Lifting Universal Masking in Schools - Covid-19 Incidence among Students and Staff.

BACKGROUND: In February 2022, Massachusetts rescinded a statewide universal masking policy in public schools, and many Massachusetts school districts lifted masking requirements during the subsequent weeks. In the greater Boston area, only two school districts - the Boston and neighboring Chelsea districts - sustained masking requirements through June 2022. The staggered lifting of masking requirements provided an opportunity to examine the effect of universal masking policies on the incidence of coronavirus disease 2019 (Covid-19) in schools. METHODS: We used a difference-in-differences analysis for staggered policy implementation to compare the incidence of Covid-19 among students and staff in school districts in the greater Boston area that lifted masking requirements with the incidence in districts that sustained masking requirements during the 2021-2022 school year. Characteristics of the school districts were also compared. RESULTS: Before the statewide masking policy was rescinded, trends in the incidence of Covid-19 were similar across school districts. During the 15 weeks after the statewide masking policy was rescinded, the lifting of masking requirements was associated with an additional 44.9 cases per 1000 students and staff (95% confidence interval, 32.6 to 57.1), which corresponded to an estimated 11,901 cases and to 29.4% of the cases in all districts during that time. Districts that chose to sustain masking requirements longer tended to have school buildings that were older and in worse condition and to have more students per classroom than districts that chose to lift masking requirements earlier. In addition, these districts had higher percentages of low-income students, students with disabilities, and students who were English-language learners, as well as higher percentages of Black and Latinx students and staff. Our results support universal masking as an important strategy for reducing Covid-19 incidence in schools and loss of in-person school days. As such, we believe that universal masking may be especially useful for mitigating effects of structural racism in schools, including potential deepening of educational inequities. CONCLUSIONS: Among school districts in the greater Boston area, the lifting of masking requirements was associated with an additional 44.9 Covid-19 cases per 1000 students and staff during the 15 weeks after the statewide masking policy was rescinded.

Profound Treg perturbations correlate with COVID-19 severity.

The hallmark of severe COVID-19 is an uncontrolled inflammatory response, resulting from poorly understood immunological dysfunction. We hypothesized that perturbations in FoxP3+ T regulatory cells (Treg), key enforcers of immune homeostasis, contribute to COVID-19 pathology. Cytometric and transcriptomic profiling revealed a distinct Treg phenotype in severe COVID-19 patients, with an increase in Treg proportions and intracellular levels of the lineage-defining transcription factor FoxP3, correlating with poor outcomes. These Tregs showed a distinct transcriptional signature, with overexpression of several suppressive effectors, but also proinflammatory molecules like interleukin (IL)-32, and a striking similarity to tumor-infiltrating Tregs that suppress antitumor responses. Most marked during acute severe disease, these traits persisted somewhat in convalescent patients. A screen for candidate agents revealed that IL-6 and IL-18 may individually contribute different facets of these COVID-19-linked perturbations. These results suggest that Tregs may play nefarious roles in COVID-19, by suppressing antiviral T cell responses during the severe phase of the disease, and by a direct proinflammatory role.

SARS-CoV-2 viral load is associated with increased disease severity and mortality.

The relationship between SARS-CoV-2 viral load and risk of disease progression remains largely undefined in coronavirus disease 2019 (COVID-19). Here, we quantify SARS-CoV-2 viral load from participants with a diverse range of COVID-19 disease severity, including those requiring hospitalization, outpatients with mild disease, and individuals with resolved infection. We detected SARS-CoV-2 plasma RNA in 27% of hospitalized participants, and 13% of outpatients diagnosed with COVID-19. Amongst the participants hospitalized with COVID-19, we report that a higher prevalence of detectable SARS-CoV-2 plasma viral load is associated with worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of inflammation, including C-reactive protein and IL-6. SARS-CoV-2 viral loads, especially plasma viremia, are associated with increased risk of mortality. Our data show that SARS-CoV-2 viral loads may aid in the risk stratification of patients with COVID-19, and therefore its role in disease pathogenesis should be further explored.

Establishment of a pediatric COVID-19 biorepository: unique considerations and opportunities for studying the impact of the COVID-19 pandemic on children.

BACKGROUND: COVID-19, the disease caused by the highly infectious and transmissible coronavirus SARS-CoV-2, has quickly become a morbid global pandemic. Although the impact of SARS-CoV-2 infection in children is less clinically apparent, collecting high-quality biospecimens from infants, children, and adolescents in a standardized manner during the COVID-19 pandemic is essential to establish a biologic understanding of the disease in the pediatric population. This biorepository enables pediatric centers world-wide to collect samples uniformly to drive forward our understanding of COVID-19 by addressing specific pediatric and neonatal COVID-19-related questions. METHODS: A COVID-19 biospecimen collection study was implemented with strategic enrollment guidelines to include patients seen in urgent care clinics and hospital settings, neonates born to SARS-CoV-2 infected mothers, and asymptomatic children. The methodology described here, details the importance of establishing collaborations between the clinical and research teams to harmonize protocols for patient recruitment and sample collection, processing and storage. It also details modifications required for biobanking during a surge of the COVID-19 pandemic. RESULTS: Considerations and challenges facing enrollment of neonatal and pediatric cohorts are described. A roadmap is laid out for successful collection, processing, storage and database management of multiple pediatric samples such as blood, nasopharyngeal and oropharyngeal swabs, sputum, saliva, tracheal aspirates, stool, and urine. Using this methodology, we enrolled 327 participants, who provided a total of 972 biospecimens. CONCLUSIONS: Pediatric biospecimens will be key in answering questions relating to viral transmission by children, differences between pediatric and adult viral susceptibility and immune responses, the impact of maternal SARS-CoV-2 infection on fetal development, and factors driving the Multisystem Inflammatory Syndrome in Children. The specimens in this biorepository will allow necessary comparative studies between children and adults, help determine the accuracy of current pediatric viral testing techniques, in addition to, understanding neonatal exposure to SARS-CoV-2 infection and disease abnormalities. The successful establishment of a pediatric biorepository is critical to provide insight into disease pathogenesis, and subsequently, develop future treatment and vaccination strategies.

Establishment of a Pediatric COVID-19 Biorepository: Unique Considerations and Opportunities for Studying the Impact of the COVID-19 Pandemic on Children.

Background : COVID-19, the disease caused by the highly infectious and transmissible coronavirus SARS-CoV-2, has quickly become a morbid global pandemic. Although the impact of SARS-CoV-2 infection in children is less clinically apparent, collecting high-quality biospecimens from infants, children and adolescents in a standardized manner during the COVID-19 pandemic is essential to establish a biologic understanding of the disease in the pediatric population. This biorepository enables pediatric centers world-wide to collect samples in a standardized manner to drive forward our understanding of COVID-19 by addressing specific pediatric and neonatal COVID-19-related questions. Methods : A broad study was implemented with strategic enrollment guidelines to include patients seen in urgent care clinics and hospital settings, neonates born to SARS-CoV-2 infected mothers, and asymptomatic children. The methodology described here, details the importance of establishing collaborations between the clinical and research teams to harmonize protocols for patient recruitment and sample collection, processing and storage. Results : Considerations and challenges facing enrollment of neonatal and pediatric cohorts are described. A roadmap is laid out for successful collection, processing, storage and database management of multiple pediatric samples such as blood, nasopharyngeal and oropharyngeal swabs, sputum, saliva, tracheal aspirates, stool, and urine. Using this methodology, we enrolled 327 participants, who provided a total of 972 biospecimens. Conclusions : Pediatric biospecimens will be key in answering questions relating to viral transmission by children, differences between pediatric and adult viral susceptibility, and, immune responses, the impact of maternal SARS-CoV-2 infection on fetal development, and factors driving the Multisystem Inflammatory Syndrome in Children. The specimens in this biorepository will allow necessary comparative studies between children and adults, help determine the accuracy of current pediatric viral testing techniques, in addition to, understanding neonatal exposure to SARS-CoV-2 infection and disease abnormalities. The successful establishment of a pediatric biorepository is critical to provide insight into disease pathogenesis, and subsequently, develop future treatment and vaccination strategies.