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+ 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+ and NK cells of COVID-19 infected patients compared to healthy controls, while NKG2A overexpression also functionally exhausts CD8+ cells and NK cells, resulting in a severely compromised innate immune response. Blocking NKG2A on CD8+ cells and NK cells in cancers modulated tumor growth, restoring CD8+ 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+ 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.
【저자키워드】 COVID-19, Innate immunity, SARS, NKG2A, Monalizumab, 【초록키워드】 viruses, SARS-CoV-2, Severe infection, immune response, Chloroquine, innate immune response, severe COVID-19, antibody, Phase 2, Cancer, neutrophil, NK cell, interferon, NK cells, clinical trials, cytotoxicity, CD8, Novel coronavirus, Disease progression, lymphocyte, outbreak, cancers, Antiviral agents, Patient, receptor, T-cell, disease, mechanism, Blood, mild infection, CTLs, tumor growth, natural, Side effect, healthy individuals, individual, healthy controls, overexpression, viral pathogen, CD8+, significantly lower, cytotoxic, inhibitory, blocking, weakened immune system, Host, cytokine secretion, effective, Cell, tumor progression, resulting, significantly, required, generate, reduced, treated, functional, inhibiting, modulated, CD8+ cell, COVID-19 infected patient, NK cell function, over-expressing, 【제목키워드】 Immunity, receptors, antiviral agent, Innate, Potential treatment, COVID-19 patient,