Laboratory of Cellular and Molecular Immunology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil; Graduate Program in Biosciences, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil.
Laboratory of Cellular and Molecular Immunology, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil; Graduate Program in Health Sciences, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil.
Int Immunopharmacol. 2022 Jul;108:108697. doi: 10.1016/j.intimp.2022.108697. Epub 2022 Mar 15.
Monocytes play a major role in the initial innate immune response to SARS-CoV-2. Although viral load may correlate with several clinical outcomes in COVID-19, much less is known regarding their impact on innate immune phenotype. We evaluated the monocyte phenotype and mitochondrial function in severe COVID-19 patients (n = 22) with different viral burden (determined by the median of viral load of the patients) at hospital admission. Severe COVID-19 patients presented lower frequency of CD14 + CD16- classical monocytes and CD39 expression on CD14 + monocytes, and higher frequency of CD14 + CD16 + intermediate and CD14-CD16 + nonclassical monocytes as compared to healthy controls independently of viral load. COVID-19 patients with high viral load exhibited increased GM-CSF, PGE-2 and lower IFN-α as compared to severe COVID-19 patients with low viral load (p < 0.05). CD14 + monocytes of COVID-19 patients with high viral load presented higher expression of PD-1 but lower HLA-DR on the cell surface than severe COVID-19 patients with low viral load. All COVID-19 patients presented decreased monocyte mitochondria membrane polarization, but high SARS-CoV-2 viral load was associated with increased mitochondrial reactive oxygen species. In this sense, higher viral load induces mitochondrial reactive oxygen species generation associated with exhaustion profile in CD14 + monocytes of severe COVID-19 patients. Altogether, these data shed light on new pathological mechanisms involving SARS-CoV-2 viral load on monocyte activation and mitochondrial function, which were associated with COVID-19 severity.
单核细胞在 SARS-CoV-2 的初始固有免疫反应中起主要作用。虽然病毒载量可能与 COVID-19 的几种临床结果相关，但对于其对固有免疫表型的影响知之甚少。我们评估了入院时病毒载量不同（通过患者病毒载量中位数确定）的 22 例重症 COVID-19 患者的单核细胞表型和线粒体功能。与健康对照组相比，重症 COVID-19 患者的 CD14+CD16-经典单核细胞和 CD14+单核细胞上 CD39 的表达频率较低，而 CD14+CD16+中间和 CD14-CD16+非经典单核细胞的频率较高，而与病毒载量无关。与病毒载量低的重症 COVID-19 患者相比，高病毒载量的 COVID-19 患者表现出 GM-CSF、PGE-2 增加和 IFN-α 降低（p<0.05）。与病毒载量低的重症 COVID-19 患者相比，高病毒载量的 COVID-19 患者的 CD14+单核细胞表面 PD-1 表达较高，但 HLA-DR 表达较低。所有 COVID-19 患者的单核细胞线粒体膜极化均降低，但高 SARS-CoV-2 病毒载量与增加的线粒体活性氧有关。在这种意义上，更高的病毒载量诱导与严重 COVID-19 患者 CD14+单核细胞耗竭特征相关的线粒体活性氧生成。总之，这些数据揭示了新的病理机制，涉及 SARS-CoV-2 病毒载量对单核细胞激活和线粒体功能的影响，这些机制与 COVID-19 的严重程度相关。
