ABSTRACT
Objectives Sotrovimab is one of several therapeutic agents that have been licensed to treat people at risk of severe outcomes following COVID-19 infection. However, there are concerns that it has reduced efficacy to treat people with the BA.2 sub-lineage of the Omicron (B.1.1.529) SARS-CoV-2 variant. We compared individuals with the BA.1 or BA.2 sub-lineage of the Omicron variant treated Sotrovimab in the community to assess their risk of hospital admission. Methods We performed a retrospective cohort study of individuals treated with Sotrovimab in the community and either had BA.1 or BA.2 variant classification. Results Using a Stratified Cox regression model it was estimated that the hazard ratios (HR) of hospital admission with a length of stay of two or more days was 1.17 for BA.2 compared to BA.1 (95% CI 0.74-1.86) and for such admissions where COVID-19 ICD-10 codes was recorded the HR was 0.98 (95% CI 0.58-1.65). Conclusion These results suggest that the risk of hospital admission is similar between BA.1 and BA.2 cases treated with Sotrovimab in the community.
Subject(s)
COVID-19ABSTRACT
Summary Some COVID-19 patients are unable to clear their infection or are at risk of severe disease, requiring treatment with neutralising monoclonal antibodies (nmAb) and/or antivirals. The rapid roll-out of novel therapeutics means there is limited understanding of the likely genetic barrier to drug resistance. Unprecedented genomic surveillance of SARS-CoV-2 in the UK has enabled a genome-first approach to the detection of emerging drug resistance. Here we report the accrual of mutations in Delta and Omicron cases treated with casirivimab+imdevimab and sotrovimab respectively. Mutations occur within the epitopes of the respective nmAbs. For casirivimab+imdevimab these are present on contiguous raw reads, simultaneously affecting both components. Using surface plasmon resonance and pseudoviral neutralisation assays we demonstrate these mutations reduce or completely abrogate antibody affinity and neutralising activity, suggesting they are driven by immune evasion. In addition, we show that some mutations also reduce the neutralising activity of vaccine-induced serum.
Subject(s)
COVID-19ABSTRACT
BackgroundThere is an urgent need to better understand whether individuals who have recovered from COVID-19 are protected from future SARS-CoV-2 infection. MethodsA large multi-centre prospective cohort was recruited from publicly funded hospital staff in the UK. Participants attended regular SARS-CoV-2 PCR and antibody testing (every 2-4 weeks) and completed fortnightly questionnaires on symptoms and exposures. At enrolment, participants were assigned to either the positive cohort (antibody positive or prior PCR/antibody test positive) or negative cohort (antibody negative, not previously known to be PCR/antibody positive). Potential reinfections were clinically reviewed and classified according to case definitions (confirmed, probable, possible (subdivided by symptom-status)) depending on hierarchy of evidence. Individuals in the primary infection were excluded from this analysis if infection was confirmed by antibody only. Reinfection rates in the positive cohort were compared against new PCR positives in the negative cohort using a mixed effective multivariable logistic regression analysis. FindingsBetween 18 June and 09 November 2020, 44 reinfections (2 probable, 42 possible) were detected in the baseline positive cohort of 6,614 participants, collectively contributing 1,339,078 days of follow-up. This compares with 318 new PCR positive infections and 94 antibody seroconversions in the negative cohort of 14,173 participants, contributing 1,868,646 days of follow-up. The incidence density per 100,000 person days between June and November 2020 was 3.3 reinfections in the positive cohort, compared with 22.4 new PCR confirmed infections in the negative cohort. The adjusted odds ratio was 0.17 for all reinfections (95% CI 0.13-0.24) compared to PCR confirmed primary infections. The median interval between primary infection and reinfection was over 160 days. InterpretationA prior history of SARS-CoV-2 infection was associated with an 83% lower risk of infection, with median protective effect observed five months following primary infection. This is the minimum likely effect as seroconversions were not included. FundingDepartment of Health and Social Care and Public Health England, with contributions from the Scottish, Welsh and Northern Irish governments.
Subject(s)
COVID-19ABSTRACT
BACKGROUND The overall risk of reinfection in individuals who have previously had COVID-19 is unknown. To determine if prior SARS-CoV-2 infection (as determined by at least one positive commercial antibody test performed in a laboratory) in healthcare workers confers future immunity to reinfection, we are undertaking a large-scale prospective longitudinal cohort study of healthcare staff across the United Kingdom. METHODS Population and Setting: staff members of healthcare organisations working in hospitals in the UK At recruitment, participants will have their serum tested for anti-SARS-CoV-2 at baseline and using these results will be initially allocated to either antibody positive or antibody negative cohorts. Participants will undergo antibody and viral RNA testing at 1-4 weekly intervals throughout the study period, and based on these results may move between cohorts. Any results from testing undertaken for other reasons (e.g. symptoms, contact tracing etc.) or prior to study entry will also be included. Individuals will complete enrolment and fortnightly questionnaires on exposures and symptoms. Follow-up will be for at least 12 months from study entry. Outcome: The primary outcome of interest is a reinfection with SARS -CoV-2 during the study period. Secondary outcomes will include incidence and prevalence (both RNA and antibody) of SARS-CoV-2, viral genomics, viral culture, symptom history and antibody/neutralising antibody titres. CONCLUSION This large study will help us to understand the impact of the presence of antibodies on the risk of reinfection with SARS-CoV-2; the results will have substantial implications in terms of national and international policy, as well as for risk management of contacts of COVID-19 cases. TRIAL REGISTRATION IRAS ID 284460, HRA and Health and Care Research Wales approval granted 22 May 2020.