Manuscript Detail

Title: Unique immunological profile in patients with COVID-19.
Authors: Varchetta, Stefania et al
Abstract: The relationship between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and host immunity is poorly understood. We performed an extensive analysis of immune responses in 32 patients with severe COVID-19, some of whom succumbed. A control population of healthy subjects was included. Patients with COVID-19 had an altered distribution of peripheral blood lymphocytes, with an increased proportion of mature natural killer (NK) cells and low T-cell numbers. NK cells and CD8+ T cells overexpressed T-cell immunoglobulin and mucin domain-3 (TIM-3) and CD69. NK cell exhaustion was attested by increased frequencies of programmed cell death protein 1 (PD-1) positive cells and reduced frequencies of natural killer group 2 member D (NKG2D)-, DNAX accessory molecule-1 (DNAM-1)- and sialic acid-binding Ig-like lectin 7 (Siglec-7)-expressing NK cells, associated with a reduced ability to secrete interferon (IFN)γ. Patients with poor outcome showed a contraction of immature CD56bright and an expansion of mature CD57+ FcεRIγneg adaptive NK cells compared to survivors. Increased serum levels of IL-6 were also more frequently identified in deceased patients compared to survivors. Of note, monocytes secreted abundant quantities of IL-6, IL-8, and IL-1β which persisted at lower levels several weeks after recovery with concomitant normalization of CD69, PD-1 and TIM-3 expression and restoration of CD8+ T cell numbers. A hyperactivated/exhausted immune response dominate in severe SARS-CoV-2 infection, probably driven by an uncontrolled secretion of inflammatory cytokines by monocytes. These findings unveil a unique immunological profile in COVID-19 patients that will help to design effective stage-specific treatments for this potentially deadly disease.
Journal: Cellular & molecular immunology
Curator: Hancock Lab
Reviewer: Aris Floratos
Author-provided data: ?

paper: Varchetta, S., Mele, D., Oliviero, B. et al. Unique immunological profile in patients with COVID-19. Cell Mol Immunol (2020). https://doi.org/10.1038/s41423-020-00557-9
contributor: Mario U. Mondelli
contributor_organization: Università di Pavia
contributor_email: mario.mondelli@unipv.it

 

    • description: Decreased frequency of CD56bright NK cells when comparing Covid-19 infected patients vs. healthy donors or dead vs. survivor patients.
    • exact_source: Fig. 1b
    • tissue: PBMC
    • immune_exposure: COVID-19 infection
    • cohort: adults (32-92)
    • comparison: COVID-19 patients versus healthy donors; dead versus survivor patients
    • repository_id:
    • platform:
    • response_components:
    • response_behavior: down
        • description: Increased frequency of CD57+ NK cells when comparing Covid-19 infected patients vs. healthy donors or dead vs. survivor patients.
        • exact_source: Fig. 1c
        • tissue: PBMC
        • immune_exposure: COVID-19 infection
        • cohort: adults (32-92)
        • comparison: COVID-19 patients versus healthy donors; dead versus survivors patients
        • repository_id:
        • platform:
        • response_components:
        • response_behavior: up
            • description: Increased frequency of adaptive NK cells when comparing dead vs. survivor Covid-19 infected patients.
            • exact_source: Fig. 1d
            • tissue: PBMC
            • immune_exposure: COVID-19 infection
            • cohort: adults (32-92)
            • comparison: Dead versus survivor patients
            • repository_id:
            • platform:
            • response_components:
            • response_behavior: up
                • description: Increased frequency of NK cells expressing CD69, TIM-3, PD1 when comparing Covid-19 infected patients vs. healthy donors
                • exact_source: Fig. 2a; Fig.2b; Fig.2c
                • tissue: PBMC
                • immune_exposure: COVID-19 infection
                • cohort: adults (32-92)
                • comparison: COVID-19 patients versus healthy donors
                • repository_id:
                • platform:
                • response_components:
                • response_behavior: up
                    • description: Decreased frequencies of NK cells expressing NKG2D, Siglec-7, DNAM-1 and CXCR6 when comparing Covid-19 infected patients vs. healthy donors
                    • exact_source: Fig. 2d; Fig.2e; Fig.2f; Fig.2g
                    • tissue: PBMC
                    • immune_exposure: COVID-19 infection
                    • cohort: adults (32-92)
                    • comparison: COVID-19 patients versus healthy donors
                    • repository_id:
                    • platform:
                    • response_components:
                    • response_behavior: down
                        • description: Decreased frequency of NK cells secreting IFN gamma when comparing Covid-19 infected patients vs. healthy donors
                        • exact_source: Fig. 3a; Fig. 3b
                        • tissue: PBMC
                        • immune_exposure: COVID-19 infection
                        • cohort: adults (32-92)
                        • comparison: COVID-19 patients versus healthy donors
                        • repository_id:
                        • platform:
                        • response_components:
                        • response_behavior: down
                            • description: Increased frequencies of CD4 and CD8 T cells expressing CD69 when comparing Covid-19 infected patients vs. healthy donors or dead vs. survivor patients.
                            • exact_source: Fig. 4c; Fig. 4d
                            • tissue: PBMC
                            • immune_exposure: COVID-19 infection
                            • cohort: adults (32-92)
                            • comparison: COVID-19 patients versus healthy donors; dead versus survivor patients
                            • repository_id:
                            • platform:
                            • response_components:
                            • response_behavior: up
                                • description: Increased frequencies of CD4 and CD8 T cells expressing TIM-3 when comparing Covid-19 infected patients vs. healthy donors
                                • exact_source: Fig. 4e; Fig. 4f
                                • tissue: PBMC
                                • immune_exposure: COVID-19 infection
                                • cohort: adults (32-92)
                                • comparison: COVID-19 patients versus healthy donors
                                • repository_id:
                                • platform:
                                • response_components:
                                • response_behavior: up
                                    • description: Decreased frequencies of CD8 T cells expressing CXCR6 when comparing Covid-19 infected patients vs. healthy donors
                                    • exact_source: Fig. 4g
                                    • tissue: PBMC
                                    • immune_exposure: COVID-19 infection
                                    • cohort: adults (32-92)
                                    • comparison: COVID-19 patients versus healthy donors
                                    • repository_id:
                                    • platform:
                                    • response_components:
                                    • response_behavior: down
                                        • description: Increased serum level of IL-6, IL8, IL10 in Covid-19 infected patients vs. healthy donors
                                        • exact_source: Fig. 6a; Fig. 6b; Fig. 6c;
                                        • tissue: Serum
                                        • immune_exposure: COVID-19 infection
                                        • cohort: adults (32-92)
                                        • comparison: COVID-19 patients versus healthy donors
                                        • repository_id:
                                        • platform:
                                        • response_components:
                                        • response_behavior: up
                                            • description: Increased serum level of IL-6 and IL10 in dead vs survivor Covid-19 infected patients.
                                            • exact_source: Fig. 6a; Fig. 6c
                                            • tissue: Serum
                                            • immune_exposure: COVID-19 infection
                                            • cohort: adults (32-92)
                                            • comparison: dead versus survivor patients
                                            • repository_id:
                                            • platform:
                                            • response_components:
                                            • response_behavior: up
                                                • description: Increased frequency of IL-6, IL-8 and IL-1beta secreted by monocytes in Covid-19 infected patients vs. healthy donors.
                                                • exact_source: Fig. 7a; Fig. 7b; Fig. 7c
                                                • tissue: Whole blood
                                                • immune_exposure: COVID-19 infection
                                                • cohort: adults (32-92)
                                                • comparison: COVID-19 patients versus healthy donors
                                                • repository_id:
                                                • platform:
                                                • response_components:
                                                • response_behavior: up