Deleterious drugs in COVID-19: a rapid systematic review and meta-analysis

Background

Concerns have been expressed about a number of drugs that potentially worsen outcomes in patients with COVID-19. We sought to identify all potentially deleterious drug groups in COVID-19 and critically assess the underpinning strength of evidence pertaining to the harmful effects of these drugs.

Methods and findings

We performed a rapid systematic review, searching Medline, Embase and two COVID-19 portfolios (WHO COVID-19 database and NIH iSearch COVID-19 portfolio) for papers and preprints related to primary studies investigating drugs identified as potentially deleterious. Primary outcomes were direct measures of susceptibility to infection, disease severity and mortality. Study quality was assessed using the National Heart, Lung, and Blood Institute quality assessment tools. Random-effects meta-analyses were used for data synthesis with further subgroup analyses where possible for specific outcome, study design, statistical adjustment and drug groups when two were combined. Sensitivity analyses were performed by removing any studies at high risk of bias and by publication status.

49 observational studies (15 peer-reviewed papers and 34 preprints) reported primary outcomes for eight drug groups hypothesised to be deleterious. Meta-analysis showed that acute inpatient corticosteroid use was associated with increased mortality (OR 2.22, 95% CI 1.26-3.90), however this result appeared to have been biased by confounding via indication. One subgroup analysis indicated an association between immunosuppressant use and susceptibility to COVID-19 among case control and cross-sectional studies (OR 1.29, 95% CI 1.19-1.40) but this was not found with cohort studies (OR 1.11, 95% CI 0.86-1.43). Studies which adjusted for multiple confounders showed that people taking angiotensin-converting-enzyme inhibitors (ACEIs) or angiotensin-II-receptor blockers (ARBs) required a lower level of care (OR 0.85, 95% CI 0.74-0.98). Furthermore, studies which combined these two drug groups in their analysis demonstrated an association with a lower mortality (OR 0.68, 95% CI 0.55-0.85).

Conclusions

We found minimal high quality or consistent evidence that any drug groups increase susceptibility, severity or mortality in COVID-19. Converse to initial hypotheses, we found some evidence that regular use of ACEIs and ARBs prior to infection may be effective in reducing the level of care required, such as requiring intensive care, in patients with COVID-19.