Human cytomegalovirus (CMV) is a widespread persistent herpes virus requiring lifelong immune surveillance to maintain latency. Such long-term interactions with the immune system may be associated with deleterious effects including immune exhaustion and senescence. Regarding the COVID-19 pandemic, we asked whether CMV-specific cellular and humoral activity could influence immune responses toward SARS-CoV-2 and/or disease severity. All adults with mild (n = 15) and severe (n = 14) COVID-19 were seropositive for anti-CMV IgG, but negative for IgM antibodies. Antibody titers did not correlate with COVID-19 severity. Six patients presented elevated frequencies of CMV-specific CD4 + and CD8 + T cells producing IFNγ, IL-17, and TNFα, designated as CMV high responders (hiT CMV). In comparison to low CMV responders, hiT CMV individuals exhibited higher frequencies of SARS-CoV-2-specific CD4 + IL-17 + and CD8 + IFNγ + , IL-17 + or TNFα + T cells. These results indicate that high frequencies of CMV-specific T cells may be associated with a SARS-CoV-2-reactive profile skewed toward Th17-dominated immunity.

Graphical abstract

中文翻译：

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高 CMV 特异性 T 细胞反应与 SARS-CoV-2 特异性 IL-17 T 细胞产生相关

人巨细胞病毒 (CMV) 是一种广泛存在的持久性疱疹病毒，需要终生免疫监视以维持潜伏期。这种与免疫系统的长期相互作用可能与包括免疫衰竭和衰老在内的有害影响有关。关于 COVID-19 大流行，我们询问了 CMV 特异性细胞和体液活动是否会影响对 SARS-CoV-2 和/或疾病严重程度的免疫反应。所有轻度（n  = 15）和重度（n = 14) COVID-19 抗 CMV IgG 血清阳性，但 IgM 抗体阴性。抗体滴度与 COVID-19 的严重程度无关。六名患者表现出产生 IFNγ、IL-17 和 TNFα 的 CMV 特异性 CD4 + 和 CD8 + T 细胞频率升高，被指定为 CMV 高反应者 (hiT CMV)。与低 CMV 反应者相比，hiT CMV 个体表现出更高频率的 SARS-CoV-2 特异性 CD4 + IL-17 + 和 CD8 + IFNγ + 、IL-17 + 或 TNFα + T 细胞。这些结果表明，高频率的 CMV 特异性 T 细胞可能与偏向 Th17 主导免疫的 SARS-CoV-2 反应谱有关。

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