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.

中文翻译：

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住院的细胞因子释放综合征和ARDS的COVID-19患者的TNF相关细胞因子，LIGHT水平增加

许多COVID-19患者表现出由细胞因子释放综合征（CRS）引起的致命呼吸道并发症。CRS中牵涉多种细胞因子，但此前尚未在这种情况下测量TNFSF14（LIGHT）。在这项研究中，我们观察到与健康年龄和性别匹配的对照患者相比，住院的COVID-19患者的血清LIGHT水平显着提高。该测定法检测到未与抑制剂诱饵受体3（DcyR3）结合的生物利用度LIGHT。通气支持和不通气支持患者的生物利用度LIGHT水平均升高，而需要机械通气的患者则趋于更高水平。在60岁以上的住院患者中，其死亡率为82％，死者的LIGHT水平显着高于幸存者（p = 0.0209）。如先前报道，这些患者的白细胞介素6（IL-6）水平也升高，与存活者相比，死亡患者中观察到的水平显着（p = 0.0076），与LIGHT水平相当。尽管尝试阻断IL-6与其受体的结合在COVID-19 CRS中显示出有限的作用，但由于LIGHT在调节抗病毒免疫反应中的核心作用，它的中和作用可能更有效。