Altered bioenergetics and mitochondrial dysfunction of monocytes in patients with COVID‐19 pneumonia

• DOI: 10.15252/emmm.202013001
• Publication Date: 2020-10-20T01:31:44Z
• Authors: Lara Gibellini; Sara De Biasi; Annamaria Paolini; Rebecca Borella; Federica Boraldi; Marco Mattioli; Domenico Lo Tartaro; Lucia Fidanza; Alfredo Caro‐Mald...; Marianna Meschiari; Vittorio Iadisernia; Erica Bacca; Giovanni Riva; Luca Cicchetti; Daniela Quaglino; Giovanni Guaraldi; Stefano Busani; Massimo Girardis; Cristina Mussini; Andrea Cossarizza
• Keywords: Adult; Male; COVID-19; inhibitory checkpoints; mitochondria; monocytes; OXPHOS; Adult; Aged; Aged, 80 and over; COVID-19; Case-Control Studies; Chemokines; Cytokines; Energy Metabolism; Female; Humans; Male; Middle Aged; Mitochondria; Monocytes; Programmed Cell Death 1 Receptor; SARS-CoV-2; Medicine (General); Programmed Cell Death 1 Receptor; QH426-470; Monocytes; 03 medical and health sciences; R5-920; COVID‐19; Report; Genetics; Humans; Aged; Aged, 80 and over; 0303 health sciences; SARS-CoV-2; COVID-19; Middle Aged; OXPHOS; Mitochondria; 3. Good health; inhibitory checkpoints; mitochondria; Case-Control Studies; Cytokines; Female; Chemokines; monocytes; Energy Metabolism

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.