Περίληψη:
Proper management of COVID-19 mandates better understanding of disease pathogenesis. Giamarellos-Bourboulis et al. describe two main features preceding severe respiratory failure associated with COVID-19: the first is macrophage activation syndrome; the second is defective antigen-presentation driven by interleukin-6. An IL-6 blocker partially rescues immune dysregulation in vitro and in patients. © 2020 Elsevier Inc.
Proper management of COVID-19 mandates better understanding of disease pathogenesis. The sudden clinical deterioration 7–8 days after initial symptom onset suggests that severe respiratory failure (SRF) in COVID-19 is driven by a unique pattern of immune dysfunction. We studied immune responses of 54 COVID-19 patients, 28 of whom had SRF. All patients with SRF displayed either macrophage activation syndrome (MAS) or very low human leukocyte antigen D related (HLA-DR) expression accompanied by profound depletion of CD4 lymphocytes, CD19 lymphocytes, and natural killer (NK) cells. Tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production by circulating monocytes was sustained, a pattern distinct from bacterial sepsis or influenza. SARS-CoV-2 patient plasma inhibited HLA-DR expression, and this was partially restored by the IL-6 blocker Tocilizumab; off-label Tocilizumab treatment of patients was accompanied by increase in circulating lymphocytes. Thus, the unique pattern of immune dysregulation in severe COVID-19 is characterized by IL-6-mediated low HLA-DR expression and lymphopenia, associated with sustained cytokine production and hyper-inflammation. © 2020 Elsevier Inc.
Συγγραφείς:
Giamarellos-Bourboulis, E.J.
Netea, M.G.
Rovina, N.
Akinosoglou, K.
Antoniadou, A.
Antonakos, N.
Damoraki, G.
Gkavogianni, T.
Adami, M.-E.
Katsaounou, P.
Ntaganou, M.
Kyriakopoulou, M.
Dimopoulos, G.
Koutsodimitropoulos, I.
Velissaris, D.
Koufargyris, P.
Karageorgos, A.
Katrini, K.
Lekakis, V.
Lupse, M.
Kotsaki, A.
Renieris, G.
Theodoulou, D.
Panou, V.
Koukaki, E.
Koulouris, N.
Gogos, C.
Koutsoukou, A.
Λέξεις-κλειδιά:
CD19 antigen; CD4 antigen; HLA DR antigen; interleukin 6; tocilizumab; tumor necrosis factor; HLA DR antigen; interleukin 6; monoclonal antibody; tocilizumab, aged; antigen expression; Article; CD4+ T lymphocyte; coronavirus disease 2019; cytokine production; cytopenia; female; human; immune dysregulation; immune response; lymphocytopenia; macrophage activation syndrome; major clinical study; male; monocyte; natural killer cell; plasma; priority journal; respiratory failure; Severe acute respiratory syndrome coronavirus 2; T cell depletion; Coronavirus infection; immunology; inflammation; macrophage activation; pandemic; pathology; respiratory failure; virus pneumonia, Aged; Antibodies, Monoclonal, Humanized; Coronavirus Infections; Female; HLA-DR Antigens; Humans; Inflammation; Interleukin-6; Killer Cells, Natural; Lymphopenia; Macrophage Activation; Male; Monocytes; Pandemics; Pneumonia, Viral; Respiratory Insufficiency
