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

Abstract

Background:Although the SARS-CoV-2 viral load detection of respiratory specimen has been widely used for novel coronavirus disease diagnosis, it is undeniable that serum SARS-CoV-2 nucleic acid (RNAaemia) could be detected in a fraction of the COVID-19 patients. However, it is not clear that if the incidence of RNAaemia could be correlated with the occurrence of cytokine storm or with the specific class of patients. Methods:This study enrolled 48 patients with COVID-19 admitted to the General Hospital of Central Theater Command, PLA, a designated hospital in Wuhan, China. The patients were divided into three groups according to the Dia gnosis and Treatment of New Coronavirus Pneumonia (version 6) published by the National Health Commission of China. The clinical and laboratory data were collected. The serum viral load detection and serum IL-6 levels were determined. Except for routine statistical analysis, Generalized Linear Models (GLMs) analysis was used to establish a patient status prediction model based on real-time RT-PCR Ct value. Findings:The Result showed that cases with RNAaemia were exclusively confirmed in critically ill patients group and appeared to reflect the illness severity. Further more, the inflammatory cytokine IL-6 levels were significantly elevated in critically ill patients, which is almost 10-folds higher than those in other patients. More importantly, the extremely high IL-6 level was closely correlated with the incidence of RNAaemia (R=0.902) and the vital signs of COVID-19 patients (R= -0.682). Interpretation:Serum SARS-CoV-2 viral load (RNAaemia) is strongly associated with cytokine storm and can be used to predict the poor prognosis of COVID-19 patients.Moreover, our results strongly suggest that cytokine IL-6 should be considered as a therapeutic target in critically ill patients with excessive inflammatory response. All rights reserved. No reuse allowed without permission. the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

Interleukin-6 as a potential biomarker of COVID-19 progression

“…Cytokines are vital in regulating immunological and inflammatory responses. Among them, IL-6 is of major importance because of its pleiotropic effects [1]. Here, we presented the evidence that circulating IL-6 levels are closely linked to the severity of COVID-19 infection.…”

“…ScienceDirect www.sciencedirect.com Letter to the editor Interleukin-6 as a potential biomarker of COVID-19 progression a r t i c l e i n f o Keywords: COVID-19 IL- 6 Biomarker The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), also known as the 2019 novel Coronavirus (2019-nCoV), has caused a recent outbreak of Coronavirus Disease (COVID-19) [1,2]. To date, COVID-19 has already affected 372,757 people globally, with a 4.35% mortality rate.…”

“…In the current situation, identification of COVID-19 disease progression mainly relies on the clinical manifestation, while no effective biomarker has been proposed. It has been suggested that one of the possible mechanisms underlying rapid disease progression is a cytokine storm [1,2]. Previous retrospective studies indicated that an elevated level of interleukin-6 (IL-6) was associated with a high case fatality of COVID-19 infection [1].…”

“…It has been suggested that one of the possible mechanisms underlying rapid disease progression is a cytokine storm [1,2]. Previous retrospective studies indicated that an elevated level of interleukin-6 (IL-6) was associated with a high case fatality of COVID-19 infection [1]. Thus, a meta-analysis of the current scientific literature was performed to investigate whether the measurement of serum IL-6 may predict disease progression of COVID-19 patients.…”

“…We initially identified 73 articles based on our search strategy, 64 of which were excluded after title, abstract, or full-text reading, because they were review articles, did not report IL-6 levels, or did not classify the condition of COVID-19 patients as non-severe and severe. Finally, only nine studies were included in this meta-analysis [1][2][3][4][5][6][7][8][9]. Although the heterogeneity was considerably high (I 2 = 89%; P < 0.00001), we observed that IL-6 levels were significantly increased in COVID-19-infected patients with severe condition compared with those with non-severe condition (SMD = 0.71, 95%CI −0.31-1.12, P = 0.0005) ( Fig.…”