Abstract
BACKGROUND: Early evidence from a nursing home in Yepes (Toledo, Spain) indicated that antihistamines combined with azithromycin prevented deaths and hospitalizations during the first COVID-19 wave. Subsequent data from the Consorci Sanitari de Terrassa (CST) showed that patients chronically taking antihistamines had significantly reduced hospital admissions and mortality. However, a concerning rise in long COVID incidence (2-5%) after the third infection and a doubling of thrombosis rates in patients over 60 were observed. OBJECTIVE: This study aimed to determine whether chronic antihistamine prescription is associated with a reduction in long COVID syndrome and thrombotic events. METHODS: We analyzed anonymized data from the CST population (n = 192,651 as of March 2025). Variables included age, gender, chronic antihistamine use, number of chronic treatments (nT), COVID-19 vaccination status, SARS-CoV-2 infection history, long COVID (LC) incidence, and aggregated thrombotic events. Odds ratios (OR) were calculated using chi-square tests. RESULTS: The prevalence of LC increased progressively with successive infections in the non-antihistamine group. No significant differences were found with the antihistamine group, which presented no LC cases among the 52 patients with three documented infections. Thrombotic events were significantly less frequent in antihistamine users with at least one chronic prescription (p < 0.0001). CONCLUSIONS: Results suggest a protective effect of antihistamines against thrombotic events. While confirmation via multicenter, randomized trials is needed, a pragmatic approach using antihistamines could be considered for symptomatic patients in the early stage of infection.