Coronavirus COVID-19 Update for September 10, 2021

Clinical Reports

Characteristics and Outcomes of Women With COVID-19 Giving Birth at US Academic Centers During the COVID-19 Pandemic
This cohort study examines 869 079 adult women, including 18 715 women with COVID-19, who underwent childbirth at 499 US medical centers between March 1, 2020, and February 28, 2021. Women with COVID-19 had increased mortality, need for intubation and ventilation, and intensive care unit admission. These findings suggest that COVID-19 was associated with increased risk of morbidity and mortality for women giving birth.

Children and COVID-19: State-Level Data Report
State-level reports are the best publicly available and timely data on child COVID-19 cases in the United States. The American Academy of Pediatrics and the Children’s Hospital Association are collaborating to collect and share all publicly available data from states on child COVID-19 cases (definition of “child” case is based on varying age ranges reported across states; see report Appendix for details and links to all data sources). As of September 2, over 5 million children have tested positive for COVID-19 since the onset of the pandemic. About 252,000 cases were added the past week, the largest number of child cases in a week since the pandemic began. After declining in early summer, child cases have increased exponentially, with over 750,000 cases added between August 5 and September 2.

Long COVID - the physical and mental health of children and non-hospitalised young people 3 months after SARS-CoV-2 infection; a national matched cohort study (The CLoCk) Study.
Post-COVID symptomatology is described in a national sample of 11-17-year-old children and young people (CYP) with PCR-confirmed SARS-CoV-2 infection compared to test-negative controls. A cohort study of test-positive (n=3,065) and age-, sex- and geographically-matched test-negative CYP (n=3,739) completed detailed questionnaires 3 months post-test. At PCR-testing, 35.4% of test-positives and 8.3% of test-negatives had any symptoms whilst 30.6% and 6.2%, respectively, had 3+ symptoms. At 3 months post-testing, 66.5% of test-positives and 53.3% of test-negatives had any symptoms, whilst 30.3% and 16.2%, respectively, had 3+ symptoms. Latent class analysis identified two classes, characterised by “few” or “multiple” symptoms. This latter class was more frequent among test-positives, females, older CYP and those with worse pre-test physical and mental health. Test-positive CYP had a similar symptom profile to test-negative CYP but with higher prevalence of single and, particularly, multiple symptoms at PCR-testing and 3 months later.

Outbreak Associated with SARS-CoV-2 B.1.617.2 (Delta) Variant in an Elementary School — Marin County, California, May–June 2021
During May 23–June 12, 2021, 26 laboratory-confirmed COVID-19 cases occurred among Marin County, California, elementary school students and their contacts following exposure to an unvaccinated infected teacher. The attack rate in one affected classroom was 50%; risk correlated with seating proximity to the teacher. Vaccines are effective against the Delta variant, but transmission risk remains elevated among unvaccinated persons in schools. In addition to vaccination, strict adherence to multiple nonpharmaceutical prevention strategies, including masking, are important to ensure safe school instruction.

1-year outcomes in hospital survivors with COVID-19: a longitudinal cohort study
The full range of long-term health consequences of COVID-19 in patients who are discharged from hospital is largely unclear. The aim of this study was to comprehensively compare consequences between 6 months and 12 months after symptom onset among hospital survivors with COVID-19. Most COVID-19 survivors had a good physical and functional recovery during 1-year follow-up, and had returned to their original work and life. The health status in the cohort of COVID-19 survivors at 12 months was still lower than that in the control population.

Antiviral Therapeutics and Vaccines

Ivermectin Intended for Animals: Letter to Stakeholders - Do Not Use in Humans as a Treatment for COVID-19
FDA is concerned about the health of consumers who may self-medicate by taking ivermectin products intended for animals, thinking they can be a substitute for ivermectin intended for humans. The FDA’s Center for Veterinary Medicine has recently become aware of increased public visibility of the antiparasitic drug ivermectin after the announcement of a research article that described the effect of ivermectin on SARS-CoV-2 in a laboratory setting. The Antiviral Research pre-publication paper, “The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro” documents how SARS-CoV-2 (the virus that causes COVID-19) responded to ivermectin when exposed in a petri dish. Ivermectin is FDA-approved for use in animals for prevention of heartworm disease in some small animal species, and for treatment of certain internal and external parasites in various animal species.

RECOMMENDATION:

People should never take animal drugs, as the FDA has only evaluated their safety and effectiveness in the particular animal species for which they are labeled. These animal drugs can cause serious harm in people.
People should not take any form of ivermectin unless it has been prescribed by a licensed health care provider and is obtained through a legitimate source.
Ivermectin is an important part of a parasite control program for certain species and should only be given to animals for approved uses or as prescribed by a veterinarian in compliance with the requirements for extra-label drug use.
If you are having difficulty locating a particular ivermectin product for your animal(s), FDA recommends that you consult with your veterinarian.

Convalescent plasma recommendations from IDSA
Observational studies have found both benefit and no benefit when convalescent plasma is used in hospitalized patients with COVID-19. The results of subsequent randomized controlled trials are mixed and are presented below. Several of the randomized, controlled trials of convalescent plasma were not powered to meet their primary objectives once enrollment dropped due to waning of COVID-19 cases, and interpretation was further complicated by heterogeneity with respect to titer of the convalescent plasma administered and serostatus of recipients. The largest trial showed no significant impact on 28-day mortality or clinical recovery from high-titer convalescent plasma. Data on whether, and under which circumstances, convalescent plasma is beneficial for patients hospitalized with COVID-19 are still emerging. Research is complicated by practical difficulties in measuring and accessing information on antibody titer or geographic provenance of convalescent plasma. Additional clinical trials are underway to further examine these questions, as are trials using convalescent plasma in the outpatient setting and as post-exposure prophylaxis. Based on the published literature, the use of convalescent plasma appears to be relatively safe, and no evidence of antibody-mediated enhancement of COVID disease severity has emerged.

Comparison of SARS-CoV-2 Antibody Response Following Vaccination With BNT162b2 and mRNA-1273
The SARS-CoV-2 messenger RNA (mRNA) vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) have each shown more than 90% efficacy in preventing COVID-19 illness¹^,² but humoral immune responses have not been compared directly. Health care workers at a tertiary care center (Ziekenhuis Oost-Limburg, Belgium) who were scheduled for vaccination with 2 doses of either mRNA-1273 or BNT162b2 were invited to participate in this prospective cohort. Serologic testing was performed prior to vaccination as well as 6 to 10 weeks after the second dose (between April 27 and May 20, 2021). Total immunoglobulin levels to the receptor-binding domain of the SARS-CoV-2 spike protein were measured with an anti–SARS-CoV-2 S enzyme immunoassay (Elecsys, Roche Diagnostics International Ltd). After vaccination, antibodies against the SARS-CoV-2 nucleocapsid protein were determined. Previous infection was defined as anti-nucleocapsid positivity at any point, anti-spike positivity before vaccination, and/or a history of positive polymerase chain reaction results on nasopharyngeal swab. This study demonstrated a significantly higher humoral immunogenicity of the SARS-CoV-2 mRNA-1273 vaccine (Moderna) compared with the BNT162b2 vaccine (Pfizer-BioNTech), in infected as well as uninfected participants, and across age categories. The higher mRNA content in mRNA-1273 compared with BNT162b2 and the longer interval between priming and boosting for mRNA-1273³ (4 weeks vs 3 weeks for BNT162b2) might explain this difference.

AZD7442 PROVENT Phase III prophylaxis trial met primary endpoint in preventing COVID-19
Positive high-level results from the PROVENT Phase III pre-exposure prophylaxis trial showed AstraZeneca's AZD7442 achieved a statistically significant reduction in the incidence of symptomatic COVID-19, the trial's primary endpoint. AZD7442, a combination of two long-acting antibodies (LAAB), reduced the risk of developing symptomatic COVID-19 by 77% (95% confidence interval (CI): 46, 90), compared to placebo. The trial accrued 25 cases of symptomatic COVID-19 at the primary analysis. There were no cases of severe COVID-19 or COVID-19-related deaths in those treated with AZD7442. In the placebo arm, there were three cases of severe COVID-19, which included two deaths. AZD7442 is the first antibody combination (non-vaccine) modified to potentially provide long-lasting protection that has demonstrated prevention of COVID-19 in a clinical trial. The trial included 5,197 participants in a 2:1 randomisation AZD7442 to placebo. The primary analysis was based on 5,172 participants who did not have SARS-CoV-2 infection at baseline. More than 75% of participants had co-morbidities, which include conditions that have been reported to cause a reduced immune response to vaccination. The LAAB was well tolerated and preliminary analyses show adverse events were balanced between the placebo and AZD7442 groups.

Effect of Early Treatment with Fluvoxamine on Risk of Emergency Care and Hospitalization Among Patients with COVID-19: The TOGETHER Randomized Platform Clinical Trial
This placebo-controlled, randomized, adaptive, platform trial conducted among symptomatic Brazilian adults confirmed positive for SARS-CoV-2 included eligible patients with a known risk factor for progression to severe disease. Patients were randomly assigned to either fluvoxamine (100 mg twice daily for 10 days) or placebo. The primary endpoint was a composite outcome of emergency room observation for >6 hours or hospitalization from COVID-19 up to 28 days post randomization. Secondary outcomes included viral clearance at day 7, time to hospitalization, mortality, and adverse drug reactions. The proportion of patients observed in an emergency room for >6 hours or admitted to hospital due to COVID-19 was lower for the fluvoxamine group compared to placebo (77/739 vs 108/733; Relative Risk [RR]: 0.71; 95% Bayesian Credible Interval [95% BCI]: 0.54 - 0.93), with a probability of superiority of 99.4% surpassing the prespecified superiority threshold of 97.6% (risk difference 4.3%). Of the composite primary outcome events, 88% were hospitalizations. There was no significant relative effects difference between the fluvoxamine and placebo groups on viral clearance at day 7 (Odds ratio [OR]: 0.75; 95% Confidence Intervals [95% CI]: 0.53 - 1.07), mortality (OR: 0.70; 95% CI: 0.36 - 1.30), time to death (Hazard ratio [HR]: 0.79; 95% CI: 0.58 - 1.08), days hospitalized (Mean Difference (MD) 1.22 days; 95% CI: 0.98 - 1.53), number of days ventilated (MD 1.10; 95% CI: 0.70 - 1.73) or other secondary outcomes. Data capturing all 28 days of follow-up will be reported after August 26^th, 2021.

Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: a prospective, community-based, nested, case-control study
COVID-19 vaccines show excellent efficacy in clinical trials and effectiveness in real-world data, but some people still become infected with SARS-CoV-2 after vaccination. This study aimed to identify risk factors for post-vaccination SARS-CoV-2 infection and describe the characteristics of post-vaccination illness. Between Dec 8, 2020, and July 4, 2021, 1 240 009 COVID Symptom Study app users reported a first vaccine dose, of whom 6030 (0·5%) subsequently tested positive for SARS-CoV-2 (cases 1), and 971 504 reported a second dose, of whom 2370 (0·2%) subsequently tested positive for SARS-CoV-2 (cases 2). In the risk factor analysis, frailty was associated with post-vaccination infection in older adults (≥60 years) after their first vaccine dose (odds ratio [OR] 1·93, 95% CI 1·50–2·48; p<0·0001), and individuals living in highly deprived areas had increased odds of post-vaccination infection following their first vaccine dose (OR 1·11, 95% CI 1·01–1·23; p=0·039). Individuals without obesity (BMI <30 kg/m²) had lower odds of infection following their first vaccine dose (OR 0·84, 95% CI 0·75–0·94; p=0·0030). For the disease profile analysis, 3825 users from cases 1 were included in cases 3 and 906 users from cases 2 were included in cases 4. Vaccination (compared with no vaccination) was associated with reduced odds of hospitalisation or having more than five symptoms in the first week of illness following the first or second dose, and long-duration (≥28 days) symptoms following the second dose. Almost all symptoms were reported less frequently in infected vaccinated individuals than in infected unvaccinated individuals, and vaccinated participants were more likely to be completely asymptomatic, especially if they were 60 years or older.

Diagnostics

Validation of an At-Home Direct Antigen Rapid Test for COVID-19
Rapid antigen tests that permit new cases to isolate immediately can be important surveillance tools. A longitudinal comparison between antigen tests performed at home and qRT-PCR has not previously been performed, to our knowledge. Authors describe implementation of high-frequency testing using inexpensive, at-home, semiquantitative, direct antigen rapid tests (DARTs) and compare their performance with that of qRT-PCR on self-collected nasal specimens. Twice-weekly surveillance with DART detected infections in 15 individuals, with 96.3% sensitivity on days 0 through 3 of symptoms. Detection on day 3 is almost as effective as detection on day 1 for reducing the incidence of COVID-19, if 75% of a population is surveilled. The prevalence of disease dictates the frequency of testing and its effectiveness for controlling potential outbreaks. Limitations of this study include low infection rates among the study population. During this study, the prevalence of COVID-19 was between less than 1% and 8%.

Epidemiology

Longitudinal analysis of SARS-CoV-2 vaccine breakthrough infections reveal limited infectious virus shedding and restricted tissue distribution
To shed light on how vaccine breakthrough infections compare with infections in immunologically naive individuals, authors examined viral dynamics and infectious virus shedding through daily longitudinal sampling in a small cohort of adults infected with SARS-CoV-2 at varying stages of vaccination. The durations of both infectious virus shedding and symptoms were significantly reduced in vaccinated individuals compared with unvaccinated individuals. Breakthrough infections are associated with strong tissue compartmentalization and are only detectable in saliva in some cases. These data indicate that vaccination shortens the duration of time of high transmission potential, minimizes symptom duration, and may restrict tissue dissemination.