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Authors:M C. Pontelli, I A Castro et al.  

Journal/ Pre-Print:BioRxiv 

Tags: Immunology/Immunity, Inflammation, Virology 

Research Highlights

  1. In vitro SARS-CoV-2 infection of human PBMCs revealed they are susceptible cell types. Both viral antigen and viral replication were assessed and identified in monocytes, CD4+ T cells, CD8+ T cells and B cells. Infection is accompanied by upregulation of apoptotic markers in T lymphocytes, suggesting a contributing mechanism for clinical lymphocytopenia. Viral entry potentially occurs independent of ACE2. 

  1. In COVID-19 hospitalized patients: SARS-CoV-2 infects circulating B cells, monocytes (and T cells to a lesser extent)with positive correlation between the frequency of infected monocytes and time after onset of symptoms.  

  1. Post-mortem analysis of lung tissues from COVID-19 patients showed the presence of SARS-CoV-2 infected CD4+ T cells, B cells and monocytes (the latter expressing IL-6 indicating their inflammatory phenotype).  

Summary  

In this study, the authors explored the susceptibility of PBMCs to SARS-CoV-2 infection. PBMCs from healthy donors were exposed to SARS-CoV-2 in vitroand monocytes, B cells and T cells (both CD4+ and CD8 T cells) showed to be susceptible to SARS-CoV-2 infection. This was assessed by immunostaining of viral antigens and viral replication (dsRNA). In a further step, PBMCs from COVID-19 patients were analysed, when authors could confirm the presence of infected monocytes and B cells in their peripheral blood. Finally, post-mortem analysis of lungs tissues from fatal COVID-19 patients allowed the detection of infected inflammatory monocytes, B cells, and T cells in situOverall, the study showed that circulating immune cells can be infected by SARS-CoV-2, which can contribute to both lymphopenia (as infection correlates with apoptotic markers) and the spread of the infection to secondary organs (still speculative role of immune cells as viral carriers). 

Impact for SARS-CoV2/COVID19 research efforts   

Understand the virology and/or cell biology of SARS-CoV-2/COVID19 

Clinical symptoms and pathogenesis of SARS-CoV-2/COVID19 

Study Type  

  • In vitro study 

  • Clinical Cohort study  

Strengths and limitations of the paper 

Novelty: The authors wanted to explore whether SARS-CoV-2 infection of PBMCs could explain the clinical lymphopenia correlating with poor COVID-19 outcome. The infection of circulating cells might also explain the dissemination of the virus to secondary infections sites (spleen and lymph nodes), as immune cells could be carriers. 

Standing in the field: The findings have not been previously reported. 

Appropriate statistics: Yes. 

Viral model used:Passage 1 (P1) of SARS-CoV-2 Brazil/SPBR-02/2020 145 isolate obtained in Vero-E6 from a COVID-19 patient in Sao Paulo. 

Translatability: This is study does not focus on translation, but on identifying possible new targets of SARS-CoV-2 infection. However, it brings evidence of a potential new strategy for virus entry in immune cells independent of ACE-2. The identification of this mechanism could have therapeutic implications. 

Main limitations:  

  • They did not look at the functionality of infected PBMCs especially the phenotype of T cells after being infected 

  • Only one sample per patient, therefore time course studies not possible. 

  • It lacks mechanistic insights: 1) they could have verified the expression levels of CD147 as a possible alternative entry receptor for SARS-CoV-2 in the cells types where they observed infection; 2) They could have made an attempt to show the possible role of infected PMBCs as viral carriers (e.g. see whether those infected circulating immune cells are able to infect other cells/organ sites). 

  • Low numbers meant that it was not possible to draw any conclusions between leukocytic infection and prognosis