Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure
(چکیده مقاله) :
Abstract :
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-a (TNF-a) 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.
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-a (TNF-a) 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.
(توضیحات تکمیلی) :
(توضیحات تکمیلی) :
Description :
مقاله ISI انگلیسی اصلی
سال انتشار: 2020
فایل ISI انگلیسی اصلی ، با فرمت Pdf
تعداد صفحات فایل ISI انگلیسی اصلی: 13 صفحه
سال انتشار: 2020
فایل ISI انگلیسی اصلی ، با فرمت Pdf
تعداد صفحات فایل ISI انگلیسی اصلی: 13 صفحه
Authors / Descriptions(نویسندگان/توضیحات): سال انتشار 2020 \ مقاله ISI انگلیسی اصلی \ نویسندگان: Evangelos J. Giamarellos-Bourboulis, Mihai G. Netea, Nikoletta Rovina, ..., Nikolaos Koulouris, Charalambos Gogos, Antonia Koutsoukou
Sent date(تاریخ ارسال) :
1399/02/11 | 4/30/2020
Number of visits(تعداد بازدید):
802
Key words (کلمات کلیدی):
COVID-19 , Severe Respiratory Failure
Number of pages(تعداد صفحات) :
13
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