Supplementary Data — Antihistamine H1RAs reduce COVID-19 risk: real-time meta analysis of 17 studies

0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ ACCROS-I Valerio-.. (DB RCT) 61% 0.39 [0.24-0.63] no recov. 61 (n) 40 (n) chlorpheniramine Improvement, RR [CI] Treatment Control ACCROS-I Valerio-.. (DB RCT) 67% 0.33 [0.09-1.24] no recov. 3/61 6/40 chlorpheniramine ACCROS-I Valerio-.. (DB RCT) 89% 0.11 [0.01-0.87] no recov. 1/61 6/40 chlorpheniramine ACCROS-I Valerio-.. (DB RCT) 53% 0.47 [0.22-1.02] no recov. 10/61 14/40 chlorpheniramine ACCROS-I Valerio-.. (DB RCT) 67% 0.33 [0.06-1.71] no recov. 2/61 4/40 chlorpheniramine ACCROS-I Valerio-.. (DB RCT) 59% 0.41 [0.14-1.16] no recov. 5/61 8/40 chlorpheniramine ACCROS-I Valerio-.. (DB RCT) 74% 0.26 [0.12-0.58] PASC 55 (n) 46 (n) chlorpheniramine ACCROS-II Valerio-Pascua 54% 0.46 [0.36-0.58] recov. time 330 (n) 330 (n) chlorpheniramine Sanchez-.. (DB RCT) 87% 0.13 [0.01-2.46] hosp. 0/32 2/13 chlorpheniramine CARVIN Klussmann (DB RCT) 66% 0.34 [0.01-7.95] no recov. 0/29 1/30 azelastine CARVIN Klussmann (DB RCT) 67% 0.33 [0.01-7.79] no recov. 0/31 1/30 azelastine CARVIN Klussmann (DB RCT) 13% 0.87 [0.57-1.33] no recov. 29 (n) 30 (n) azelastine CARVIN Klussmann (DB RCT) -33% 1.33 [0.81-2.17] no recov. 31 (n) 30 (n) azelastine CARVIN Klussmann (DB RCT) 14% 0.86 [0.67-1.09] viral load 29 (n) 30 (n) azelastine CARVIN Klussmann (DB RCT) 7% 0.93 [0.74-1.16] viral load 31 (n) 30 (n) azelastine CARVIN Klussmann (DB RCT) 22% 0.78 [0.62-0.99] viral+ 29 (n) 30 (n) azelastine CARVIN Klussmann (DB RCT) 6% 0.94 [0.77-1.15] viral+ 31 (n) 30 (n) azelastine Mura (PSM) 25% 0.75 [0.39-1.46] death 88 (n) 88 (n) Salvucci 29% 0.71 [0.51-1.01] PASC 10/14 13/13 LONG COVID CARVIN-II Meiser (DB RCT) 12% 0.88 [0.64-1.20] recovery 122 (n) 129 (n) azelastine CARVIN-II Meiser (DB RCT) 6% 0.94 [0.91-0.96] viral load 122 (n) 129 (n) azelastine CARVIN-II Meiser (DB RCT) 2% 0.98 [0.97-0.99] viral load 122 (n) 129 (n) azelastine CARVIN-II Meiser (DB RCT) 1% 0.99 [0.98-1.00] viral load 122 (n) 129 (n) azelastine CARVIN-II Meiser (DB RCT) 3% 0.97 [0.96-0.98] viral+ 122 (n) 129 (n) azelastine Vila-Corcoles 61% 0.39 [0.12-1.21] cases Hoertel 58% 0.42 [0.25-0.71] death 138 (n) 7,207 (n) hydroxyzine Vila-Córcoles 53% 0.47 [0.22-1.01] cases Reznikov 34% 0.66 [0.58-0.75] cases n/a n/a Reznikov 37% 0.63 [0.44-0.90] cases n/a n/a Reznikov 17% 0.83 [0.62-1.12] cases n/a n/a Reznikov 48% 0.52 [0.16-1.64] cases n/a n/a Reznikov 52% 0.48 [0.34-0.67] cases n/a n/a Reznikov 43% 0.57 [0.42-0.78] cases n/a n/a Reznikov 62% 0.38 [0.11-1.32] cases n/a n/a Reznikov -33% 1.33 [0.50-3.57] cases n/a n/a Reznikov 34% 0.66 [0.48-0.89] cases n/a n/a Reznikov 26% 0.74 [0.55-0.99] cases n/a n/a Reznikov 35% 0.65 [0.52-0.79] cases n/a n/a Reznikov 14% 0.86 [0.71-1.05] cases n/a n/a Reznikov 74% 0.26 [0.07-1.01] cases n/a n/a Reznikov 78% 0.22 [0.05-1.00] cases n/a n/a Reznikov 36% 0.64 [0.33-1.25] cases n/a n/a Reznikov 8% 0.92 [0.47-1.75] cases n/a n/a Reznikov 59% 0.41 [0.25-0.68] cases n/a n/a Reznikov 29% 0.71 [0.44-1.15] cases n/a n/a McKeigue -30% 1.30 [1.13-1.51] severe case case control Sánchez-Rico 46% 0.54 [0.31-0.89] death 18/164 1,571/14,939 hydroxyzine Monserrat .. (PSM) 80% 0.20 [0.02-0.93] death n/a n/a loratadine Hunt 43% 0.57 [0.49-0.66] death 260/7,600 1,352/18,908 Loucera 40% 0.60 [0.43-0.84] death 251 (n) 15,717 (n) Loucera 30% 0.70 [0.48-1.00] death 251 (n) 15,717 (n) Loucera 51% 0.49 [0.32-0.77] death 233 (n) 15,735 (n) Hoertel -7% 1.07 [0.88-1.31] death 962 (n) 4,810 (n) desloratadine/hydroxyzine Hoertel 8% 0.92 [0.49-1.76] death 11/94 62/470 desloratadine/hydroxyzine Hoertel -9% 1.09 [0.89-1.35] death 104/962 591/4,810 desloratadine/hydroxyzine Antihistamine H1RA COVID-19 outcomes c19early.org December 2025 Favors H1RAs Favors control
Fig. S1. All outcomes.
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Fig. S2. Comparison of results for RCTs versus observational studies. For COVID-19 treatments, there is no significant difference between the results of RCTs and observational studies. Observational studies do not systematically over or underestimate efficacy. For high-cost treatments, there is a non-significant trend towards RCTs showing greater efficacy.