Effects of previous exposure to different medications on the clinical course of COVID-19 patients in Istanbul, Turkey

Chronic drug use and COVID-19

Authors

DOI:

DOI:

https://doi.org/10.28982/josam.1087527

Keywords:

COVID-19, SARS-CoV-2, epidemiology, pharmacoepidemiology, hypoglycemic agents, calcium channel blockers

Abstract

Background/Aim: Multiple studies have investigated the effects of drugs that alter ACE2 expression, such as renin-angiotensin system inhibitors, non-steroidal anti-inflammatory drugs, and thiazolidinediones, on the clinical course of coronavirus disease-2019 (COVID-19). But a consensus has not yet been reached, and it has been stated that they do not have any effect. There are publications in which metformin is associated with low mortality and insulin with high mortality. Data from different parts of the world are important given that the rate of spread of COVID-19 may be related to the expression status of ACE2 or TMPRSS2 receptors or some other unknown genetic factors. This study aims to examine the effects of medications used chronically in the last 6 months before contracting COVID-19 on the clinical course of COVID-19 in a sample of Istanbul, Turkey.

Methods: In this retrospective cohort study, which included 525 patients diagnosed with COVID-19 between March and November 2020 from four family health centers in Istanbul, the records of the patients were retrospectively analyzed. In addition to demographic information, all medications chronically used by the patients in the last 6 months before the diagnosis of COVID-19 were noted. The effects of demographic data and medications on the three main endpoints of the study, which were hospitalization, intensive care unit (ICU) admission, and mortality, were analyzed using logistic regression models.

Results: Of the 525 COVID-19 patients included in the study, 109 (20.8%) were hospitalized, 18 (3.4%) were treated in ICU, and 11 (2.1%) patients died. Increasing age is associated with hospitalization, ICU admission and mortality. Also, the presence of COVID-19 thoracic computed tomography (CT) findings and polypharmacy was associated with increased hospitalization. Living alone and the presence of COVID-19 thoracic CT findings was associated with increased ICU admission. When adjusted for age and comorbidity, logistic regression models revealed that medications for diabetes mellitus (DM) increased the probability of hospitalization (OR: 3.9, 95% CI 1.2-13.0), and calcium channel blockers (CCBs) increased the probability of ICU admission (OR: 15.8, 95% CI 2.1–120.2) and mortality (OR: 295.1, 95% CI 4.6–18946.6).

Conclusion: Previous use of DM medications and CCBs may negatively affect the clinical course of COVID-19.

Downloads

Download data is not yet available.

References

Semenzato L, Botton J, Drouin J, Baricault B, Vabre C, Cuenot F, et al. Antihypertensive drugs and COVID-19 risk: a cohort study of 2 million hypertensive patients. Hypertension. 2021 Mar 3;77(3):833-42. doi: 10.1161/HYPERTENSIONAHA.120.16314. Epub 2021 11 January. PMID: 33423528; PMCID: PMC7884243. DOI: https://doi.org/10.1161/HYPERTENSIONAHA.120.16314

Williamson EJ, Walker AJ, Bhaskaran K, Bacon S, Bates C, Morton CE, et al. Factors associated with COVID-19-related death using OpenSAFELY. Nature. 2020 Aug;584(7821):430-6. doi: 10.1038/s41586-020-2521-4. Epub 2020 8 July. PMID: 32640463; PMCID: PMC7611074. DOI: https://doi.org/10.1038/s41586-020-2521-4

Yang J, Zheng Y, Gou X, Pu K, Chen Z, Guo Q, et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int J Infect Dis. 2020 May;94:91-5. doi: 10.1016/j.ijid.2020.03.017. Epub 2020 12 March. PMID: 32173574; PMCID: PMC7194638. DOI: https://doi.org/10.1016/j.ijid.2020.03.017

Reilev M, Kristensen KB, Pottegård A, Lund LC, Hallas J, Ernst MT, et al. Characteristics and predictors of hospitalization and death in the first 11 122 cases with a positive RT-PCR test for SARS-CoV-2 in Denmark: a nationwide cohort. Int J Epidemiol. 2020 1 October;49(5):1468-81. doi: 10.1093/ije/dyaa140. PMID: 32887982; PMCID: PMC7499657. DOI: https://doi.org/10.1093/ije/dyaa140

Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020 Apr 16;181(2):271-80.e8. doi: 10.1016/j.cell.2020.02.052. Epub 2020 5 March. PMID: 32142651; PMCID: PMC7102627. DOI: https://doi.org/10.1016/j.cell.2020.02.052

Morales DR, Conover MM, You SC, Pratt N, Kostka K, Duarte-Salles T, et al. Renin-angiotensin system blockers and susceptibility to COVID-19: a multinational open science cohort study. medRxiv [Preprint]. 2020 Jun 12:2020.06.11.20125849. doi: 10.1101/2020.06.11.20125849. Update in: Lancet Digit Health. 2020 Dec 17;: PMID: 32587982; PMCID: PMC7310640.

Asiimwe IG, Pushpakom S, Turner RM, Kolamunnage-Dona R, Jorgensen AL, Pirmohamed M. Cardiovascular drugs and COVID-19 clinical outcomes: a living systematic review and meta-analysis. Br J Clin Pharmacol. 2021;87(12):4534–45. doi: 10.1111/bcp.14927 DOI: https://doi.org/10.1111/bcp.14927

Trifirò G, Massari M, Da Cas R, Menniti Ippolito F, Sultana J, Crisafulli S, et al. ITA-COVID-19: RAAS inhibitor group. Renin-angiotensin-aldosterone system inhibitors and risk of death in patients hospitalised with COVID-19: a retrospective Italian cohort study of 43,000 patients. Drug Saf. 2020 Dec;43(12):1297-308. doi: 10.1007/s40264-020-00994-5. PMID: 32852721; PMCID: PMC7450482. DOI: https://doi.org/10.1007/s40264-020-00994-5

Moore N, Bosco-Levy P, Thurin N, Blin P, Droz-Perroteau C. NSAIDs and COVID- 19: a systematic review and meta-analysis. Drug Saf. 2021;44:929-38. doi: 10.1007/S40264-021-01089-5 DOI: https://doi.org/10.1007/s40264-021-01089-5

Drake TM, Fairfield CJ, Pius R, Knight SR, Norman L, Girvan M, et al. Non-steroidal anti-inflammatory drug use and outcomes of COVID-19 in the ISARIC Clinical Characterisation Protocol UK cohort: a matched, prospective cohort study. Lancet Rheumatol. 2021;3:e498–506. 10.1016/S2665-9913(21)00104-1

Khunti K, Knighton P, Zaccardi F, Bakhai C, Barron E, Holman N, et al. Prescription of glucose-lowering therapies and risk of COVID-19 mortality in people with type 2 diabetes: a nationwide observational study in England. Lancet Diabetes Endocrinol. 2021 May;9(5):293-303. doi: 10.1016/S2213-8587(21)00050-4. Epub 2021 30 March. PMID: 33798464; PMCID: PMC8009618. DOI: https://doi.org/10.1016/S2213-8587(21)00050-4

Yang W, Sun X, Zhang J, Zhang K. The effect of metformin on mortality and severity in COVID-19 patients with diabetes mellitus. Diabetes Res Clin Pract. 2021;178:108977. 10.1016/J.DIABRES.2021.108977 DOI: https://doi.org/10.1016/j.diabres.2021.108977

Bramante CT, Buse J, Tamaritz L, Palacio A, Cohen K, Vojta D, et al. Outpatient metformin use is associated with reduced severity of COVID-19 disease in adults with overweight or obesity. J Med Virol. 2021 Jul;93(7):4273-9. doi: 10.1002/jmv.26873. Epub 2021 23 March. PMID: 33580540; PMCID: PMC8013587. DOI: https://doi.org/10.1002/jmv.26873

Lalau JD, Al-Salameh A, Hadjadj S, Goronflot T, Wiernsperger N, Pichelin M, et al. CORONADO investigators. Metformin use is associated with a reduced risk of mortality in patients with diabetes hospitalised for COVID-19. Diabetes Metab. 2021 Sep;47(5):101216. doi: 10.1016/j.diabet.2020.101216. Epub 2020 10 December. PMID: 33309936; PMCID: PMC7832745. DOI: https://doi.org/10.1016/j.diabet.2020.101216

Rakhmat II, Kusmala YY, Handayani DR, Juliastuti H, Nawangsih EN, Wibowo A, et al. Dipeptidyl peptidase-4 (DPP-4) inhibitor and mortality in coronavirus disease 2019 (COVID-19)-a systematic review, meta-analysis, and meta-regression. Diabetes Metab Syndr. 2021 May-Jun;15(3):777-82. doi: 10.1016/j.dsx.2021.03.027. Epub 2021 1 April. PMID: 33838614; PMCID: PMC8012165. DOI: https://doi.org/10.1016/j.dsx.2021.03.027

Hariyanto TI, Kurniawan A. Dipeptidyl peptidase 4 (DPP4) inhibitor and outcome from coronavirus disease 2019 (COVID-19) in diabetic patients: a systematic review, meta-analysis, and meta-regression. J Diabetes Metab Disord. 2021;20:543–50. doi: 10.1007/s40200-021-00777-4. DOI: https://doi.org/10.1007/s40200-021-00777-4

Asselta R, Paraboschi EM, Mantovani A, Duga S. ACE2 and TMPRSS2 variants and expression as candidates to sex and country differences in COVID-19 severity in Italy. Aging (Albany NY). 2020;12:10087–98. doi: 10.18632/aging.103415. DOI: https://doi.org/10.18632/aging.103415

Hou Y, Zhao J, Martin W, Kallianpur A, Chung MK, Jehi L, et al. New insights into genetic susceptibility of COVID-19: an ACE2 and TMPRSS2 polymorphism analysis. BMC Med. 2020;18:. doi: 10.1186/s12916-020-01673-z DOI: https://doi.org/10.1186/s12916-020-01673-z

Ren L, Yu S, Xu W, Overton JL, Chiamvimonvat N, Thai PN. Lack of association of antihypertensive drugs with the risk and severity of COVID-19: a meta-analysis. J Cardiol. 2021;77:482–91. 10.1016/J.JJCC.2020.10.015 DOI: https://doi.org/10.1016/j.jjcc.2020.10.015

Xu J, Teng Y, Shang L, Gu X, Fan G, Chen Y, et al. The effect of prior angiotensin-converting enzyme inhibitor and angiotensin receptor blocker treatment on coronavirus disease 2019 (covid-19) susceptibility and outcome: a systematic review and meta-analysis. Clin Infect Dis. 2021 1 June;72(11):e901-13. doi: 10.1093/cid/ciaa1592. PMID: 33079200; PMCID: PMC7665377. DOI: https://doi.org/10.1093/cid/ciaa1592

Yu B, Li C, Sun Y, Wang DW. Insulin treatment is associated with increased mortality in patients with COVID-19 and type 2 diabetes. Cell Metab. 2021;33:65-77. doi: 10.1016/j.cmet.2020.11.014 DOI: https://doi.org/10.1016/j.cmet.2020.11.014

Mendez SR, Frank RC, Stevenson EK, Chung M, Silverman MG. Dihydropyridine calcium channel blockers and the risk of severe COVID-19. Chest. 2021;160:89-93. doi: 10.1016/j.chest.2021.01.073 DOI: https://doi.org/10.1016/j.chest.2021.01.073

Jackson BR, Gold JAW, Natarajan P, Rossow J, Neblett Fanfair R, da Silva J, et al. Predictors at admission of mechanical ventilation and death in an observational cohort of adults hospitalized with coronavirus disease 2019. Clin Infect Dis. 2021 6 December;73(11):e4141-51. doi: 10.1093/cid/ciaa1459. PMID: 32971532; PMCID: PMC7543323. DOI: https://doi.org/10.1093/cid/ciaa1459

Yan H, Valdes AM, Vijay A, Wang S, Liang L, Yang S, et al. Role of Drugs Used for Chronic Disease Management on Susceptibility and Severity of COVID-19: A Large Case-Control Study. Clin. Pharmacol. Ther. 2020;108:1185-94. doi: 10.1002/cpt.2047 DOI: https://doi.org/10.1002/cpt.2047

Chouchana L, Beeker N, Garcelon N, Rance B, Paris N, Salamanca E, et al. AP-HP/Universities/Inserm COVID-19 research collaboration, AP-HP Covid CDR Initiative, and “Entrepôt de Données de Santé” AP-HP Consortium”. Association of antihypertensive agents with the risk of in-hospital death in patients with COVID-19. Cardiovasc Drugs Ther. 2022 Jun;36(3):483-8. doi: 10.1007/s10557-021-07155-5. Epub 2021 17 February. Erratum in: Cardiovasc Drugs Ther. 2021 Mar 4;: PMID: 33595761; PMCID: PMC7887412. DOI: https://doi.org/10.1007/s10557-021-07164-4

Kow CS, Ramachandram DS, Hasan SS. Clinical outcomes of hypertensive patients with COVID-19 receiving calcium channel blockers: a systematic review and meta-analysis. Hypertens Res. Published Online First. 2021 doi: 10.1038/s41440-021-00786-z DOI: https://doi.org/10.1038/s41440-021-00786-z

Dietl P, Haller T, Frick M. Spatio-temporal aspects, pathways and actions of Ca2+ in surfactant secreting pulmonary alveolar type II pneumocytes. Cell Calcium. 2012;52:296–302. doi: 10.1016/J.CECA.2012.04.010 DOI: https://doi.org/10.1016/j.ceca.2012.04.010

Lodhi FAK, Shogren SL, Vedre JG, Haque N, Reriani M, Ali R. Calcium channel blocker toxicity causing acute respiratory distress syndrome: a commonly used drug triggering a life-threatening condition. Wis Med J. 2020;119:66–8.

Alsagaff MY, Mulia EPB, Maghfirah I, Luke K, Nugraha D, Rachmi DA, et al. Association of calcium channel blocker use with clinical outcome of COVID-19: a meta-analysis. Diabetes Metab Syndr. 2021 Sep-Oct;15(5):102210. doi: 10.1016/j.dsx.2021.102210. Epub 2021 16 July. PMID: 34298269; PMCID: PMC8282943. DOI: https://doi.org/10.1016/j.dsx.2021.102210

Magdalan J, Antończyk A, Kowalski K, Przewłocki M, Kochman K, Wasylko-Smolarek M. Severe pulmonary complications of massive intoxication with calcium channel blockers and isosorbide mononitrate-a case report. Przegl Lek. 2004;61:405–7.

Humbert VH, Munn NJ, Hawkins RF. Noncardiogenic pulmonary edema complicating massive diltiazem overdose. Chest. 1991, 99:258–9. doi: 10.1378/CHEST.99.1.258 DOI: https://doi.org/10.1378/chest.99.1.258

Marini JJ, Gattinoni L. Management of COVID-19 respiratory distress. JAMA. 2020, 323:2329-30. 10.1001/JAMA.2020.6825 DOI: https://doi.org/10.1001/jama.2020.6825

Sweeney RM, McAuley DF. Acute respiratory distress syndrome. Lancet. 2016 Nov 12;388(10058):2416-2430. doi: 10.1016/S0140-6736(16)00578-X. Epub 2016 28 April. Erratum in: Lancet. 2016 Nov 12;388(10058):2354. PMID: 27133972; PMCID: PMC7138018. DOI: https://doi.org/10.1016/S0140-6736(16)00578-X

Simonneau G, Escourrou P, Duroux P, Lockhart A. Inhibition of hypoxic pulmonary vasoconstriction by nifedipine. N Engl J Med 1981;304:1582-5. doi: 10.1056/NEJM198106253042606 DOI: https://doi.org/10.1056/NEJM198106253042606

Mishra A, Reed RM, Eberlein M. Severe, rapidly reversible hypoxemia in the early period after bilateral lung transplantation. Ann Am Thorac Soc. 2016;13:979–85. 10.1513/ANNALSATS.201602-107CC/SUPPL_FILE/DISCLOSURES.PDF DOI: https://doi.org/10.1513/AnnalsATS.201602-107CC

D’elia JA, Weinrauch LA. Calcium ion channels: roles in infection and sepsis mechanisms of calcium channel blocker benefits in immunocompromised patients at risk for infection. Int J Mol Sci. 2018, 19:1–17. 10.3390/ijms19092465 DOI: https://doi.org/10.3390/ijms19092465

Crespi B, Alcock J. Conflicts over calcium and the treatment of COVID-19. Evol Med Public Heal. 2020, 9:149–56. doi: 10.1093/EMPH/EOAA046 DOI: https://doi.org/10.1093/emph/eoaa046

Straus MR, Bidon MK, Tang T, Jaimes JA, Whittaker GR, Daniel S. Inhibitors of L-type calcium channels show therapeutic potential for treating SARS-CoV-2 infections by preventing virus entry and spread. ACS Infect Dis. Published Online First. 2021, 7:2807-2815. 10.1021/ACSINFECDIS.1C00023 DOI: https://doi.org/10.1021/acsinfecdis.1c00023

Silva IVG, De Figueiredo RC, Rios DRA. Effect of different classes of antihypertensive drugs on endothelial function and inflammation. Int J Mol Sci. 2019;20:5–9. 10.3390/ijms20143458 DOI: https://doi.org/10.3390/ijms20143458

Ettman CK, Abdalla SM, Cohen GH, Sampson L, Vivier PM, Galea S. Prevalence of depression symptoms in US adults before and during the COVID-19 pandemic. JAMA Netw Open. 2020;3:2019686-2019686. 10.1001/JAMANETWORKOPEN.2020.19686 DOI: https://doi.org/10.1001/jamanetworkopen.2020.19686

Hossain MM, Tasnim S, Sultana A, Faizah F, Mazumder H, Zou L, et al. Epidemiology of mental health problems in COVID-19: a review. F1000Res. 2020 23 June;9:636. doi: 10.12688/f1000research.24457.1. PMID: 33093946; PMCID: PMC7549174. DOI: https://doi.org/10.12688/f1000research.24457.1

Şenkal N, Meral R, Medetalibeyoğlu A, Konyaoğlu H, Kose M, Tukek T. Association between chronic ACE inhibitor exposure and decreased odds of severe disease in patients with COVID-19. Anatol J Cardiol. 2020;24:21-9. doi: 10.14744/ANATOLJCARDIOL.2020.57431. DOI: https://doi.org/10.14744/AnatolJCardiol.2020.57431

Downloads

Published

2023-01-20

Issue

Vol. 7 No. 1 (2023): 79-85

Section

Research Article

How to Cite

1.
Ünal Ülkü S, Yananlı HR, Ünal Ömer K, Kaya YD, Keskin M, Güngören F, Karaalp A. Effects of previous exposure to different medications on the clinical course of COVID-19 patients in Istanbul, Turkey: Chronic drug use and COVID-19. J Surg Med [Internet]. 2023 Jan. 20 [cited 2024 Oct. 5];7(1):79-85. Available from: https://jsurgmed.com/article/view/1087527

License

Copyright (c) 2023 Ülkü Sur Ünal , Hasan Raci Yananlı , Ömer Kays Ünal , Yasemin Doğan Kaya , Merve Keskin , Fikriye Güngören , Atila Karaalp

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Citations

Crossref
Scopus
Google Scholar
Europe PMC
#7692