Coronavirus COVID-19 Update for September 15, 2021

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Clinical Reports

Trends in COVID-19 Cases, Emergency Department Visits, and Hospital Admissions Among Children and Adolescents Aged 0–17 Years — United States, August 2020–August 2021
Severe illness from COVID-19 can and does occur in children and adolescents. COVID-19 cases, emergency department visits, and hospital admissions increased from June to August 2021 among persons aged 0-17 years. Emergency department visits and hospital admissions in a 2-week period in August 2021 were higher in states with lower population vaccination coverage and lower in states with higher vaccination coverage. Community vaccination, in coordination with testing strategies and other prevention measures, is critical to protecting pediatric populations from SARS-CoV-2 infection and severe COVID-19.

American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: May 2021 update on the use of intermediate intensity anticoagulation in critically ill patients
COVID-19 related critical illness is associated with an increased risk of venous thromboembolism (VTE). These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians and other health care professionals in decisions about the use of anticoagulation for thromboprophylaxis in patients with COVID-19-related critical illness who do not have confirmed or suspected VTE. Methods: ASH formed a multidisciplinary guideline panel, including three patient representatives, and applied strategies to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline development process, including performing systematic evidence reviews (up to March 5, 2021). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to assess evidence and make recommendations, which were subject to public comment. This is an update on guidelines published in February 2021. The panel agreed on one additional recommendation. The panel issued a conditional recommendation in favor of prophylactic-intensity over intermediate-intensity anticoagulation in patients with COVID-19 related-critical illness who do not have confirmed or suspected VTE. This recommendation was based on low certainty in the evidence, underscoring the need for further high-quality, randomized controlled trials comparing different intensities of anticoagulation in critically ill patients. Other key research priorities include better evidence on predictors of thrombosis and bleeding risk in critically ill patients with COVID-19 and the impact of non-anticoagulant therapies (e.g., antiviral agents, corticosteroids) on thrombotic risk.

Long-Term Symptoms Among Adults Tested for SARS-CoV-2 — United States, January 2020–April 2021
Long-term symptoms associated with COVID-19 represent an emerging public health concern. In a nonprobability-based sample of U.S. adults tested for SARS-CoV-2, symptoms often associated with SARS-CoV-2 infection were common; 65.9% of respondents whose SARS-CoV-2 test results were positive reported symptoms lasting >4 weeks compared with 42.9% of those whose test results were negative. More persons who received positive test results (76.2%) reported persistence (>4 weeks) of at least one initially occurring symptom compared with those whose test results were negative (69.6%). These findings can aid efforts to address post-COVID conditions and messaging on potential benefits of vaccination.

Severe COVID-19 is associated with sustained biochemical disturbances and prolonged symptomatology; A retrospective single-centre cohort study
Coronavirus disease 2019 (COVID-19) is associated with significant acute clinical manifestations, and reports indicate that some patients experience prolonged symptomatology and morbidity. These late clinical manifestations have been termed Post-Acute Sequelae of COVID-19 (PASC) and hypothesized to be associated with clinical severity in the acute infection phase and biochemical abnormalities. Aim of this study was to evaluate the incidence of PASC in previously hospitalized COVID-19 patients and compare the admission and follow-up levels of biochemical parameters stratified according to baseline clinical severity. N = 168 COVID-19 patients previously hospitalized at the Zan Mitrev Clinic in Skopje, North Macedonia, with matched laboratory data at baseline and follow-up clinical visit > 30 days post-discharge, were stratified according to National Institute of Health clinical severity guidelines as mild, moderate, severe or critical according to admission clinical presentation. Authors assessed the incidence of PASC and compared the biochemical profile. The median hospitalization and clinical follow-up period were 11 (9-20) and 53 (30-105) days. The overall incidence of PASC was 56.5% (95/168); most PASC cases were confined to the severe sub-group (61/101, 61.4%). Contrary to mild and moderate cases and a healthy “non-COVID-19” control cohort, severe COVID-19 cases experienced sustained biochemical disturbances, most notably elevated D-dimers and Ferritin of 600 ng/ml (283-1168) and 432 ng/ml (170-916), respectively. Previously hospitalized severe COVID-19 patients are more likely to experience Post-Acute Sequelae of COVID-19 and prolonged biochemical disturbances, evident by abnormal values of D-dimers and Ferritin.

Clinical Recommendations

Overlooked Shortcomings of Observational Studies of Interventions in Coronavirus Disease 2019: An Illustrated Review for the Clinician
The rapid spread of severe acute respiratory syndrome coronavirus 2 infection across the globe triggered an unprecedented increase in research activities that resulted in an astronomical publication output of observational studies. However, most studies failed to apply fully the necessary methodological techniques that systematically deal with different biases and confounding, which not only limits their scientific merit but may result in harm through misleading information. In this article, authors address a few important biases that can seriously threaten the validity of observational studies of coronavirus disease 2019 (COVID-19). The focus is on treatment selection bias due to patients' preference on goals of care, medical futility and disability bias, survivor bias, competing risks, and the misuse of propensity score analysis. The article attempts to raise awareness and to help readers assess shortcomings of observational studies of interventions in COVID-19.

Critical Review of the Scientific Evidence and Recommendations in COVID-19 Management Guidelines
Little is known about the quality and potential impacts of the guidelines for coronavirus disease 2019 (COVID-19) management. Authors systematically searched PubMed, Web of Science, Cochrane Library, guideline databases, and specialty society websites to evaluate the quality of the retrieved guidelines using the Appraisal of Guidelines for Research and Evaluation II. A total of 66 guidelines were identified. Only 24% were categorized as “recommended” for clinical practice. The 211 identified recommendations for COVID-19 management were classified into 4 topics: respiratory support (27), acute respiratory distress syndrome management (31), antiviral or immunomodulatory therapy (95), or other medicines (58). Only 63% and 56% of recommendations were supported by, respectively, assessment of the strength of the recommendations or level of evidence. There were notable discrepancies between the different guidelines regarding the recommendations on COVID-19 management. The quality of the guidelines for COVID-19 management is heterogeneous, and the recommendations are rarely supported by evidence.

Antiviral Therapeutics and Vaccines

Correlation of SARS-CoV-2 Breakthrough Infections to Time-from-vaccine; Preliminary Study
The short-term effectiveness of a two-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine was widely demonstrated. However, long term effectiveness is still unknown. A nationwide vaccination campaign was initiated early in Israel, allowing for a real-world evaluation of the interaction between protection and time-from-vaccine. The Delta (B.1.617.2) variant became the dominant strain in Israel in June 2021, as Israel is currently experiencing a new surge of cases. Leveraging the centralized computerized database of Maccabi Healthcare Services (MHS), authors assessed the correlation between time-from-vaccine and incidence of breakthrough infection. The risk for infection was significantly higher for early vaccinees compared to those vaccinated later. This preliminary finding should prompt further investigations into long-term protection against different strains, and prospective clinical trials to examine the effect of a booster vaccine against breakthrough infection.

Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial
In this phase 3, double-blind, randomised, placebo-controlled trial, participants were enrolled from 101 centres across 12 countries in Asia, Europe, North America, and South America. Hospitalised adults with COVID-19 receiving standard of care were randomly assigned (1:1) to receive once-daily baricitinib (4 mg) or matched placebo for up to 14 days. Standard of care included systemic corticosteroids, such as dexamethasone, and antivirals, including remdesivir. The composite primary endpoint was the proportion who progressed to high-flow oxygen, non-invasive ventilation, invasive mechanical ventilation, or death by day 28, assessed in the intention-to-treat population. All-cause mortality by day 28 was a key secondary endpoint, and all-cause mortality by day 60 was an exploratory endpoint; both were assessed in the intention-to-treat population. Safety analyses were done in the safety population defined as all randomly allocated participants who received at least one dose of study drug and who were not lost to follow-up before the first post-baseline visit. Although there was no significant reduction in the frequency of disease progression overall, treatment with baricitinib in addition to standard of care (including dexamethasone) had a similar safety profile to that of standard of care alone, and was associated with reduced mortality in hospitalised adults with COVID-19.

Epidemiology

Estimated US Infection- and Vaccine-Induced SARS-CoV-2 Seroprevalence Based on Blood Donations, July 2020-May 2021
Based on blood donations in the US from July 2020 through May 2021, how did infection- and vaccine-induced SARS-CoV-2 seroprevalence vary over time by demographic group and by geographic region? In this repeated cross-sectional study that included 1 443 519 blood donation specimens from a catchment area representing 74% of the US population, estimated SARS-CoV-2 seroprevalence weighted for differences between the study sample and general population increased from 3.5% in July 2020 to 20.2% for infection-induced antibodies and 83.3% for combined infection- and vaccine-induced antibodies in May 2021. Seroprevalence differed by age, race and ethnicity, and geographic region of residence, but these differences changed over the course of the study. Based on a sample of blood donations in the US from July 2020 through May 2021, estimated SARS-CoV-2 seroprevalence increased over time and varied by age, race and ethnicity, and geographic region.

Prevalence of SARS-CoV-2 Antibodies From a National Serosurveillance of Kenyan Blood Donors, January-March 2021
High SARS-CoV-2 antibody levels have been achieved in most of the population in high-income countries through vaccination. However, global inequity exists in COVID-19 vaccine distribution, as highlighted at the June 2021 G7 Summit, which committed to providing 1 billion doses to low-income countries. This focus on doses overlooks the pace of transmission in low-income settings. To monitor seroprevalence in Kenya, authors began surveillance of blood donors (aged 16-64 years) in April 2020. The national prevalence of SARS-CoV-2 antibodies was estimated at 4.3% in April to June 2020² and 9.1% in August to September 2020. In this article authors estimate seroprevalence for January to March 2021. the adjusted estimate of seroprevalence among those aged 16 to 64 years in Kenya was 48.5% (95% CI, 45.2%-52.1%. The prevalence of SARS-CoV-2 antibodies in blood donors in Kenya increased from 4.3%² to 48.5% over 1 year.