# Evaluating the impact of sickle cell disease on COVID-19 susceptibility and severity: a retrospective cohort study based on electronic health record

## TL;DR

This study finds that sickle cell disease, but not sickle cell trait, is linked to increased risk of severe COVID-19 outcomes using advanced statistical methods.

## Contribution

The novel use of causal inference approaches reveals the independent effect of sickle cell disease on COVID-19 outcomes despite confounding factors.

## Key findings

- Sickle cell disease is consistently associated with higher odds of COVID-19-related pneumonia and pain.
- Causal inference methods balance covariates better than traditional regression in this population.
- No significant association was found between sickle cell trait and COVID-19 outcomes.

## Abstract

Sickle cell trait/disease (SCT/SCD) are enriched among Black people and associated with various comorbidities. The overrepresentation of these characteristics prevents traditional regression approach obtaining convincing evidence for the independent effect of SCT/SCD on other health outcomes. This study aims to investigate the association between SCT/SCD and COVID-19-related outcomes using causal inference approaches that balance the covariate.

We leveraged electronic health record (EHR) data from the University of Chicago Medicine between March 2020 and December 2021. Demographic characteristics were retrieved. Medical conditions were identified using ICD-10 codes. Five approaches, including two traditional regression approaches (unadjusted and adjusted) and three causal inference approaches [covariate balancing propensity score (CBPS) matching, CBPS weighting, and CBPS adjustment], were employed.

A total of 112,334 patients were included in the study, among which 504 had SCT and 388 SCD. Patients with SCT/SCD were more likely to be non-Hispanic Black people, younger, female, non-smokers, and had a diagnosis of diabetes, heart failure, asthma, and cerebral infarction. Causal inference approaches achieved a balanced distribution of these covariates while traditional approaches failed. Across these approaches, SCD was consistently associated with COVID-19-related pneumonia (odds ratios (OR) estimates, 3.23 (95% CI: 2.13–4.89) to 2.57 (95% CI: 1.10–6.00)) and pain (OR estimates, 6.51 (95% CI: 4.68–9.06) to 2.47 (95% CI: 1.35–4.49)). While CBPS matching suggested an association between SCD and COVID-19-related acute respiratory distress syndrome (OR = 2.01, 95% CI: 0.97–4.17), this association was significant in other approaches (OR estimates, 2.96 (95% CI: 1.69–5.18) to 2.50 (95% CI: 1.43–4.37)). No association was observed between SCT and COVID-19-related outcomes in causal inference approaches.

Using causal inference approaches, we provide comprehensive evidence for the link between SCT/SCD and COVID-19-related outcomes.