Unique immunological profile in patients with COVID-19

• Published in: Cellular & molecular immunology Vol. 18; no. 3; pp. 604 - 612
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2021; Nature Publishing Group
• Subjects: 631/250/127/1213; 631/250/1619/382; 631/250/1619/554; 631/250/2504/342; 631/250/255/2514; Adult; Aged; Aged, 80 and over; Antibodies; Antigens, Differentiation - immunology; Apoptosis; Biomedical and Life Sciences; Biomedicine; CD226 antigen; CD57 antigen; CD69 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; Cell death; Contraction; Coronaviruses; COVID-19; COVID-19 - immunology; COVID-19 - pathology; Cytokines - immunology; Female; Humans; IL-1β; Immune response; Immunoglobulins; Immunology; Inflammation; Interferon; Interleukin 6; Interleukin 8; Killer Cells, Natural - immunology; Killer Cells, Natural - pathology; Lymphocytes T; Male; Medical Microbiology; Microbiology; Middle Aged; Monocytes; Mucin; Natural killer cells; NKG2 antigen; PD-1 protein; Peripheral blood; SARS-CoV-2 - immunology; Serum levels; Severe acute respiratory syndrome coronavirus 2; Severity of Illness Index; Vaccine; COVID-19; NK cells; IL6; Monocytes; TIM-3
• ISSN: 1672-7681; 2042-0226; 2042-0226
• DOI: 10.1038/s41423-020-00557-9

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 CD56 bright and an expansion of mature CD57 + FcεRIγ neg 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.