Severity of Omicron (B.1.1.529) and Delta (B.1.1.617.2) SARS-CoV-2 infection among hospitalised adults: a prospective cohort study

BackgroundThere is an urgent public health need to evaluate disease severity in adults hospitalised with Delta and Omicron SARS-CoV-2 variant infections. However, limited data exist assessing severity of disease in adults hospitalised with Omicron SARS-CoV-2 infections, and to what extent patient-factors, including vaccination, age, frailty and pre-existing disease, affect variant-dependent disease severity. MethodsA prospective cohort study of adults ([&ge;]18 years of age) hospitalised with acute lower respiratory tract disease at acute care hospitals in Bristol, UK conducted over 10-months. Delta or Omicron SARS-CoV-2 infection was defined by positive SARS-CoV-2 PCR and variant identification or inferred by dominant circulating variant. We constructed adjusted regression analyses to assess disease severity using three different measures: FiO2 >28% (fraction inspired oxygen), World Health Organization (WHO) outcome score >5 (assessing need for ventilatory support), and hospital length of stay (LOS) >3 days following admission for Omicron or Delta infection. FindingsIndependent of other variables, including vaccination, Omicron variant infection in hospitalised adults was associated with lower severity than Delta. Risk reductions were 58%, 67%, and 16% for supplementary oxygen with >28% FiO2 [Relative Risk (RR)=0{middle dot}42 (95%CI: 0{middle dot}34-0{middle dot}52), P<0.001], WHO outcome score >5 [RR=0{middle dot}33 (95%CI: 0{middle dot}21-0{middle dot}50), P<0.001], and to have had a LOS>3 days [RR=0{middle dot}84 (95%CI: 0{middle dot}76-0{middle dot}92), P<0.001]. Younger age and vaccination with two or three doses were also independently associated with lower COVID-19 severity. InterpretationWe provide reassuring evidence that Omicron infection results in less serious adverse outcomes than Delta in hospitalised patients. Despite lower severity relative to Delta, Omicron infection still resulted in substantial patient and public health burden and an increased admission rate of older patients with Omicron which counteracts some of the benefit arising from less severe disease. FundingAvonCAP is an investigator-led project funded under a collaborative agreement by Pfizer. RESEARCH IN CONTEXTO_ST_ABSEvidence before this studyC_ST_ABSThe burden of COVID-19 on hospital services is determined by the prevalence and severity of SARS-CoV-2 variants, and modified by individual factors such as age, frailty and vaccination status. Real world data suggest that vaccine effectiveness is lower and may wane faster over time against symptomatic disease with Omicron (B.1.1.529) than with Delta (B.1.617.2) SARS-CoV-2 variant. However, numbers of hospitalisations as a case proportion during the Omicron wave have been considerably lower than previous waves. Several reports have compared the risk of hospitalisation or severe disease based on SARS-CoV-2 variant, some suggesting that Omicron is probably less severe than Delta in vaccinated and unvaccinated individuals. Added value of this studyThis study provides robust data assessing the relative severity of Delta and Omicron SARS-CoV-2 variants in patients admitted to hospital, including the first analysis assessing risk for any positive pressure ventilatory support, as well as risk of supplementary oxygen requirement and extended hospital admission, that may guide resource planning in hospitals. We found evidence that infection with Omicron was associated with a milder clinical course following hospital admission than that caused by Delta and that vaccination was independently associated with lower in-hospital disease severity using these three separate severity measures. Specifically, compared to Delta, Omicron-related hospitalizations were 58%, 67%, and 16% less likely to require high flow oxygen >28% FiO2, positive pressure ventilatory support or more critical care, and to have a hospital stay lasting more than three days, respectively. This study reports the considerable morbidity resulting from Omicron infection, with 18% of Omicron admissions requiring oxygen supplementation FiO2 >28%, 6% requiring positive pressure ventilation, 62% needing hospitalization [&ge;]four days, and 4% in-hospital mortality. In determining the reduced requirement of increased oxygen requirement and total positive pressure requirement, including non-invasive ventilation, this analysis should contribute to future hospital care and service planning assessments. Implications of all the available evidenceThe risk of severe outcomes following SARS-CoV-2 infection is substantially lower for Omicron than for Delta, with greater reductions for more severe disease outcomes. Significant variation in risk occurs with age and vaccination status, with older and unvaccinated individuals remaining at particular risk of adverse outcome. These results highlight the importance of maintaining high levels of vaccine coverage in patient groups at risk of severe disease. The impact of lower severity Omicron-related hospitalization must be balanced against increased transmissibility and overall higher numbers of infections with this variant and there remains a substantial patient and public health burden. The increased admission rate of older patients with Omicron counteracts some of the benefit arising from less severe disease. Despite the risk reduction in high level oxygen supplementation requirement and high dependency care with Omicron compared to earlier variants at the individual level, healthcare systems could still be overwhelmed.