OHDSI COVID-19 Studyathon: ICARIUS - Susceptibility study


The Observational Health Data Sciences and Informatics (OHDSI) international community hosted a COVID-19 virtual study-a-thon March 26-29 to inform healthcare decision-making in response to the current global pandemic. The preliminary research results on this web-based application are from a retrospective, real-world, observational study in support of this activity and will subsequently be submitted to a peer-reviewed, scientific journal. During manuscript development and the subsequent review period, these results are considered under embargo and should not be disclosed without explicit permission and consent from the authors.

Below is the abstract of the manuscript that summarizes the findings:

Introduction: Angiotensin converting enzyme inhibitors (ACEs) and angiotensin receptor blockers (ARBs) could influence infection risk of coronavirus disease (COVID-19). Observational studies to date lack pre-specification, transparency, rigorous ascertainment adjustment and international generalizability, with contradictory results.

Methods: Using electronic health records from Spain (SIDIAP) and the United States (Columbia University Irving Medical Center and Department of Veterans Affairs), we conducted a systematic cohort study with prevalent ACE, ARB, calcium channel blocker (CCB) and thiazide diuretic (THZ) users to determine relative risk of COVID-19 diagnosis and related hospitalization outcomes. The study minimized confounding through large-scale propensity score adjustment and negative control experiments.

Results: Following over 1.1 million antihypertensive users identified between November 2019 and January 2020, we observed no significant difference in relative COVID-19 diagnosis risk comparing ACE/ARB vs CCB/THZ monotherapy (hazard ratio: 0.98; 95% CI 0.84 - 1.14), nor any difference for mono/combination use (1.01; 0.90 - 1.15). ACE alone and ARB alone similarly showed no relative risk difference when compared to CCB/THZ monotherapy or mono/combination use. Directly comparing ACE vs. ARB demonstrated no difference in monotherapy users (0.85; 0.69 - 1.05) but a modestly lower risk in mono/combination users (0.88; 0.79 - 0.99). We observed, however, no significant difference between users for COVID-19 hospitalization or pneumonia risk across all comparisons.

Conclusion: There is no clinically significant increased risk of COVID-19 diagnosis or hospitalization with ACE or ARB use. Users should not discontinue or change their treatment to avoid COVID-19.

Below are links for study-related artifacts that have been made available as part of this study:

Table 3. Fitted propensity model, listing all coviates with non-zero coefficients. Positive coefficients indicate predictive of the target exposure.
Figure 2. Preference score distribution. The preference score is a transformation of the propensity score that adjusts for differences in the sizes of the two treatment groups. A higher overlap indicates subjects in the two groups were more similar in terms of their predicted probability of receiving one treatment over the other.
Figure 4. Systematic error. Effect size estimates for the negative controls (true hazard ratio = 1) and positive controls (true hazard ratio > 1), before and after calibration. Estimates below the diagonal dashed lines are statistically significant (alpha = 0.05) different from the true effect size. A well-calibrated estimator should have the true effect size within the 95 percent confidence interval 95 percent of times.