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29 TMPRSS2 inhibitor COVID-19 controlled studies, 25 RCTs
Supplementary Data — TMPRSS2 inhibitors reduce COVID-19 risk: real-time meta analysis of 29 studies
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2+ Ansarin (RCT) 91% 0.09 [0.01-1.59] death 0/39 5/39 bromhexine Improvement, RR [CI] Treatment Control Ansarin (RCT) 89% 0.11 [0.01-0.84] ventilation 1/39 9/39 bromhexine Ansarin (RCT) 82% 0.18 [0.04-0.77] ICU 2/39 11/39 bromhexine CAMELOT Sagent P.. (DB RCT) -152% 2.52 [0.10-61.3] death 1/194 0/101 camostat CAMELOT Sagent P.. (DB RCT) 13% 0.87 [0.32-2.32] progression 10/194 6/101 camostat CAMELOT Sagent P.. (DB RCT) 16% 0.84 [0.60-1.18] viral+ 58/194 36/101 camostat COPS-2003 Parsonnet (DB RCT) -392% 4.92 [0.25-97.5] progression 2/25 0/24 camostat COPS-2003 Parsonnet (DB RCT) 35% 0.65 [0.32-1.33] no recov. 25 (n) 24 (n) camostat COPS-2003 Parsonnet (DB RCT) 86% 0.14 [0.01-2.58] misc. 0/25 3/24 camostat COPS-2003 Parsonnet (DB RCT) 41% 0.59 [0.24-1.43] viral+ 25 (n) 24 (n) camostat Chupp (DB RCT) 0% 1.00 [0.07-15.4] hosp. 1/35 1/35 camostat Chupp (DB RCT) 37% 0.63 [0.36-1.09] no recov. 12/35 19/35 camostat SPIKE-1 Dhaliwal (RCT) 14% 0.86 [0.17-4.45] hosp. 2/14 3/18 camostat CANDLE Kinoshita (DB RCT) 67% 0.33 [0.01-8.05] progression 0/74 1/74 camostat CANDLE Kinoshita (DB RCT) 50% 0.50 [0.16-1.59] oxygen 4/74 8/74 camostat CANDLE Kinoshita (DB RCT) -1% 1.01 [0.72-1.42] no recov. 30/53 29/52 camostat CANDLE Kinoshita (DB RCT) -1% 1.01 [0.71-1.67] viral+ 78 (n) 77 (n) camostat Tobback (RCT) -36% 1.36 [0.15-12.6] hosp. 3/66 1/30 camostat Tobback (RCT) 8% 0.92 [0.46-1.87] no recov. 61 (n) 29 (n) camostat Vila Méndez (RCT) 67% 0.33 [0.01-7.94] oxygen 0/98 1/93 bromhexine Vila Méndez (RCT) 67% 0.33 [0.01-7.94] hosp. 0/98 1/93 bromhexine Vila Méndez (RCT) 71% 0.29 [0.03-2.68] no recov. 1/52 3/45 bromhexine Vila Méndez (RCT) -187% 2.87 [0.12-68.6] no recov. 1/52 0/45 bromhexine Vila Méndez (RCT) -7% 1.07 [0.64-1.77] viral load 98 (n) 93 (n) bromhexine Vila Méndez (RCT) 17% 0.83 [0.41-1.66] viral load 98 (n) 93 (n) bromhexine Vila Méndez (RCT) -41% 1.41 [0.71-2.80] viral load 98 (n) 93 (n) bromhexine Vila Méndez (RCT) 13% 0.87 [0.68-1.11] viral+ 52/98 57/93 bromhexine Vila Méndez (RCT) -14% 1.14 [0.94-1.37] viral+ 73/98 61/93 bromhexine Kim (DB RCT) 8% 0.92 [0.70-1.19] no recov. 161 (n) 162 (n) camostat Kim (DB RCT) 25% 0.75 [0.43-1.30] no recov. 109 (n) 104 (n) camostat Kim (DB RCT) 46% 0.54 [0.28-1.03] no recov. 77 (n) 78 (n) camostat Kim (DB RCT) 40% 0.60 [0.26-1.33] no recov. 109 (n) 104 (n) camostat Kim (DB RCT) 58% 0.42 [0.17-1.03] no recov. 77 (n) 78 (n) camostat Okugawa (RCT) 33% 0.67 [0.50-0.89] viral load 19 (n) 10 (n) nafamostat Okugawa (RCT) 60% 0.40 [0.19-0.83] viral load 19 (n) 10 (n) nafamostat DAWN Tare (DB RCT) 33% 0.67 [0.22-2.09] no recov. 4/19 5/16 camostat DAWN Tare (DB RCT) 23% 0.77 [0.48-1.24] no recov. 11/19 12/16 camostat Li (RCT) 75% 0.25 [0.05-1.35] no disch. 2/12 4/6 bromhexine Li (RCT) 50% 0.50 [0.09-2.73] oxygen 2/12 2/6 bromhexine Mareev (RCT) 11% 0.89 [0.65-1.22] no recov. 33 (n) 33 (n) bromhexine CT2 Mareev (RCT) 39% 0.61 [0.14-0.97] no recov. 14/24 20/21 bromhexine CT2 Mareev (RCT) 8% 0.92 [0.77-1.09] hosp. time 33 (n) 33 (n) bromhexine CT2 Mareev (RCT) 87% 0.13 [0.01-2.25] viral+ 0/17 3/13 bromhexine CT2 Tolouian (RCT) 76% 0.24 [0.01-8.03] death 48 (n) 52 (n) bromhexine Tolouian (RCT) 76% 0.24 [0.01-7.69] no improv. 48 (n) 52 (n) bromhexine Tolouian (RCT) -75% 1.75 [1.13-2.71] viral+ 29/48 18/52 bromhexine Sakr (PSM) 69% 0.31 [0.15-0.60] death 6/61 18/61 camostat Sakr (PSM) 10% 0.90 [0.39-2.06] ventilation 9/61 10/61 camostat Sakr (PSM) -17% 1.17 [0.85-1.61] hosp. time 61 (n) 61 (n) camostat CamoCO-19 Gunst (DB RCT) 18% 0.82 [0.24-2.79] death 8/137 4/68 camostat CamoCO-19 Gunst (DB RCT) 31% 0.69 [0.14-3.44] ventilation 13/137 3/68 camostat CamoCO-19 Gunst (DB RCT) 20% 0.80 [0.34-1.91] ICU 14/137 8/68 camostat CamoCO-19 Gunst (DB RCT) 15% 0.85 [0.62-1.15] no recov. 137 (n) 68 (n) camostat Zhuravel (RCT) 76% 0.24 [0.03-2.08] death 1/52 4/50 nafamostat Zhuravel (RCT) 42% 0.58 [0.23-1.47] no improv. 6/52 10/50 nafamostat Zhuravel (RCT) 42% 0.58 [0.23-1.47] no recov. 6/52 10/50 nafamostat Zhuravel (RCT) 41% 0.59 [0.32-1.09] no recov. 52 (n) 50 (n) nafamostat Inokuchi -27% 1.27 [0.61-2.64] death 121 (n) 15,738 (n) nafamostat DEFINE Quinn (RCT) 0% 1.00 [0.23-4.40] death 3/21 3/21 nafamostat DEFINE Quinn (RCT) -48% 1.48 [0.81-2.69] hosp. time 21 (n) 21 (n) nafamostat Terada (RCT) 54% 0.46 [0.04-4.92] death 1/61 2/56 camostat CT2 Terada (RCT) 8% 0.92 [0.37-2.28] progression 8/61 8/56 camostat CT2 Terada (RCT) 40% 0.60 [0.37-0.97] no disch. 61 (n) 56 (n) camostat CT2 ACOVACT Karolyi (RCT) 72% 0.28 [0.06-1.33] death 2/101 7/100 camostat OT1 ACOVACT Karolyi (RCT) 70% 0.30 [0.10-0.90] ventilation 4/101 13/100 camostat OT1 ACOVACT Karolyi (RCT) 60% 0.40 [0.16-0.98] death/int. 6/101 15/100 camostat OT1 ACOVACT Karolyi (RCT) 18% 0.82 [0.71-0.94] recov. time 101 (n) 100 (n) camostat OT1 ACOVACT Karolyi (RCT) 8% 0.92 [0.86-0.99] recov. time 101 (n) 100 (n) camostat OT1 ACOVACT Karolyi (RCT) 14% 0.86 [0.75-0.98] hosp. time 101 (n) 100 (n) camostat OT1 Soma 80% 0.20 [0.01-4.11] death 0/31 2/33 nafamostat Soma -6% 1.06 [0.51-2.20] severe case 10/31 10/33 nafamostat ACTIV-2 Jilg (RCT) 1% 0.99 [0.06-15.6] death 1/106 1/105 camostat ACTIV-2 Jilg (RCT) -198% 2.98 [0.12-72.4] death 1/109 0/107 camostat ACTIV-2 Jilg (RCT) -18% 1.18 [0.37-3.74] hosp. 6/109 5/107 camostat ACTIV-2 Jilg (RCT) 10% 0.90 [0.79-1.02] progression 85/109 93/107 camostat ACTIV-2 Jilg (RCT) 13% 0.87 [0.46-1.64] no recov. 15/109 17/107 camostat ACTIV-2 Jilg (RCT) 14% 0.86 [0.56-1.30] no recov. 109 (n) 107 (n) camostat ACTIV-2 Jilg (RCT) 14% 0.86 [0.21-3.47] no recov. 109 (n) 107 (n) camostat ACTIV-2 Jilg (RCT) 8% 0.92 [0.54-1.56] no recov. 109 (n) 107 (n) camostat RACONA Seccia (DB RCT) 67% 0.33 [0.02-7.02] death 0/7 1/7 nafamostat RACONA Seccia (DB RCT) 20% 0.80 [0.36-1.77] no recov. 4/7 5/7 nafamostat ASCOT Morpeth (RCT) 55% 0.45 [0.14-1.42] ventilation 4/82 8/73 nafamostat ASCOT Morpeth (RCT) 57% 0.43 [0.13-1.29] progression 4/82 8/73 nafamostat ASCOT Morpeth (RCT) 28% 0.72 [0.36-1.45] no recov. 82 (n) 73 (n) nafamostat RECOVER Bryce (DB RCT) 25% 0.75 [0.18-3.18] death 3/50 4/50 camostat Huh -14% 1.14 [0.31-4.18] cases case control camostat Mikhaylov (RCT) 80% 0.20 [0.01-3.97] hosp. 0/25 2/25 bromhexine Mikhaylov (RCT) 91% 0.09 [0.01-1.56] symp. case 0/25 5/25 bromhexine Mikhaylov (RCT) 71% 0.29 [0.07-1.24] cases 2/25 7/25 bromhexine Tolouian (DB RCT) 33% 0.67 [0.04-10.5] death 0/187 1/185 bromhexine Tolouian (DB RCT) 70% 0.30 [0.05-1.78] hosp. 1/187 6/185 bromhexine Tolouian (DB RCT) 53% 0.47 [0.25-0.87] symp. case 16/187 34/185 bromhexine Tolouian (DB RCT) 50% 0.50 [0.24-0.99] cases 13/187 26/185 bromhexine TMPRSS2 inhibitor COVID-19 outcomes c19 early .org October 2025 1 OT: comparison with other treatment 2 CT: study uses combined treatment Favors TMPRSS2 inh. Favors control
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.
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