Abstract
Many COVID-19 patients demonstrate lethal respiratory complications caused by cytokine release syndrome (CRS). Multiple cytokines have been implicated in CRS, but TNFSF14 (LIGHT) has not been previously measured in this setting. In this study, we observed significantly elevated serum LIGHT levels in hospitalized COVID-19 patients as compared to healthy age and gender matched control patients. The assay detected bioavailable LIGHT unbound to the inhibitor Decoy receptor-3 (DcR3). Bioavailable LIGHT levels were elevated in patients both on and off ventilatory support, with a trend toward higher levels in patients requiring mechanical ventilation. In hospitalized patients over the age of 60, who exhibited a mortality rate of 82%, LIGHT levels were significantly higher (p=0.0209) in those who died compared to survivors. As previously reported, interleukin 6 (IL-6) levels were also elevated in these patients with significantly (p=0.0076) higher levels observed in patients who died vs. survivors, paralleling the LIGHT levels. Although attempts to block IL-6 binding to its receptor have shown limited effect in COVID-19 CRS, neutralization of LIGHT may prove to be more effective owing to its more central role in regulating antiviral immune responses.
Competing Interest Statement
Dr. Carl Ware is an author of patents to CERC-002 and a consultant to Cerecor.
Dr. Garry A. Neil is an officer of Cerecor and shareholder.
Lori Roadcap is an employee and shareholder of Cerecor.
Dr. Inbal Zafir Lavie is a paid consultants to Cerecor.
Shane Raines is a paid consultants to Cerecor.
Funding Statement
This study was funded by Cerecor Inc.
Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
Specimens were consented and collected under IRB approved study PRO18-1002, Hackensack Meridian Health Network Biorepository Project, A Multi-Center collection of Biospecimens and Associated Clinical Data (HMH BIoR). Samples were released de identified for downstream research under a man approved non human subject research determination.
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Data Availability
N/A data was generated in this study