Supplementary Data — Proton Pump Inhibitors increase COVID-19 risk: real-time meta analysis of 40 studies

@CovidAnalysis, December 2025, Version 27V27
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Zhou (PSM) -165% 2.65 [1.75-4.00] severe case 151/524 173/2,620 Improvement, RR [CI] Treatment Control Yao -600% 7.00 [4.57-10.7] severe case 694 (n) 2,330 (n) Yao -2501% 26.01 [14.11-48.0] severe case 82 (n) 2,330 (n) Yao -95% 1.95 [1.09-3.48] severe case 537 (n) 2,330 (n) Liwang -204% 3.04 [1.22-7.60] death 216 (n) 149 (n) LD​1​ Yan -240% 3.40 [2.00-5.79] severe case 16/32 20/136 Blanc 56% 0.44 [0.23-0.82] cases 63 (n) 116 (n) Freedberg (PSM) -34% 1.34 [1.06-1.69] death/int. 8/84 332/1,536 Argenziano 1% 0.99 [0.73-1.34] ICU 38/163 198/837 Argenziano -9% 1.09 [1.03-1.15] hosp. 149/163 701/837 Vila-Corcoles -9% 1.09 [0.80-1.50] cases 11,807 (n) 23,129 (n) Lee (PSM) -79% 1.79 [1.30-3.10] severe case 267 (n) 267 (n) Lee (PSM) -63% 1.63 [1.03-2.53] severe case 267 (n) 267 (n) Lee (PSM) 10% 0.90 [0.78-1.01] cases 13,873 (n) 13,873 (n) Luxenburger -248% 3.48 [1.29-9.39] death 12/62 5/90 Luxenburger -124% 2.24 [1.13-4.45] ARDS 17/62 11/90 Luxenburger -86% 1.86 [1.06-2.83] misc. 30/62 18/90 Almario -179% 2.79 [1.65-4.70] cases Almario -267% 3.67 [2.93-4.60] cases Almario -115% 2.15 [1.90-2.44] cases García-Menaya -228% 3.28 [1.22-9.94] death 15/54 5/59 García-Menaya -392% 4.92 [1.06-32.6] ICU 9/54 2/59 Mas Romero 26% 0.74 [0.38-1.45] death 11/82 21/116 Mas Romero -8% 1.08 [0.89-1.31] symp. case 58/82 76/116 Fan (PSM) -17% 1.17 [0.65-2.90] death n/a n/a Fan (PSM) 4% 0.96 [0.59-1.55] death n/a n/a Fan (PSM) 14% 0.86 [0.52-1.45] death n/a n/a Fan (PSM) 20% 0.80 [0.58-1.11] death n/a n/a Fan (PSM) -22% 1.22 [0.93-1.60] cases n/a n/a Fan (PSM) -8% 1.08 [0.89-1.31] cases n/a n/a McKeigue -44% 1.44 [1.31-1.58] severe case case control Zhang (PSM) -11% 1.11 [0.92-1.33] hosp. time 29 (n) 29 (n) Zhang 6% 0.94 [0.57-1.54] no disch. 35 (n) 119 (n) Zhang 37% 0.63 [0.40-1.01] viral+ 35 (n) 119 (n) Elmunzer 13% 0.87 [0.66-1.14] death 417 (n) 1,429 (n) Elmunzer -2% 1.02 [0.73-1.43] ventilation 417 (n) 1,429 (n) Morán Blanco 31% 0.69 [0.36-1.33] symp. case 12/48 13/36 Cheung 25% 0.75 [0.07-6.00] severe case 4 (n) 948 (n) Liu -127% 2.27 [1.64-3.13] death 68/227 53/459 Jimenez -124% 2.24 [1.80-2.80] death 1,357 (all patients) Jimenez -118% 2.18 [1.64-2.91] death 1,357 (all patients) Jimenez -133% 2.33 [1.66-3.27] death 1,357 (all patients) Israelsen (PSM) 5% 0.95 [0.74-1.22] death 166/3,955 189/3,955 Israelsen (PSM) 12% 0.88 [0.72-1.08] death 166/3,955 189/3,955 Israelsen (PSM) -8% 1.08 [0.71-1.64] ventilation 55/3,955 55/3,955 Israelsen (PSM) 0% 1.00 [0.69-1.45] ventilation 55/3,955 55/3,955 Israelsen (PSM) -5% 1.05 [0.75-1.46] ICU 92/3,955 95/3,955 Israelsen (PSM) 3% 0.97 [0.73-1.29] ICU 92/3,955 95/3,955 Israelsen (PSM) -22% 1.22 [1.06-1.40] hosp. 734/3,955 650/3,955 Israelsen (PSM) -13% 1.13 [1.03-1.24] hosp. 734/3,955 650/3,955 Israelsen -8% 1.08 [1.03-1.13] cases case control Shah 3% 0.97 [0.85-1.10] death 6,262 (n) 8,696 (n) Shah -21% 1.21 [0.99-1.48] ventilation 6,262 (n) 8,696 (n) Shah -13% 1.13 [0.99-1.28] ICU 6,262 (n) 8,696 (n) Shah -5% 1.05 [0.97-1.15] hosp. 6,262 (n) 8,696 (n) Ramachandran -92% 1.92 [1.11-2.99] death 16/46 40/249 Ramachandran -80% 1.80 [1.13-2.56] progression 18/46 55/249 Shafrir (PSM) -47% 1.47 [0.77-2.80] severe case 22/655 15/655 Shafrir -16% 1.16 [0.88-1.51] severe case Shafrir (PSM) 8% 0.92 [0.85-1.00] cases 880/6,835 956/6,835 Shafrir 5% 0.95 [0.90-1.01] cases population-based cohort Wu (PSW) -197% 2.97 [1.63-5.42] death 1,046 (n) 3,588 (n) Wu (PSM) -10% 1.10 [1.01-1.19] viral+ 1,046 (n) 3,588 (n) Shupp 19% 0.81 [0.54-1.22] death 448 (n) 2,048 (n) Shupp -10% 1.10 [0.83-1.45] hosp. 448 (n) 2,048 (n) Kodvanj 7% 0.93 [0.85-1.02] death Kodvanj -4% 1.04 [0.97-1.13] hosp. Kim (PSM) -28% 1.28 [0.48-3.37] death 9/437 7/437 Kim (PSM) -75% 1.75 [0.51-5.79] ventilation 7/437 4/437 Kim (PSM) -150% 2.50 [0.79-7.65] ICU 10/437 4/437 Kim (PSM) -21% 1.21 [0.61-2.39] progression 17/437 14/437 Kim (PSM) 37% 0.63 [0.53-0.75] cases 226/9,913 341/9,913 Shokri -81% 1.81 [1.01-3.25] severe case 121 (n) 549 (n) Shokri -138% 2.38 [1.41-3.34] severe case 40 (n) 549 (n) Shokri -30% 1.30 [0.64-1.96] severe case 81 (n) 549 (n) Elkanzi -17% 1.17 [0.76-1.81] death 36/159 29/150 Elkanzi -25% 1.25 [1.00-1.56] ICU 90/159 68/150 Elkanzi -126% 2.26 [0.82-6.27] progression 12/159 5/150 Elkanzi -33% 1.33 [1.09-1.62] progression 104/159 74/150 Elkanzi 19% 0.81 [0.60-1.10] hosp. time 159 (n) 150 (n) Patil -48% 1.48 [1.32-1.66] death 4,566 (n) 15,349 (n) Patil -119% 2.19 [1.91-2.50] ARDS 4,566 (n) 15,349 (n) Patil -88% 1.88 [1.73-2.05] misc. 4,566 (n) 15,349 (n) Patil -73% 1.73 [1.48-2.02] oxygen 4,566 (n) 15,349 (n) Gramont (PSW) -59% 1.59 [1.18-2.14] severe case 424 (n) 410 (n) Cheung -49% 1.49 [1.13-1.98] death population-based cohort Cheung -54% 1.54 [1.21-1.97] death population-based cohort Cheung 21% 0.79 [0.23-2.81] death population-based cohort Cheung -36% 1.36 [0.79-2.35] severe case population-based cohort Cheung -57% 1.57 [1.24-1.98] severe case population-based cohort Cheung 21% 0.79 [0.27-2.28] severe case population-based cohort Cheung -20% 1.20 [1.09-1.32] hosp. population-based cohort Cheung -20% 1.20 [1.08-1.32] hosp. population-based cohort Cheung -21% 1.21 [0.92-1.60] hosp. population-based cohort Cheung -9% 1.09 [1.05-1.13] cases population-based cohort Cheung -7% 1.07 [1.05-1.10] cases population-based cohort Cheung -11% 1.11 [1.07-1.15] cases population-based cohort Hirsch 15% 0.85 [0.64-1.13] hosp. 116,209 (all patients) Hirsch 15% 0.85 [0.76-0.94] cases 116,209 (all patients) Al-Momani -100% 2.00 [0.46-8.71] death 3/69 4/184 Al-Momani -48% 1.48 [0.51-4.27] ventilation 5/69 9/184 Al-Momani -25% 1.25 [0.57-2.77] ICU 8/69 17/184 Zeng -46% 1.46 [1.05-2.03] death population-based cohort Zeng -33% 1.33 [1.09-1.61] severe case population-based cohort Zeng -8% 1.08 [0.99-1.17] cases population-based cohort Pinto -57% 1.57 [0.90-2.74] hosp. 15/104 38/414 Bianconi -37% 1.37 [0.95-1.97] death/ICU 447 (n) 640 (n) Bianconi -96% 1.96 [1.39-2.75] misc. 447 (n) 640 (n) Bianconi -67% 1.67 [1.21-2.31] misc. 447 (n) 640 (n) Nowak -58% 1.58 [1.24-2.01] death/hosp. 2,947 (n) 2,877 (n) Proton pump inhibitor COVID-19 outcomes c19early.org December 2025 ​1​ LD: comparison with low dose treatment Favors PPIs Favors control
Fig. S1. All outcomes.