Infection of human lymphomononuclear cells by SARS-CoV-2.
Marjorie Cornejo PontelliItalo Araujo CastroRonaldo B MartinsFlávio P VerasLeonardo La SerraDaniele C NascimentoRicardo S CardosoRoberta RosalesThais M LimaJuliano P SouzaDiego B CaetitéMikhael H F de LimaJuliana T KawahisaMarcela C GianniniLetícia P BonjornoMaria I F LopesSabrina S BatahLi SiyuanRodrigo L AssadSergio C L AlmeidaFabiola R OliveiraMaíra N BenattiLorena L F PontesRodrigo C SantanaFernando C VilarMaria A MartinsThiago M CunhaRodrigo T CaladoJosé C Alves-FilhoDario Simões ZamboniAlexandre FabroPaulo Louzada-JuniorRene D R OliveiraFernando Q CunhaEurico ArrudaPublished in: bioRxiv : the preprint server for biology (2020)
Although SARS-CoV-2 severe infection is associated with a hyperinflammatory state, lymphopenia is an immunological hallmark, and correlates with poor prognosis in COVID-19. However, it remains unknown if circulating human lymphocytes and monocytes are susceptible to SARS-CoV-2 infection. In this study, SARS-CoV-2 infection of human peripheral blood mononuclear cells (PBMCs) was investigated both in vitro and in vivo . We found that in vitro infection of whole PBMCs from healthy donors was productive of virus progeny. Results revealed that monocytes, as well as B and T lymphocytes, are susceptible to SARS-CoV-2 active infection and viral replication was indicated by detection of double-stranded RNA. Moreover, flow cytometry and immunofluorescence analysis revealed that SARS-CoV-2 was frequently detected in monocytes and B lymphocytes from COVID-19 patients, and less frequently in CD4 + T lymphocytes. The rates of SARS-CoV-2-infected monocytes in PBMCs from COVID-19 patients increased over time from symptom onset. Additionally, SARS-CoV-2-positive monocytes and B and CD4+T lymphocytes were detected by immunohistochemistry in post mortem lung tissue. SARS-CoV-2 infection of blood circulating leukocytes in COVID-19 patients may have important implications for disease pathogenesis, immune dysfunction, and virus spread within the host.
Keyphrases
- sars cov
- respiratory syndrome coronavirus
- peripheral blood
- poor prognosis
- endothelial cells
- flow cytometry
- dendritic cells
- induced pluripotent stem cells
- pluripotent stem cells
- long non coding rna
- single cell
- oxidative stress
- cell proliferation
- atomic force microscopy
- pi k akt
- data analysis
- nucleic acid
- real time pcr