Monocytes and macrophages, targets of SARS-CoV-2: the clue for Covid-19 immunoparalysis

Boumaza, Asma; Gay, Laetitia; Mezouar, Soraya; Bestion, Eloïne; Diallo, Aïssatou Bailo; Michel, Moise; Desnues, Benoit; Raoult, Didier; La Scola, Bernard; Halfon, Philippe; Vitte, Joana; Olive, Daniel; Mege, Jean-Louis

BACKGROUND: Covid-19 clinical expression is pleiomorphic, severity is related to age and comorbidities such as diabetes and hypertension, and pathophysiology involves aberrant immune activation and lymphopenia. We wondered if the myeloid compartment was affected during Covid-19 and if monocytes and macrophages could be infected by SARS-CoV-2. METHODS: Monocytes and monocyte-derived macrophages from Covid-19 patients and controls were infected with SARS-CoV-2, and extensively investigated with immunofluorescence, viral RNA extraction and quantification, total RNA extraction followed by reverse transcription and q-PCR using specific primers, supernatant cytokines (IL-10, TNF-α, IL-1β, IFN-β, TGF-β1 and IL-6), flow cytometry. The effect of M1- versus M2-type or no polarization prior to infection was assessed. RESULTS: SARS-CoV-2 efficiently infected monocytes and MDMs but their infection is abortive. Infection was associated with immunoregulatory cytokines secretion and the induction of a macrophagic specific transcriptional program characterized by the upregulation of M2-type molecules. In vitro polarization did not account for permissivity to SARS-CoV-2, since M1- and M2-type MDMs were similarly infected. In Covid-19 patients, monocytes exhibited lower counts affecting all subsets, decreased expression of HLA-DR, and increased expression of CD163, irrespective of severity. CONCLUSION: SARS-CoV-2 drives monocytes and macrophages to induce host immunoparalysis for the benefit of Covid-19 progression.