In-Hospital Use of Statins Is Associated with a Reduced Risk of Mortality among Individuals with COVID-19

Abstract

Statins are lipid-lowering therapeutics with favorable anti-inflammatory profiles and have been proposed as an adjunct therapy for COVID-19. However, statins may increase the risk of SARS-CoV-2 viral entry by inducing ACE2 expression. Here, we performed a retrospective study on 13,981 patients with COVID-19 in Hubei Province, China, among which 1,219 received statins. Based on a mixed-effect Cox model after propensity score-matching, we found that the risk for 28-day all-cause mortality was 5.2% and 9.4% in the matched statin and non-statin groups, respectively, with an adjusted hazard ratio of 0.58. The statin use-associated lower risk of mortality was also observed in the Cox time-varying model and marginal structural model analysis. These results give support for the completion of ongoing prospective studies and randomized controlled trials involving statin treatment for COVID-19, which are needed to further validate the utility of this class of drugs to combat the mortality of this pandemic.

Keywords: ACEi/ARB; COVID-19; SARS-COV-2; mortality; statin.

Graphical abstract

Figure 1

The Flowchart Showing the Strategy of Participant Enrollment A schematic overview illustrating participant enrollment and the exclusion and inclusion criteria. ^∗297 participants without a medical history of hypertension or with hypertension but not taking antihypertensive medication were excluded from subgroup analyses.

Figure 2

Survival Curves of the Statin Group versus the Non-statin Group after PSM Adjusted HR was calculated based on the mixed-effect Cox model with adjustment of age, gender, and SpO2 at admission. The 95% confidence intervals were represented by shaded regions. The association between statin usage and 28-day all-cause death was calculated with an adjusted HR of 0.58 (95%CI, 0.43–0.80; p = 0.001) compared to non-statin group. The table below the graph indicates accumulated numbers at risk, death, discharge, and loss of follow-up at each indicated time point. The number of “at-risk” was defined as the total number of individuals subtracting the number of “death” and the number of “loss of follow-up.” Participants in the “loss of follow-up” group were those still in the hospital, but who did not meet the criteria for 28-day follow-up at the end of our study follow-up day.

Figure 3

Dynamic Change of Inflammatory Factors in Statin and Non-statin Groups during Hospitalization (A–C) Dynamic profiles of CRP (A), IL-6 (B), and neutrophil count (C) levels during the 28-day follow-up duration in the baseline matched individuals, with 95% confidence interval represented by the shaded regions. (D–F) Dynamic profiles of CRP (D), IL-6 (E), and neutrophil count (F) levels during the 28-day follow-up duration in the baseline matched survival individuals, with 95% confidence interval represented by shaded regions. The sample sizes for each parameter in each group are labeled in the parentheses of the legends.