Analysis of the Effect of Proton-Pump Inhibitors on the Course of COVID-19

Figures & data

Figure 1 Study cohort.

Table 1 Baseline Data Among the Enrolled Cases of COVID-19

	PPI Group (n=35)	Control Group (n=119)	P
Age (years)	50(35–65)	52(36–64)	0.947
Sex,male (%)	18(51.4)	62(52.1)	0.944
HPT (%)	7(20)	28(23.5)	0.661
DM (%)	2(5.7)	10(8.4)	0.870
CVR (%)	2(5.7)	5(4.2)	1.000
COPD (%)	1(2.9)	2(1.7)	0.541
CLD (%)	1(2.9)	3(2.5)	1.000
CGD (%)	0(0)	2(1.7)	1.000
CKD (%)	2(5.7)	0(0)	0.051
MT (%)	0(0)	3(2.5)	1.000
NPLI	3(2–5)	4(2–5)	0.660
The onset times (days)	3(2–6)	4(2–7)	0.418
SARS-CoV-2 clearance (days)	7(6–9)	7(6–11)	0.691
Hospital stays (days)	21(16–25)	20(15–26)	0.507
ALT (U/L)	21(15–30)	22(16–35)	0.643
AST (U/L)	26(20–42)	25(20–33)	0.533
CK (U/L)	102(55–194)	80(55–127)	0.190
LDH (U/L)	231(193–305)	219(190–293)	0.745
ALB (g/L)	41.0(37.9–44.0)	41.2(38.1–44.1)	0.528
PA (mg/L)	151(93–193)	158(104–207)	0.355
Cr (µmol/L)	70.5(52.4–77.3)	61.3(50.5–77.1)	0.328
D-D (mg/L)	0.36(0.28–0.50)	0.37(0.26–0.64)	0.828
WBC (×10^9/L)	4.4(3.7–5.7)	4.9(4.0–5.9)	0.227
Neu (%)	65.4(55.2–70.6)	66.6(58.2–72.6)	0.255
Lym (×10^9/L)	1.04(0.73–1.38)	1.13(0.79–1.52)	0.196
PLT (×10^9/L)	163(121–201)	176(143–218)	0.218
CD4 (cell/µl)	411(264–717)	456(302–650)	0.711

Abbreviations: PPIs, proton-pump inhibitors; HPT, hypertension; DM, diabetes mellitus; CVD, cardiovascular disease; COPD, chronic obstructive pulmonary disease; CLD, chronic liver disease; CGD, chronic gastric disease; CKD, chronic kidney disease; MT, malignant tumor; NPLI, number of pulmonary lobe inflammation; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CK, creatine kinase; LDH, lactate dehydrogenase; ALB, albumin; PA, prealbumin; Cr, creatinine; D-D, D-dimer; WBC, leukocyte; Neu, neutrophils; Lym, lymphocyte; PLT, blood platelet; CD4, CD4 cells, CD4-positive T-lymphocytes.

Figure 2 Cumulative probability of SARS-CoV-2 clearance and discharge in COVID-19 patients between PPI group and control group. Kaplan–Meier curves of SARS-CoV-2 clearance (A) and discharge (B) in the enrolled cases.

Table 2 Univariate and Multivariate Analyses of Predictive Factors for SARS-CoV-2 Clearance in COVID-19 Patients

Variables	Univariate Analysis		Multivariate Analysis
	HR	P	HR	P
Age:≥60/<60 years	0.837(0.599–1.169)	0.297	0.984(0.645–1.502)	0.941
Sex: male/female	0.946(0.686–1.304)	0.734	0.824(0.566–1.200)	0.313
PPIs/not-PPIs	1.309(0.893–1.918)	0.168	1.575(0.993–2.499)	0.054
HPT/not-HPT	1.187(0.813–1.733)	0.374	1.576(0.959–2.589)	0.073
DM/not-DM	0.909(0.503–1.642)	0.751	1.136(0.513–2.517)	0.754
CVD/not-CVD	0.596(0.292–1.218)	0.156	0.414(0.161–1.065)	0.067
COPD/not-COPD	1.397(0.443–4.403)	0.568	1.344(0.385–4.696)	0.643
CLD/not-CLD	2.037(0.750–5.532)	0.163	2.293(0.642–8.193)	0.201
CGD/not-CGD	15.202(3.331–69.377)	<0.001	20.924(3.547–123.447)	<0.001
CKD/not-CKD	0.944(0.233–3.821)	0.935	1.105(0.151–8.087)	0.922
MT/not-MT	1.144(0.364–3.599)	0.818	0.666(0.155–2.859)	0.584
NPLI	1.012(0.913–1.121)	0.821	0.999(0.870–1.146)	0.985
The onset times (days)	0.993(0.952–1.035)	0.735	0.993(0.948–1.040)	0.764
CK: ≥198/<198 U/L	1.028(0.658–1.606)	0.904	0.908(0.527–1.567)	0.730
LDH: ≥252/<152 U/L	1.090(0.785–1.514)	0.607	1.026(0.643–1.635)	0.916
ALB: <35/≥35 g/L	1.259(0.662–2.395)	0.483	0.985(0.408–2.377)	0.973
PA: <280/≥280 mg/L	2.075(0.512–8.410)	0.307	2.812(0.427–18.515)	0.282
Cr: ≥104/<104 µmol/L	0.933(0.345–2.527)	0.892	0.929(0.270–3.200)	0.907
D-D: ≥0.5/<0.5 mg/L	1.053(0.743–1.493)	0.771	1.006(0.601–1.685)	0.981
WBC
<4/4–10 (×10^9/L)	1.425(0.450–4.517)	0.547	1.414(0.332–6.015)	0.639
>10/4–10 (×10^9/L)	1.251(0.385–4.063)	0.710	1.322(0.310–5.643)	0.706
Neu: >70/≤70 (%)	1.067(0.754–1.510)	0.713	1.236(0.778–1.964)	0.370
LYM: <1.1/≥1.1 (×10^9/L)	0.911(0.660–1.257)	0.570	0.910(0.589–1.408)	0.673
PLT
<100/100–300 (×10^9/L)	0.713(0.176–2.892)	0.636	1.502(0.277–8.152)	0.638
>300/100–300 (×10^9/L)	0.817(0.164–4.069)	0.805	1.662(0.217–12.737)	0.625
CD4: <500/≥500 cells/µl	0.955(0.689–1.325)	0.784	0.796(0.509–1.246)	0.319
ALT: >60/≤60 U/L	1.709(0.919–3.177)	0.090	1.739(0.865–3.493)	0.120
AST: >60/≤60 U/L	1.717(0.834–3.533)	0.142	1.387(0.466–4.128)	0.557

Abbreviations: PPIs, proton-pump inhibitors; HPT, hypertension; DM, diabetes mellitus; CVD, cardiovascular disease; COPD, chronic obstructive pulmonary disease; CLD, chronic liver disease; CGD, chronic gastric disease; CKD, chronic kidney disease; MT, malignant tumor; NPLI, number of pulmonary lobe inflammation; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CK, creatine kinase; LDH, lactate dehydrogenase; ALB, albumin; PA, prealbumin; Cr, creatinine; D-D, D-dimer; WBC, leukocyte; Neu, neutrophils; Lym, lymphocyte; PLT, blood platelet; CD4, CD4 cells, CD4-positive T-lymphocytes.

Table 3 Univariate and Multivariate Analyses of Predictive Factors for Discharge in COVID-19 Patients

Variables	Univariate Analysis		Multivariate Analysis
	HR	P	HR	P
Age:≥60/<60 years	0.759(0.543–1.063)	0.108	0.652 (0.410–1.039)	0.072
Sex: male/female	0.894(0.651–1.230)	0.492	0.962 (0.655–1.414)	0.845
PPIs/not-PPIs	1.044(0.714–1.528)	0.823	1.064 (0.651–1.740)	0.805
HPT/not-HPT	1.250(0.854–1.829)	0.250	1.820 (1.073–3.085)	0.026
DM/not-DM	1.051(0.581–1.899)	0.870	0.595 (0.255–1.389)	0.230
CVD/not-CVD	0.917(0.429–1.962)	0.823	1.304 (0.481–3.538)	0.602
COPD/not-COPD	2.993(0.946–9.474)	0.062	4.370 (1.205–15.844)	0.025
CLD/not-CLD	6.183(2.180–17.534)	<0.001	9.011 (2.681–30.290)	<0.001
CGD/not-CGD	4.155(1.011–17.078)	0.048	1.855 (0.370–9.292)	0.452
CKD/not-CKD	1.404(0.346–5.699)	0.635	1.911 (0.344–10.621)	0.459
MT/not-MT	2.051(0.650–6.470)	0.220	5.270 (1.237–22.456)	0.025
NPLI	0.995(0.897–1.104)	0.928	1.027 (0.886–1.191)	0.724
The onset times (days)	1.000(0.961–1.041)	0.993	1.017 (0.972–1.064)	0.463
SARS-CoV-2 clearance (days)	0.911(0.876–0.948)	<0.001	0.907 (0.869–0.947)	<0.001
CK: ≥198/<198 U/L	0.900(0.576–1.405)	0.642	0.949 (0.537–1.678)	0.858
LDH: ≥252/<152 U/L	1.019(0.734–1.415)	0.909	0.967 (0.597–1.566)	0.892
ALB: <35/≥35 g/L	0.979(0.514–1.865)	0.949	0.630 (0.290–1.369)	0.243
PA: <280/≥280 mg/L)	1.596(0.395–6.454)	0.512	1.200 (0.244–5.900)	0.822
Cr: ≥104/<104 µmol/L	1.017(0.376–2.753)	0.974	0.885 (0.276–2.836)	0.837
D-D: ≥0.5/<0.5 mg/L	1.101(0.778–1.558)	0.586	1.232 (0.755–2.010)	0.404
WBC
<4/4–10 (×10^9/L)	1.071(0.339–3.381)	0.907	0.574 (0.163–2.021)	0.387
>10/4–10 (×10^9/L)	0.869(0.267–2.824)	0.815	0.540 (0.152–1.917)	0.341
Neu: >70/≤70 (%)	1.091(0.773–1.540)	0.620	1.392 (0.872–2.223)	0.166
LYM: <1.1/≥1.1 (10^9/L)	0.822(0.596–1.134)	0.233	0.751 (0.480–1.173)	0.208
PLT
<100/100–300 (×109/L)	1.138(0.280–4.619)	0.856	0.927 (0.162–5.297)	0.932
>300/100–300 (×10^9/L)	1.228(0.246–6.117)	0.802	0.866 (0.123–6.097)	0.886
CD4:<500/≥500 cell/µl	0.885(0.640–1.224)	0.459	1.055 (0.659–1.688)	0.824
ALT:>60/≤60 U/L	1.511(0.811–2.815)	0.193	1.311 (0.643–2.674)	0.456
AST:>60/≤60 U/L	1.001(0.490–2.045)	0.998	0.760 (0.267–2.158)	0.606

Abbreviations: PPIs, proton-pump inhibitors; HPT, hypertension; DM, diabetes mellitus; CVD, cardiovascular disease; COPD, chronic obstructive pulmonary disease; CLD, chronic liver disease; CGD, chronic gastric disease; CKD, chronic kidney disease; MT, malignant tumor; NPLI, number of pulmonary lobe inflammation; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CK, creatine kinase; LDH, lactate dehydrogenase; ALB, albumin; PA, prealbumin; Cr, creatinine; D-D, D-dimer; WBC, leukocyte; Neu, neutrophils; Lym, lymphocyte; PLT, blood platelet; CD4, CD4 cells, CD4-positive T-lymphocytes.

Table 4 Baseline Data of the Enrolled Cases After 1:1 PS-Matching

	PPI Group (n=29)	Control Group (n=29)	P
Age (years)	48(35–67)	51(36–66)	0.508
Sex,male (%)	16(55.2)	16(55.2)	1.000
HPT (%)	4(13.8)	4(13.8)	1.000
DM (%)	1(3.4)	1(3.4)	1.000
CVR (%)	2(6.9)	2(6.9)	1.000
COPD (%)	0(0)	0(0)	1.000
CLD (%)	1(3.4)	1(3.4)	1.000
CGD (%)	0(0)	0(0)	1.000
CKD(%)	0(0)	0(0)	1.000
MT (%)	0(0)	0(0)	1.000
NPLI	4(2–5)	4(2–5)	0.923
The onset times (days)	3(3–7)	5(2–6.5)	0.981
SARS-CoV-2 clearance (days)	8(6–9)	8(7–11)	0.616
Hospital stay (days)	21(16–27)	19(16–24)	0.478
ALT (U/L)	20(15–35)	20(15–34)	0.957
AST (U/L)	27(19–47)	26(19–46)	0.852
CK (U/L)	102(51–181)	109(51–189)	0.785
LDH (U/L)	244(186–326)	238(185–324)	0.715
ALB (g/L)	42.3(37.0–44.2)	42.6(36.8–44.4)	0.969
PA (mg/L)	153(92–192)	155(89–201)	0.750
Cr (µmol/L)	64.9(51.5–80.6)	64.3(51.2–80.2)	0.797
D-D (mg/L)	0.34(0.27–0.61)	0.33(0.27–0.52)	0.744
WBC (×10^9/L)	4.3(3.8–6.0)	4.4(3.9–5.9)	0.864
Neu (%)	62.8(52.5–73.3)	63.1(52.15–73.0)	0.864
Lym (×10^9/L)	1.07(0.70–1.40)	1.04(0.7–1.39)	0.901
PLT (×10^9/L)	165(119–202)	167(119–204)	0.981
CD4 (cells/µl)	406(236–732)	403(229–724)	0.932

Abbreviations: PPIs, proton-pump inhibitors; HPT, hypertension; DM, diabetes mellitus; CVD, cardiovascular disease; COPD, chronic obstructive pulmonary disease; CLD, chronic liver disease; CGD, chronic gastric disease; CKD, chronic kidney disease; MT, malignant tumor; NPLI, number of pulmonary lobe inflammation; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CK, creatine kinase; LDH, lactate dehydrogenase; ALB, albumin; PA, prealbumin; Cr, creatinine; D-D, D-dimer; WBC, leukocyte; Neu, neutrophils; Lym, lymphocyte; PLT, blood platelet; CD4, CD4 cells, CD4-positive T-lymphocytes.

Figure 3 Cumulative probability of SARS-CoV-2 clearance and discharge in COVID-19 patients between PPI group and control group after 1:1 propensity score matching. Kaplan–Meier curves of SARS-CoV-2 clearance (A) and discharge (B) after 1:1 propensity score matching.