Escuela de Doctorado, Universidad Católica de Valencia San Vicente Mártir, Valencia, Spain.
Geneuro-Innovation, Bioparc Laënnec, Lyon, France.
Front Immunol. 2022 Oct 27;13:1020064. doi: 10.3389/fimmu.2022.1020064. eCollection 2022.
Due to the wide scope and persistence of COVID-19´s pandemic, post-COVID-19 condition represents a post-viral syndrome of unprecedented dimensions. SARS-CoV-2, in line with other infectious agents, has the capacity to activate dormant human endogenous retroviral sequences ancestrally integrated in human genomes (HERVs). This activation was shown to relate to aggravated COVID-19 patient´s symptom severity. Despite our limited understanding of how HERVs are turned off upon infection clearance, or how HERVs mediate long-term effects when their transcription remains aberrantly on, the participation of these elements in neurologic disease, such as multiple sclerosis, is already settling the basis for effective therapeutic solutions. These observations support an urgent need to identify the mechanisms that lead to HERV expression with SARS-CoV-2 infection, on the one hand, and to answer whether persistent HERV expression exists in post-COVID-19 condition, on the other. The present study shows, for the first time, that the HERV-W ENV protein can still be actively expressed long after SARS-CoV-2 infection is resolved in post-COVID-19 condition patients. Moreover, increased anti-SARS-CoV-2 immunoglobulins in post-COVID-19 condition, particularly high anti-SARS-CoV-2 immunoglobulin levels of the E isotype (IgE), seem to strongly correlate with deteriorated patient physical function (r=-0.8057, p<0.01). These results indicate that HERV-W ENV antigenemia and anti-SARS-CoV-2 IgE serology should be further studied to better characterize post-COVID-19 condition pathogenic drivers potentially differing in subsets of patients with various symptoms. They also point out that such biomarkers may serve to design therapeutic options for precision medicine in post-COVID-19 condition.
由于 COVID-19 大流行的广泛范围和持续存在，新冠后状况代表了一种前所未有的病毒性后遗症。SARS-CoV-2 与其他传染病原体一样，具有激活人类基因组中远古整合的潜伏人类内源性逆转录病毒序列（HERV）的能力。这种激活被证明与加重的 COVID-19 患者症状严重程度有关。尽管我们对 HERV 在感染清除时如何关闭、或 HERV 在转录异常持续时如何介导长期影响的了解有限，但这些元素在神经疾病（如多发性硬化症）中的参与已经为有效的治疗解决方案奠定了基础。这些观察结果支持迫切需要确定导致 SARS-CoV-2 感染时 HERV 表达的机制，一方面，另一方面要回答在新冠后状况中是否存在持续的 HERV 表达。本研究首次表明，在新冠后状况患者中，SARS-CoV-2 感染得到解决后很长时间，HERV-W ENV 蛋白仍可被积极表达。此外，新冠后状况中增加的抗 SARS-CoV-2 免疫球蛋白，特别是 SARS-CoV-2 免疫球蛋白 E 同种型（IgE）的高水平，似乎与患者身体功能恶化强烈相关（r=-0.8057，p<0.01）。这些结果表明，应进一步研究 HERV-W ENV 抗原血症和抗 SARS-CoV-2 IgE 血清学，以更好地描述新冠后状况的潜在致病驱动因素，这些驱动因素在具有不同症状的患者亚群中可能有所不同。它们还指出，这些生物标志物可用于为新冠后状况的精准医学设计治疗选择。
