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21 fluvoxamine COVID-19 controlled studies, 10 RCTs
 
Supplementary Data — Fluvoxamine reduces COVID-19 risk: real-time meta analysis of 21 studies 
 0 
0.25 
0.5 
0.75 
1 
1.25 
1.5 
1.75 
2+ STOP COVID Lenze (DB RCT) 93% 0.07 [0.01-0.52] 1,200mg progression 0/80 6/72 Improvement, RR [CI] Dose (4d) Treatment Control STOP COVID Lenze (DB RCT) 82% 0.18 [0.05-0.65] 1,200mg hosp. 1/80 5/72 Seftel (QR) 72% 0.28 [0.01-6.68] 500mg death 0/77 1/48 Seftel (QR) 84% 0.16 [0.01-3.29] 500mg death/ICU 0/77 2/48 Seftel (QR) 94% 0.06 [0.01-0.37] 500mg hosp. 0/77 6/48 Seftel (QR) 99% 0.01 [0.00-0.21] 500mg no recov. 0/77 29/48 STOP COVID 2 Reiersen (DB RCT) -201% 3.01 [0.12-73.6] 800mg oxygen 1/272 0/275 STOP COVID 2 Reiersen (DB RCT) 33% 0.67 [0.24-1.87] 800mg oxygen 6/272 9/275 STOP COVID 2 Reiersen (DB RCT) 38% 0.62 [0.16-2.46] 800mg oxygen 3/164 6/205 STOP COVID 2 Reiersen (DB RCT) 9% 0.91 [0.38-2.20] 800mg hosp. 9/272 10/275 STOP COVID 2 Reiersen (DB RCT) 12% 0.88 [0.42-1.81] 800mg progression 13/272 15/275 Seo (SB RCT) 0% 1.00 [0.15-6.57] 800mg progression 2/26 2/26 Seo (SB RCT) 34% 0.66 [0.06-6.73] 800mg progression 1/19 2/25 Seo (SB RCT) 13% 0.87 [0.71-1.06] 800mg progression 26 (n) 26 (n) COVID-OUT Bramante (DB RCT) -11% 1.11 [0.33-3.61] 400mg death/hosp. 6/329 5/324 OT​1 ​  COVID-OUT Bramante (DB RCT) -16% 1.16 [0.58-2.25] 400mg progression 18/329 15/324 OT​1 ​  COVID-OUT Bramante (DB RCT) 2% 0.98 [0.29-3.37] 400mg hosp. 5/329 5/324 OT​1 ​  COVID-OUT Bramante (DB RCT) 2% 0.98 [0.29-3.37] 400mg hosp. 5/329 5/324 OT​1 ​  COVID-OUT Bramante (DB RCT) 5% 0.95 [0.72-1.25] 400mg progression 79/329 80/321 OT​1 ​  Pineda 94% 0.06 [0.01-0.52] 800mg death 1/594 4/63 Pineda 73% 0.27 [0.14-0.54] 800mg oxygen 15/594 13/63 Pineda 51% 0.49 [0.26-0.95] 800mg hosp. 23/594 11/63 Pineda -71% 1.71 [0.94-3.14] 800mg hosp. time 23 (n) 11 (n) Farahani (DB RCT) 51% 0.49 [0.24-1.02] 400mg PASC 42 (n) 43 (n) LONG COVID Farahani (DB RCT) 44% 0.56 [0.23-1.37] 400mg PASC 6/42 11/43 LONG COVID Farahani (DB RCT) 62% 0.38 [0.11-1.35] 400mg PASC 3/42 8/43 LONG COVID Farahani (DB RCT) 52% 0.48 [0.25-0.95] 400mg PASC 9/42 19/43 LONG COVID Farahani (DB RCT) 49% 0.51 [0.14-1.91] 400mg PASC 3/42 6/43 LONG COVID Farahani (DB RCT) 59% 0.41 [0.08-2.00] 400mg PASC 2/42 5/43 LONG COVID Farahani (DB RCT) -17% 1.17 [0.47-2.94] 400mg PASC 8/42 7/43 LONG COVID Farahani (DB RCT) 8% 0.92 [0.42-2.04] 400mg PASC 9/42 10/43 LONG COVID Farahani (DB RCT) 74% 0.26 [0.03-2.20] 400mg PASC 1/42 4/43 LONG COVID Farahani (DB RCT) 85% 0.15 [0.02-1.14] 400mg PASC 1/42 7/43 LONG COVID Farahani (DB RCT) 37% 0.63 [0.29-1.36] 400mg PASC 8/42 13/43 LONG COVID Farahani (DB RCT) 27% 0.73 [0.25-2.12] 400mg PASC 5/42 7/43 LONG COVID Farahani (DB RCT) 6% 0.94 [0.75-1.17] 400mg PASC 32/42 35/43 LONG COVID TOGETHER Reis (DB RCT) -200% 3.00 [0.12-73.5] 800mg death 1/738 0/738 CT​2 ​  TOGETHER Reis (DB RCT) 12% 0.88 [0.32-2.40] 800mg hosp. 7/738 8/738 CT​2 ​  TOGETHER Reis (DB RCT) 50% 0.50 [0.25-0.92] 800mg progression 13/738 27/738 CT​2 ​  EFFaCo Siripongbo.. (RCT) -2% 1.02 [0.26-4.00] 400mg oxygen 4/162 4/165 EFFaCo Siripongbo.. (RCT) -22% 1.22 [0.38-3.93] 400mg hosp. 6/162 5/165 Tsiakalos 67% 0.33 [0.01-7.84] 800mg ICU 0/53 1/50 Tsiakalos 84% 0.16 [0.02-1.26] 800mg hosp. 1/53 6/50 Tsiakalos 86% 0.14 [0.02-0.74] 800mg progression 2/53 8/50 Fluvoxa Siripongboonsitti 59% 0.41 [0.02-9.98] 400mg death 0/234 1/518 Fluvoxa Siripongboonsitti -48% 1.48 [0.25-8.77] 400mg ventilation 2/234 3/518 Fluvoxa Siripongboonsitti 26% 0.74 [0.15-3.63] 400mg ICU 2/234 6/518 Fluvoxa Siripongboonsitti -67% 1.67 [1.10-2.54] 400mg oxygen 34/234 45/518 Fluvoxa Siripongboonsitti 42% 0.58 [0.32-1.05] 400mg progression 13/217 49/475 Fluvoxa Siripongboonsitti 35% 0.65 [0.43-0.99] 400mg progression 23/166 88/413 Fluvoxa Siripongboonsitti 33% 0.67 [0.51-0.89] 400mg progression 51/217 132/377 Fluvoxa Siripongboonsitti -48% 1.48 [0.25-8.77] 400mg progression 2/234 3/518 Fluvoxa Siripongboonsitti 34% 0.66 [0.59-0.75] 400mg no recov. 234 (n) 518 (n) Fluvoxa Siripongboonsitti -8% 1.08 [1.00-1.17] 400mg no recov. 234 (n) 518 (n) Fluvoxa Siripongboonsitti -3% 1.03 [0.95-1.12] 400mg no recov. 234 (n) 518 (n) Fluvoxa Siripongboonsitti -4% 1.04 [0.91-1.19] 400mg viral+ 130/210 218/365 Wannigama (RCT) 98% 0.02 [0.00-0.34] 500mg ventilation 0/162 32/336 Wannigama (RCT) 98% 0.02 [0.00-0.40] 500mg ventilation 0/162 27/336 Wannigama (RCT) 97% 0.03 [0.00-0.56] 500mg ventilation 0/162 19/336 Wannigama (RCT) 89% 0.11 [0.06-0.21] 500mg oxygen 9/162 171/336 Wannigama (RCT) 100% 0.00 [0.00-0.07] 500mg oxygen 0/162 150/336 Wannigama (RCT) 99% 0.01 [0.00-0.09] 500mg oxygen 0/162 117/336 Wannigama (RCT) 94% 0.06 [0.03-0.11] 500mg hosp. 9/162 321/336 Wannigama (RCT) 98% 0.02 [0.00-0.40] 500mg hosp. 0/162 27/336 Wannigama (RCT) 97% 0.03 [0.00-0.56] 500mg hosp. 0/162 19/336 Wannigama (RCT) 40% 0.60 [0.53-0.68] 500mg PASC 97/162 336/336 TOGETHER Reis (DB RCT) 30% 0.70 [0.37-1.26] 800mg death 17/741 25/756 TOGETHER Reis (DB RCT) 91% 0.09 [0.01-0.47] 800mg death 1/548 12/618 TOGETHER Reis (DB RCT) 22% 0.78 [0.46-1.28] 800mg ventilation 26/741 34/756 TOGETHER Reis (DB RCT) 22% 0.78 [0.61-1.03] 800mg hosp. 75/741 97/756 TOGETHER Reis (DB RCT) 32% 0.68 [0.52-0.88] 800mg hosp./ER 79/741 119/756 TOGETHER Reis (DB RCT) 31% 0.69 [0.53-0.90] 800mg hosp./ER 78/740 115/752 TOGETHER Reis (DB RCT) 66% 0.34 [0.21-0.54] 800mg hosp./ER 541 (n) 609 (n) TOGETHER Reis (DB RCT) -49% 1.49 [0.94-2.38] 800mg viral+ 167/207 163/221 Calusic (ICU) 42% 0.58 [0.36-0.94] 1,200mg death 30/51 39/51 ICU patients Kirenga 68% 0.32 [0.19-0.53] 800mg death 29/94 126/222 Kirenga 53% 0.47 [0.23-0.97] 800mg recovery 94 (n) 222 (n) ACTIV-6 Stewart (DB RCT) 31% 0.69 [0.27-1.21] 700mg progression 14/589 21/586 ACTIV-6 Stewart (DB RCT) 34% 0.66 [0.23-1.16] 700mg clin. ord. 589 (n) 586 (n) ACTIV-6 Stewart (DB RCT) -15% 1.15 [0.51-1.83] 700mg clin. ord. 589 (n) 586 (n) ACTIV-6 Stewart (DB RCT) 6% 0.94 [0.29-1.74] 700mg clin. ord. 589 (n) 586 (n) ACTIV-6 Stewart (DB RCT) -1% 1.01 [0.92-1.12] 700mg no recov. 589 (n) 586 (n) ACTIV-6 Stewart (DB RCT) 49% 0.51 [0.05-5.64] 700mg hosp. 1/589 2/586 Oskotsky (PSM) -58% 1.58 [0.42-5.93] n/a death 2/11 19/165 Oskotsky (PSM) 26% 0.74 [0.55-0.99] n/a death 48/481 956/7,215 Fritz 19% 0.81 [0.26-2.22] n/a hosp./ER 4/17 1,896/20,457 Fritz 12% 0.88 [0.79-0.99] n/a hosp./ER 707/3,414 1,896/20,457 Fritz 12% 0.88 [0.77-0.99] n/a hosp./ER 559/2,744 1,896/20,457 Fritz 10% 0.90 [0.81-0.99] n/a hosp./ER 971/4,577 1,896/20,457 Diaz (PSM) 28% 0.72 [0.63-0.81] n/a cases 4,558 (n) 4,558 (n) Trkulja (PSM) 27% 0.73 [0.35-1.55] n/a death Trkulja (PSM) -37% 1.37 [0.56-3.33] n/a hosp. Visos-Varela -103% 2.03 [0.24-17.4] n/a death case control Visos-Varela -395% 4.95 [0.34-71.4] n/a ICU case control Visos-Varela 40% 0.60 [0.19-1.92] n/a hosp. case control Visos-Varela 32% 0.68 [0.18-2.50] n/a progression case control Visos-Varela 12% 0.88 [0.54-1.43] n/a cases case control Fluvoxamine COVID-19 outcomes c19 early .org October 2025 ​1 ​  OT: comparison with other treatment ​2 ​  CT: study uses combined treatment Favors fluvoxamine 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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