tetano
Editor, Senior Moderator
Med Hypotheses. 2020 Apr 22;140:109777. doi: 10.1016/j.mehy.2020.109777. [Epub ahead of print]
Innate immunity in COVID-19 patients mediated by NKG2A receptors, and potential treatment using Monalizumab, Cholroquine, and antiviral agents.
Yaqinuddin A[SUP]1[/SUP], Kashir J[SUP]2[/SUP].
Author information
Abstract
Following the outbreak of a novel coronavirus (SARS-CoV-2), studies suggest that the resultant disease (COVID-19) is more severe in individuals with a weakened immune system. Cytotoxic T-cells (CTLs) and Natural Killer (NK) cells are required to generate an effective immune response against viruses, functional exhaustion of which enables disease progression. Patients with severe COVID-19 present significantly lower lymphocyte, and higher neutrophil, counts in blood. Specifically, CD8[SUP]+[/SUP] lymphocytes and NK cells were significantly reduced in cases of severe infection compared to patients with mild infection and healthy individuals. The NK group 2 member A (NKG2A) receptor transduces inhibitory signalling, suppressing NK cytokine secretion and cytotoxicity. Overexpression of NKG2A has been observed on CD8[SUP]+[/SUP] and NK cells of COVID-19 infected patients compared to healthy controls, while NKG2A overexpression also functionally exhausts CD8[SUP]+[/SUP] cells and NK cells, resulting in a severely compromised innate immune response. Blocking NKG2A on CD8[SUP]+[/SUP] cells and NK cells in cancers modulated tumor growth, restoring CD8[SUP]+[/SUP] T and NK cell function. A recently proposed mechanism via which SARS-CoV-2 overrides innate immune response of the host is by over-expressing NKG2A on CD[SUP]+[/SUP] T and NK cells, culminating in functional exhaustion of the immune response against the viral pathogen. Monalizumab is an inhibiting antibody against NKG2A which can restore the function of CD8 + T and NK cells in cancers, successfully ceasing tumor progression with no significant side effects in Phase 2 clinical trials. We hypothesize that patients with severe COVID-19 have a severely compromised innate immune response and could be treated via the use of Monalizumab, interferon α, chloroquine, and other antiviral agents.
Copyright ? 2020 Elsevier Ltd. All rights reserved.
KEYWORDS:
COVID-19; Innate immunity; Monalizumab; NKG2A; SARS
PMID:32344314DOI:10.1016/j.mehy.2020.109777
Innate immunity in COVID-19 patients mediated by NKG2A receptors, and potential treatment using Monalizumab, Cholroquine, and antiviral agents.
Yaqinuddin A[SUP]1[/SUP], Kashir J[SUP]2[/SUP].
Author information
Abstract
Following the outbreak of a novel coronavirus (SARS-CoV-2), studies suggest that the resultant disease (COVID-19) is more severe in individuals with a weakened immune system. Cytotoxic T-cells (CTLs) and Natural Killer (NK) cells are required to generate an effective immune response against viruses, functional exhaustion of which enables disease progression. Patients with severe COVID-19 present significantly lower lymphocyte, and higher neutrophil, counts in blood. Specifically, CD8[SUP]+[/SUP] lymphocytes and NK cells were significantly reduced in cases of severe infection compared to patients with mild infection and healthy individuals. The NK group 2 member A (NKG2A) receptor transduces inhibitory signalling, suppressing NK cytokine secretion and cytotoxicity. Overexpression of NKG2A has been observed on CD8[SUP]+[/SUP] and NK cells of COVID-19 infected patients compared to healthy controls, while NKG2A overexpression also functionally exhausts CD8[SUP]+[/SUP] cells and NK cells, resulting in a severely compromised innate immune response. Blocking NKG2A on CD8[SUP]+[/SUP] cells and NK cells in cancers modulated tumor growth, restoring CD8[SUP]+[/SUP] T and NK cell function. A recently proposed mechanism via which SARS-CoV-2 overrides innate immune response of the host is by over-expressing NKG2A on CD[SUP]+[/SUP] T and NK cells, culminating in functional exhaustion of the immune response against the viral pathogen. Monalizumab is an inhibiting antibody against NKG2A which can restore the function of CD8 + T and NK cells in cancers, successfully ceasing tumor progression with no significant side effects in Phase 2 clinical trials. We hypothesize that patients with severe COVID-19 have a severely compromised innate immune response and could be treated via the use of Monalizumab, interferon α, chloroquine, and other antiviral agents.
Copyright ? 2020 Elsevier Ltd. All rights reserved.
KEYWORDS:
COVID-19; Innate immunity; Monalizumab; NKG2A; SARS
PMID:32344314DOI:10.1016/j.mehy.2020.109777