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28 acetaminophen COVID-19 controlled studies, 2 RCTs
Supplementary Data — Acetaminophen increases COVID-19 risk: real-time meta analysis of 27 studies
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2+ Rinott -473% 5.73 [0.30-109] death 3/85 0/49 OT1 Improvement, RR [CI] Treatment Control Rinott -534% 6.34 [0.84-47.6] oxygen 11/85 1/49 OT1 Lapi (ES) -15% 1.15 [0.92-1.43] death/hosp. n/a n/a Lapi (ES) -29% 1.29 [0.61-2.73] death/hosp. n/a n/a Sharif -77% 1.77 [0.39-8.09] death 9/361 2/142 Chen -32% 1.32 [0.98-1.78] PASC 98/232 39/122 LONG COVID Chen -1% 1.01 [0.67-1.52] PASC 16/41 121/313 LONG COVID Rahman -23% 1.23 [0.96-1.56] hosp. 84/244 100/356 Ravichandran (PSM) -2700% 28.00 [3.91-200] oxygen 28/72 1/72 OT1 Ravichandran -75% 1.75 [1.48-2.06] recov. time 72 (n) 72 (n) OT1 Ravichandran -117% 2.17 [1.72-2.72] recov. time 72 (n) 72 (n) OT1 Ravichandran -167% 2.67 [2.00-3.56] recov. time 72 (n) 72 (n) OT1 Manjani -220% 3.20 [1.51-6.82] death 64/388 7/136 Manjani -434% 5.34 [1.98-14.4] ventilation 388 (n) 136 (n) Manjani -244% 3.44 [1.49-8.54] progression 132 (n) 136 (n) Manjani -201% 3.01 [1.40-7.07] progression 256 (n) 136 (n) Manjani -100% 2.00 [1.33-3.02] hosp. time 388 (n) 136 (n) Lerner -27% 1.27 [0.96-1.68] death 5,783 (all patients) Ravichandran (RCT) -43% 1.43 [1.14-1.78] no recov. 77/107 52/103 OT1 Ravichandran (RCT) -3925% 40.25 [2.47-657] progression 20/107 0/103 OT1 Ravichandran (RCT) -133% 2.33 [1.82-3.00] recov. time 107 (n) 103 (n) OT1 Ravichandran (RCT) -75% 1.75 [1.48-2.06] recov. time 107 (n) 103 (n) OT1 Ravichandran (RCT) -75% 1.75 [1.48-2.06] recov. time 107 (n) 103 (n) OT1 Ravichandran (RCT) -20% 1.20 [0.93-1.56] viral+ 43/60 37/62 OT1 Lapi -75% 1.75 [1.40-2.18] death/hosp. n/a n/a Abolhassani -56% 1.56 [0.58-4.18] death 3/6 8/25 Baldia (ICU) 12% 0.88 [0.72-1.07] death 1,166 (n) 1,480 (n) ICU patients Baldia (ICU) 14% 0.86 [0.72-1.03] death 1,166 (n) 1,480 (n) ICU patients Stufano -19% 1.19 [0.70-2.02] PASC 11/23 23/57 Sobhy (DB RCT) -110% 2.10 [1.05-4.20] ICU 21/90 10/90 OT1 Sobhy (DB RCT) -110% 2.10 [1.05-4.20] oxygen 21/90 10/90 OT1 Sobhy (DB RCT) -36% 1.36 [1.07-1.73] hosp. time 90 (n) 90 (n) OT1 Sobhy (DB RCT) -33% 1.33 [0.31-5.79] no recov. 4/90 3/90 OT1 Sobhy (DB RCT) -75% 1.75 [0.77-3.97] no recov. 14/90 8/90 OT1 Sobhy (DB RCT) -92% 1.92 [1.05-3.52] no recov. 25/90 13/90 OT1 Sobhy (DB RCT) -70% 1.70 [1.06-2.72] no recov. 34/90 20/90 OT1 Blanc -51% 1.51 [0.82-2.84] cases 60 (n) 119 (n) Kolin -23% 1.23 [1.05-1.43] cases 397,064 (all patients) Park (PSM) 25% 0.75 [0.35-1.59] death 12/397 16/397 OT1 Park (PSM) 38% 0.62 [0.19-1.89] ventilation 5/397 8/397 OT1 Gálvez-Barrón -47% 1.47 [0.66-3.33] death 43 (n) 60 (n) Gálvez-Barrón 23% 0.77 [0.35-1.71] severe case 43 (n) 60 (n) Reese (PSM) -61% 1.61 [1.40-1.84] death 20,826 (n) 20,826 (n) Reese (PSM) -816% 9.16 [8.72-9.63] severe case 20,826 (n) 20,826 (n) Chandan (PSM) -18% 1.18 [0.83-1.64] death 71/8,595 79/8,595 OT1 CT2 Chandan (PSM) -27% 1.27 [0.90-1.75] cases 8,595 (n) 8,595 (n) OT1 CT2 Oh 2% 0.98 [0.38-2.49] death 58 (n) 7,655 (n) Leal 7% 0.93 [0.91-0.96] cases n/a n/a Moreno-Martos -29% 1.29 [1.27-1.32] hosp. Moreno-Martos -52% 1.52 [1.28-1.79] hosp. 103/178 196/514 Moreno-Martos -5% 1.05 [0.91-1.22] hosp. 87/144 360/626 Moreno-Martos 22% 0.78 [0.63-0.98] hosp. 64/319 1,585/6,181 Moreno-Martos -16% 1.16 [1.13-1.20] hosp. Moreno-Martos -57% 1.57 [1.50-1.65] hosp. 1,090/1,868 3,414/9,188 Moreno-Martos -47% 1.47 [1.40-1.54] hosp. 1,397/2,875 3,214/9,735 MacFadden -48% 1.48 [1.44-1.51] cases n/a n/a Campbell (PSW) -1% 1.01 [0.99-1.02] death 2,074 (n) 20,311 (n) Campbell (PSW) 0% 1.00 [0.99-1.02] death 2,074 (n) 20,311 (n) Xie -5% 1.05 [0.70-1.56] hosp. population-based cohort OT1 Xie 3% 0.97 [0.72-1.29] cases population-based cohort OT1 Kim (PSM) -71% 1.71 [0.69-4.24] death 12/162 7/162 OT1 Kim (PSM) -14% 1.14 [0.42-3.08] ventilation 8/162 7/162 OT1 Kim (PSM) 40% 0.60 [0.15-2.47] ICU 3/162 5/162 OT1 Kim (PSM) -9% 1.09 [0.64-1.86] oxygen 24/162 22/162 OT1 Ritsinger -21% 1.21 [1.17-1.25] death 24,641 (n) 20,225 (n) Acetaminophen COVID-19 outcomes c19 earlyMay 2025 1 OT: comparison with other treatment 2 CT: study uses combined treatment Favors acetaminophen Favors control
Figure 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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