Respiratory Section, Department of Translational Medicine, University of Ferrara, Ferrara, Italy.
Azienda Ospedaliera Universitaria Ferrara, Ferrara, Italy.
Front Immunol. 2021 Mar 9;12:648004. doi: 10.3389/fimmu.2021.648004. eCollection 2021.
Deficient interferon responses have been proposed as one of the relevant mechanisms prompting severe manifestations of COVID-19. To evaluate the interferon (IFN)-α levels in a cohort of COVID-19 patients in relation to severity, evolution of the clinical manifestations and immune/inflammatory profile. This is prospective study recruiting consecutive hospitalized patients with respiratory failure associated with SARS-COV-2 infection and matched controls. After enrollment, patients were assessed every 7 ± 2 days for additional 2 consecutive visits, for a total of 21 days. The severity of the clinical condition was ranked based on the level of respiratory support required. At each time-point blood samples were obtained to assess immune cells and mediators by multiplex immunoassay. Fifty-four COVD-19 and 11 control patients matched for severity were enrolled. At recruitment, lower levels of blood IFN-α were found in COVID-19 patients compared to controls (3.8-fold difference, < 0.01). Improvements in COVID-19 severity were paralleled by a significant increase of blood IFN-α levels. A significant increase in blood IFN-α was found over the study period in survivors (70% of the study population). A similar trend was found for blood IFN-β with IFN-β levels below the threshold of detectability in a substantial proportion of subjects. Significantly higher values of blood lymphocytes and lower levels of IL-10 were found at each time point in patients who survived compared to patients who died. In patients who clinically improved and survived during the study, we found an inverse association between IL-10 and IFN-α levels. The study identifies a blood immune profile defined by deficient IFN-α levels associated with increased IL-10 expression in patients progressing to severe/life threatening COVID-19 conditions, suggesting the involvement of immunological pathways that could be target of pharmacological intervention. ClinicalTrials.gov identifier NCT04343053.
干扰素反应不足被认为是促使 COVID-19 严重表现的相关机制之一。为了评估 COVID-19 患者队列中干扰素 (IFN)-α 水平与严重程度、临床表现的演变以及免疫/炎症特征的关系。这是一项前瞻性研究，招募了因 SARS-COV-2 感染而导致呼吸衰竭的连续住院患者和匹配的对照组。入组后，患者每 7 ± 2 天评估一次，连续评估 2 次，共 21 天。根据所需呼吸支持的水平对临床病情的严重程度进行分级。在每个时间点采集血液样本，通过多重免疫测定法评估免疫细胞和介质。共纳入 54 例 COVID-19 患者和 11 例严重程度匹配的对照组患者。入组时，COVID-19 患者的血液 IFN-α 水平低于对照组 (差异 3.8 倍， < 0.01)。COVID-19 严重程度的改善与血液 IFN-α 水平的显著增加平行。在研究期间，幸存者的血液 IFN-α水平显著增加 (研究人群的 70%)。在大量受试者中，IFN-β 水平低于可检测阈值，血液 IFN-β 也出现了类似的趋势。与死亡患者相比，存活患者在每个时间点的血液淋巴细胞计数更高，IL-10 水平更低。在研究期间临床改善并存活的患者中，我们发现 IL-10 和 IFN-α 水平之间存在负相关。该研究确定了一种血液免疫特征，其特征是进展为严重/危及生命 COVID-19 状态的患者中 IFN-α 水平降低，同时伴有 IL-10 表达增加，表明涉及免疫途径，这些途径可能是药物干预的靶点。ClinicalTrials.gov 标识符 NCT04343053。
