Coronavirus COVID-19 Update for October 29, 2021

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Clinical Reports

WHO estimate: 115,000 health workers have died from Covid-19, as calls for vaccine access grow
Some 115,000 health care workers died from Covid-19 from January 2020 to May of this year, according to a new World Health Organization estimate, as the agency pushed once again for efforts to address vaccine inequity. Globally, 2 in 5 health care workers are fully vaccinated, WHO Director-General Tedros Adhanom Ghebreyesus said at a briefing Thursday. But, he added, “that average masks huge differences across regions and economic groupings.” In most high-income countries, more than 80% of health care workers are fully vaccinated, Tedros said. But in Africa, the rate is less than 1 in 10.
Virologic features of SARS-CoV-2 infection in children
Data on pediatric COVID-19 has lagged behind adults throughout the pandemic. An understanding of SARS-CoV-2 viral dynamics in children would enable data-driven public health guidance. Respiratory swabs were collected from children with COVID-19. Viral load was quantified by RT-PCR; viral culture was assessed by direct observation of cytopathic effects and semiquantitative viral titers. Correlations with age, symptom duration, and disease severity were analyzed. SARS-CoV-2 whole genome sequences were compared with contemporaneous sequences. 110 children with COVID-19 (median age 10 years, range 2 weeks-21 years) were included in this study. Age did not impact SARS-CoV-2 viral load. Children were most infectious within the first five days of illness, and severe disease did not correlate with increased viral loads. Pediatric SARS-CoV-2 sequences were representative of those in the community and novel variants were identified. Symptomatic and asymptomatic children can carry high quantities of live, replicating SARS-CoV-2, creating a potential reservoir for transmission and evolution of genetic variants. As guidance around social distancing and masking evolves following vaccine uptake in older populations, a clear understanding of SARS-CoV-2 infection dynamics in children is critical for rational development of public health policies and vaccination strategies to mitigate the impact of COVID-19.
COVID-19 Vaccination and Non–COVID-19 Mortality Risk — Seven Integrated Health Care Organizations, United States, December 14, 2020–July 31, 2021
Although deaths after COVID-19 vaccination have been reported to the Vaccine Adverse Events Reporting System, few studies have been conducted to evaluate mortality not associated with COVID-19 among vaccinated and unvaccinated groups. During December 2020–July 2021, COVID-19 vaccine recipients had lower rates of non–COVID-19 mortality than did unvaccinated persons after adjusting for age, sex, race and ethnicity, and study site. There is no increased risk for mortality among COVID-19 vaccine recipients. This finding reinforces the safety profile of currently approved COVID-19 vaccines in the United States. All persons aged ≥12 years should receive a COVID-19 vaccine.
Association of Statins and 28-Day Mortality in Patients Hospitalized with SARS CoV-2 Infection
Statins may be protective in SARS-CoV-2 infection. The aim of this study was to evaluate the effect of in-hospital statin use on 28-day mortality and ICU admission among patients with SARS-CoV-2 stratified into 4 groups: those who used statins prior to hospitalization (continued, discontinued) and those who did not (newly initiated, never). In a cohort study of 1179 patients with SARS-CoV-2, chart review was used to assess demographics, laboratory measurements, comorbidities, and time from admission to death, ICU admission, or discharge. Using marginal structural Cox models, authors estimated hazard ratios for mortality and ICU admission. Among 1179 patients, 676 (57 %) were male, 443 (37 %) were at least 65 years old, and 493 (46%) had a BMI ≥30. Inpatient statin use reduced the hazard of death (HR 0.566, P = 0.008). This association held among patients who did and did not use statins prior to hospitalization (HR 0.270, P=0.003; HR 0.493, P=0.038). Statin use was associated with improved time-to-death for patients >65 years, but not patients ≤65 years. Statin use during hospitalization for SARS-CoV-2 infection was associated with reduced 28-day mortality. Well-designed randomized control trials are needed to better define this relationship.
Assessment of Cognitive Function in Patients After COVID-19 Infection
People who have survived COVID-19 frequently complain of cognitive dysfunction, which has been described as brain fog. The prevalence of post–COVID-19 cognitive impairment and the association with disease severity are not well characterized. Previous studies on the topic have been limited by small sample sizes and suboptimal measurement of cognitive functioning. Authors investigated rates of cognitive impairment in survivors of COVID-19 who were treated in outpatient, emergency department (ED), or inpatient hospital settings. We analyzed data in this cross-sectional study from April 2020 through May 2021 from a cohort of patients with COVID-19 followed up through a Mount Sinai Health System registry. Study participants were 18 years or older, spoke English or Spanish, tested positive for SARS-CoV-2 or had serum antibody positivity, and had no history of dementia. Participant demographic characteristics (eg, age, race, and ethnicity) were collected via self-report. Cognitive functioning was assessed using well-validated neuropsychological measures: Number Span forward (attention) and backward (working memory), Trail Making Test Part A and Part B (processing speed and executive functioning, respectively), phonemic and category fluency (language), and the Hopkins Verbal Learning Test–Revised (memory encoding, recall, and recognition). The Mount Sinai Health System Institutional Review Board approved this study, and informed consent was obtained from study participants. The study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline. Authors calculated the frequency of impairment on each measure, defined as a z score of less than or equal to 1.5 SDs below measure-specific age-, educational level–, and sex-adjusted norms.²^,³ Logistic regression assessed the association between cognitive impairment and COVID-19 care site (outpatient, ED, or hospital), adjusting for race and ethnicity, smoking, body mass index, comorbidities, and depression. The threshold for statistical significance was α = .05, and the tests were 2-tailed. Analyses were performed using SAS, version 9.4 (SAS Institute). The mean (IQR) age of 740 participants was 49 (38-59) years, 63% (n = 464) were women, and the mean (SD) time from COVID-19 diagnosis was 7.6 (2.7) months (Table 1). Participants self-identified as Black (15%), Hispanic (20%), or White (54%) or selected multiracial or other race and ethnicity (11%; other race included Asian [4.5%, n = 33)] and those who selected “other” as race). The most prominent deficits were in processing speed (18%, n = 133), executive functioning (16%, n = 118), phonemic fluency (15%, n = 111) and category fluency (20%, n = 148), memory encoding (24%, n = 178), and memory recall (23%, n = 170; Table 2). In adjusted analyses, hospitalized patients were more likely to have impairments in attention (odds ratio [OR]: 2.8; 95% CI: 1.3-5.9), executive functioning (OR: 1.8; 95% CI: 1.0-3.4), category fluency (OR: 3.0; 95% CI: 1.7-5.2), memory encoding (OR: 2.3; 95% CI: 1.3-4.1), and memory recall (OR: 2.2; 95% CI: 1.3-3.8) than those in the outpatient group. Patients treated in the ED were more likely to have impaired category fluency (OR: 1.8; 95% CI: 1.1-3.1) and memory encoding (OR: 1.7; 95% CI: 1.0-3.0) than those treated in the outpatient setting. No significant differences in impairments in other domains were observed between groups.

Antiviral Therapeutics and Vaccines

Covid-19 Breakthrough Infections in Vaccinated Health Care Workers
Despite the high efficacy of the BNT162b2 messenger RNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rare breakthrough infections have been reported, including infections among health care workers. Data are needed to characterize these infections and define correlates of breakthrough and infectivity. At the largest medical center in Israel, breakthrough infections were by performing extensive evaluations of health care workers who were symptomatic (including mild symptoms) or had known infection exposure. These evaluations included epidemiologic investigations, repeat reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assays, antigen-detecting rapid diagnostic testing (Ag-RDT), serologic assays, and genomic sequencing. Correlates of breakthrough infection were assessed in a case–control analysis. Patients with breakthrough infection who had antibody titers obtained within a week before SARS-CoV-2 detection (peri-infection period) were matched with four to five uninfected controls and used generalized estimating equations to predict the geometric mean titers among cases and controls and the ratio between the titers in the two groups. The correlation between neutralizing antibody titers and N gene cycle threshold (Ct) values with respect to infectivity was also assessed. Among 1497 fully vaccinated health care workers for whom RT-PCR data were available, 39 SARS-CoV-2 breakthrough infections were documented. Neutralizing antibody titers in case patients during the peri-infection period were lower than those in matched uninfected controls (case-to-control ratio, 0.361; 95% confidence interval, 0.165 to 0.787). Higher peri-infection neutralizing antibody titers were associated with lower infectivity (higher Ct values). Most breakthrough cases were mild or asymptomatic, although 19% had persistent symptoms (>6 weeks). The B.1.1.7 (alpha) variant was found in 85% of samples tested. A total of 74% of case patients had a high viral load (Ct value, <30) at some point during their infection; however, of these patients, only 17 (59%) had a positive result on concurrent Ag-RDT. No secondary infections were documented. Among fully vaccinated health care workers, the occurrence of breakthrough infections with SARS-CoV-2 was correlated with neutralizing antibody titers during the peri-infection period. Most breakthrough infections were mild or asymptomatic, although persistent symptoms did occur.
Coronavirus (COVID-19) Update: FDA Takes Additional Actions on the Use of a Booster Dose for COVID-19 Vaccines
The U.S. Food and Drug Administration took action to expand the use of a booster dose for COVID-19 vaccines in eligible populations. The agency is amending the emergency use authorizations (EUA) for COVID-19 vaccines to allow for the use of a single booster dose as follows:
- The use of a single booster dose of the Moderna COVID-19 Vaccine that may be administered at least 6 months after completion of the primary series to individuals:
  - 65 years of age and older
  - 18 through 64 years of age at high risk of severe COVID-19
  - 18 through 64 years of age with frequent institutional or occupational exposure to SARS-CoV-2
- The use of a single booster dose of the Janssen (Johnson and Johnson) COVID-19 Vaccine may be administered at least 2 months after completion of the single-dose primary regimen to individuals 18 years of age and older.
- The use of each of the available COVID-19 vaccines as a heterologous (or “mix and match”) booster dose in eligible individuals following completion of primary vaccination with a different available COVID-19 vaccine.
- To clarify that a single booster dose of the Pfizer-BioNTech COVID-19 Vaccine may be administered at least 6 months after completion of the primary series to individuals 18 through 64 years of age with frequent institutional or occupational exposure to SARS-CoV-2.
FACT SHEET FOR HEALTH CARE PROVIDERS: EMERGENCY USE AUTHORIZATION (EUA) OF REGEN-COV The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) to permit the emergency use of the unapproved product, REGEN-COV (casirivimab and imdevimab) co-formulated product and REGEN-COV (casirivimab and imdevimab) supplied as individual vials to be administered together, for the treatment of mild to moderate coronavirus disease 2019 (COVID-19) in adult and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death.
Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial
Recent evidence indicates a potential therapeutic role of fluvoxamine for COVID-19. In the TOGETHER trial for acutely symptomatic patients with COVID-19, authors aimed to assess the efficacy of fluvoxamine versus placebo in preventing hospitalisation defined as either retention in a COVID-19 emergency setting or transfer to a tertiary hospital due to COVID-19. This placebo-controlled, randomised, adaptive platform trial done among high-risk symptomatic Brazilian adults confirmed positive for SARS-CoV-2 included eligible patients from 11 clinical sites in Brazil with a known risk factor for progression to severe disease. Patients were randomly assigned (1:1) to either fluvoxamine (100 mg twice daily for 10 days) or placebo (or other treatment groups not reported here). The trial team, site staff, and patients were masked to treatment allocation. The primary outcome was a composite endpoint of hospitalisation defined as either retention in a COVID-19 emergency setting or transfer to tertiary hospital due to COVID-19 up to 28 days post- random assignment on the basis of intention to treat. Modified intention to treat explored patients receiving at least 24 h of treatment before a primary outcome event and per-protocol analysis explored patients with a high level adherence (>80%). Authors used a Bayesian analytic framework to establish the effects along with probability of success of intervention compared with placebo. The trial is registered at ClinicalTrials.gov (NCT04727424) and is ongoing. The study team screened 9803 potential participants for this trial. The trial was initiated on June 2, 2020, with the current protocol reporting randomisation to fluvoxamine from Jan 20 to Aug 5, 2021, when the trial arms were stopped for superiority. 741 patients were allocated to fluvoxamine and 756 to placebo. The average age of participants was 50 years (range 18–102 years); 58% were female. The proportion of patients observed in a COVID-19 emergency setting for more than 6 h or transferred to a teritary hospital due to COVID-19 was lower for the fluvoxamine group compared with placebo (79 [11%] of 741 vs 119 [16%] of 756); relative risk [RR] 0·68; 95% Bayesian credible interval [95% BCI]: 0·52–0·88), with a probability of superiority of 99·8% surpassing the prespecified superiority threshold of 97·6% (risk difference 5·0%). Of the composite primary outcome events, 87% were hospitalisations. Findings for the primary outcome were similar for the modified intention-to-treat analysis (RR 0·69, 95% BCI 0·53–0·90) and larger in the per-protocol analysis (RR 0·34, 95% BCI, 0·21–0·54). There were 17 deaths in the fluvoxamine group and 25 deaths in the placebo group in the primary intention-to-treat analysis (odds ratio [OR] 0·68, 95% CI: 0·36–1·27). There was one death in the fluvoxamine group and 12 in the placebo group for the per- protocol population (OR 0·09; 95% CI 0·01–0·47). Authors found no significant differences in number of treatment emergent adverse events among patients in the fluvoxamine and placebo groups. Treatment with fluvoxamine (100 mg twice daily for 10 days) among high-risk outpatients with early diagnosed COVID-19 reduced the need for hospitalisation defined as retention in a COVID-19 emergency setting or transfer to a tertiary hospital.
Routine Vaccination Coverage — Worldwide, 2020
Global coverage with the third dose of diphtheria and tetanus toxoids and pertussis-containing vaccine (DTP3) and of polio vaccine (Pol3) and the first dose of measles-containing vaccine (MCV1) remained between 84% and 86% during 2010–2019. In 2020, estimated global coverage with DTP3 and Pol3 decreased to 83%; MCV1 coverage decreased to 84%. Globally, 17.1 million zero-dose children did not receive the first DTP dose, an increase of 3.5 million from 2019. Full recovery from COVID-19–associated disruptions will require targeted, context-specific strategies to identify and catch up zero-dose and undervaccinated children, introduce interventions to minimize missed vaccinations, monitor coverage, and respond to program setbacks.

Diagnostics

Antibody Testing Is Not Currently Recommended to Assess Immunity After COVID-19 Vaccination: FDA Safety Communication
The U.S. Food and Drug Administration (FDA) is reminding the public and health care providers that results from currently authorized SARS-CoV-2 antibody tests should not be used to evaluate a person’s level of immunity or protection from COVID-19 at any time, and especially after the person received a COVID-19 vaccination. While a positive antibody test result can be used to help identify people who may have had a prior SARS-CoV-2 infection, more research is needed in people who have received a COVID-19 vaccination. Currently authorized SARS-CoV-2 antibody tests have not been evaluated to assess the level of protection provided by an immune response to COVID-19 vaccination. If antibody test results are interpreted incorrectly, there is a potential risk that people may take fewer precautions against SARS-CoV-2 exposure. Taking fewer steps to protect against SARS-CoV-2 can increase their risk of SARS-CoV-2 infection and may result in the increased spread of SARS-CoV-2.
The Flawed Science of Antibody Testing for SARS-CoV-2 Immunity
Early in the COVID-19 pandemic, developers designed SARS-CoV-2 antibody tests to detect whether people had been infected. Some experts thought the blood tests eventually would help to ease lockdowns. One idea was that those with antibodies likely would be immune to reinfection at least temporarily, allowing them to reenter society without putting themselves or others at risk. But as the pandemic unfolded, the concept of an immunity passport based on having antibodies didn’t pan out. The early consumer tests’ accuracy was unproven, making the results somewhat dubious. More fundamentally, the so-called correlates of protection were unknown. Which specific antibodies guarded against SARS-CoV-2 reinfection? How high did their levels need to be? And how long would they provide a reliable defense? As the assays’ usefulness for individual patients became less clear and testing for active infections expanded, the public’s clamor for antibody testing waned. But for some, the arrival of COVID-19 vaccines revived their interest in serology. Could a simple blood test reveal whether the vaccine was working or, later, if it was time for a booster shot? No, says the US Food and Drug Administration (FDA), which discouraged antibody testing as a do-it-yourself immunity check in a communication to the public and clinicians this past spring.