Long-Term Outcomes of SARS-CoV-2 Variants and Other Respiratory Infections: Evidence from the Virus Watch Prospective Cohort in England

Abstract

AbstractBackgroundGiven the considerable prevalence of long-term sequelae following SARS-CoV-2 infection, understanding pathogen-related factors that influence long-term outcomes is warranted. We aimed to compare the likelihood of long-term symptoms for SARS-CoV-2 variants, other acute respiratory infections (ARIs) and non-infected individuals.MethodData were from 5,630 individuals participating in Virus Watch, a prospective community cohort study of SARS-CoV-2 epidemiology in England. We used logistic regression to compare the predicted probability of developing long-term symptoms (>2 months duration) during different variant dominance periods according to infection status (SARS-CoV-2, other ARI, or no infection), adjusting for confounding by demographic and clinical factors and vaccination status.ResultsPredicted probability of long-term sequelae was greater following SARS-CoV-2 infection during the Wild Type (adjusted predicted probability (PP) 0.28, 95% confidence interval (CI) =0.14-0.43), Alpha (PP= 0.28, 95% CI =0.14-0.42), Delta (PP= 0.34, 95% CI=0.25-0.43) and Omicron BA.1 periods (PP= 0.27, 95% CI =0.22-0.33) compared to later Omicron sub-variants (PP range from 0.11, 95% CI 0.08-0.15 to 0.14, 95% CI 0.10-0.18). While differences between SARS-CoV-2 and other ARIs (PP range 0.08, 95% CI 0.04-0.11 to 0.23, 95% CI 0.18-0.28) varied by period, estimates for long-term symptoms following both infection types substantially exceeded those for non-infected participants (PP range 0.01, 95% CI 0.00,0.02 to 0.03, 95% CI 0.01-0.06) across all variant periods.ConclusionsBetween-variant differences influenced the likelihood of post-infection sequelae for SARS-CoV-2, with lower predicted probabilities for recent Omicron sub-variants similar to those for other contemporaneous ARIs. Both SARS-CoV-2 and other ARIs were associated with long-term symptom development, and further aetiological investigation including between-pathogen comparison is recommended.