Severe immunosuppression and not a cytokine storm characterizes COVID-19 infections

COVID-19-associated morbidity and mortality have been attributed to a pathologic host response. Two divergent hypotheses have been proposed: hyperinflammatory cytokine storm; and failure of host protective immunity that results in unrestrained viral dissemination and organ injury. A key explanation...

Celý popis

Uloženo v:
Podrobná bibliografie
Vydáno v:JCI insight Ročník 5; číslo 17
Hlavní autoři: Remy, Kenneth E., Mazer, Monty, Striker, David A., Ellebedy, Ali H., Walton, Andrew H., Unsinger, Jacqueline, Blood, Teresa M., Mudd, Philip A., Yi, Daehan J., Mannion, Daniel A., Osborne, Dale F., Martin, R. Scott, Anand, Nitin J., Bosanquet, James P., Blood, Jane, Drewry, Anne M., Caldwell, Charles C., Turnbull, Isaiah R., Brakenridge, Scott C., Moldwawer, Lyle L., Hotchkiss, Richard S.
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States American Society for Clinical Investigation 03.09.2020
Témata:
Adaptive Immunity - immunology
Adolescent
Adult
Aged
Aged, 80 and over
Antibodies
Betacoronavirus
Case-Control Studies
Coronavirus Infections - immunology
Coronaviruses
COVID-19
Critical Illness
Cytokine Release Syndrome - immunology
Cytokine storm
Enzyme-linked immunosorbent assay
Enzyme-Linked Immunospot Assay
Female
Healthy Volunteers
Humans
Immune response
Immune status
Immune Tolerance - immunology
Immunity, Innate - immunology
Immunoassay
Immunosuppression
Infections
Innate immunity
Interferon-gamma - immunology
Interferon-gamma - metabolism
Interleukin-6 - immunology
Leukocytes (mononuclear)
Lymphocytes
Lymphocytes T
Male
Middle Aged
Monocytes
Monocytes - immunology
Monocytes - metabolism
Morbidity
Mortality
Pandemics
Patients
Plasma
Pneumonia, Viral - immunology
SARS-CoV-2
Sepsis
Sepsis - immunology
T-Lymphocyte Subsets - immunology
T-Lymphocyte Subsets - metabolism
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Tumor Necrosis Factor-alpha - immunology
Tumor Necrosis Factor-alpha - metabolism
Tumor necrosis factor-α
Young Adult
COVID-19
Adaptive immunity
ISSN:2379-3708, 2379-3708
On-line přístup:Získat plný text
Tagy: Přidat tag
Žádné tagy, Buďte první, kdo vytvoří štítek k tomuto záznamu!
Popis
Shrnutí:COVID-19-associated morbidity and mortality have been attributed to a pathologic host response. Two divergent hypotheses have been proposed: hyperinflammatory cytokine storm; and failure of host protective immunity that results in unrestrained viral dissemination and organ injury. A key explanation for the inability to address this controversy has been the lack of diagnostic tools to evaluate immune function in COVID-19 infections. ELISpot, a highly sensitive, functional immunoassay, was employed in 27 patients with COVID-19, 51 patients with sepsis, 18 critically ill nonseptic (CINS) patients, and 27 healthy control volunteers to evaluate adaptive and innate immune status by quantitating T cell IFN-ɣ and monocyte TFN-α production. Circulating T cell subsets were profoundly reduced in COVID-19 patients. Additionally, stimulated blood mononuclear cells produced less than 40%-50% of the IFN-ɣ and TNF-α observed in septic and CINS patients, consistent with markedly impaired immune effector cell function. Approximately 25% of COVID-19 patients had increased IL-6 levels that were not associated with elevations in other canonical proinflammatory cytokines. Collectively, these findings support the hypothesis that COVID-19 suppresses host functional adaptive and innate immunity. Importantly, IL-7 administered ex vivo restored T cell IFN-ɣ production in COVID-19 patients. Thus, ELISpot may functionally characterize host immunity in COVID-19 and inform prospective therapies.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ISSN:2379-3708
2379-3708
DOI:10.1172/jci.insight.140329