 vaccine breakthrough infections in health care workers
SARS-CoV-2 vaccines are highly effective at preventing COVID-19-related morbidity and mortality. As no vaccine is 100% effective, breakthrough infections are expected to occur. The virological characteristics of 161 vaccine breakthrough infections in a population of 24,706 vaccinated healthcare workers (HCWs), were analyzed using RT-PCR and virus culture. The delta variant (B.1.617.2) was identified in the majority of cases. Despite similar Ct-values, lower probability of infectious virus detection was observed in respiratory samples of vaccinated HCWs with breakthrough infections compared to unvaccinated HCWs with primary SARS-CoV-2 infections. Nevertheless, infectious virus was found in 68.6% of breakthrough infections and Ct-values decreased throughout the first 3 days of illness. Rare vaccine breakthrough infections occur, but infectious virus shedding is reduced in these cases.

COVID-19 Transmission Dynamics Among Close Contacts of Index Patients With COVID-19
This study addresses whether there is an association between the timing of exposure to and severity of COVID-19 disease in close contacts of index patients with COVID-19. In this cohort study of 730 index patients with a COVID-19 diagnosis and 8852 close contacts, transmission potential was greatest in the first 2 days before and 3 days after onset of symptoms in the index patient. When contacts received a diagnosis of COVID-19 infection, they were more likely to present asymptomatically if they had been exposed to an asymptomatic patient. These results suggest that the quantity of exposure to a patient with COVID-19 may be associated with clinical presentation among close contacts who develop COVID-19.

Terminal Curiosities

COVID-19 false dichotomies and a comprehensive review of the evidence regarding public health, COVID-19 symptomatology, SARS-CoV-2 transmission, mask wearing, and reinfection
Scientists across disciplines, policymakers, and journalists have voiced frustration at the unprecedented polarization and misinformation around coronavirus disease 2019 (COVID-19) pandemic. Several false dichotomies have been used to polarize debates while oversimplifying complex issues. In this comprehensive narrative review, the authors deconstruct six common COVID-19 false dichotomies, address the evidence on these topics, identify insights relevant to effective pandemic responses, and highlight knowledge gaps and uncertainties. The topics of this review are: 1) Health and lives vs. economy and livelihoods, 2) Indefinite lockdown vs. unlimited reopening, 3) Symptomatic vs. asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, 4) Droplet vs. aerosol transmission of SARS-CoV-2, 5) Masks for all vs. no masking, and 6) SARS-CoV-2 reinfection vs. no reinfection. The importance of multidisciplinary integration (health, social, and physical sciences), multilayered approaches to reducing risk (“Emmentaler cheese model”), harm reduction, smart masking, relaxation of interventions, and context-sensitive policymaking for COVID-19 response plans are discussed. The challenges in understanding the broad clinical presentation of COVID-19, SARS-CoV-2 transmission, and SARS-CoV-2 reinfection are also discussed. These key issues of science and public health policy have been presented as false dichotomies during the pandemic. However, they are hardly binary, simple, or uniform, and therefore should not be framed as polar extremes. A nuanced understanding of the science is needed, not black-or-white messaging, all-or-nothing guidance, and one-size-fits-all approaches. There is a need for meaningful public health communication and science-informed policies that recognize shades of gray, uncertainties, local context, and social determinants of health.