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

October 2026

Proton pump inhibitor COVID-19 outcomes

StudyImprovementRR · 95% CIOutcomeTreatmentControlRelative Risk
Zhou (PSM)−165%2.65 · 1.75–4.00severe case151/524173/2,620 Yao−600%7.00 · 4.57–10.71severe case694 (n)2,330 (n) Yao−2501%26.01 · 14.11–47.95severe case82 (n)2,330 (n) Yao−95%1.95 · 1.09–3.48severe case537 (n)2,330 (n) Liwang−204%3.04 · 1.22–7.60death216 (n)149 (n)LD1 Yan−240%3.40 · 2.00–5.79severe case16/3220/136 Blanc56%0.44 · 0.23–0.82cases63 (n)116 (n) Freedberg (PSM)−34%1.34 · 1.06–1.69death/int.8/84332/1,536 Argenziano1%0.99 · 0.73–1.34ICU38/163198/837 Argenziano−9%1.09 · 1.03–1.15hosp.149/163701/837 Vila-Corcoles−9%1.09 · 0.80–1.50cases11,807 (n)23,129 (n) Lee (PSM)−79%1.79 · 1.30–3.10severe case267 (n)267 (n) Lee (PSM)−63%1.63 · 1.03–2.53severe case267 (n)267 (n) Lee (PSM)10%0.90 · 0.78–1.01cases13,873 (n)13,873 (n) Luxenburger−248%3.48 · 1.29–9.39death12/625/90 Luxenburger−124%2.24 · 1.13–4.45ARDS17/6211/90 Luxenburger−86%1.86 · 1.06–2.83misc.30/6218/90 Almario−179%2.79 · 1.65–4.70cases Almario−267%3.67 · 2.93–4.60cases Almario−115%2.15 · 1.90–2.44cases García-Menaya−228%3.28 · 1.22–9.94death15/545/59 García-Menaya−392%4.92 · 1.06–32.61ICU9/542/59 Mas Romero26%0.74 · 0.38–1.45death11/8221/116 Mas Romero−8%1.08 · 0.89–1.31symp. case58/8276/116 Fan (PSM)−17%1.17 · 0.65–2.90deathn/an/a Fan (PSM)4%0.96 · 0.59–1.55deathn/an/a Fan (PSM)14%0.86 · 0.52–1.45deathn/an/a Fan (PSM)20%0.80 · 0.58–1.11deathn/an/a Fan (PSM)−22%1.22 · 0.93–1.60casesn/an/a Fan (PSM)−8%1.08 · 0.89–1.31casesn/an/a McKeigue−44%1.44 · 1.31–1.58severe casecase-control study Zhang (PSM)−11%1.11 · 0.92–1.33hosp. time29 (n)29 (n) Zhang6%0.94 · 0.57–1.54no disch.35 (n)119 (n) Zhang37%0.63 · 0.40–1.01viral+35 (n)119 (n) Elmunzer13%0.87 · 0.66–1.14death417 (n)1,429 (n) Elmunzer−2%1.02 · 0.73–1.43ventilation417 (n)1,429 (n) Morán Blanco31%0.69 · 0.36–1.33symp. case12/4813/36 Cheung25%0.75 · 0.07–6.00severe case4 (n)948 (n) Liu−127%2.27 · 1.64–3.13death68/22753/459 Jimenez−124%2.24 · 1.80–2.80death1,357 (all patients) Jimenez−118%2.18 · 1.64–2.91death1,357 (all patients) Jimenez−133%2.33 · 1.66–3.27death1,357 (all patients) Israelsen (PSM)5%0.95 · 0.74–1.22death166/3,955189/3,955 Israelsen (PSM)12%0.88 · 0.72–1.08death166/3,955189/3,955 Israelsen (PSM)−8%1.08 · 0.71–1.64ventilation55/3,95555/3,955 Israelsen (PSM)0%1.00 · 0.69–1.45ventilation55/3,95555/3,955 Israelsen (PSM)−5%1.05 · 0.75–1.46ICU92/3,95595/3,955 Israelsen (PSM)3%0.97 · 0.73–1.29ICU92/3,95595/3,955 Israelsen (PSM)−22%1.22 · 1.06–1.40hosp.734/3,955650/3,955 Israelsen (PSM)−13%1.13 · 1.03–1.24hosp.734/3,955650/3,955 Israelsen−8%1.08 · 1.03–1.13casescase-control study Shah3%0.97 · 0.85–1.10death6,262 (n)8,696 (n) Shah−21%1.21 · 0.99–1.48ventilation6,262 (n)8,696 (n) Shah−13%1.13 · 0.99–1.28ICU6,262 (n)8,696 (n) Shah−5%1.05 · 0.97–1.15hosp.6,262 (n)8,696 (n) Ramachandran−92%1.92 · 1.11–2.99death16/4640/249 Ramachandran−80%1.80 · 1.13–2.56progression18/4655/249 Shafrir (PSM)−47%1.47 · 0.77–2.80severe case22/65515/655 Shafrir−16%1.16 · 0.88–1.51severe case Shafrir (PSM)8%0.92 · 0.85–1.00cases880/6,835956/6,835 Shafrir5%0.95 · 0.90–1.01casespopulation-based cohort Wu (PSW)−197%2.97 · 1.63–5.42death1,046 (n)3,588 (n) Wu (PSM)−10%1.10 · 1.01–1.19viral+1,046 (n)3,588 (n) Shupp19%0.81 · 0.54–1.22death448 (n)2,048 (n) Shupp−10%1.10 · 0.83–1.45hosp.448 (n)2,048 (n) Kodvanj7%0.93 · 0.85–1.02death Kodvanj−4%1.04 · 0.97–1.13hosp. Kim (PSM)−28%1.28 · 0.48–3.37death9/4377/437 Kim (PSM)−75%1.75 · 0.51–5.79ventilation7/4374/437 Kim (PSM)−150%2.50 · 0.79–7.65ICU10/4374/437 Kim (PSM)−21%1.21 · 0.61–2.39progression17/43714/437 Kim (PSM)37%0.63 · 0.53–0.75cases226/9,913341/9,913 Shokri−81%1.81 · 1.01–3.25severe case121 (n)549 (n) Shokri−138%2.38 · 1.41–3.34severe case40 (n)549 (n) Shokri−30%1.30 · 0.64–1.96severe case81 (n)549 (n) Elkanzi−17%1.17 · 0.76–1.81death36/15929/150 Elkanzi−25%1.25 · 1.00–1.56ICU90/15968/150 Elkanzi−126%2.26 · 0.82–6.27progression12/1595/150 Elkanzi−33%1.33 · 1.09–1.62progression104/15974/150 Elkanzi19%0.81 · 0.60–1.10hosp. time159 (n)150 (n) Patil−48%1.48 · 1.32–1.66death4,566 (n)15,349 (n) Patil−119%2.19 · 1.91–2.50ARDS4,566 (n)15,349 (n) Patil−88%1.88 · 1.73–2.05misc.4,566 (n)15,349 (n) Patil−73%1.73 · 1.48–2.02oxygen4,566 (n)15,349 (n) Gramont (PSW)−59%1.59 · 1.18–2.14severe case424 (n)410 (n) Cheung−49%1.49 · 1.13–1.98deathpopulation-based cohort Cheung−54%1.54 · 1.21–1.97deathpopulation-based cohort Cheung21%0.79 · 0.23–2.81deathpopulation-based cohort Cheung−36%1.36 · 0.79–2.35severe casepopulation-based cohort Cheung−57%1.57 · 1.24–1.98severe casepopulation-based cohort Cheung21%0.79 · 0.27–2.28severe casepopulation-based cohort Cheung−20%1.20 · 1.09–1.32hosp.population-based cohort Cheung−20%1.20 · 1.08–1.32hosp.population-based cohort Cheung−21%1.21 · 0.92–1.60hosp.population-based cohort Cheung−9%1.09 · 1.05–1.13casespopulation-based cohort Cheung−7%1.07 · 1.05–1.10casespopulation-based cohort Cheung−11%1.11 · 1.07–1.15casespopulation-based cohort Hirsch15%0.85 · 0.64–1.13hosp.116,209 (all patients) Hirsch15%0.85 · 0.76–0.94cases116,209 (all patients) Al-Momani−100%2.00 · 0.46–8.71death3/694/184 Al-Momani−48%1.48 · 0.51–4.27ventilation5/699/184 Al-Momani−25%1.25 · 0.57–2.77ICU8/6917/184 Zeng−46%1.46 · 1.05–2.03deathpopulation-based cohort Zeng−33%1.33 · 1.09–1.61severe casepopulation-based cohort Zeng−8%1.08 · 0.99–1.17casespopulation-based cohort Pinto−57%1.57 · 0.90–2.74hosp.15/10438/414 Bianconi−37%1.37 · 0.95–1.97death/ICU447 (n)640 (n) Bianconi−96%1.96 · 1.39–2.75misc.447 (n)640 (n) Bianconi−67%1.67 · 1.21–2.31misc.447 (n)640 (n) Nowak−58%1.58 · 1.24–2.01death/hosp.2,947 (n)2,877 (n)
00.511.52+
1 LD: comparison with low dose treatment
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← PPIs
reduce risk
PPIs
increase risk →
Fig. S1. All outcomes.