Long-term sequelae post-hospitalization for respiratory syncytial virus vs. Omicron SARS-CoV-2 or influenza in adults and children: a retrospective cohort study.

Objective: Risk of long-term sequelae after COVID-19 hospitalization is well documented in adults and children; however, less is known about long-term sequelae after hospitalization for other respiratory viral infections (RVIs), such as respiratory syncytial virus (RSV). We sought to compare long-term sequelae after RSV hospitalization, contrasted against Omicron COVID-19 and influenza, in children and adults.

Methods: This retrospective population-based cohort study in Singapore included all hospitalizations for RSV/influenza from 1 January 2017 to 3 September 2023, and all COVID-19 hospitalizations after Omicron emergence (1 January 2022-3 September 2023). Risks of new-incident diagnoses/symptoms 31-300 days following (a) RSV vs. COVID-19 hospitalization; (b) RSV vs. influenza hospitalization, across multiple organ systems, were estimated using Cox regression, adjusted for between-group sociodemographic and clinical differences using overlap weighting.

Results: 24 340 paediatric RVI hospitalizations (RSV = 8640; influenza = 9400; COVID-19 = 6300) and 82 635 adult RVI hospitalizations (RSV = 1553; influenza = 10 454; COVID-19 = 70 628) were included. In children, post-RSV hospitalization, higher risk and excess burden (EB) per 1000 individuals of any overall new-incident diagnosis were observed when contrasted against COVID-19/influenza (COVID-19: adjusted hazard ratio [aHR] = 1.63 [95% CI: 1.24-2.14], EB = 9.83 [95% CI: 5.26-14.41]; influenza: aHR = 1.76 [95% CI: 1.37-2.28], EB = 10.91 [95% CI: 6.78-15.04]); risks of respiratory sequelae predominated. In adults, though there was no significant difference in overall risk of post-acute sequelae between RSV and COVID-19/influenza, elevated risk of cardiovascular symptoms (aHR = 1.58 [95% CI: 1.13-2.22]) and other neurological disorders (aHR = 1.92 [95% CI: 1.31-2.80]) was observed in RSV hospitalizations vs. COVID-19.

Conclusions: Although risks of predominantly respiratory sequelae were elevated post-RSV hospitalization in children vs. COVID-19 or influenza, higher risk of extra-pulmonary sequelae (cardiovascular/neurological complications) was observed post-RSV hospitalization vs. COVID-19 in adults. Elevated risks at extremes of age highlight the importance of RSV vaccination in these vulnerable groups.