Viral Load is Associated with Mitochondrial Dysfunction and Altered Monocyte Phenotype in Acute Severe SARS-CoV-2 Infection

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. In this study, we evaluated the monocyte phenotype and mitochondrial function in severe COVID-19 patients with different viral load levels (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 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 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. 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.