Open AccessAltered bioenergetics and mitochondrial dysfunction of monocytes in patients with COVID‐19 pneumonia
Author(s) -
Gibellini Lara,
De Biasi Sara,
Paolini Annamaria,
Borella Rebecca,
Boraldi Federica,
Mattioli Marco,
Lo Tartaro Domenico,
Fidanza Lucia,
CaroMaldonado Alfredo,
Meschiari Marianna,
Iadisernia Vittorio,
Bacca Erica,
Riva Giovanni,
Cicchetti Luca,
Quaglino Daniela,
Guaraldi Giovanni,
Busani Stefano,
Girardis Massimo,
Mussini Cristina,
Cossarizza Andrea
Publication year - 2020
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.202013001
Subject(s) - bioenergetics , covid-19 , pneumonia , betacoronavirus , medicine , immunology , mitochondrion , virology , biology , pathology , microbiology and biotechnology , disease , infectious disease (medical specialty) , outbreak
In patients infected by SARS‐CoV‐2 who experience an exaggerated inflammation leading to pneumonia, monocytes likely play a major role but have received poor attention. Thus, we analyzed peripheral blood monocytes from patients with COVID‐19 pneumonia and found that these cells show signs of altered bioenergetics and mitochondrial dysfunction, had a reduced basal and maximal respiration, reduced spare respiratory capacity, and decreased proton leak. Basal extracellular acidification rate was also diminished, suggesting reduced capability to perform aerobic glycolysis. Although COVID‐19 monocytes had a reduced ability to perform oxidative burst, they were still capable of producing TNF and IFN‐γ in vitro . A significantly high amount of monocytes had depolarized mitochondria and abnormal mitochondrial ultrastructure. A redistribution of monocyte subsets, with a significant expansion of intermediate/pro‐inflammatory cells, and high amounts of immature monocytes were found, along with a concomitant compression of classical monocytes, and an increased expression of inhibitory checkpoints like PD‐1/PD‐L1. High plasma levels of several inflammatory cytokines and chemokines, including GM‐CSF, IL‐18, CCL2, CXCL10, and osteopontin, finally confirm the importance of monocytes in COVID‐19 immunopathogenesis.