Coronavirus COVID-19 Update for April 11, 2021

Clinical Reports

Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19
In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support–free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of −1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support–free days was 1 (interquartile range, −1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, −1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis. In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis

Six-Month Outcomes in Patients Hospitalized with Severe COVID-19
To determine whether symptoms persist further or improve over time, patients were followed who were discharged after hospitalization for severe COVID-19 to characterize their overall health status and their physical and mental health at 6 months post-hospital discharge. Patients ≥ 18 years hospitalized for COVID-19 at a single health system, who required at minimum 6 l of supplemental oxygen during admission, had intact baseline functional status and were discharged alive. Overall health status, physical health, mental health, and dyspnea were assessed with validated surveys: the PROMIS® Global Health-10 and PROMIS® Dyspnea Characteristics instruments. Of 152 patients who completed the 1-month post-discharge survey, 126 (83%) completed the 6-month survey. The median age of 6-month respondents was 62; 40% were female. Ninety-three (74%) patients reported that their health had not returned to baseline at 6 months, and endorsed a mean of 7.1 symptoms. Participants' summary t-scores in both the physical health and mental health domains at 6 months (45.2, standard deviation [SD] 9.8; 47.4, SD 9.8, respectively) remained lower than their baseline (physical health 53.7, SD 9.4; mental health 54.2, SD 8.0; p<0.001). Overall, 79 (63%) patients reported shortness of breath within the prior week (median score 2 out of 10 (interquartile range [IQR] 0-5), vs 42 (33%) pre-COVID-19 infection (0, IQR 0-1)). A total of 11/124 (9%) patients without pre-COVID oxygen requirements still needed oxygen 6 months post-hospital discharge. One hundred and seven (85%) were still experiencing fatigue at 6 months post-discharge. Even 6 months after hospital discharge, the majority of patients report that their health has not returned to normal. Support and treatments to return these patients back to their pre-COVID baseline are urgently needed.

Antiviral Therapeutics and Vaccines

Vaccine effectiveness against SARS-CoV-2 transmission and infections among household and other close contacts of confirmed cases, the Netherlands, February to May 2021.
An important question when making prognoses of the pandemic in the near future and of the need on non-pharmaceutical control measures is to what extent the vaccines reduce the likelihood of transmission from infected vaccinees. Based on routine contact monitoring data, authors estimate the vaccine effectiveness against transmission (VET) and the vaccine effectiveness against infection (VE) among household and other close contacts of confirmed cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the Netherlands, between 1 February and 27 May 2021. The Alpha variant (Phylogenetic Assignment of Named Global Outbreak (Pango) lineage designation B.1.1.7) was the dominant variant in the area at that time. The study showed that the COVID-19 vaccines not only protect the vaccine against SARS-CoV-2 infection but also offer protection against transmission to close contacts after completing the full schedule. This finding underscores the importance of full vaccination of close contacts of vulnerable persons.

Interim Public Health Recommendations for Fully Vaccinated People

Updated information for fully vaccinated people given new evidence on the B.1.617.2 (Delta) variant currently circulating in the United States.
Added a recommendation for fully vaccinated people to wear a mask in public indoor settings in areas of substantial or high transmission.
Added information that fully vaccinated people might choose to wear a mask regardless of the level of transmission, particularly if they are immunocompromised or at increased risk for severe disease from COVID-19, or if they have someone in their household who is immunocompromised, at increased risk of severe disease or not fully vaccinated.
Added a recommendation for fully vaccinated people who have come into close contact with someone with suspected or confirmed COVID-19 to be tested 3-5 days after exposure, and to wear a mask in public indoor settings for 14 days or until they receive a negative test result.
CDC recommends universal indoor masking for all teachers, staff, students, and visitors to schools, regardless of vaccination status.

Elapsed time since BNT162b2 vaccine and risk of SARS-CoV-2 infection in a large cohort
Israel was among the first countries to launch a large-scale COVID-19 vaccination campaign, and quickly vaccinated its population, achieving early control over the spread of the virus. However, the number of COVID-19 cases is now rapidly increasing, which may indicate that vaccine protection decreases over time. The objective of this study is to determine whether the time elapsed since the second BNT162b2 messenger RNA (mRNA) vaccine (Pfizer-BioNTech) injection is significantly associated with the risk of post-vaccination COVID-19 infection. This is a retrospective cohort study performed in a large state-mandated health care organization in Israel. All fully vaccinated adults who have received a RT-PCR test between May 15, 2021, and July 26, 2021, at least two weeks after their second vaccine injection were included. Patients with a history of past COVID-19 infection were excluded. The cohort included 33,993 fully vaccinated adults, 49% women, with a mean age of 47 years (SD, 17 years), who received an RT-PCR test for SARS-CoV-2 during the study period. The median time between the second dose of the vaccine and the RT-PCR test was 146 days, interquartile range [121-167] days. 608 (1.8%) patients had positive test results. There was a significantly higher rate of positive results among patients who received their second vaccine dose at least 146 days before the RT-PCR test compared to patients who have received their vaccine less than 146 days before: odds ratio for infection was 3.00 for patients aged over 60 (95% CI 1.86-5.11); 2.29 for patients aged between 40 and 59 (95% CI 1.67-3.17); and 1.74 for patients aged between 18 and 39 (95% CI 1.27-2.37); P<0.001 in each age group. In this large population study of patients tested for SARS-CoV-2 by RT-PCR following two doses of mRNA BNT162b2 vaccine, a significant increase in the risk of infection was observed in individuals who received their last vaccine dose since at least 146 days ago, particularly among patients older than 60.

Reduced Risk of Reinfection with SARS-CoV-2 After COVID-19 Vaccination — Kentucky, May–June 2021
Reinfection with human coronaviruses, including SARS-CoV-2, the virus that causes COVID-19, has been documented. Currently, limited evidence concerning the protection afforded by vaccination against reinfection with SARS-CoV-2 is available. Among Kentucky residents infected with SARS-CoV-2 in 2020, the vaccination status of those reinfected during May–June 2021 was compared with that of residents who were not reinfected. In this case-control study, being unvaccinated was associated with 2.34 times the odds of reinfection compared with being fully vaccinated. To reduce their likelihood of future infection, all eligible persons should be offered COVID-19 vaccine, even those with previous SARS-CoV-2 infection.

Diagnostics

Modelling the effectiveness and social costs of daily lateral flow antigen tests versus quarantine in preventing onward transmission of COVID-19 from traced contacts
Quarantining close contacts of individuals infected with SARS-CoV-2 for 10 to 14 days is a key strategy in reducing transmission. However, quarantine requirements are often unpopular, with low adherence, especially when a large fraction of the population has been vaccinated. Daily contact testing (DCT), in which contacts are required to isolate only if they test positive, is an alternative to quarantine for mitigating the risk of transmission from traced contacts. In this study, the authors developed an integrated model of COVID-19 transmission dynamics and compared the strategies of quarantine and DCT with regard to reduction in transmission and social/economic costs (days of quarantine/self-isolation). Specifically, 10-day quarantine to 7 days of self-testing was examined using rapid lateral flow antigen tests, starting 3 days after exposure to a case. Both incomplete adherence to quarantine and incomplete adherence to DCT were modeled Results indicate that DCT reduces transmission from contacts with similar effectiveness, at much lower social/economic costs, especially for highly vaccinated populations. The findings were robust across a spectrum of scenarios with varying assumptions on the speed of contact tracing, the sensitivity of lateral flow antigen tests, adherence to quarantine, and uptake of testing. Daily tests would also allow rapid initiation of a new round of tracing from infected contacts.