We read with much interest the article “Are certain drugs associated with enhanced mortality in COVID -19” by Goldstein et al your esteemed Journal. Authors have discussed the theoretical basis of angiotensin receptor blockers, statins in worsening outcome of COVID – 19 patients.(1) We believe that this topic is rapidly evolving and requires further evidence and discussion for understanding the multiple factors which contribute to the pathogenesis and outcome. We have the following comments

Mishra, Ajay Kumar

Sahu, Kamal Kant

Sargent, Jennifer B.

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University of Massachusetts Medical School eScholarship@UMMS Coronavirus COVID-19 Publications by UMMS Authors 2020-04-14 Cardiac drugs and outcome in COVID-19 Ajay Kumar Mishra Saint Vincent Hospital Et al. Let us know how access to this document benefits you. Follow this and additional works at: https://escholarship.umassmed.edu/covid19  Part of the Cardiology Commons, Cardiovascular Diseases Commons, Infectious Disease Commons, and the Virus Diseases Commons Repository Citation Mishra AK, Sahu KK, Sargent JB. (2020). Cardiac drugs and outcome in COVID-19. Coronavirus COVID-19 Publications by UMMS Authors. https://doi.org/10.1093/qjmed/hcaa127. Retrieved from https://escholarship.umassmed.edu/covid19/10 This material is brought to you by eScholarship@UMMS. It has been accepted for inclusion in Coronavirus COVID-19 Publications by UMMS Authors by an authorized administrator of eScholarship@UMMS. For more information, please contact Lisa.Palmer@umassmed.edu. Title pageType of article: Letter to Editor  Title: Cardiac drugs and outcome in COVID - 19Ajay Kumar Mishra*MD, Kamal Kant Sahu*MD, Jennifer Sargent**DOCorresponding author,Dr. Ajay Kumar Mishra, MDDepartment of Internal Medicine Saint Vincent HospitalWorcester, MassachusettsUSA, 01608Ajay.Mishra@stvincenthospital.comPhone: 5083635000Word count: 466Number of Pages: 3* Postgraduate in Internal Medicine, Saint Vincent Hospital, Worcester, Massachusetts ** Assistant Professor in Internal Medicine, University of Massachusetts Medical School, Saint Vincent Hospital, Worcester, Massachusetts https://mc.manuscriptcentral.com/qjm© The Author(s) 2020. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com Downloaded from https://academic.oup.com/qjmed/article-abstract/doi/10.1093/qjmed/hcaa127/5820020 by Medical Center Library user on 15 April 20202. Kamal Kant Sahu, MDDepartment of Internal Medicine Saint Vincent HospitalWorcester, MassachusettsUSA, 01608kamalkant.sahu@stvincenthospital.com3. Jennifer Sargent, DO, FACPDepartment of Internal Medicine,Saint Vincent Hospital, andUniversity of Massachusetts Medical SchoolWorcester, MassachusettsUSA, 01608Jennifer.Sargent@stvincenthospital.com04162282500CONFLICT OF INTEREST: Authors have no conflicts of interest to declare.ETHICAL STATEMENT: The article doesn’t contain the participation of any humanbeing and animal.VERIFICATION: All authors have seen the manuscript and agree to the content anddata. All the authors played a significant role in the paper.Patient consent: Not applicablehttps://mc.manuscriptcentral.com/qjmDownloaded from https://academic.oup.com/qjmed/article-abstract/doi/10.1093/qjmed/hcaa127/5820020 by Medical Center Library user on 15 April 2020Type: Letter to the editor Title: Cardiac drugs and outcome in COVID - 19We read with much interest the article “Are certain drugs associated with enhanced mortality in COVID -19” by Goldstein et al your esteemed Journal. Authors have discussed the theoretical basis of angiotensin receptor blockers, statins in worsening outcome of COVID – 19 patients.(1) We believe that this topic is rapidly evolving and requires further evidence and discussion for understanding the multiple factors which contribute to the pathogenesis and outcome. We have the following comments.Goldstein et al. have discussed that ARB’s facilitate viral entry by increasing the expression of ACE 2 receptors resulting in greater disease severity. Cao et al have compared the genetic analysis of COVID -19 receptor ACE -2 in different populations. They have shown that the expression level and pattern of ACE-2 receptors is different in different tissue and different populations. (2) Even though they have shown that the East Asian population has a higher expression of the same, surprisingly reported mortality in this population has not been high compared to certain other countries. (3)  Zheng et al have reported that patients with cardiovascular diseases have increased ACE- 2 as compared to individuals. As it is expressed in the heart and is involved in counteracting the effects of angiotensin II, its levels are elevated in hypertension, congestive heart failure, atherosclerosis, coronary artery disease due to activation of training angiotensin system.(4) They also have mentioned that renin – angiotensin- aldosterone system inhibitors can also increase ACE-2 levels, hence any antihypertensive agent including ARBs, ACE inhibitors could possibly worsen the outcome in patients with COVID -19.(4) In animal models Administration of aldosterone has also shown to downregulate ACE 2 mRNA levels. Hence https://mc.manuscriptcentral.com/qjmDownloaded from https://academic.oup.com/qjmed/article-abstract/doi/10.1093/qjmed/hcaa127/5820020 by Medical Center Library user on 15 April 2020possibly its antagonists could also increase ACE-2 levels.(5) Similarly, in the animal model binding of SARS-CoV spike protein to ACE 2 has been soon to cause downregulation of ACE 2, resulting in an increase in angiotensin II and worsening lung injury. Recombinant ACE 2 and Losartan is shown to reduce lung injury in such case. (6) Surprisingly randomized controlled trials of losartan for patients with COVID -19 are being held in both hospitalized and non-hospitalized patients. (6,7)We agree with the authors that increase expression of ACE 2 receptor potentially increases viral entry and disease severity, however the data regarding only ARB’s causing the same might not be enough.(6,8) While awaiting further studies it would be prudent to discontinue ACE inhibitors, ARB’s, and other RAAS antagonist on clinical ground as per the treating physician’s discretion.(9) Though at present there is not enough evidence of any potential benefit or harm of most prescribed medications including the ARBs, ACEi, Statins, Antiviral agents we strongly agree with the authors that meticulous and detailed reporting of medications of COVID -19 affected patients is crucial in order to further understand the multifaceted interaction of the virus, medications, and clinical outcome.References:1. Goldstein MR, Poland GA, Graeber CW. Are certain drugs associated with enhanced mortality in COVID-19? QJM: An International Journal of Medicine, hcaa103, https://doi.org/10.1093/qjmed/hcaa103https://mc.manuscriptcentral.com/qjmDownloaded from https://academic.oup.com/qjmed/article-abstract/doi/10.1093/qjmed/hcaa127/5820020 by Medical Center Library user on 15 April 20202. Cao Y, Li L, Feng Z, Wan S, Huang P, Sun X et al. Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations. Cell Discov. 2020 Feb 24;6:11. doi: 10.1038/s41421-020-0147-1. eCollection 2020. PubMed PMID: 321331533. Sahu KK, Mishra AK, Lal A. Novel coronavirus (2019-nCoV): Update on 3rd Coronavirus Outbreak of 21st Century. QJM. 2020 Mar 3. pii: hcaa081. doi: 10.1093/qjmed/hcaa081. [Epub ahead of print] PubMed PMID: 32125418.4. Zheng YY, Ma YT, Zhang JY, Xie X. COVID-19 and the cardiovascular system. Nat Rev Cardiol. 2020 Mar 5. doi: 10.1038/s41569-020-0360-5. [Epub ahead of print]PubMed PMID: 321399045. Clarke NE, Turner AJ. Angiotensin-converting enzyme 2: the first decade. Int J Hypertens. 2012;2012:307315. doi:10.1155/2012/3073156. Clerkin KJ, Fried JA, Raikhelkar J, Sayer G, Griffin JM, Masoumi A et al. Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease. Circulation. 2020 Mar 21. doi: 10.1161/CIRCULATIONAHA.120.046941. [Epub ahead of print] PubMed PMID: 32200663. 7. ClinicalTrials.gov. Randomized Controlled Trial of Losartan for Patients With OVID19 Not Requiring Hospitalization. Identifier: NCT04311177. March 17, 2020.https://clinicaltrials.gov/ct2/show/NCT04311177.8. Mishra AK, Sahu KK, Lal A. Reporting of all cardiac medications and their outcome in COVID – 19. J Med Virol. 2020. [Epub ahead of print]https://mc.manuscriptcentral.com/qjmDownloaded from https://academic.oup.com/qjmed/article-abstract/doi/10.1093/qjmed/hcaa127/5820020 by Medical Center Library user on 15 April 2020

Cardiac drugs and outcome in COVID-19

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Cardiac drugs and outcome in COVID-19

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