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

Abstract

To date, the Covid-19 pandemic affected more than 18 million individuals and caused more than 690, 000 deaths. Its clinical expression is pleiomorphic and severity is related to age and comorbidities such as diabetes and hypertension. The pathophysiology of the disease relies on aberrant activation of immune system and lymphopenia that has been recognized as a prognosis marker. We wondered if the myeloid compartment was affected in Covid-19 and if monocytes and macrophages could be infected by SARS-CoV-2. We show here that SARS-CoV-2 efficiently infects monocytes and macrophages without any cytopathic effect. Infection was associated with the secretion of immunoregulatory cytokines (IL-6, IL-10, TGF-β) and the induction of a macrophagic specific transcriptional program characterized by the upregulation of M2-type molecules. In addition, we found that in vitro macrophage polarization did not account for the permissivity to SARS-CoV-2, since M1-and M2-type macrophages were similarly infected. Finally, in a cohort of 76 Covid-19 patients ranging from mild to severe clinical expression, all circulating monocyte subsets were decreased, likely related to massive emigration into tissues. Monocytes from Covid-19 patients exhibited decreased expression of HLA-DR and increased expression of CD163, irrespective of the clinical status. Hence, SARS-CoV-2 drives circulating monocytes and macrophages inducing immunoparalysis of the host for the benefit of Covid-19 disease progression.

Systemic Tissue and Cellular Disruption from SARS-CoV-2 Infection revealed in COVID-19 Autopsies and Spatial Omics Tissue Maps

“…For example, DEGs observed from NP swabs showed high correlation to tissue specific DEGs in the early stages of infection, but very little correlation later infection. To explain this phenotype, recent evidence has suggested that monocytes can migrate into tissues as the SARS-CoV-2 infection progresses 15 , and this response can potentially explain the different correlations. It has also been reported that monocyte depletion/migration is associated with kidney disease, inducing lupus like symptoms 16 , which could potentially explain the correlation with kidney tissue.…”

Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19

“…Interestingly, monocytes express ACE2 [ 184 ] and are permissive for SARS-CoV-1 [ 186 ], suggesting that they may also be susceptible to SARS-CoV-2 infection. To date, only abortive infection of SARS-CoV-2 has been described in monocytes and monocyte-derived macrophages [ 187 , 188 ]. Non-productive monocyte/macrophage infection by SARS-CoV-2 is also associated with production of immunoregulatory cytokines (IL-6, IL-10, IFN-α, IFN-β, IL-1) [ 187 , 188 ], which were shown to induce infected cell apoptosis via IFN-α/β receptor engagement [ 188 ].…”

“…To date, only abortive infection of SARS-CoV-2 has been described in monocytes and monocyte-derived macrophages [ 187 , 188 ]. Non-productive monocyte/macrophage infection by SARS-CoV-2 is also associated with production of immunoregulatory cytokines (IL-6, IL-10, IFN-α, IFN-β, IL-1) [ 187 , 188 ], which were shown to induce infected cell apoptosis via IFN-α/β receptor engagement [ 188 ]. It is therefore possible that abortive infection of monocytes/macrophages impairs the antiviral response against SARS-CoV-2 and contributes to disease progression [ 187 , 188 ].…”

“…Non-productive monocyte/macrophage infection by SARS-CoV-2 is also associated with production of immunoregulatory cytokines (IL-6, IL-10, IFN-α, IFN-β, IL-1) [ 187 , 188 ], which were shown to induce infected cell apoptosis via IFN-α/β receptor engagement [ 188 ]. It is therefore possible that abortive infection of monocytes/macrophages impairs the antiviral response against SARS-CoV-2 and contributes to disease progression [ 187 , 188 ]. Finally, a study of 69 COVID-19 patients found that CD4 expression on monocytes was decreased in the 16 patients with severe COVID-19 [ 189 ].…”

RGD‐binding integrins and TGF‐β in SARS‐CoV‐2 infections – novel targets to treat COVID‐19 patients?

“…Boumaza et al showed in vitro that SARS-CoV-2 efficiently infects monocytes and macrophages, which resulted in the secretion of TGF-b. 32 There are no reports though that show that this occurs in COVID-19 patients. In an additional study, TGF-b1 was increased in two different subsets of CD4 + immune cells of the COVID-19 patient group compared to the healthy control group.…”