key: cord-263739-xoum5e0k authors: Zhang, X.-Y.; Wu, H.-B.; Ling, Y.; Qian, Z.-P.; Chen, L. title: Analysis of the effect of proton pump inhibitors on the course of common COVID-19 date: 2020-06-09 journal: nan DOI: 10.1101/2020.06.07.20124776 sha: doc_id: 263739 cord_uid: xoum5e0k Background/aims: To evaluate the effect of proton pump inhibitors on the course of common COVID-19. Methods: Clinical data of common COVID-19 patients admitted to the Shanghai public health clinical center for treatment from January 20, 2020 to March 16, 2020 were collected. A retrospective study was conducted and the patients were divided into two groups according to whether they used proton pump inhibitors or not. The differences in SARS-CoV-2 clearance and hospital stay between the two groups were compared by univariate and multivariate analyses. Results: A total of 154 COVID-19 common cases were included in this study, including 80 males (51.9%), 35 patients (22.7%) in the proton pump inhibitors group, and 119 patients (77.3%) in the control group. In the proton pump inhibitors group and the control group, the duration of SARS-CoV-2 clearance were 7(6-9) and 7(6-11) days, and the duration of hospital stay was 21(16-25) and 20(15-26) days, respectively. There was no significant difference between the two groups in the cumulative incidence of SARS-CoV-2 clearance and the cumulative incidence of discharge, and the same after Propensity Score Match, all P > 0.05. Multivariate analysis suggested that chronic gastropathy prolonged the duration of SARS-CoV-2 clearance, the HR was 20.924(3.547-123.447). Hypertension, chronic obstructive pulmonary disease, chronic liver disease and malignant tumor all increased the duration of hospital stay for COVID-19, and the HR were 1.820 (1.073-3.085), 4.370 (1.205-15.844), 9.011 (2.681-30.290) and 5.270 (1.237-22.456), respectively; the duration of hospital stay in COVID-19 patients was shortened by SARS-CoV-2 clearance, and the HR was 0.907 (0.869-0.947); all P < 0.05. Conclusion: Proton pump inhibitors use have no effect on the prolonging or shortening of the course of adults hospitalized with COVID-19. E-mail addresses 10 Xiao-Yu Zhang, zhangxiaoyu@shphc.org.cnļ¼zhangxiaoyuPRC@163.com 11 Hai-Bing Wu, wuhaibing@shphc.org.cn 12 Yun Ling, lingyun@shphc.org.cn 13 Zhi-Ping Qian, qianzhiping@shphc.org.cn 14 Liang Chen, chenliang@shphc.org. cn 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 Introduction 89 90 The disease burdens of coronavirus disease 2019 (COVID-19), caused by severe 91 acute respiratory syndrome coronavirus-2 (SARS-CoV-2), have been 92 continuously increasing. [ the nucleic acid test of SARS-CoV-2 was continuous; (6) patients in the PPIs 174 group were those who had used PPIs for at least 3 days before the SARS-CoV-2 175 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 9, 2020. . clearance, while patients in the control group were those who had not used drugs 176 to inhibit gastric acid secretion; (7) the daily dose of omeprazole was 20mg or 177 40mg, or the daily dose of rabeprazole was 20mg. 178 Case exclusion criteria: (1) the patients used drugs to inhibit the secretion of 179 gastric acid within 30 days before admission; (2) Specimens used for SARS-CoV-180 2 nucleic acid testing were collected at an interval of more than 48 hours; (3) 181 cases with incomplete research data; (4) the patients with COVID-19 died in the 182 course of hospitalization. Case grouping and requirements 185 PPIs group: the patients were exposed to PPIs and met the above inclusion and 186 exclusion criteria. A total of 35 patients met the criteria and were included in the 187 PPIs group. 188 Control group: the patients were not exposed to drugs that inhibited the 189 secretion of gastric acid and met the above inclusion and exclusion criteria. A 190 total of 119 cases met the criteria and were included in the control group. Data sources and indicators 193 The demographic and clinical data was collected from electronic medical record 194 (EMR) including hospital information system (HIS), laboratory information system 195 (LIS) and radiology information system (RIS) of Shanghai Public Health Clinical 196 Center. The demographic and clinical data included age and sex of the patients, The nucleic acid test specimens of SARS-CoV-2 in this study were 209 nasopharyngeal swabs, which were tested by Center of Diseases Prevention and 210 Control of Shanghai before admission, and sampled and tested in the Shanghai 211 Public Health Clinical Center after admission. All the cases admitted to the 212 Shanghai Public Health Clinical Center tested positive for SARS-CoV-2 nucleic 213 acid in Center of Diseases Prevention and Control of Shanghai before 214 hospitalization. Statistical analyses 217 Date are described as median (quartile spacing) or numbers(%). Person chi-218 square test and fisher exact probability method were used for counting data. The 219 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 9, 2020. . normality of continuous variables was tested by K-S test. T test was used for the 220 differences between data groups conforming to normal distribution, while Manny-221 Whitney U test was used for the differences between data groups not conforming 222 to normal distribution. 223 The cumulative probability of SARS-CoV-2 clearance or discharge from 224 COVID-19 cases were conducted through Kaplan-Meier statistics, and the 225 difference was examined by Log-rank test. The possible risk factors of SARS-226 CoV-2 clearance or discharge from COVID-19 cases were investigated with Cox 227 proportional hazards (PH) regression models for univariate and multivariate 228 analyses to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). PH 229 assumption was verified using Schoenfeld residuals. 230 In order to reduce the selectivity bias and control the influence of confounding 231 factors, the propensity score method was adopted by logistic regression based on 232 the demographic and clinical indicators in this study. The difference between the 233 two groups was balanced by 1:1 propensity matching. SPSS software version 23.0 (SPSS Inc. Chicago, IL, USA,) was used for 235 statistical analysis of the data. The P value of two-sided less than 0.05 was 236 considered as statistically significant . 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 257 258 259 260 261 262 263 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 9, 2020. . Baseline Comparison of virus clearance and hospital stay in the baseline status 280 The duration of SARS-CoV-2 clearance in the PPIs group and the control group 281 was 7(6-9) and 7(6-11) days, respectively. There was no significant difference in 282 the cumulative incidence of SARS-CoV-2 clearance between the two groups, 283 P=0 There was no significant difference in the remainder, and all P > 0.05. See table 2 307 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 9, 2020. . for details. 308 309 PS-matched analysis of virus clearance and hospital stay 310 A total of 29 pairs of cases were collected by 1:1 propensity matching, and the 311 corresponding data are shown in table 3. The duration of SARS-CoV-2 clearance 312 in the PPIs group and the control group was 8(6-9) and 8(7-11) days, 313 respectively. There was no significant difference in the cumulative incidence of 314 SARS-CoV-2 clearance between the two groups, P=0.355. The duration of 315 hospital stay for COVID-19 cases was 21(16-27) days in the PPIs group and 316 19(16-24) days in the control group. There was no significant difference between 317 the two groups in the cumulative incidence of discharge for COVID-19 cases, 318 P=0.817. See table 4 and figure 3 for details . 319 320 321 322 323 324 325 326 327 328 329 330 331 332 333 334 335 336 337 338 339 340 341 342 343 344 345 346 347 348 349 350 351 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 9, 2020. were not included in the statistical analysis. Key findings 372 In this study, we found that PPIs use in common COVID-19 did not prolong or 373 shorten the duration of SARS-CoV-2 clearance or hospital stay. the studies suggested that PPIs did not increase the incidence of pneumonia. They suggested that the increased incidence of pneumonia caused by PPIs was 395 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 9, 2020. . due to confounders, and proton pump itself was not an independent factor 396 affecting the occurrence of pneumonia. The baseline data of our study lacked the viral load of SARS-CoV-2, but 429 lymphocytes and CD4+ cells were included as the baseline reference and 430 matching analysis was performed to make up for the deficiencies in our study, 431 because it was proved that SARS-CoV-2 would affect the change of lymphocyte 432 and CD4+ cell counts [22] [23] [24] . This study included only common COVID-19, due 433 to the low number of severe and critical COVID-19 cases, and severe and critical 434 cases were not included in the study; therefore, the study does not fully 435 represent the effect of proton pump inhibitors on the course of severe or critical 436 COVID-19. Since the subjects we included in this study are common COVID-19 437 cases, and PPIs have been used for a short time and at a conventional dose, so 438 the study cannot represent the long-term or high-dose impact of PPIs on the 439 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 9, 2020. . https://doi.org/10.1101/2020.06.07.20124776 doi: medRxiv preprint course of COVID-19. Conclusions 442 The use of proton pump inhibitors does not prolong or shorten the duration of 443 SARS-CoV-2 clearance or hospital stay. Therefore, the appropriate use of proton 444 pump inhibitors in the treatment or prevention of the related diseases will not 445 affect the course of COVID-19 . 446 447 448 449 450 451 452 453 454 455 456 457 458 459 460 461 462 463 464 465 466 467 468 469 470 471 472 473 474 475 476 477 478 479 480 481 482 483 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 9, 2020. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 9, 2020. . . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 9, 2020. . 572 573 574 575 576 577 578 579 580 581 582 583 584 585 586 587 588 589 590 591 592 593 594 FIG 1. Study Cohort. 595 596 597 598 599 600 601 602 603 604 605 606 607 608 609 610 611 612 613 614 615 154 eligible cases were enrolled in the study 298 adults admitted were diagnosed with common covid-19 in the first three days after admission298 144 were excluded 27 were given PPIs for less than 3 days before SARS-CoV-2 clearance 12 had no nucleic acid test in the first three days after admission 104 lacked continuous detection data 1 died who not exposed to PPIs 119 were assigned to the control group 35 were assigned to the control group . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 9, 2020. . is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 9, 2020. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted June 9, 2020. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 9, 2020. 2(6.9) 2(6.9) 1.000 COPD(%) 0(0) 0(0) . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted June 9, 2020. . https://doi.org/10.1101/2020.06.07.20124776 doi: medRxiv preprint Vital surveillances: the epidemiological characteristics of an 487 outbreak of 2019 novel coronavirus diseases (COVID-19) -China Clinical features of patients 492 infected with 2019 novel coronavirus in Wuhan Clinical Characteristics of Coronavirus Disease 496 2019 in China FIG 2. Cumulative probability of SARS-CoV-2 clearance and discharge in COVID-19 643 patients between PPIs group and control group Kaplan-Meier curves of (A) SARS-CoV-2 clearance and (B) discharge in the enrolled cases Cumulative probability of SARS-CoV-2 clearance and discharge in COVID-19 676 patients between PPIs group and control group by 1:1 PS-matching analysis Kaplan-Meier curves of (C) SARS-CoV-2 clearance and (D) discharge by 1:1 PS-matching 678 Formal analysis, Xiao-Yu Zhang; Supervision, Liang Chen; Writing -709 original draft, Xiao-Yu Zhang; Writing -review & editing All authors have read and agreed to the published 711 version of the manuscript. 712 Funding: This research received no external funding Acknowledgments: This study was supported by the Shanghai Public Health Clinical Center for 714 data access. 715 Conflicts of Interest: The authors declare no conflict of interest Ethical approval: Informed consents of patients were obtained for diagnosis and treatment, 717 and the study. Protocol was approved by the Shanghai Public Health Clinical All the data received Institutional Review Board (IRB) approval by the Ethics 719 Committee. The IRB number was