key: cord-1016200-r79djqen
authors: Vrachatis, Dimitrios A.; Giannopoulos, George V.; Giotaki, Sotiria G.; Raisakis, Konstantinos; Kossyvakis, Charalampos; Iliodromitis, Konstantinos E.; Reimers, Bernhard; Tousoulis, Dimitrios; Cleman, Michael; Stefanadis, Christodoulos; Lansky, Alexandra; Deftereos, Spyridon G.
title: Impact of colchicine on mortality in patients with COVID-19. A meta-analysis.
date: 2021-01-06
journal: Hellenic J Cardiol
DOI: 10.1016/j.hjc.2020.11.012
sha: fb112642a4044928150cbe091091127a9761be84
doc_id: 1016200
cord_uid: r79djqen

nan

Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has urged clinicians to utilize traditional and novel drugs in a struggle against the virus and its complications 1 . Inflammatory over-reaction and cytokine storm are postulated to play a deleterious role in COVID-19 affecting not only the pulmonary but the cardiovascular system as well 2 . As expected, laboratory evidence of myocardial injury has been reported to be adversely related to short-term mortality in COVID-19 patients and therefore could be utilized in patient risk stratification 3 . However, while a wide range of myocardial injury patterns in COVID-19 patients has been reported (e.g. supply-demand imbalance, acute coronary syndromes, microvascular thrombosis, stress cardiomyopathy, inflammation, myocarditis), it is not yet clear (a) whether there is a prominent mechanism and (b) if and which long-term consequences exist 4, 5 . In this context, colchicine -along with other drugs with anti-inflammatory properties -has been proposed to have a beneficial effect in terms of clinical outcomes COVID-19 6,7 . Colchicine's potential COVID-19 is speculated to be mainly mediated by its inhibitory effect on the activation, destabilization, and degradation of inflammasomes, while a potential antiviral effect could be exerted through microtubule polymerization inhibition 1, 8 . Published studies suggest a clinical benefit of colchicine therapy including mortality. We aimed to provide a quantitative assessment of the effect of colchicine on mortality in patients with COVID-19.

We performed a systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2009 guidelines. On November 6 th 2020, we searched PubMed, Medrxiv.org using the following query: "colchicine AND ("COVID" OR "COVID-19" OR "SARS-COV-2" OR "CORONAVIRUS DISEASE" OR dispersion between studies due to differences in interventions in the standard-of-care arm and variations in disease severity, a random effects (DerSimonian-Laird) model was adopted.

Heterogeneity was assessed using I 2 , with values between 50% and 90% representing substantial heterogeneity. All analyses were performed using STATA/MP version 16.0, Texas, USA software.

A total of 112 articles were screened, 106 were excluded since they did not meet inclusion criteria (Figure 1 ). A total of six studies, four published after peer-review 7,9-11 and two preprints 12,13 including 881 patients with confirmed COVID-19 were evaluated, 406 of whom were treated with colchicine in addition to standard-of-care (Table) . To address one study 12 that reported no events in both arms, a value of 0.5 was added to the respective cells 14 . The pooled odds ratio for mortality was 0.35 (95% confidence interval 0.24-0.52) and a similar significant trend was observed in terms of the risk difference ( Figure 2A ). The analysis was also conducted including only peer-reviewed articles (i.e. excluding pre-prints) and the pooled odds ratio for mortality was 0.28 (95% confidence interval 0.18-0.44) ( Figure 2B ).

Heterogeneity was low in the odds ratio analysis (Figure 2 ). Further, a contour-enhanced funnel plot, centered at 0 is provided in Figure 3 . Although the small number of studies does not allow for safe conclusions, the plot does not suggest significant publication bias.

The findings of the present meta-analysis suggest a definite signal of benefit of mortality with the addition of colchicine in patients with COVID-19. The small number of studies and the relatively small absolute number of patients included certainly warrant caution as to any definitive conclusion, but this signal cannot be ignored, considering the scarcity of effective treatments for COVID-19. The need for randomized controlled trials (RCTs) involving adequately numbered populations has been well stressed during this pandemic. On the other hand, a year after the first COVID-19 cases, current standards-of-care is not based upon such evidence. Study limitations include the lack of patient-level data which did not allow to assess or control for possible differences in baseline or procedural variables. 

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Impact of myocardial injury on mortality in patients with COVID-19: a meta-analysis

COVID-19 myocardial injury: We have much more to discover

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