TY - JOUR
T1 - Viral load is associated with mitochondrial dysfunction and altered monocyte phenotype in acute severe SARS-CoV-2 infection
AU - Romão, Pedro RT
AU - Teixeira, Paula C.
AU - Schipper, Lucas
AU - da Silva, Igor
AU - Santana Filho, Paulo
AU - Júnior, Luiz Carlos Rodrigues
AU - Peres, Alessandra
AU - Gonçalves da Fonseca, Simone
AU - Chagas Monteiro, Marta
AU - Lira, Fabio S.
AU - Andrey Cipriani Frade, Marco
AU - Comerlato, Juliana
AU - Comerlato, Carolina
AU - Sant'Anna, Fernando Hayashi
AU - Bessel, Marina
AU - Abreu, Celina Monteiro
AU - Wendland, Eliana M.
AU - Dorneles, Gilson P.
N1 - Funding Information:
We are grateful to the Brazilian agencies Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) – Finance Code 001. This study was supported in part by the Hospital Moinhos de Vento through the Program for Supporting the Institutional Development of the Public Health System (PROADISUS), supported by the Ministry of Health of Brazil, FIOCRUZ Ribeirão Preto - TED 163/ 2019 - Processo: N˚ 25380.102201/2019-62/ Projeto Fiotec: PRES-009-FIO-20 and Universidade Federal de Ciências da Saúde de Porto Alegre (Programa de Fomento a Pesquisa). GPD is supported by postdoctoral fellowship from CAPES. PRTR, AP, MCM, FSL, MACF are grateful to CNPq for the PQ productivity scholarship.
Funding Information:
We are grateful to the Brazilian agencies Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) ? Finance Code 001. This study was supported in part by the Hospital Moinhos de Vento through the Program for Supporting the Institutional Development of the Public Health System (PROADISUS), supported by the Ministry of Health of Brazil, FIOCRUZ Ribeir?o Preto - TED 163/ 2019 - Processo: N? 25380.102201/2019-62/ Projeto Fiotec: PRES-009-FIO-20 and Universidade Federal de Ci?ncias da Sa?de de Porto Alegre (Programa de Fomento a Pesquisa). GPD is supported by postdoctoral fellowship from CAPES. PRTR, AP, MCM, FSL, MACF are grateful to CNPq for the PQ productivity scholarship. Data accessibility statement: The data will be available when requested.
Publisher Copyright:
© 2022
PY - 2022/7
Y1 - 2022/7
N2 - 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.
AB - 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.
KW - CD39
KW - COVID-19
KW - HLA-DR
KW - Immune checkpoints
KW - PD-1
KW - Reactive oxygen species
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U2 - 10.1016/j.intimp.2022.108697
DO - 10.1016/j.intimp.2022.108697
M3 - Article
C2 - 35405594
AN - SCOPUS:85127755814
SN - 1567-5769
VL - 108
JO - International immunopharmacology
JF - International immunopharmacology
M1 - 108697
ER -