key: cord-0894952-l28zz70m authors: Aftab, Owais M.; Modak, Anurag; Patel, Jai C. title: Temporal variation, socioeconomic status, and out‐of‐hospital deaths as factors that influence mortality rates among hospitalized COVID‐19 patients receiving ACEIs/ARBs date: 2022-03-21 journal: J Clin Hypertens (Greenwich) DOI: 10.1111/jch.14473 sha: 8ba99a6cad1c6807adb58945a2a5d59af9636971 doc_id: 894952 cord_uid: l28zz70m nan To the Editor, We read with great pleasure the article by Jia, et al., titled "Influence of angiotensin converting enzyme inhibitors/angiotensin receptor blockers on the risk of all-cause mortality and other clinical outcomes in patients with confirmed COVID-19: A systemic review and metaanalysis," which found that angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) were not associated with in-hospital mortality in COVID-19 patients from March to November 2020. 1 In fact, it was found that there may even be a decreased risk of all-cause mortality in patients taking ACEIs or ARBs. 1 Upon comparison with related trials and research on COVID-19 in-hospital mortality associated with ACEIs/ARBs, we would like to note the following limitations in interpreting the conclusions: 1. There is temporal variation in mortality that may complicate any conclusions made. The authors conducted an electronic search to include articles from the inception of the pandemic to November 12, 2020. However, mortality rates in the early stages of the pandemic in March 2020 differed significantly from mortality rates later on in October and November 2020. 2 In fact, in-hospital mortality rates decreased in the US over the course of 2020 from March to November, even after adjusting for age, sex, comorbidites, and disease severity at admission. 2 As such, a retrospective analysis during this time period would be strengthened by accounting for this variation. 2. In addition, socioeconomic and sociocultural variations in mortality rates exist across countries. The hygiene hypothesis featured prominently during the early phase of the pandemic. Data from India's first COVID-19 surge in October 2020 noted that infected individuals were protected from severe manifestations of the disease and experienced reduced mortality rates compared to Western nations due to cross-immunity from other pathogens, which was confirmed serologically. 3 More generally, it has been found that less-developed nations with a higher burden of pediatric mortality as well as mortality from preventable disease had lower rates of COVID-19 mortality. 4 Despite these limitations, the findings of the systematic review discussed does warrant further investigation, especially as the full breadth of COVID-19-related side-effects is currently not understood. In developing nations, such as India, ACEIs/ARBs are not routinely given to hospitalized patients unless previously prescribed to the patients due to limitations on available medical resources, 7,8 so this area of research is particularly critical and the findings are immediately actionable. Influence of angiotensin converting enzyme inhibitors/angiotensin receptor blockers on the risk of all-cause mortality and other clinical outcomes in patients with confirmed COVID-19: a systemic review and meta-analysis Trends in patient characteristics and COVID-19 in-hospital mortality in the United States During the COVID-19 Pandemic Of cross-immunity, herd immunity and country-specific plans: experiences from COVID-19 in India Global variation of COVID-19 mortality rates in the initial phase. Osong Public Health Res Perspect Individualistic values are related to an increase in the outbreaks of infectious diseases and zoonotic diseases Out-of-hospital cardiac arrest during the COVID-19 pandemic Association of ACE2 receptor and ACEIs/ARBs with disease severity in COVID-19 Angiotensin-converting-enzyme 2 and reninangiotensin system inhibitors in COVID-19: an update Effect of discontinuing vs continuing angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on days alive and out of the hospital in patients admitted With COVID-19: a randomized clinical trial The authors declare that they have no conflicts of interests.