Manuscript Detail

Title: Immune Profile in Patients With COVID-19: Lymphocytes Exhaustion Markers in Relationship to Clinical Outcome
Authors: Bobcakova, Anna et al
Abstract: The velocity of the COVID-19 pandemic spread and the variable severity of the disease course has forced scientists to search for potential predictors of the disease outcome. We examined various immune parameters including the markers of immune cells exhaustion and activation in 21 patients with COVID-19 disease hospitalised in our hospital during the first wave of the COVID-19 pandemic in Slovakia. The results showed significant progressive lymphopenia and depletion of lymphocyte subsets (CD3(+), CD4(+), CD8(+) and CD19(+)) in correlation to the disease severity. Clinical recovery was associated with significant increase in CD3(+) and CD3(+)CD4(+) T-cells. Most of our patients had eosinopenia on admission, although no significant differences were seen among groups with different disease severity. Non-survivors, when compared to survivors, had significantly increased expression of PD-1 on CD4(+) and CD8(+) cells, but no significant difference in Tim-3 expression was observed, what suggests possible reversibility of immune paralysis in the most severe group of patients. During recovery, the expression of Tim-3 on both CD3(+)CD4(+) and CD3(+)CD8(+) cells significantly decreased. Moreover, patients with fatal outcome had significantly higher proportion of CD38(+)CD8(+) cells and lower proportion of CD38(+)HLA-DR(+)CD8(+) cells on admission. Clinical recovery was associated with significant decrease of proportion of CD38(+)CD8(+) cells. The highest AUC values within univariate and multivariate logistic regression were achieved for expression of CD38 on CD8(+) cells and expression of PD1 on CD4(+) cells alone or combined, what suggests, that these parameters could be used as potential biomarkers of poor outcome. The assessment of immune markers could help in predicting outcome and disease severity in COVID-19 patients. Our observations suggest, that apart from the degree of depletion of total lymphocytes and lymphocytes subsets, increased expression of CD38 on CD3(+)CD8(+) cells alone or combined with increased expression of PD-1 on CD3(+)CD4(+) cells, should be regarded as a risk factor of an unfavourable outcome in COVID-19 patients. Increased expression of PD-1 in the absence of an increased expression of Tim-3 on CD3(+)CD4(+) and CD3(+)CD8(+) cells suggests potential reversibility of ongoing immune paralysis in patients with the most severe course of COVID-19.
Journal: Front Cell Infect Microbiol
Curator: Jane Wang
Reviewer: Aris Floratos
Author-provided data: ?

paper: Bobcakova, A., Petriskova, J., Vysehradsky, R., Kocan, I., Kapustova, L., Barnova, M., Diamant, Z. and Jesenak, M. (2021). Immune Profile in Patients With COVID-19: Lymphocytes Exhaustion Markers in Relationship to Clinical Outcome. Front Cell Infect Microbiol https://doi.org/10.3389/fcimb.2021.646688
contributor: Anna Bobcakova, Milos Jesenak
contributor_organization: Comenius University in Bratislava
contributor_email: abobcakova@gmail.com, jesenak@gmail.com

 

    • description: Total lymphocytes count on admission of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
    • exact_source: Figure 3
    • tissue: total lymphocytes
    • immune_exposure: Covid-19 infection
    • cohort: hospitalized adult patients
    • comparison: fatal vs. mild/moderate on admission
    • repository_id: not applicable
    • platform: total lymphocytes
    • response_components:
    • response_behavior: down
        • description: Total lymphocytes count on admission of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
        • exact_source: Figure 3
        • tissue: total lymphocytes
        • immune_exposure: Covid-19 infection
        • cohort: hospitalized adult patients
        • comparison: fatal vs. severe on admission
        • repository_id: not applicable
        • platform: total lymphocytes
        • response_components:
        • response_behavior: down
            • description: Total lymphocytes count on admission of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
            • exact_source: Figure 3
            • tissue: total lymphocytes
            • immune_exposure: Covid-19 infection
            • cohort: hospitalized adult patients
            • comparison: critical vs. mild/moderate on admission
            • repository_id: not applicable
            • platform: total lymphocytes
            • response_components:
            • response_behavior: down
                • description: Total lymphocytes count on admission of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
                • exact_source: Figure 3
                • tissue: total lymphocytes
                • immune_exposure: Covid-19 infection
                • cohort: hospitalized adult patients
                • comparison: severe vs. mild/moderate on admission
                • repository_id: not applicable
                • platform: total lymphocytes
                • response_components:
                • response_behavior: down
                    • description: The lowest lymphocyte count during hospitalization of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
                    • exact_source: Figure 4
                    • tissue: total lymphocytes
                    • immune_exposure: Covid-19 infection
                    • cohort: hospitalized adult patients
                    • comparison: fatal vs. severe
                    • repository_id: not applicable
                    • platform: total lymphocytes
                    • response_components:
                    • response_behavior: down
                        • description: The lowest lymphocyte count during hospitalization of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
                        • exact_source: Figure 4
                        • tissue: total lymphocytes
                        • immune_exposure: Covid-19 infection
                        • cohort: hospitalized adult patients
                        • comparison: fatal vs. mild/moderate
                        • repository_id: not applicable
                        • platform: total lymphocytes
                        • response_components:
                        • response_behavior: down
                            • description: The lowest lymphocyte count during hospitalization of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
                            • exact_source: Figure 4
                            • tissue: total lymphocytes
                            • immune_exposure: Covid-19 infection
                            • cohort: hospitalized adult patients
                            • comparison: critilal vs. severe
                            • repository_id: not applicable
                            • platform: total lymphocytes
                            • response_components:
                            • response_behavior: down
                                • description: The lowest lymphocyte count during hospitalization of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
                                • exact_source: Figure 4
                                • tissue: total lymphocytes
                                • immune_exposure: Covid-19 infection
                                • cohort: hospitalized adult patients
                                • comparison: critical vs. mild/moderate
                                • repository_id: not applicable
                                • platform: total lymphocytes
                                • response_components:
                                • response_behavior: down
                                    • description: Neutrophil-to-lymphocyte ratio on admission of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
                                    • exact_source: Figure 5B
                                    • tissue: neutrophils-to-lymphocytes ratio
                                    • immune_exposure: Covid-19 infection
                                    • cohort: hospitalized adult patients
                                    • comparison: fatal vs. mild/moderate
                                    • repository_id: not applicable
                                    • platform: neutrophils, lymphocytes
                                    • response_components:
                                    • response_behavior: up
                                        • description: Neutrophil-to-lymphocyte ratio on admission of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
                                        • exact_source: Figure 5B
                                        • tissue: neutrophils-to-lymphocytes ratio
                                        • immune_exposure: Covid-19 infection
                                        • cohort: hospitalized adult patients
                                        • comparison: fatal vs. severe
                                        • repository_id:
                                        • platform: neutrophils, lymphocytes
                                        • response_components:
                                        • response_behavior: up
                                            • description: Neutrophil-to-lymphocyte ratio on admission of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
                                            • exact_source: Figure 5B
                                            • tissue: neutrophils-to-lymphocytes ratio
                                            • immune_exposure: Covid-19 infection
                                            • cohort: hospitalized adult patients
                                            • comparison: critical vs. mild/moderate
                                            • repository_id:
                                            • platform: neutrophils, lymphocytes
                                            • response_components:
                                            • response_behavior: up
                                                • description: Neutrophil-to-lymphocyte ratio on admission of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
                                                • exact_source: Figure 5B
                                                • tissue: neutrophils-to-lymphocytes ratio
                                                • immune_exposure: Covid-19 infection
                                                • cohort: hospitalized adult patients
                                                • comparison: critical vs.severe
                                                • repository_id:
                                                • platform: neutrophils, lymphocytes
                                                • response_components:
                                                • response_behavior: up
                                                    • description: Neutrophil-to-lymphocyte ratio on admission of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
                                                    • exact_source: Figure 5B
                                                    • tissue: neutrophils-to-lymphocytes ratio
                                                    • immune_exposure: Covid-19 infection
                                                    • cohort: hospitalized adult patients
                                                    • comparison: severe vs mild/moderate
                                                    • repository_id:
                                                    • platform: neutrophils, lymphocytes
                                                    • response_components:
                                                    • response_behavior: up
                                                        • description: CD3-positive T cells on admission of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
                                                        • exact_source: Figure 6A
                                                        • tissue: CD3-positive T cells
                                                        • immune_exposure: Covid-19 infection
                                                        • cohort: hospitalized adult patients
                                                        • comparison: fatal vs. severe
                                                        • repository_id:
                                                        • platform: CD3-positive T cells
                                                        • response_components:
                                                        • response_behavior: down
                                                            • description: CD3-positive T cells on admission of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
                                                            • exact_source: Figure 6A
                                                            • tissue: CD3-positive T cells
                                                            • immune_exposure: Covid-19 infection
                                                            • cohort: hospitalized adult patients
                                                            • comparison: fatal vs mild/moderate
                                                            • repository_id:
                                                            • platform: CD3-positive T cells
                                                            • response_components:
                                                            • response_behavior: down
                                                                • description: CD3-positive T cells on admission of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
                                                                • exact_source: Figure 6A
                                                                • tissue: CD3-positive T cells
                                                                • immune_exposure: Covid-19 infection
                                                                • cohort: hospitalized adult patients
                                                                • comparison: critical vs. severe
                                                                • repository_id:
                                                                • platform: CD3-positive T cells
                                                                • response_components:
                                                                • response_behavior: down
                                                                    • description: CD3-positive T cells on admission of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
                                                                    • exact_source: Figure 6A
                                                                    • tissue: CD3-positive T cells
                                                                    • immune_exposure: Covid-19 infection
                                                                    • cohort: hospitalized adult patients
                                                                    • comparison: critical vs mild/moderate
                                                                    • repository_id:
                                                                    • platform: CD3-positive T cells
                                                                    • response_components:
                                                                    • response_behavior: down
                                                                        • description: CD3-positive T cells on admission of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
                                                                        • exact_source: Figure 6A
                                                                        • tissue: CD3-positive T cells
                                                                        • immune_exposure: Covid-19 infection
                                                                        • cohort: hospitalized adult patients
                                                                        • comparison: severe vs mild/moderate
                                                                        • repository_id:
                                                                        • platform: CD3-positive T cells
                                                                        • response_components:
                                                                        • response_behavior: down
                                                                            • description: CD4-positive helper T cells on admission of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
                                                                            • exact_source: Figure 6B
                                                                            • tissue: CD4-positive helper T cells
                                                                            • immune_exposure: Covid-19 infection
                                                                            • cohort: hospitalized adult patients
                                                                            • comparison: fatal vs mild/moderate
                                                                            • repository_id:
                                                                            • platform: CD4-positive helper T cells
                                                                            • response_components:
                                                                            • response_behavior: down
                                                                                • description: CD8-positive cytotoxic T cells on admission of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
                                                                                • exact_source: Figure 6C
                                                                                • tissue: CD8-positive cytotoxic T cells
                                                                                • immune_exposure: Covid-19 infection
                                                                                • cohort: hospitalized adult patients
                                                                                • comparison: fatal vs severe
                                                                                • repository_id:
                                                                                • platform: CD8-positive cytotoxic T cells
                                                                                • response_components:
                                                                                • response_behavior: down
                                                                                    • description: CD8-positive cytotoxic T cells on admission of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
                                                                                    • exact_source: Figure 6C
                                                                                    • tissue: CD8-positive cytotoxic T cells
                                                                                    • immune_exposure: Covid-19 infection
                                                                                    • cohort: hospitalized adult patients
                                                                                    • comparison: fatal vs mild/moderate
                                                                                    • repository_id:
                                                                                    • platform: CD8-positive cytotoxic T cells
                                                                                    • response_components:
                                                                                    • response_behavior: down
                                                                                        • description: CD8-positive cytotoxic T cells on admission of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
                                                                                        • exact_source: Figure 6C
                                                                                        • tissue: CD8-positive cytotoxic T cells
                                                                                        • immune_exposure: Covid-19 infection
                                                                                        • cohort: hospitalized adult patients
                                                                                        • comparison: critical vs severe
                                                                                        • repository_id:
                                                                                        • platform: CD8-positive cytotoxic T cells
                                                                                        • response_components:
                                                                                        • response_behavior: down
                                                                                            • description: CD8-positive cytotoxic T cells on admission of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
                                                                                            • exact_source: Figure 6C
                                                                                            • tissue: CD8-positive cytotoxic T cells
                                                                                            • immune_exposure: Covid-19 infection
                                                                                            • cohort: hospitalized adult patients
                                                                                            • comparison: critical vs mild/moderate
                                                                                            • repository_id:
                                                                                            • platform: CD8-positive cytotoxic T cells
                                                                                            • response_components:
                                                                                            • response_behavior: down
                                                                                                • description: CD8-positive cytotoxic T cells on admission of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
                                                                                                • exact_source: Figure 6C
                                                                                                • tissue: CD8-positive cytotoxic T cells
                                                                                                • immune_exposure: Covid-19 infection
                                                                                                • cohort: hospitalized adult patients
                                                                                                • comparison: severe vs mild/moderate
                                                                                                • repository_id:
                                                                                                • platform: CD8-positive cytotoxic T cells
                                                                                                • response_components:
                                                                                                • response_behavior: down
                                                                                                    • description: CD19-positive B-cells on admission of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
                                                                                                    • exact_source: Figure 6D
                                                                                                    • tissue: CD19-positive B-cells
                                                                                                    • immune_exposure: Covid-19 infection
                                                                                                    • cohort: hospitalized adult patients
                                                                                                    • comparison: fatal vs severe
                                                                                                    • repository_id:
                                                                                                    • platform: CD19-positive B-cells
                                                                                                    • response_components:
                                                                                                    • response_behavior: down
                                                                                                        • description: CD19-positive B-cells on admission of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
                                                                                                        • exact_source: Figure 6D
                                                                                                        • tissue: CD19-positive B-cells
                                                                                                        • immune_exposure: Covid-19 infection
                                                                                                        • cohort: hospitalized adult patients
                                                                                                        • comparison: fatal vs mild/moderate
                                                                                                        • repository_id:
                                                                                                        • platform: CD19-positive B-cells
                                                                                                        • response_components:
                                                                                                        • response_behavior: down
                                                                                                            • description: CD19-positive B-cells on admission of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
                                                                                                            • exact_source: Figure 6D
                                                                                                            • tissue: CD19-positive B-cells
                                                                                                            • immune_exposure: Covid-19 infection
                                                                                                            • cohort: hospitalized adult patients
                                                                                                            • comparison: critical vs mild/moderate
                                                                                                            • repository_id:
                                                                                                            • platform: CD19-positive B-cells
                                                                                                            • response_components:
                                                                                                            • response_behavior: down
                                                                                                                • description: CD19-positive B-cells on admission of adult patients hospitalized with Covid-19 when comparing mild/moderate; severe; critical and fatal course of the disease
                                                                                                                • exact_source: Figure 6D
                                                                                                                • tissue: CD19-positive B-cells
                                                                                                                • immune_exposure: Covid-19 infection
                                                                                                                • cohort: hospitalized adult patients
                                                                                                                • comparison: critical vs severe
                                                                                                                • repository_id:
                                                                                                                • platform: CD19-positive B-cells
                                                                                                                • response_components:
                                                                                                                • response_behavior: down
                                                                                                                    • description: The dynamics of CD3-positive T cells from admission to recovery in symptomatic survivors (critical, severe patients)
                                                                                                                    • exact_source: Figure 7A
                                                                                                                    • tissue: CD3-positive T cells
                                                                                                                    • immune_exposure: Covid-19 infection
                                                                                                                    • cohort: hospitalized adult patients
                                                                                                                    • comparison: recovery vs admission
                                                                                                                    • repository_id:
                                                                                                                    • platform: CD3-positive T cells
                                                                                                                    • response_components:
                                                                                                                    • response_behavior: up
                                                                                                                        • description: The dynamics of CD4-positive helper T cells from admission to recovery in symptomatic survivors (critical, severe patients)
                                                                                                                        • exact_source: Figure 7B
                                                                                                                        • tissue: CD4-positive helper T cells
                                                                                                                        • immune_exposure: Covid-19 infection
                                                                                                                        • cohort: hospitalized adult patients
                                                                                                                        • comparison: recovery vs. admission
                                                                                                                        • repository_id:
                                                                                                                        • platform: CD4-positive helper T cells
                                                                                                                        • response_components:
                                                                                                                        • response_behavior: up
                                                                                                                            • description: PD1 positive helper T-cells in hospitalized patients with Covid-19, when comparing survivors and non-survivors
                                                                                                                            • exact_source: Figure 8A
                                                                                                                            • tissue: PD1 positive helper T-cells
                                                                                                                            • immune_exposure: Covid-19 infection
                                                                                                                            • cohort: hospitalized adult patients
                                                                                                                            • comparison: survivors vs non-survivors
                                                                                                                            • repository_id:
                                                                                                                            • platform: PD1 positive helper T-cells
                                                                                                                            • response_components:
                                                                                                                            • response_behavior: down
                                                                                                                                • description: PD1 positive cytotoxic T-cells in hospitalized patients with Covid-19, when comparing survivors and non-survivors
                                                                                                                                • exact_source: Figure 8B
                                                                                                                                • tissue: PD1 positive cytotoxic T-cells
                                                                                                                                • immune_exposure: Covid-19 infection
                                                                                                                                • cohort: hospitalized adult patients
                                                                                                                                • comparison: survivors vs non-survivors
                                                                                                                                • repository_id:
                                                                                                                                • platform: PD1 positive cytotoxic T-cells
                                                                                                                                • response_components:
                                                                                                                                • response_behavior: down
                                                                                                                                    • description: The dynamics of Tim-3 positive cytotoxic T-cells in hospitalized patients with Covid-19, from admission to recovery in symptomatic survivors (critical, severe patients)
                                                                                                                                    • exact_source: Figure 9B
                                                                                                                                    • tissue: Tim-3 positive cytotoxic T-cells
                                                                                                                                    • immune_exposure: Covid-19 infection
                                                                                                                                    • cohort: hospitalized adult patients
                                                                                                                                    • comparison: recovery vs admission
                                                                                                                                    • repository_id:
                                                                                                                                    • platform: Tim-3 positive cytotoxic T-cells
                                                                                                                                    • response_components:
                                                                                                                                    • response_behavior: down
                                                                                                                                        • description: The dynamics of Tim-3 positive helper T-cells in hospitalized patients with Covid-19, from admission to recovery in symptomatic survivors (critical, severe patients)
                                                                                                                                        • exact_source: Figure 9A
                                                                                                                                        • tissue: Tim-3 positive helper T-cells
                                                                                                                                        • immune_exposure: Covid-19 infection
                                                                                                                                        • cohort: hospitalized adult patients
                                                                                                                                        • comparison: recovery vs admission
                                                                                                                                        • repository_id:
                                                                                                                                        • platform: Tim-3 positive helper T-cells
                                                                                                                                        • response_components:
                                                                                                                                        • response_behavior: down
                                                                                                                                            • description: CD38 positive cytotoxic T-cells in hospitalized patients with Covid-19, when comparing survivors and non-survivors
                                                                                                                                            • exact_source: Figure 10A
                                                                                                                                            • tissue: CD38 positive cytotoxic T-cells
                                                                                                                                            • immune_exposure: Covid-19 infection
                                                                                                                                            • cohort: hospitalized adult patients
                                                                                                                                            • comparison: survivors vs non-survivors
                                                                                                                                            • repository_id:
                                                                                                                                            • platform: CD38 positive cytotoxic T-cells
                                                                                                                                            • response_components:
                                                                                                                                            • response_behavior: down
                                                                                                                                                • description: CD38 positive HLA-DR positive cytotoxic T-cells in hospitalized patients with Covid-19, when comparing survivors and non-survivors
                                                                                                                                                • exact_source: Figure 10B
                                                                                                                                                • tissue: CD38 positive HLA-DR positive cytotoxic T-cells
                                                                                                                                                • immune_exposure: Covid-19 infection
                                                                                                                                                • cohort: hospitalized adult patients
                                                                                                                                                • comparison: survivors vs non-survivors
                                                                                                                                                • repository_id:
                                                                                                                                                • platform: CD38 positive HLA-DR positive cytotoxic T-cells
                                                                                                                                                • response_components:
                                                                                                                                                • response_behavior: up
                                                                                                                                                    • description: The dynamics of CD38 positive cytotoxic T-cells in hospitalized patients with Covid-19, from admission to recovery in symptomatic survivors (critical, severe patients)
                                                                                                                                                    • exact_source: Figure 10C
                                                                                                                                                    • tissue: CD38 positive cytotoxic T-cells
                                                                                                                                                    • immune_exposure: Covid-19 infection
                                                                                                                                                    • cohort: hospitalized adult patients
                                                                                                                                                    • comparison: recovery vs admission
                                                                                                                                                    • repository_id:
                                                                                                                                                    • platform: CD38 positive cytotoxic T-cells
                                                                                                                                                    • response_components:
                                                                                                                                                    • response_behavior: down

 

Spreadsheet: Link to curation spreadsheet