Objectives: Angiotensin-converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARBs), and HMG-CoA reductase inhibitors ("statins") have been hypothesized to affect COVID-19 severity. However, up to now, no studies investigating this association have been conducted in the most vulnerable and affected population groups (ie, older adults residing in nursing homes). The objective of this study was to explore the association of ACEi/ARB and/or statins with clinical manifestations in COVID-19einfected older adults residing in nursing homes. Design: We undertook a retrospective multicenter cohort study to analyze the association between ACEi/ ARB and/or statin use with clinical outcome of COVID-19. The outcomes were (1) serious COVID-19 defined as long-stay hospital admission or death within 14 days of disease onset, and (2) asymptomatic (ie, no disease symptoms in the whole study period while still being diagnosed by polymerase chain reaction). Setting and participants: A total of 154 COVID-19epositive subjects were identified, residing in 1 of 2 Belgian nursing homes that experienced similar COVID-19 outbreaks. Measures: Logistic regression models were applied with age, sex, functional status, diabetes, and hypertension as covariates. Results: We found a statistically significant association between statin intake and the absence of symptoms during COVID-19 (odds ratio [OR] 2.91; confidence interval [CI] 1.27e6.71), which remained statistically significant after adjusting for covariates (OR 2.65; CI 1.13e6.68). Although the effects of statin intake on serious clinical outcome were in the same beneficial direction, these were not statistically significant (OR 0.75; CI 0.24e1.87). There was also no statistically significant association between ACEi/ ARB and asymptomatic status (OR 2.72; CI 0.59e25.1) or serious clinical outcome (OR 0.48; CI 0.10e1.97).

34Background. COVID-19 infection has limited preventive or therapeutic drug options at this 35 stage. Some of common existing drugs like angiotensin-converting enzyme inhibitors (ACEi), 36 angiotensin II receptor blockers (ARB) and the HMG-CoA reductase inhibitors ('statins') have 37 been hypothesised to impact on disease severity. However, up till now, no studies investigating 38 this association were conducted in the most vulnerable and affected population groups, i.e. older 39 people residing in nursing homes. The purpose of this study has been to explore the association 40 of ACEi/ARB and/or statins with clinical manifestations in COVID-19 infected older people 41 residing in nursing homes. 42 Methods and Findings. We undertook a retrospective multi-centre cohort study in two Belgian 43 nursing homes that experienced similar COVID-19 outbreaks. COVID-19 diagnoses were 44 based on clinical suspicion and/or viral presence using PCR of nasopharyngeal samples. A total 45 of 154 COVID-19 positive subjects was identified. The outcomes were 1) serious COVID-19 46 defined as a long-stay hospital admission (length of stay ≥ 7 days) or death (at hospital or 47 O Ref: 2020-120l Page 3 of 16 remained statistically significant after adjusting for age, sex, functional status, diabetes mellitus 58 and hypertension. The strength of this association was considerable and clinically important. 59Although the effects of statin intake on serious clinical outcome (long-stay hospitalisation or 60 death) were in the same beneficial direction, these were not statistically significant (OR 0.75; 61 CI 0.25-1.85; p=0.556). There was also no statistically significant association between 62 ACEi/ARB and asymptomatic status (OR 1.52; p=0.339) or serious clinical 63 outcome (OR 0.79; CI 0.26-1.95; p=0.629). 64Conclusions. Our data indicate that statin intake in old, frail people could be associated with a 65 considerable beneficial effect on COVID-19 related clinical symptoms. The role of statins and 66 any interaction with renin-angiotensin system drugs need to be further explored in larger 67 observational studies as well as randomised clinical trials. 68 69

The COVID-19 pandemic has disrupted life throughout the world. Newly developed vaccines promise relief to people who live in high-income countries, although vaccines and expensive new treatments are unlikely to arrive in time to help people who live in low-and middle-income countries. The pathogenesis of COVID-19 is characterized by endothelial dysfunction. Several widely available drugs like statins, ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have immunometabolic activities that (among other things) maintain or restore endothelial cell function. For this reason, we undertook an observational study in four Belgian hospitals to determine whether in-hospital treatment with these drugs could improve survival in 959 COVID-19 patients. We found that treatment with statins and ACEIs/ARBs reduced 28-day mortality in hospitalized COVID-19 patients. Moreover, combination treatment with these drugs resulted in a 3-fold reduction in the odds of hospital mortality (OR = 0.33; 95% CI 0.17–0.69). These findings were in general agreement with other published studies. Additional observational studies and clinical trials are needed to convincingly show that in-hospital treatment with statins, ACEIs/ARBs, and especially their combination saves lives.

The COVID-19 pandemic has disrupted life throughout the world. Newly developed vaccines promise relief to people who live in high-income countries, although vaccines and expensive new treatments are unlikely to arrive in time to help people who live in low-and middle-income countries. The pathogenesis of COVID-19 is characterized by endothelial dysfunction. Several widely available drugs like statins, ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have immunometabolic activities that (among other things) maintain or restore endothelial cell function. For this reason, we undertook an observational study in four Belgian hospitals to determine whether in-hospital treatment with these drugs could improve survival in 959 COVID-19 patients. We found that treatment with statins and ACEIs/ARBs reduced 28-day mortality in hospitalized COVID-19 patients. Moreover, combination treatment with these drugs resulted in a 3-fold reduction in the odds of hospital mortality (OR=0.33; 95% CI 0.17-0.69). These findings were in general agreement with other published studies. Additional observational studies and clinical trials are needed to convincingly show that in-hospital treatment with statins, ACEIs/ARBs, and especially their combination saves lives.

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