Many coronavirus disease 2019 (COVID-19) patients demonstrate lethal respiratory complications caused by cytokine release syndrome (CRS). Multiple cytokines have been implicated in CRS, but levels of tumor necrosis factor superfamily 14 (TNFSF14) (LIGHT) have not been previously measured in this setting. In this study, we observed significantly elevated serum LIGHT levels in hospitalized COVID-19 patients 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 than in 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 than in survivors, paralleling the LIGHT levels. Although attempts to block IL-6 binding to its receptor have shown limited success in COVID-19 CRS, neutralization of LIGHT may prove to be more effective owing to its more central role in regulating antiviral immune responses. The findings presented here demonstrate that LIGHT is a cytokine which may play an important role in COVID-19 patients presenting with acute respiratory distress syndrome (ARDS) and CRS and suggest that LIGHT neutralization may be beneficial to COVID-19 patients.

中文翻译：

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患有细胞因子释放综合征和 ARDS 的住院 COVID-19 患者中 TNF 相关细胞因子 LIGHT 水平增加。


许多 2019 年冠状病毒病 (COVID-19) 患者出现由细胞因子释放综合征 (CRS) 引起的致命呼吸道并发症。 CRS 涉及多种细胞因子，但之前尚未在这种情况下测量肿瘤坏死因子超家族 14 (TNFSF14) (LIGHT) 的水平。在这项研究中，我们观察到，与年龄和性别匹配的健康对照患者相比，住院的 COVID-19 患者的血清 LIGHT 水平显着升高。该测定检测到未与抑制剂诱饵受体 3 (DcR3) 结合的生物可用 LIGHT。无论是否接受通气支持，患者的生物可利用 LIGHT 水平均升高，且需要机械通气的患者的生物可利用 LIGHT 水平有升高的趋势。在死亡率为 82% 的 60 岁以上住院患者中，死亡患者的 LIGHT 水平显着高于幸存者 ( P = 0.0209)。正如之前报道的，这些患者的白细胞介素 6 (IL-6) 水平也升高，死亡患者的水平显着高于幸存者 ( P = 0.0076)，与 LIGHT 水平平行。尽管阻断 IL-6 与其受体结合的尝试在 COVID-19 CRS 中取得的成功有限，但由于 LIGHT 在调节抗病毒免疫反应中发挥更重要的作用，中和 LIGHT 可能更有效。本文提出的研究结果表明，LIGHT 是一种细胞因子，可能在出现急性呼吸窘迫综合征 (ARDS) 和 CRS 的 COVID-19 患者中发挥重要作用，并表明 LIGHT 中和可能对 COVID-19 患者有益。