Statins reduce death, mechanical ventilation use in hospitalized COVID-19 patients

Hospitalized patients with COVID-19 who are treated with statins are less likely to undergo invasive mechanical ventilation or die, according to the results of a multicentre study in the US.

“Our study found that the use of statins was independently associated with a significantly lower risk of in-hospital mortality and mechanical ventilation in patients hospitalized with COVID-19,” the researchers said.

This retrospective study at the largest municipal healthcare system in the US included adult patients who were hospitalized for COVID-19 between 1 March and 1 December 2020. In-hospital death was the primary endpoint.

The researchers carried out propensity score matching to balance potential confounding variables between patients receiving statins during hospitalization (statin group) and those not receiving statins (nonstatin group). They also used multivariate logistic regression to assess the relationship of statin use and other variables with in-hospital outcomes.

A total of 8,897 patients met the eligibility criteria, of which 3,359 were on statins and 5,538 were not. Both the statin and nonstatin groups included 2,817 patients after propensity score matching. [Am J Med 2022;135:897-905]

On multivariate logistic regression analysis, patients in the statin group showed a markedly lower risk of in-hospital mortality (odds ratio [OR], 0.71, 95 percent confidence interval [CI], 0.63‒0.80; p<0.001) and mechanical ventilation (OR, 0.80, 95 percent CI, 0.71‒0.90; p<0.001) than those in the nonstatin group.

Cytokine storm

COVID-19 could produce an accentuated immune response that activates a systemic inflammatory cascade called “cytokine storm,” according to the researchers, noting that interaction of the SARS-CoV-2 with the host immune system inhibits the lymphopoiesis and accelerates lymphocyte apoptosis. [JAMA 2020;324:782-793; Front Immunol 2020;11:1446; Emerg Microbes Infect 2020;9:761-770]

Such effect has been verified in clinical studies. For instance, use of high-dose atorvastatin correlated with a substantial decrease in the levels of C-reactive protein, interleukin-1, interleukin-6, tumour necrosis factor, and adhesions molecules. [Atherosclerosis 2004;177:161-166]

“Anti-inflammatory agents such as dexamethasone, tocilizumab, and baricitinib are proven efficacious treatments for selected patients with severe COVID-19,” the researchers said. [N Engl J Med 2020;383:1813-1826; N Engl J Med 2021;384:693-704; N Engl J Med 2021;384:795-807; JAMA 2021;326:499-518]

“Given that the proven benefit of these agents is attributed to their anti-inflammatory properties, the association of statins with lower in-hospital mortality identified by our study suggests that this can also be attributed to their anti-inflammatory effects,” they added.

Apart from their cholesterol-lowering effects, statins have also been shown to provide anti-inflammatory effects. For instance, in vitro studies have found statins to reduce the expression of cellular adhesion molecules, which then inhibits leukocyte adhesion to endothelial cells. [Circulation 2004;109:II18-II26; Biochem J 2001;360:363-370]

Statins could also lower the expression of the integrin dimer CD11b and monocyte chemotactic protein-1 on monocytes and selectively inhibit leukocyte function antigen-1, according to the researchers. [Circulation 2004;109:II18-II26; Curr Pharm Des 2012;18:1519-1530]

“By binding to a novel regulatory site within the β2 integrin, statins inhibit leukocyte function antigen-1 and adhesion of lymphocytes to endothelial cells. This selective inhibition results in termination of the inflammatory cascade at a preliminary stage,” they further explained. [Nat Med 2001;7:687-692]