Viral load is associated with mitochondrial dysfunction and altered monocyte phenotype in acute severe SARS-CoV-2 infection

• Autor(a) principal: Romão, Pedro RT
• Data de Publicação: 2022
• Outros Autores: Teixeira, Paula C, Schipper, Lucas, da Silva, Igor, Santana Filho, Paulo, Júnior, Luiz Carlos Rodrigues, Peres, Alessandra, Gonçalves da Fonseca, Simone, Chagas Monteiro, Marta, Lira, Fabio S [UNESP], Andrey Cipriani Frade, Marco, Comerlato, Juliana, Comerlato, Carolina, Sant'Anna, Fernando Hayashi, Bessel, Marina, Abreu, Celina Monteiro, Wendland, Eliana M, Dorneles, Gilson P
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.1016/j.intimp.2022.108697; http://hdl.handle.net/11449/231651
• topic: CD39; COVID-19; HLA-DR; Immune checkpoints; PD-1; Reactive oxygen species

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.