Acute viral respiratory infections are not associated with an increased IMMune Age indeX (IMMAX) four weeks after infection: a prospective observational cohort study

Abstract Background The factors that determine how quickly immunosenescence occurs in individuals are not yet fully understood. Viral infections throughout one’s life span are suggested to be a relevant modulator. Latent chronic infections, such as CMV or EBV, occupy immune space and are associated with advanced immunological ageing as measured by biomarkers. The IMMune Age indeX (IMMAX) is a validated surrogate for the IMM-AGE metric based on flow cytometry. It is currently unknown whether light to moderate acute, community-acquired infections with common viruses in Western Europe provoke an increase in biomarkers assessing an individual’s immunological age. Therefore, this study examined IMMAX changes from pre- to post-viral infection, while additionally exploring IMMAX responses during the acute phase of a respiratory illness. Methods A prospective observational study was conducted involving a cohort of 77 participants aged between 21 and 65 years. Baseline assessment (t0) included recording demographic data and IMMAX calculation. In the event of symptoms of a respiratory infection, blood samples were taken within the first 72 h (t1), after one week (t2) and after four weeks (t3) for IMMAX follow-up assessment. Viral multiplex PCR was performed at t1 to identify the causative pathogen. Additionally, participants who remained clinically healthy for over 6 months underwent a second IMMAX assessment (t4) and acted as a control group. The primary outcome was the change in IMMAX from t0 to t3, while time- and etiology-dependent differences were evaluated using linear mixed-effects modeling. Results Twenty-six participants caught a respiratory infection including human rhinovirus ( n = 9), SARS-CoV-2 ( n = 9), parainfluenza virus ( n = 1) and 7 cases of PCR-negative respiratory illness. Over the confirmed viral infection cohort ( n = 19), IMMAX values transiently increased during the early acute phase of infection, which was no longer observed after recovery. However, subgroup analysis of all cases of acute respiratory illness ( n = 26) revealed a remarkable difference: participants with SARS-CoV-2 infection exhibited significantly higher IMMAX values at t1 and lower IMMAX values at t3 compared to baseline, with all nine participants having fully recovered clinically by t3. Conclusions This observational cohort study prospectively investigates community-acquired infections with concomitant immune age determination. Mild to moderate viral infections followed by complete recovery were not associated with an increased IMMAX score four weeks after infection, regardless of the underlying etiology. Nevertheless, acute SARS-CoV-2 infections lead to distinct shifts in systemic immune cell proportions, highlighting their immunological demands.