- Virologic features of SARS-CoV-2 infection in children
Data on pediatric COVID-19 has lagged behind adults throughout the pandemic. An understanding of SARS-CoV-2 viral dynamics in children would enable data-driven public health guidance. Respiratory swabs were collected from children with COVID-19. Viral load was quantified by RT-PCR; viral culture was assessed by direct observation of cytopathic effects and semiquantitative viral titers. Correlations with age, symptom duration, and disease severity were analyzed. SARS-CoV-2 whole genome sequences were compared with contemporaneous sequences. 110 children with COVID-19 (median age 10 years, range 2 weeks-21 years) were included in this study. Age did not impact SARS-CoV-2 viral load. Children were most infectious within the first five days of illness, and severe disease did not correlate with increased viral loads. Pediatric SARS-CoV-2 sequences were representative of those in the community and novel variants were identified. Symptomatic and asymptomatic children can carry high quantities of live, replicating SARS-CoV-2, creating a potential reservoir for transmission and evolution of genetic variants. As guidance around social distancing and masking evolves following vaccine uptake in older populations, a clear understanding of SARS-CoV-2 infection dynamics in children is critical for rational development of public health policies and vaccination strategies to mitigate the impact of COVID-19.
- Steroids use in non-oxygen requiring COVID-19 patients: a systematic review and meta-analysis
Corticosteroids have become the mainstay treatment in severe COVID-19. However, its role is mild disease is controversial due to lack of robust scientific evidence. This systematic review and meta-analysis were conducted to assess effect of steroids in mild COVID-19 patients. PubMed, EMBASE, Web of Science and medRxiv were searched from 31 December 2019 to 14 May 2021 for studies that reported effectiveness of steroids in non-oxygen requiring COVID-19 patients in terms of progressing to severe disease, mortality, duration of fever, duration of viral clearance and length of hospital stay (LOHS). Studies on inhalational steroids, case reports and reviews were excluded. Risk of bias (ROB) was assessed by the Cochrane’s ROB tool and ROBANS tool. Quantitative data synthesis was done using the generic inverse variance method. A total of 6411 studies were identified, 2990 articles were screened after exclusion. Seven studies which fit the criteria (involving 2214 non-oxygen requiring COVID-19 patients) were included and analysed. Overall odds of progression to severe disease among the non-oxygen requiring COVID-19 patients receiving steroids was 5.97 [95% confidence interval (CI): 1.27–27.99, I2 = 0%] and odds of death (OR: 1.35, 95% CI: 1.01–1.79; I2= 0%) as compared to the patients not receiving steroids. Mean duration of fever (7.4 days), duration to viral clearance (18.9 days) and LOHS (20.8 days) were significantly higher in the steroid arm, as compared to that in no-steroid arm (6.7, 16.5 and 15.2 days, respectively). Steroids in non-oxygen requiring COVID-19 patients can be more detrimental than beneficial.
- NIH builds large nationwide study population of tens of thousands to support research on long-term effects of COVID-19
The National Institutes of Health awarded nearly $470 million to build a national study population of diverse research volunteers and support large-scale studies on the long-term effects of COVID-19. The NIH REsearching COVID to Enhance Recovery (RECOVER) Initiative made the parent award to New York University (NYU) Langone Health, New York City, which will make multiple sub-awards to more than 100 researchers at more than 30 institutions and serves as the RECOVER Clinical Science Core. This major new award to NYU Langone supports new studies of COVID-19 survivors and leverages existing long-running large cohort studies with an expansion of their research focus. This combined population of research participants from new and existing cohorts, called a meta-cohort, will comprise the RECOVER Cohort. This funding was supported by the American Rescue Plan. NIH launched the RECOVER Initiative to learn why some people have prolonged symptoms (referred to as long COVID) or develop new or returning symptoms after the acute phase of infection from SARS-CoV-2, the virus that causes COVID-19. The most common symptoms include pain, headaches, fatigue, “brain fog,” shortness of breath, anxiety, depression, fever, chronic cough, and sleep problems.
- The COVID-19 Hospitalization Metric in the Pre- and Post-vaccination Eras as a Measure of Pandemic Severity: A Retrospective, Nationwide Cohort Study
Since the early days of the pandemic, COVID-19 hospitalizations have been used as a measure of pandemic severity. However, case definitions do not include assessments of disease severity, which may be impacted by prior vaccination. Purpose of this study was to measure how the severity of respiratory disease changed among inpatients with documented SARS-CoV-2 infection and to measure the impact of vaccination status on these trends, in order to evaluate the accuracy of the metric of “hospitalization plus a positive SARS-CoV-2 test” for tracking pandemic severity. Subjects were VA patients admitted to a VA hospital with a laboratory-confirmed SARS-CoV-2 infection within the 14-days prior to admission or during the hospital admission. Among 47,742 admissions in 38,508 unique patients with laboratory-confirmed SARS-CoV-2, N=28,731 met the criteria for moderate-to-severe COVID-19. The proportion with moderate-to-severe disease prior to widespread vaccine availability was 64.0% (95% CI, 63.1-64.9%) versus 52.0% in the later period (95% CI, 50.9-53.2%), p-value for non-constant effect, <0.001. Disease severity in the vaccine era among hospitalized patients was lower among both unvaccinated (55.0%, 95% CI, 53.7-56.4%) and vaccinated patients (42.6%, 95% CI, 40.6-44.8%). The proportion of hospitalizations that are due to severe COVID-19 has changed with vaccine availability, thus, increasing proportions of mild and asymptomatic cases are included in hospitalization reporting metrics. The addition of simple measures of disease severity to the case definition of a SARS-CoV-2 hospitalization is a straightforward and objective change that should improve the value of the metric for tracking SARS-CoV-2 disease burden.
- High genetic barrier to escape from human polyclonal SARS-CoV-2 neutralizing antibodies
The number and variability of the neutralizing epitopes targeted by polyclonal antibodies in SARS-CoV-2 convalescent and vaccinated individuals are key determinants of neutralization breadth and, consequently, the genetic barrier to viral escape. Using chimeric viruses and antibody-selected viral mutants, authors show that multiple neutralizing epitopes, within and outside the viral receptor binding domain (RBD), are variably targeted by polyclonal plasma antibodies and coincide with sequences that are enriched for diversity in natural SARS-CoV-2 populations. By combining plasma-selected spike substitutions, authors generated synthetic ‘polymutant’ spike proteins that resisted polyclonal antibody neutralization to a similar degree as currently circulating variants of concern (VOC). Importantly, by aggregating VOC-associated and plasma-selected spike substitutions into a single polymutant spike protein, authors show that 20 naturally occurring mutations in SARS-CoV-2 spike are sufficient to confer near-complete resistance to the polyclonal neutralizing antibodies generated by convalescents and mRNA vaccine recipients. Strikingly however, plasma from individuals who had been infected and subsequently received mRNA vaccination, neutralized this highly resistant SARS-CoV-2 polymutant, and also neutralized diverse sarbecoviruses. Thus, optimally elicited human polyclonal antibodies against SARS-CoV-2 should be resilient to substantial future SARS-CoV-2 variation and may confer protection against future sarbecovirus pandemics.
- Considerations in boosting COVID-19 vaccine immune responses
A new wave of COVID-19 cases caused by the highly transmissible delta variant is exacerbating the worldwide public health crisis, and has led to consideration of the potential need for, and optimal timing of, booster doses for vaccinated populations. Although the idea of further reducing the number of COVID-19 cases by enhancing immunity in vaccinated people is appealing, any decision to do so should be evidence-based and consider the benefits and risks for individuals and society. COVID-19 vaccines continue to be effective against severe disease, including that caused by the delta variant. Most of the observational studies on which this conclusion is based are, however, preliminary and difficult to interpret precisely due to potential confounding and selective reporting. Careful and public scrutiny of the evolving data will be needed to assure that decisions about boosting are informed by reliable science more than by politics. Even if boosting were eventually shown to decrease the medium-term risk of serious disease, current vaccine supplies could save more lives if used in previously unvaccinated populations than if used as boosters in vaccinated populations.
- HHS Announces State/territory-coordinated Distribution System for Monoclonal Antibody Therapeutics
The increased incidence of the Delta variant of SARS-CoV-2 has caused a substantial surge in the utilization of monoclonal antibody (mAb) drugs, particularly in areas of the country with low vaccination rates. HHS is committed to helping ensure consistent availability of these critical drugs for current and future patients in all geographic areas of the country. As such, the distribution process for mAbs has been updated. On Monday, September 13, HHS transitioned from a direct ordering process to a state/territory-coordinated distribution system similar to that used for the distribution of mAbs from November 2020 – February 2021. State and territorial health departments know best where product is needed in their areas. Transitioning to a state/territory-coordinated distribution system gives health departments maximum flexibility to get these critical drugs where they are needed most. HHS will determine the weekly amount of mAb products each state and territory receives based on COVID-19 case burden and mAb utilization. State and territorial health departments will subsequently identify which sites in their respective jurisdictions receive product as well as the amount each site receives.
- Daily testing for contacts of individuals with SARS-CoV-2 infection and attendance and SARS-CoV-2 transmission in English secondary schools and colleges: an open-label, cluster-randomised trial
School-based COVID-19 contacts in England have been asked to self-isolate at home, missing key educational opportunities. Authors trialled daily testing of contacts as an alternative to assess whether this resulted in similar control of transmission, while allowing more school attendance. Daily contact testing of school-based contacts was non-inferior to self-isolation for control of COVID-19 transmission, with similar rates of symptomatic infections among students and staff with both approaches. Infection rates in school-based contacts were low, with very few school contacts testing positive. Daily contact testing should be considered for implementation as a safe alternative to home isolation following school-based exposures.
- SARS-CoV-2 Transmission to Masked and Unmasked Close Contacts of University Students with COVID-19 — St. Louis, Missouri, January–May 2021
During January–May 2021, Saint Louis University implemented a modified quarantine protocol that considered mask use when determining which close contacts required quarantine among an almost entirely unvaccinated student population. Compared with only masked exposure, close contacts with any unmasked exposure had higher adjusted odds of a positive test result. Each additional exposure was associated with a 40% increase in odds of a positive test. Universal masking and fewer encounters in close proximity to persons with COVID-19 can limit the spread of SARS-CoV-2 in university settings.
- A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa
The progression of the SARS-CoV-2 pandemic in Africa has so far been heterogeneous and the full impact is not yet well understood. Here, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. Authors show that the epidemics in most countries were initiated by importations predominantly from Europe, which diminished following the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1 and C.1.1. Although distorted by low sampling numbers and blind spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a source for new variants.