Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Feb 2:12:603563.
doi: 10.3389/fimmu.2021.603563. eCollection 2021.

Impaired Cellular Immunity to SARS-CoV-2 in Severe COVID-19 Patients

Affiliations

Impaired Cellular Immunity to SARS-CoV-2 in Severe COVID-19 Patients

Ling Ni et al. Front Immunol. .

Abstract

The high infection rate and rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) make it a world-wide pandemic. Individuals infected by the virus exhibited different degrees of symptoms, and most convalescent individuals have been shown to develop both cellular and humoral immune responses. However, virus-specific adaptive immune responses in severe patients during acute phase have not been thoroughly studied. Here, we found that in a group of COVID-19 patients with acute respiratory distress syndrome (ARDS) during hospitalization, most of them mounted SARS-CoV-2-specific antibody responses, including neutralizing antibodies. However, compared to healthy controls, the percentages and absolute numbers of both NK cells and CD8+ T cells were significantly reduced, with decreased IFNγ expression in CD4+ T cells in peripheral blood from severe patients. Most notably, their peripheral blood lymphocytes failed in producing IFNγ against viral proteins. Thus, severe COVID-19 patients at acute infection stage developed SARS-CoV-2-specific antibody responses but were impaired in cellular immunity, which emphasizes on the role of cellular immunity in COVID-19.

Keywords: SARS-CoV-2; T cells; acute respiratory distress syndrome; adaptive immunity; interferon gamma; neutralization antibody.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Presence of SARS-CoV-2 NP- and S-RBD-specific antibodies in severe COVID-19 patients. (A) Titration of individual serum samples. (B) Data from the same experiments as (A) were presented as area under curve (AUC). (C) IgG isotypes of 10 COVID-19 patients to recombinant NP and S-RBD. (D) Serum ELISA titers to NP and S-RBD in sera from convalescent individuals (n=14), severe patients (n=10) and HD (n=10). The experiment was performed in duplicates. NP, nucleocapsid protein. S-RBD, receptor binding domain of spike protein. HD, healthy donor; Pt, patient; AUC, area under curve. HD#1-9, the sera were collected before SARS-CoV-2 outbreak. *P<0.05, 0.05<**P<0.001. ns, not significant.
Figure 2
Figure 2
Measurement of neutralizing antibodies in severe patients. (A) Neutralizing antibody titers of 10 severe COVID-19 patients. (B) Comparison of NAT50 between convalescent subjects (n=14) and severe patients (n=10). Date are presented as Mean ± SEM. (C) Pie plot showing NAT50 range in severe and convalescent patients. HD, healthy donor; Pt, patient; NAT50, neutralizing antibody titers. ns, not significant.
Figure 3
Figure 3
Phenotypic analysis of blood lymphocytes in severe COVID-19 patients. (A) Phenotypic analysis of PBMCs from one representative COVID-19 patient. (B) Summarized data on the frequencies of different immune cell subsets in COVID-19 patients and the ratio of CD4:CD8 T cells. (C) Summarized data on the absolute numbers of different immune cell subsets in COVID-19 patients. HD, healthy donors (HD#10-14); Pt, patients (n=7). Data are presented as Mean ± SEM. *P<0.05, 0.05<**P<0.001, ***P<0.001. ns, not significant.
Figure 4
Figure 4
SARS-CoV-2-specific T cell responses in COVID-19 patients. (A) Intracellular cytokine staining of CD3+CD56-CD8- T cells. (B) Summarized data on the frequencies of cytokine-producing CD3+CD56-CD8- T cells as indicated. (C) Summarized data on the frequencies of polyfunctional CD3+CD56-CD8- T cells as indicated. (D) Representative FACS plots showing polyfunctional CD3+CD56-CD8- T cells. (E) IFNγ ELISpot analysis of PBMCs from severe COVID-19 patients (n=7) and convalescent individuals (n=7) to anti-CD3 antibody. (F) IFNγ ELISpot analysis of PBMCs from severe COVID-19 patients (n=7) and convalescent individuals (n=14) to and viral proteins. The experiment with patients was performed in duplicates. (G) The ratios of IFNγ-producing T cells in response to NP or anti-CD3 stimulation in both convalescent (n=14) and severe (n=7) patients. (H) Correlation between NAT50 and the percentage of TNFα+ CD4+ T cells. Date are presented as Mean ± SEM. *P<0.05, 0.05<**P<0.001. ns, not significant.

References

    1. Wang C, Horby PW, Hayden FG, Gao GF. A novel coronavirus outbreak of global health concern. Lancet (2020) 395:470–3. 10.1016/S0140-6736(20)30185-9 - DOI - PMC - PubMed
    1. Di Pierro F, Bertuccioli A, Cavecchia I. Possible therapeutic role of a highly standardized mixture of active compounds derived from cultured Lentinula edodes mycelia (AHCC) in patients infected with 2019 novel coronavirus. Minerva Gastroenterol Dietol (2020) 66(2):172–176. 10.23736/S1121-421X.20.02697-5 - DOI - PubMed
    1. Gruszecka J, Filip R. Preliminary information on prevention of infections caused by SARS-COV-2 virus in endoscopic laboratories. Ann Agric Environ Med (2020) 27:171–4. 10.26444/aaem/122137 - DOI - PubMed
    1. Ni L, Ye F, Cheng ML, Feng Y, Deng YQ, Zhao H, et al. Detection of SARS-CoV-2-Specific Humoral and Cellular Immunity in COVID-19 Convalescent Individuals. Immunity (2020) 52:971–7e973. 10.1016/j.immuni.2020.04.023 - DOI - PMC - PubMed
    1. Wu F, Liu M, Wang A, Lu L, Wang Q, Gu C, et al. Evaluating the Association of Clinical Characteristics With Neutralizing Antibody Levels in Patients Who Have Recovered From Mild COVID-19 in Shanghai, China. JAMA Intern Med (2020) 180(10):1356–62. 10.1001/jamainternmed.2020.4616 - DOI - PMC - PubMed

Publication types