Post-Acute Sequelae of Non-COVID-19 Respiratory Viral Infections: A Systematic Review

Respiratory viral infections (RVIs) affect millions annually, yet long-term consequences outside COVID-19 are poorly defined. Post-acute sequelae, encompassing persistent or new physical, cognitive, and mental health impairments, are increasingly recognised as clinically important. We systematically reviewed evidence on post-acute outcomes in adults following non-COVID RVIs to characterise pathogen-specific patterns and highlight areas for future research. Major databases were searched from January 2004 to August 2025 for observational studies reporting symptoms, functional impairment, or new diagnoses ≥ 4 weeks after RVIs. Study characteristics, pathogens, follow-up duration, and organ-specific outcomes were extracted. Risk of bias was evaluated using ROBINS-I, and certainty of evidence was determined with the GRADE approach. Narrative synthesis was performed owing to heterogeneity. Thirteen studies (n = 631,863) met eligibility criteria. Influenza was the most studied pathogen and consistently associated with long-term pulmonary dysfunction, reduced diffusion capacity, dyspnoea, fatigue, and poorer quality of life. Large cohorts corroborated substantial pulmonary morbidity and less frequent cardiovascular and neuropsychiatric burdens. Two RSV cohorts (n = 1553 and n = 471) showed a predominance of cardiovascular sequelae; respiratory and neurological outcomes were less frequent. A single HMPV cohort (n = 92) reported persistent symptoms in 55% of adults at 90-270 days, most commonly dyspnoea, fatigue, and cough. Overall, the available evidence suggests that non-COVID RVIs are associated with post-acute multi-organ sequelae, particularly following severe infection. Nevertheless, evidence remains fragmented due to inconsistent study designs, limited pathogen coverage, and low certainty. Standardised, prospective, pathogen-specific studies are required to refine these preliminary signals and inform clinical follow-up and prevention strategies.