COVID-19 Pandemic Waves and 2024-2025 Winter Season in Relation to Angiotensin-Converting Enzyme Inhibitors, Angiotensin Receptor Blockers and Amantadine

Abstract

Early pandemic reports suggested improved outcomes inhypertensive COVID-19 patients treated with angiotensin-converting enzyme inhibitors(ACEI) or amantadine. This study evaluates their impact on disease progression.Methods: We analyzed 55,936 infected patients (March 2020–January 2025) and 2024hospital admissions within a free-access Barcelona metropolitan health consortium (n =192,651 as of March 2025). Hospitalizations, stratified by polypharmacy level (nT), werecompared via Chi-square tests. ICU admissions and length of stay in hospitalized patientswere assessed during the first month of key waves: initial A2a + B3a + B9 (n = 184, March2020), Delta (n = 158, July 2021), Omicron21K (n = 142, January 2022), and Omicron 24F (n= 8, January 2025). Results: Non-survivors were predominantly aged >60 years (96.3%) inthe first wave and >70 years (100%) in Delta/Omicron waves. Post-vaccination, mortalitydecreased in high-comorbidity groups, though hospitalizations/ICU admissions inyounger patients surpassed first-wave levels during Delta. Vaccinated ACEI/ARB-treatedpatients showed reduced hospitalizations across all polypharmacy groups: OR(noACEI/ACEI) = 1.21 (≥2 nT) to 4.26 (1 nT, p = 0.014); OR (noARB/ARB) = 1.24 (≥8 nT) to1.74 (2–7 nT, p = 0.01). No hospitalizations occurred in amantadine-treated patients aged<70. Conclusions: These findings suggest a potential protective effect of ACEI, ARBs, andamantadine against severe COVID-19 and support the safety and continuity of thesetreatments. Multicentric studies incorporating post-COVID syndrome data are needed tovalidate these observations if hospitalizations persist.