Abstract
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.
Keywords: CD39; COVID-19; HLA-DR; Immune checkpoints; PD-1; Reactive oxygen species.
【저자키워드】 COVID-19, PD-1, CD39, HLA-DR, Immune checkpoints, Reactive oxygen species., 【초록키워드】 Monocytes, SARS-CoV-2, Mitochondria, innate immune response, severe COVID-19, GM-CSF, severity, COVID-19 severity, oxygen, monocyte, PD-1, Clinical outcome, Viral, Viral load, phenotype, membrane, Hospital admission, expression, patients, HLA-DR, reactive oxygen species, COVID-19 patients, CD16, innate immune, Frequency, COVID-19 patient, IFN-α, the cell, mitochondrial, determined by, cell surface, Monocyte activation, healthy control, These data, high viral load, SARS-CoV-2 viral load, severe COVID-19 patients, healthy controls, CD14, classical monocytes, viral burden, Mitochondrial function, Cell, pathological mechanism, initial, evaluated, exhibited, less, induce, reactive oxygen specy, classical monocyte, severe COVID-19 patient, the median, with COVID-19, 【제목키워드】 Infection, phenotype, mitochondrial dysfunction, severe SARS-CoV-2,