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

ABSTRACT

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.