tetano
Editor, Senior Moderator
mBio
. 2021 Apr 27;12(2):e00085-21.
doi: 10.1128/mBio.00085-21.
Analysis of the Long-Term Impact on Cellular Immunity in COVID-19-Recovered Individuals Reveals a Profound NKT Cell Impairment
Jia Liu[SUP] #[/SUP][SUP] 1 2 [/SUP], Xuecheng Yang[SUP] #[/SUP][SUP] 3 2 [/SUP], Hua Wang[SUP] 3 [/SUP], Ziwei Li[SUP] 3 2 [/SUP], Hui Deng[SUP] 3 2 [/SUP], Jing Liu[SUP] 3 2 [/SUP], Shue Xiong[SUP] 3 2 [/SUP], Junyi He[SUP] 3 2 [/SUP], Xuemei Feng[SUP] 3 2 [/SUP], Chunxia Guo[SUP] 3 [/SUP], Weixian Wang[SUP] 3 [/SUP], Gennadiy Zelinskyy[SUP] 4 2 [/SUP], Mirko Trilling[SUP] 4 2 [/SUP], Kathrin Sutter[SUP] 4 2 [/SUP], Tina Senff[SUP] 5 [/SUP], Christopher Menne[SUP] 5 [/SUP], Joerg Timm[SUP] 5 [/SUP], Yanfang Zhang[SUP] 6 [/SUP], Fei Deng[SUP] 6 [/SUP], Yinping Lu[SUP] 3 2 [/SUP], Jun Wu[SUP] 3 2 [/SUP], Mengji Lu[SUP] 4 2 [/SUP], Dongliang Yang[SUP] 3 2 [/SUP], Ulf Dittmer[SUP] 4 2 [/SUP], Baoju Wang[SUP] 1 2 [/SUP], Xin Zheng[SUP] 3 2 [/SUP]
Affiliations
Abstract
The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affected over 120 million people and killed over 2.7 million individuals by March 2021. While acute and intermediate interactions between SARS-CoV-2 and the immune system have been studied extensively, long-term impacts on the cellular immune system remain to be analyzed. Here, we comprehensively characterized immunological changes in peripheral blood mononuclear cells in 49 COVID-19-convalescent individuals (CI) in comparison to 27 matched SARS-CoV-2-unexposed individuals (UI). Despite recovery from the disease for more than 2 months, CI showed significant decreases in frequencies of invariant NKT and NKT-like cells compared to UI. Concomitant with the decrease in NKT-like cells, an increase in the percentage of annexin V and 7-aminoactinomycin D (7-AAD) double-positive NKT-like cells was detected, suggesting that the reduction in NKT-like cells results from cell death months after recovery. Significant increases in regulatory T cell frequencies and TIM-3 expression on CD4 and CD8 T cells were also observed in CI, while the cytotoxic potential of T cells and NKT-like cells, defined by granzyme B (GzmB) expression, was significantly diminished. However, both CD4 and CD8 T cells of CI showed increased Ki67 expression and were fully able to proliferate and produce effector cytokines upon T cell receptor (TCR) stimulation. Collectively, we provide a comprehensive characterization of immune signatures in patients recovering from SARS-CoV-2 infection, suggesting that the cellular immune system of COVID-19 patients is still under a sustained influence even months after the recovery from disease.IMPORTANCE Wuhan was the very first city hit by SARS-CoV-2. Accordingly, the patients who experienced the longest phase of convalescence following COVID-19 reside here. This enabled us to investigate the "immunological scar" left by SARS-CoV-2 on cellular immunity after recovery from the disease. In this study, we characterized the long-term impact of SARS-CoV-2 infection on the immune system and provide a comprehensive picture of cellular immunity of a convalescent COVID-19 patient cohort with the longest recovery time. We revealed that the cellular immune system of COVID-19 patients is still under a sustained influence even months after the recovery from disease; in particular, a profound NKT cell impairment was found in the convalescent phase of COVID-19.
Keywords: COVID-19; NKT cell; SARS-CoV-2; cellular immunity.
. 2021 Apr 27;12(2):e00085-21.
doi: 10.1128/mBio.00085-21.
Analysis of the Long-Term Impact on Cellular Immunity in COVID-19-Recovered Individuals Reveals a Profound NKT Cell Impairment
Jia Liu[SUP] #[/SUP][SUP] 1 2 [/SUP], Xuecheng Yang[SUP] #[/SUP][SUP] 3 2 [/SUP], Hua Wang[SUP] 3 [/SUP], Ziwei Li[SUP] 3 2 [/SUP], Hui Deng[SUP] 3 2 [/SUP], Jing Liu[SUP] 3 2 [/SUP], Shue Xiong[SUP] 3 2 [/SUP], Junyi He[SUP] 3 2 [/SUP], Xuemei Feng[SUP] 3 2 [/SUP], Chunxia Guo[SUP] 3 [/SUP], Weixian Wang[SUP] 3 [/SUP], Gennadiy Zelinskyy[SUP] 4 2 [/SUP], Mirko Trilling[SUP] 4 2 [/SUP], Kathrin Sutter[SUP] 4 2 [/SUP], Tina Senff[SUP] 5 [/SUP], Christopher Menne[SUP] 5 [/SUP], Joerg Timm[SUP] 5 [/SUP], Yanfang Zhang[SUP] 6 [/SUP], Fei Deng[SUP] 6 [/SUP], Yinping Lu[SUP] 3 2 [/SUP], Jun Wu[SUP] 3 2 [/SUP], Mengji Lu[SUP] 4 2 [/SUP], Dongliang Yang[SUP] 3 2 [/SUP], Ulf Dittmer[SUP] 4 2 [/SUP], Baoju Wang[SUP] 1 2 [/SUP], Xin Zheng[SUP] 3 2 [/SUP]
Affiliations
- PMID: 33906918
- DOI: 10.1128/mBio.00085-21
Abstract
The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) affected over 120 million people and killed over 2.7 million individuals by March 2021. While acute and intermediate interactions between SARS-CoV-2 and the immune system have been studied extensively, long-term impacts on the cellular immune system remain to be analyzed. Here, we comprehensively characterized immunological changes in peripheral blood mononuclear cells in 49 COVID-19-convalescent individuals (CI) in comparison to 27 matched SARS-CoV-2-unexposed individuals (UI). Despite recovery from the disease for more than 2 months, CI showed significant decreases in frequencies of invariant NKT and NKT-like cells compared to UI. Concomitant with the decrease in NKT-like cells, an increase in the percentage of annexin V and 7-aminoactinomycin D (7-AAD) double-positive NKT-like cells was detected, suggesting that the reduction in NKT-like cells results from cell death months after recovery. Significant increases in regulatory T cell frequencies and TIM-3 expression on CD4 and CD8 T cells were also observed in CI, while the cytotoxic potential of T cells and NKT-like cells, defined by granzyme B (GzmB) expression, was significantly diminished. However, both CD4 and CD8 T cells of CI showed increased Ki67 expression and were fully able to proliferate and produce effector cytokines upon T cell receptor (TCR) stimulation. Collectively, we provide a comprehensive characterization of immune signatures in patients recovering from SARS-CoV-2 infection, suggesting that the cellular immune system of COVID-19 patients is still under a sustained influence even months after the recovery from disease.IMPORTANCE Wuhan was the very first city hit by SARS-CoV-2. Accordingly, the patients who experienced the longest phase of convalescence following COVID-19 reside here. This enabled us to investigate the "immunological scar" left by SARS-CoV-2 on cellular immunity after recovery from the disease. In this study, we characterized the long-term impact of SARS-CoV-2 infection on the immune system and provide a comprehensive picture of cellular immunity of a convalescent COVID-19 patient cohort with the longest recovery time. We revealed that the cellular immune system of COVID-19 patients is still under a sustained influence even months after the recovery from disease; in particular, a profound NKT cell impairment was found in the convalescent phase of COVID-19.
Keywords: COVID-19; NKT cell; SARS-CoV-2; cellular immunity.