key: cord-0801731-ayvhadm6
authors: Zhu, Jieyun; Pang, Jielong; Ji, Pan; Zhong, Zhimei; Li, Hongyuan; Li, Bocheng; Zhang, Jianfeng
title: Elevated interleukin‐6 is associated with severity of COVID‐19: a meta‐analysis
date: 2020-05-29
journal: J Med Virol
DOI: 10.1002/jmv.26085
sha: c00b6c1ea20cf1343f80e83b5302da938549483a
doc_id: 801731
cord_uid: ayvhadm6

Coronavirus disease 2019 (COVID‐19) has spread rapidly around the world since its emergence in humans last December. Previous studies suggested that numerous markers of inflammation were elevated in patients in with severe disease relative to patients with milder conditions, and an elevated level of interleukin‐6 (IL‐6) was associated with a high case fatality of COVID‐19 infection. This article is protected by copyright. All rights reserved.

The sensitivity analysis was employed to explore the source of heterogeneity. Funnel plot together with Egger's regression asymmetry test and Begg's test were used to evaluate publication bias. A two-tailed P< 0.05 was regarded as statistically significant.

In the end, we meta-analysed 23 studies involving 3,400 COVID-19 patients (Supplementary file 2). Although the heterogeneity was considerably high, the pooled results revealed that compared with severe group, the IL-6 levels were lower in mild group (WMD -24.49, 95%CI -34.64 to -14.34, P＜0.001) but significantly increased in critically ill group (WMD 30.66, 95%CI 7.53 to 53.78, P=0.009) (Fig.1) . A subgroup analysis comparing patients by survival, found an even higher IL-6 levels was observed in patients who died (WMD 41.32, 95%CI 28.15 to 54.49, P＜0.001) (Fig.1) .

The meta-analyses of IL-6 levels from all included studies were repeated after omitting each study in turn, and the results were similar to those obtained with the entire dataset. Nonsignificant P values were obtained when all studies were analysed using Egger's test (0.108) and Begg's test (0.540), suggesting no significant risk of publication bias (Supplementary File 3).

Compared to the nine studies involving 1,426 patients in the most recent relevant meta-analysis [5] , the present work includes 23 studies published up to 1 May 2020 and a total pooled population of 3,400 COVID-19 patients. Our results indicate that elevated IL-6 levels occur more often in severe and critically ill than mild COVID-19, and they occur more often in patients who die from the disease than in those who survive. Our results are consistent with the idea that IL-6 levels positively correlate with COVID-19 severity and risk of fatality [3, 9] .

Relationships among lymphocyte subsets, cytokines, and the pulmonary inflammation index in coronavirus (COVID-19) infected patients

Dysregulation of immune response in patients w ithCOVID-19 in Wuhan, China

Detectable serum SARS-CoV-2 viral load (RNAae mia)is closely correlated with drastically elevated interleukin 6 (IL-6) level in critically ill COVID-19 patients

Interleukin-6 as a potential biomarker of COVID-19 pr ogression

Elevated Interleukin-6 and Severe COVID-19: A Meta-Analy sis

Meta-analysis of Observational Studi es inEpidemiology: A Proposal for Reporting

Critical evaluation of the Newcastle-Ottawa scale for the assessment ofthe quality of nonrandomized studies in meta-analyses

Estimating the mean and variance from the median, range, and the size of a sample

Analysis of clinical features of 29 patients w ith 2019 novel coronavirus pneumonia

The authors have declared that no competing interests exist.