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First Author: Jia Liu 

Journal/preprint name: medrxiv 

Tags: Immunology/Immunity 


Liu et al. performed a phenotypic study of peripheral blood mononuclear cells in convalescent patients with mild/moderate COVID-19. They utilized samples from two cohorts, a Chinese cohort (n=30 convalescent individuals (CI) and n=26 matched uninfected individuals (UI)) and a German cohort for invariant NKT analysis (n=16 CI and n=6 UI) at 3.5 months and 1.5 months respectively after initial diagnosis. They report reduced frequencies of invariant NKT and NKT-like cells in CI relative to UI, likely due to increased cell death in the recovery phase, and an expansion of DCs in CI. Analysis of the T cell compartment showed an increase in the frequency of regulatory T cells, higher expression of TIM-3 on CD4 and CD8 T cells, lower GzmB expression with slightly enhanced proliferation status in CI and intact effector function to TCR stimulation. DCs and B cells showed increased expression of costimulatory molecules, suggesting a slightly enhanced activation status. Together these data suggest that SARS-Cov-2 infection elicits a sustained impact on immune cell composition in the extended convalescent phase and an ongoing restoration of immune homeostasis 

Research Highlights : 

  1. A decline in invariant NKT and NKT-like cells in convalescent COVID compared to controls. 

  1. Increased proportion NKT-like cells of convalescent COVID that are undergoing apoptosis and/or necroptosis even after recovery from COVID-19 

  1. Long-term suppression of cytotoxic capacity, as based on GzmB production, of T and NKT-like cells after resolving from SARS-CoV2 infection.  

  1. No differences in PD-1 expression but 20-30% increase of other exhaustion markers as Tim-3 and TOX in both CD4 and CD8 T cell populations. 

  1. General effector functions maintained, with enhanced activation and proliferation of T cells, suggesting ongoing restoration of the immune homeostasis. 

Impact for COVID-19 research:  

  • Understand long-term of SARS-CoV2 infection in cellular immune cells 


  • Study Typee.g. in vitro and ex vivo 

  • Important cell lines/viral models used: PBMCs from SARS-CoV-2 patients and healthy donors. Viral model was natural infection of SARS-CoV-2. 

  • Key Techniques: flow cytometry analysis. 


  • Phenotypic analysis is limited and it is not integrated with antibody levels, clinical phenotypes (presence of co-morbidities), length of recovery and/or persistent symptoms in the extended convalescent phase. As such only limited conclusions can be reached from this study.  

  • iNKT cells were studied from a different demographically distinct cohort (German cohort) with more recent COVID-19 recovery and what looks like milder disease on the basis of the limited information provided. Further studies are needed to corroborate these findings and investigate whether potential redistribution of iNKT cells could contribute to the reduced frequencies observed in the peripheral blood.   

  • The authors performed ex-vivo analysis based on GzmB, as a marker of cytotoxicity. A wider evaluation of functional responses/cytotoxicity of NKT-cells in response to innate cytokine stimulation and iNKT cells in responding to α-GalCer stimulation would strengthen these observations.  

  • The study analyzed T cell responses and their proliferating capacity to TCR stimulation. However, this is limited to n=5 CI and n=5 UI and shows a wide range of responses particularly for IL-2 and TNFa production in the CI group. It is unclear how the donors were selected for the functional study i.e disease severity and how the functional data relate to phenotype and transcription profile.  

  • Although not a limitation per se, it would be of great interest to examine responses to SARS-CoV2 antigens and analyze virus-specific populations.