Coronavirus COVID-19 Update for April 29, 2021

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Clinical Reports

The Global Case-Fatality Rate of COVID-19 Has Been Declining Since May 2020
The objective of this study was to evaluate the trend of reported case fatality rate (rCFR) of COVID-19 over time, using globally reported COVID-19 cases and mortality data. Daily COVID-19 diagnoses and mortality data from the WHO’s daily situation reports dated January 1 to December 31, 2020 were collected. Three time-series models [simple exponential smoothing, auto-regressive integrated moving average, and automatic forecasting time-series (Prophet)] were performed to identify the global trend of rCFR for COVID-19. Beta regression models were used to investigate the association between the rCFR and potential predictors of each country and reported incidence rate ratios (IRRs) of each variable. The weekly global cumulative COVID-19 rCFR reached a peak at 7.23% during the 17th week (April 22–28, 2020). A positive and increasing trend for global daily rCFR values of COVID-19 until the 17th week (pre-peak period) was found and then a strong declining trend up until the 53rd week (post-peak period) toward 2.2% (December 29–31, 2020). In pre-peak of rCFR, the percentage of people aged 65 and above and the prevalence of obesity were significantly associated with the COVID-19 rCFR. The declining trend of global COVID-19 rCFR was not merely because of increased COVID-19 testing, because COVID-19 tests per 1,000 population had poor predictive value. Decreasing rCFR could be explained by an increased rate of infection in younger people or by the improvement of health care management, shielding from infection, and/or repurposing of several drugs that had shown a beneficial effect on reducing fatality because of COVID-19
High-dimensional characterization of post-acute sequalae of COVID-19
Authors use the national healthcare databases of the US Department of Veterans Affairs to systematically and comprehensively identify 6-month incident sequalae including diagnoses, medication use, and laboratory abnormalities in 30-day survivors of COVID-19. They show that beyond the first 30 days of illness, people with COVID-19 exhibit higher risk of death and health resource utilization. Our high dimensional approach identifies incident sequalae in the respiratory system and several others including nervous system and neurocognitive disorders, mental health disorders, metabolic disorders, cardiovascular disorders, gastrointestinal disorders, malaise, fatigue, musculoskeletal pain, and anemia. Authors show increased incident use of several therapeutics including pain medications (opioids and non-opioids), antidepressants, anxiolytics, antihypertensives, and oral hypoglycemics and evidence of laboratory abnormalities in multiple organ systems. Analysis of an array of pre-specified outcomes reveals a risk gradient that increased across severity of the acute COVID-19 infection (non-hospitalized, hospitalized, admitted to intensive care). The findings show that beyond the acute illness, substantial burden of health loss — spanning pulmonary and several extrapulmonary organ systems — is experienced by COVID-19 survivors. The results provide a roadmap to inform health system planning and development of multidisciplinary care strategies to reduce chronic health loss among COVID-19 survivors.

Antiviral Therapeutics and Vaccines

When You’ve Been Fully Vaccinated: How to Protect Yourself and Others
COVID-19 vaccines are effective at protecting you from getting sick. Based on what we know about COVID-19 vaccines, people who have been fully vaccinated can start to do some things that they had stopped doing because of the pandemic. In indoor public spaces, the vaccination status of other people or whether they are at increased risk for severe COVID-19 is likely unknown. Therefore, fully vaccinated people should continue to wear a mask that fits snugly against the sides of your face and doesn’t have gaps, cover coughs and sneezes, wash hands often, and follow any applicable workplace or school guidance. These recommendations can help you make decisions about daily activities after you are fully vaccinated. They are not intended for healthcare settings.
Updated Recommendations from the Advisory Committee on Immunization Practices for Use of the Janssen (Johnson & Johnson) COVID-19 Vaccine After Reports of Thrombosis with Thrombocytopenia Syndrome Among Vaccine Recipients — United States, April 2021
On April 13, 2021, CDC and the Food and Drug Administration (FDA) recommended pausing use of the Janssen COVID-19 vaccine after reports of thrombosis with thrombocytopenia syndrome (TTS) among vaccine recipients. On April 23, the Advisory Committee on Immunization Practices concluded that the benefits of resuming Janssen COVID-19 vaccination among persons aged ≥18 years outweighed the risks and reaffirmed its interim recommendation under FDA’s Emergency Use Authorization, which includes a new warning for rare clotting events among women aged 18–49 years. Resuming use of the Janssen COVID-19 vaccine will ensure flexibility, choice, and improved access. Education about TTS risk with Janssen COVID-19 vaccine is critical.
B.1.526 SARS-CoV-2 Variants Identified in New York City Are Neutralized by Vaccine-Elicited and Therapeutic Monoclonal Antibodies
Neutralizing activity elicited by prior SARS-CoV-2 infection, mRNA vaccines (Pfizer-BioNTech and Moderna), or the Regeneron monoclonal antibody cocktail (REGN10933 and REGN10987) were similar against the B.1.526 variant with the S477N mutation compared to the widely circulating strain with the D614G mutation. In contrast, similar to other E484K harboring variants, the B.1.526 variant with the E484K mutation reduced neutralizing titers of sera from convalescent and vaccinated individuals by nearly 4-fold. REGN10933 alone had a 12-fold reduction in neutralizing activity, but the combined Regeneron cocktail was able to neutralize the B.1.526 E484K variant. Both versions of the B.1.526 variant (S477N mutation and E484K mutation) were first identified in New York City in November 2020, and rapidly spread to account for 12% of detected genomes by mid-February 2021.
PFIZER INITIATES PHASE 1 STUDY OF NOVEL ORAL ANTIVIRAL THERAPEUTIC AGENT AGAINST SARS-COV-2
Pfizer Inc. announced today that it is progressing to multiple ascending doses after completing the dosing of single ascending doses in a Phase 1 study in healthy adults to evaluate the safety and tolerability of an investigational, novel oral antiviral therapeutic for SARS-CoV-2, the virus that causes COVID-19. This Phase 1 trial is being conducted in the United States. The oral antiviral clinical candidate PF-07321332, a SARS-CoV2-3CL protease inhibitor, has demonstrated potent in vitro anti-viral activity against SARS-CoV-2, as well as activity against other coronaviruses, suggesting potential for use in the treatment of COVID-19 as well as potential use to address future coronavirus threats. Protease inhibitors bind to a viral enzyme (called a protease), preventing the virus from replicating in the cell. Protease inhibitors have been effective at treating other viral pathogens such as HIV and hepatitis C virus, both alone and in combination with other antivirals. Currently marketed therapeutics that target viral proteases are not generally associated with toxicity and as such, this class of molecules may potentially provide well-tolerated treatments against COVID-19. The Phase 1 trial is a randomized, double-blind, sponsor-open, placebo-controlled, single- and multiple-dose escalation study in healthy adults evaluating the safety, tolerability and pharmacokinetics of PF-07321332.
Merck and Ridgeback Biotherapeutics Provide Update on Progress of Clinical Development Program for Molnupiravir, an Investigational Oral Therapeutic for the Treatment of Mild-to-Moderate COVID-19
Merck and Ridgeback Biotherapeutics today provided an update on the clinical development program for molnupiravir (MK-4482/ EIDD-2801), an investigational orally available antiviral therapeutic. Based on a planned interim analysis of data from the Phase 2, dose-finding portion (Part 1) of two ongoing placebo-controlled Phase 2/3 trials evaluating molnupiravir administered twice a day for five days in outpatients (MOVe-OUT) and hospitalized patients (MOVe-IN) with COVID-19, and from a previously completed Phase 2a dose-ranging study in outpatients, the decision has been made to proceed with the Phase 3 portion (Part 2) of MOVe-OUT in outpatients with COVID-19, evaluating the 800 mg dose of molnupiravir twice daily. Data from MOVe-IN indicate that molnupiravir is unlikely to demonstrate a clinical benefit in hospitalized patients, who generally had a longer duration of symptoms prior to study entry; therefore, the decision has been made not to proceed to Phase 3.

Epidemiology

Guidance for Operating Youth and Summer Camps During COVID-19
This guidance is intended for all types of youth day camps with additional guidance provided for overnight camps. Organizations that provide summer day camps on school grounds should use the guidance. Consistent and layered use of multiple prevention strategies can help camps open safely for in-person activities; protect children, families, and staff; and slow the spread of the virus that causes COVID-19. This guidance describes physical distancing recommendations for day camps that align with current evidence for physical distancing in schools, including at least 3 feet physical distance between campers in the same cohort, except when eating and drinking (at least 6 feet); at least 6 feet physical distance between campers and staff; and at least 6 feet between campers in different cohorts. Additional guidance on physical distancing in overnight camps is also provided. This guidance outlines strategies that camp programs can use to maintain healthy environments and operations, lower the risk of COVID-19 spread in their programs, prepare for when someone is sick with COVID-19, and support coping and resilience.