A standardised protocol for assessment of relative SARS-CoV-2 variant severity, with application to severity risk for COVID-19 cases infected with Omicron BA.1 compared to Delta variants in six European countries (preprint)

Several SARS-CoV-2 variants that evolved during the COVID-19 pandemic have appeared to differ in severity, based on analyses of single-country datasets. With decreased SARS-CoV-2 testing and sequencing, international collaborative studies will become increasingly important for timely assessment of the severity of newly emerged variants. The Joint WHO Regional Office for Europe and ECDC Infection Severity Working Group was formed to produce and pilot a standardised study protocol to estimate relative variant case-severity in settings with individual-level SARS-CoV-2 testing and COVID-19 outcome data during periods when two variants were co-circulating. To assess feasibility, the study protocol and its associated statistical analysis code was applied by local investigators in Denmark, England, Luxembourg, Norway, Portugal and Scotland to assess the case-severity of Omicron BA.1 relative to Delta cases. After pooling estimates using meta-analysis methods (random effects estimates), the risk of hospital admission (adjusted hazard ratio [aHR]=0.41, 95% CI 0.31-0.54), ICU admission (aHR=0.12, 95% CI 0.05-0.27), and death (aHR=0.31, 95% CI 0.28-0.35) was lower for Omicron BA.1 compared to Delta cases. The aHRs varied by age group and vaccination status. In conclusion, this study has demonstrated the feasibility of conducting variant severity analyses in a multinational collaborative framework. The results add further evidence for the reduced severity of the Omicron BA.1 variant.

Impact of COVID-19 related maternal stress on fetal brain development: A Multimodal MRI study (preprint)

Background: Disruptions in perinatal care and support due to the COVID-19 pandemic was an unprecedented but significant stressor among pregnant women. Various neuro-structural differences have been reported among fetuses and infants born during the pandemic compared to pre-pandemic counterparts. The relationship between maternal stress due to pandemic related disruptions and fetal brain is yet unexamined. Methods: Pregnant participants with healthy pregnancies were prospectively recruited in 2020-2022 in the greater Los Angeles Area. Participants completed multiple self-report assessments for experiences of pandemic related disruptions, perceived stress, and coping behaviors and underwent fetal MRI. Maternal perceived stress exposures were correlated with quantitative multimodal MRI measures of fetal brain development using multivariate models. Results: Fetal brain stem volume increased with increased maternal perception of pandemic related stress positively correlated with normalized fetal brainstem volume (suggesting accelerated brainstem maturation). In contrast, increased maternal perception of pandemic related stress correlated with reduced global fetal brain temporal functional variance (suggesting reduced functional connectivity). Conclusions: We report alterations in fetal brainstem structure and global functional fetal brain activity associated with increased maternal stress due to pandemic related disruptions, suggesting altered fetal programming. Long term follow-up studies are required to better understand the sequalae of these early multi-modal brain disruptions among infants born during the COVID-19 pandemic.

Early warning and rapid public health response to prevent COVID-19 outbreaks in long-term care facilities (LTCF) by monitoring SARS-CoV-2 RNA in LTCF site-specific sewage samples and assessment of antibodies response in this population: prospective study protocol

IntroductionThe COVID-19 pandemic has an excessive impact on residents in long-term care facilities (LTCF), causing high morbidity and mortality. Early detection of presymptomatic and asymptomatic COVID-19 cases supports the timely implementation of effective outbreak control measures but repetitive screening of residents and staff incurs costs and discomfort. Administration of vaccines is key to controlling the pandemic but the robustness and longevity of the antibody response, correlation of neutralising antibodies with commercial antibody assays, and the efficacy of current vaccines for emerging COVID-19 variants require further study. We propose to monitor SARS-CoV-2 in site-specific sewage as an early warning system for COVID-19 in LTCF and to study the immune response of the staff and residents in LTCF to COVID-19 vaccines.Methods and analysisThe study includes two parts: (1) detection and quantification of SARS-CoV-2 in LTCF site-specific sewage samples using a molecular assay followed by notification of Public Health within 24 hours as an early warning system for appropriate outbreak investigation and control measures and cost–benefit analyses of the system and (2) testing for SARS-CoV-2 antibodies among staff and residents in LTCF at various time points before and after COVID-19 vaccination using commercial assays and neutralising antibody testing performed at a reference laboratory.Ethics and disseminationEthics approval was obtained from the University of Alberta Health Research Ethics Board with considerations to minimise risk and discomforts for the participants. Early recognition of a COVID-19 case in an LTCF might prevent further transmission in residents and staff. There was no direct benefit identified to the participants of the immunity study. Anticipated dissemination of information includes a summary report to the immunity study participants, sharing of study data with the scientific community through the Canadian COVID-19 Immunity Task Force, and prompt dissemination of study results in meeting s and manuscripts in peer-reviewed journals.