| Autor: |
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. |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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