Angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers are not associated with increased risk of SARS-CoV-2 infection

Abstract: Journal of Travel Medicine, 2020, 1–3 doi: 10.1093/jtm/taaa069 Advance Access Publication Date: 14 May 2020 Research Letter Research Letter Gabriel Chodick , PhD1,2,*, Amir Nutman, MD1,3, Naama Yiekutiel, MSc2 and Varda Shalev, MD1,2 1 Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, 2 Maccabi Institute for Research & Innovation, Maccabi Healthcare Services, 27 Hamered Street, Tel Aviv, 68125 Israel and 3 National Center for Infection Control and Antibiotic Resistance, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel *To whom correspondence should be addressed. Tel: +972-3-5143755, Email: hodik_g@mac.org.il Submitted 25 March 2020; Revised 6 April 2020; Editorial Decision 28 April 2020; Accepted 28 April 2020 Key words: Covid19, Israel, anti-hypertensive, Vitamin D, BMI, body mass index, hypertension, obesity, ACE2 receptor The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has swept across the globe and put millions of lives at stake.1 SARS-CoV-2 binds to the host cell’s membrane via angiotensin-converting enzyme 2 (ACE2), an enzyme that physiologically inhibits the renin–angiotensin system (RAS).2 Consequently, concerns were raised regarding the use of RAS inhibitors, including angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) and their potential role in increasing ACE2 expression and subsequent elevated risk of COVID-19 infection.3–6 Currently, data from COVID-19 patients regarding the use of RAS inhibitors and infection risk are limited. The objective of this cross-sectional real-world data analysis was therefore to assess whether the use of RAS inhibitors may increase the likelihood of positive results among tested members of Maccabi Health Services (MHS), a large health organization in Israel. Using MHS database, we have identified all 14 520 confirmed cases of COVID-19, defined as a positive result on real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay of nasal and throat swab specimens. Criteria for testing were according to guidelines published by the Ministry of Health (Guidelines for coping with the novel coronavirus, 2020, Ministry of Health, Israel). A total of 1317 (9%) cases were found positive. We collected information on demographics, the most recent document body mass index (BMI), medical conditions, lab tests results (e.g. last vitamin D and B12) and dispensed of prescribed medications, including RAS inhibitors, anytime between 1 January 2020 and the date of first SARS-COV-2 test. Multivariable logistic regression model was used to assess the independent adjusted relationship between the history of dispensed medication and SARS-COV-2 positivity with adjustment to age, sex, socioeconomic status (SES), BMI and co-morbidities. Interactions between ACEI status and age were examined and found insignificant. Assuming that the prevalence of patients treated for hypertension with ACEIs/ARBs in MHS is 10%, a minimum of 623 positive patients were required to calculate an odds ratio (OR) of two or above at a P value < 0.05 and a statistical power of 95%. All analyses were conducted with IBM-SPSS version 25 and R software version 3.6. In contrast to SARS-COV-19 negative cases, positive cases were significantly (P < 0.001) more likely to be males (59.8% vs 46.1%), older (40.6 vs 37.0 year), and reside in low SES areas (27.9 vs 12.7%), primarily in ultra-orthodox..