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Unique immunological profile in patients with COVID-19.
Varchetta, Stefania; Mele, Dalila; Oliviero, Barbara; Mantovani, Stefania; Ludovisi, Serena; Cerino, Antonella; Bruno, Raffaele; Castelli, Alberto; Mosconi, Mario; Vecchia, Marco; Roda, Silvia; Sachs, Michele; Klersy, Catherine; Mondelli, Mario U.
  • Varchetta S; Division of Infectious Diseases II and Immunology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
  • Mele D; Division of Infectious Diseases II and Immunology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
  • Oliviero B; Division of Infectious Diseases II and Immunology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
  • Mantovani S; Division of Infectious Diseases II and Immunology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
  • Ludovisi S; Division of Infectious Diseases II and Immunology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
  • Cerino A; Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
  • Bruno R; Division of Infectious Diseases II and Immunology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
  • Castelli A; Division of Infectious Diseases I, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
  • Mosconi M; Department of Clinical, Surgical, Diagnostic, and Pediatric Sciences, University of Pavia, Pavia, Italy.
  • Vecchia M; Division of Orthopaedics and Traumatology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
  • Roda S; Division of Orthopaedics and Traumatology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
  • Sachs M; Department of Clinical-Surgical, Diagnostic and Pediatric Sciences, University of Pavia, Pavia, Italy.
  • Klersy C; Division of Infectious Diseases I, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
  • Mondelli MU; Division of Infectious Diseases II and Immunology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Cell Mol Immunol ; 18(3): 604-612, 2021 03.
Article in English | MEDLINE | ID: covidwho-872685
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-1ß 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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Killer Cells, Natural / Antigens, Differentiation / Cytokines / CD8-Positive T-Lymphocytes / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Cell Mol Immunol Journal subject: Allergy and Immunology Year: 2021 Document Type: Article Affiliation country: S41423-020-00557-9

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Killer Cells, Natural / Antigens, Differentiation / Cytokines / CD8-Positive T-Lymphocytes / SARS-CoV-2 / COVID-19 Type of study: Prognostic study Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Cell Mol Immunol Journal subject: Allergy and Immunology Year: 2021 Document Type: Article Affiliation country: S41423-020-00557-9