Coronavirus COVID-19 Update for April 11, 2021

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Clinical Reports

Clinical and Genetic Risk Factors for Acute Incident Venous Thromboembolism in Ambulatory Patients With COVID-19
In this population-based cohort study of patients with COVID-19, ambulatory COVID-19 was associated with a substantially increased risk of incident VTE, but this risk was greatly reduced in fully vaccinated people with breakthrough infection. Older age, male sex, and obesity were clinical risk factors for post-COVID-19 VTE; factor V Leiden thrombophilia was additionally associated with double the risk, comparable with the risk of 10-year aging. These findings may reinforce the need for vaccination, inform VTE risk stratification, and call for targeted VTE prophylaxis strategies for unvaccinated outpatients with COVID-19.
Transmission of SARS-CoV-2: A Review of Viral, Host, and Environmental Factors
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), has spread globally in a few short months. Substantial evidence now supports preliminary conclusions about transmission that can inform rational, evidence-based policies and reduce misinformation on this critical topic. This article presents a comprehensive review of the evidence on transmission of this virus. Although several experimental studies have cultured live virus from aerosols and surfaces hours after inoculation, the real-world studies that detect viral RNA in the environment report very low levels, and few have isolated viable virus. Strong evidence from case and cluster reports indicates that respiratory transmission is dominant, with proximity and ventilation being key determinants of transmission risk. In the few cases where direct contact or fomite transmission is presumed, respiratory transmission has not been completely excluded. Infectiousness peaks around a day before symptom onset and declines within a week of symptom onset, and no late linked transmissions (after a patient has had symptoms for about a week) have been documented. The virus has heterogeneous transmission dynamics: Most persons do not transmit virus, whereas some cause many secondary cases in transmission clusters called “superspreading events.” Evidence-based policies and practices should incorporate the accumulating knowledge about transmission of SARS-CoV-2 to help educate the public and slow the spread of this virus.
Onset and window of SARS-CoV-2 infectiousness and temporal correlation with symptom onset: a prospective, longitudinal, community cohort study
In conclusion, researchers defined the infectious window and dynamics of SARS-CoV-2 infectiousness and its interindividual variability. Preliminary evidence from this study has already informed policy and the real-world evidence presented here could be used to improve infection control policies and optimize guidance on self-isolation to minimize secondary transmission.
Variant Influenza Virus Infections: Recommendations for Identification, Treatment, and Prevention for Summer and Fall 2022
The Centers for Disease Control and Prevention (CDC) is issuing this Health Alert Network (HAN) Health Advisory to provide updates on recent variant¹influenza virus infections and summarize CDC’s recommendations for identification, treatment, and prevention of variant influenza virus infection for the summer and fall of 2022.

Antiviral Therapeutics and Vaccines

Low levels of monkeypox virus neutralizing antibodies after MVA-BN vaccination in healthy individuals
In July 2022, the ongoing monkeypox (MPX) outbreak was declared a public health emergency of international concern by the World Health Organization. Modified vaccinia virus Ankara (MVA-BN, also known as Imvamune, Jynneos, or Imvanex) is a 3^rdgeneration smallpox vaccine that was generated by serial passaging of the more pathogenic parental vaccinia virus (VACV), and is authorized as a vaccine against MPX in humans in a two-shot regimen. Up to now, there is a lack of data that demonstrate MPX virus (MPXV)-neutralizing antibodies in vaccinated individuals and vaccine efficacy data against MPXV infection. Here, we measure MVA-, VACV-, and MPXV-reactive binding and neutralizing antibodies with validated in-house assays in cohorts of historically smallpox-vaccinated, MPXV PCR-positive, and recently MVA-BN-vaccinated individuals. We show that MPXV neutralizing antibodies were detected across all cohorts in individuals with MPXV exposure as well as those who received historic (VACV) vaccination. However, a primary MVA-BN immunization series in non-primed individuals yields relatively low levels of MPXV neutralizing antibodies. As the role of MPXV neutralizing antibodies for protection against disease and transmissibility is currently unclear and no correlate of protection against MPXV infection has been identified yet, this raises the question how well vaccinated individuals are protected. Dose-sparing leads to lower antibody levels, whereas a third MVA vaccination further boosts the antibody response. Cohort studies following vaccinated individuals are necessary to further assess vaccine efficacy in risk populations and determine correlates of protection for this emerging pathogen.
Antibody Persistence and Safety through 6 Months after Heterologous Orally Aerosolized Ad5-nCoV in individuals primed with two-dose COVID vaccine
This study implied that policymakers could use aerosolized Ad5-nCoV vaccine as a third booster for persons who have received two-dose COVID vaccines. Besides enhancing antibody responses, orally administered aerosolized vaccines’ potential advantages over injected vaccines include ease of administration, perhaps even self-administration, which may speed up the vaccination process. Disposal of sharps after mass vaccination campaigns was avoided by not using needles and syringes. Each aerosolized Ad5-nCoV vaccination uses only one-fifth intramuscular injection dose, which has the advantage of maximize allocation of vaccine resources and being economically feasible in terms of cost-efficiency. In conclusion, our study demonstrated that heterologous orally aerosolized Ad5-nCoV plus two-dose COVID vaccines had a good long-term safety profile and was persistently more immunogenic than three-dose COVID vaccines, providing additional support for using a mix-and-match approach.
Administration of Anti–SARS-CoV-2 Monoclonal Antibodies After US Food and Drug Administration Deauthorization
According to the results of this serial cross-sectional study, hospitals and health systems administered more than 158 000 anti–SARS-CoV-2 mAb doses in early 2022, despite FDA deauthorization because of a lack of efficacy against the Omicron variant. Medicare payments for mAb administration range from $450 to $750 per dose, indicating that spending on these deauthorized treatments likely exceeds $71 million. These findings suggest that the use of deauthorized mAb products was widespread, even though patients had a minimal likelihood of benefit. Whether deauthorized treatments will be covered by payers and whether the FDA will take regulatory action against entities violating its guidance remains unknown. The continued use of deauthorized anti–SARS-CoV-2 mAb treatments may reflect conflicting state government guidance, lack of hospital awareness of deauthorization, or other factors. Although the FDA announcements clearly stated that these mAbs were no longer authorized for use, the agency did not fully revoke their emergency use authorizations because of the possibility that future COVID-19 variants could retain susceptibility, which could have led to misinterpretation. Limitations of this study include a reliance on hospital reporting, which does not include other mAb administration sites (eg, federal health systems and correctional facilities). Reporting data are not yet publicly available for other COVID-19 therapeutics. All public data on mAb administration are aggregated to the state level; thus, we were unable to explore facility variation in mAb use. Efforts to improve transparency, equity, and value in the COVID-19 response should include public release of facility-level reporting for all therapeutics.
Timely administration of tocilizumab improves outcome of hospitalized COVID-19 patients
A total of 354 patients (67% men; median age 66 years) were enrolled of whom 88% received dexamethasone. Thirty-day mortality was 19% (95% CI 14%-26%) in the standard arm versus 12% (95% CI: 8%-18%) in the tocilizumab arm, hazard ratio (HR) = 0.62 (90% CI 0.39-0.98; p = 0.086). 17% of patients were admitted to the ICU in each arm (p = 0.89). The median stay in the ICU was 14 days (IQR 9-28) in the standard arm versus 9 days (IQR 5-14) in the tocilizumab arm (p = 0.014). Mechanical ventilation or death at thirty days was 31% (95% CI 24%-38%) in the standard arm versus 21% (95% CI 16%-28%) in the tocilizumab arm, HR = 0.65 (95% CI 0.42-0.98; p = 0.042). This randomized phase II study supports efficacy for tocilizumab when given early in the disease course in hospitalized patients who need oxygen support, especially when concomitantly treated with dexamethasone.