Human Metapneumovirus Infection in Adults and Its Role in Differential Diagnosis of COVID-19

Introduction: Human metapneumovirus (HMPV), though commonly perceived as a pediatric pathogen, significantly impacts adults, yet its role in acute respiratory tract infections (ARTIs) remains underappreciated. The COVID-19 pandemic has reshaped respiratory virus epidemiology and amplified the need for comprehensive differential diagnosis. This study aimed to comprehensively investigate the prevalence, clinical characteristics, and post-COVID-19 trends of HMPV infection in adults and to elucidate its critical role in the differential diagnosis of ARTIs by distinguishing it from other common viral pathogens. Methods: This was a retrospective, multicenter study conducted across six hospitals within the Acibadem Hospitals Group in Istanbul, Turkey. Data were collected from two periods: January 2016 to January 2020 (pre-COVID-19) and January 2021 to September 2023 (post-COVID-19), excluding the peak pandemic phase (March 2020 to May 2021). Respiratory samples (sputum, BAL, nasopharyngeal/nasal/throat swabs) were analyzed using multiplex PCR (Seegene RV12-ACE), with an expanded panel including SARS-CoV-2 in the post-COVID-19 era. Demographic data, comorbidities, symptoms, hospitalization, and ICU admission rates were collected. Results: In the post-COVID-19 period, 2197 positive viral panels were recorded, an increase from 1357 in the pre-COVID period, reflecting enhanced testing. HMPV prevalence reached 9.7% post-COVID-19, making it the fourth most common respiratory virus in adults (8.7% of 644 positive adult tests), following SARS-CoV-2 (26.4%), influenza A (21.3%), and rhinovirus (17.5%). The average age of HMPV-infected adults was 52.14 years (18–90 years); 64% were female. While 52% had no comorbidities, common underlying conditions included hypertension (24%), cancer (12%), and diabetes (10%). Weakness (34%), lower respiratory symptoms (16%), and fever (12%) were frequent. A significant proportion of HMPV patients required hospitalization (34%) and ICU admission (18%), with 40% receiving antibiotics. Despite potential severity, the mortality rate was low (2.8%). No significant difference in severity was observed between HMPV monoinfection and co-infected groups (e.g., with influenza A, rhinovirus, SARS-CoV-2, parainfluenza virus 2). Conclusion: Our findings establish HMPV as a significant and increasingly prevalent respiratory pathogen among adults in Istanbul in the post-COVID-19 era. Its non-specific clinical presentation underscores the critical importance of multiplex PCR for accurate differential diagnosis, enabling appropriate patient management and antimicrobial stewardship. While HMPV can lead to severe outcomes requiring hospitalization and ICU admission, particularly in patients with comorbidities, the overall mortality rate remains low. Given the lack of specific antiviral treatments and vaccines, sustained surveillance and continued research into targeted interventions are crucial.