TY - JOUR
TI - Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure
AU - Giamarellos-Bourboulis, E.J.
AU - Netea, M.G.
AU - Rovina, N.
AU - Akinosoglou, K.
AU - Antoniadou, A.
AU - Antonakos, N.
AU - Damoraki, G.
AU - Gkavogianni, T.
AU - Adami, M.-E.
AU - Katsaounou, P.
AU - Ntaganou, M.
AU - Kyriakopoulou, M.
AU - Dimopoulos, G.
AU - Koutsodimitropoulos, I.
AU - Velissaris, D.
AU - Koufargyris, P.
AU - Karageorgos, A.
AU - Katrini, K.
AU - Lekakis, V.
AU - Lupse, M.
AU - Kotsaki, A.
AU - Renieris, G.
AU - Theodoulou, D.
AU - Panou, V.
AU - Koukaki, E.
AU - Koulouris, N.
AU - Gogos, C.
AU - Koutsoukou, A.
JO - Cell Host and Microbe
PY - 2020
VL - 27
TODO - 6
SP - 992-1000.e3
PB - Cell Press
SN - null
TODO - 10.1016/j.chom.2020.04.009
TODO - 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
TODO - 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.
ER -