September 23, 2021

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.

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.

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.

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. 

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.