Exhausted NK cells and cytokine storms in COVID-19: Whether NK cell therapy could be a therapeutic choice |
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Affiliation: | 1. Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine, Tehran, Iran;2. Iran University of Medical Science, Tehran, Iran;3. Department of Immunology, Alfred Medical Research and Education Precinct, Monash University, Melbourne, Victoria, Australia;4. Australian Centre for Blood Diseases, Monash University, Melbourne, Victoria, Australia |
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Abstract: | The global outbreak of coronavirus-2019 (COVID-19) still claims more lives daily around the world due to the lack of a definitive treatment and the rapid tendency of virus to mutate, which even jeopardizes vaccination efficacy. At the forefront battle against SARS-CoV-2, an effective innate response to the infection has a pivotal role in the initial control and treatment of disease. However, SARS-CoV-2 subtly interrupts the equations of immune responses, disrupting the cytolytic antiviral effects of NK cells, while seriously activating infected macrophages and other immune cells to induce an unleashed “cytokine storm”, a dangerous and uncontrollable inflammatory response causing life-threatening symptoms in patients. Notably, the NK cell exhaustion with ineffective cytolytic function against the sources of exaggerated cytokine release, acts as an Achilles’ heel which exacerbates the severity of COVID-19. Given this, approaches that improve NK cell cytotoxicity may benefit treatment protocols. As a suggestion, adoptive transfer of NK or CAR-NK cells with proper cytotolytic potentials and the lowest capacity of cytokine-release (for example CD56dim NK cells brightly express activating receptors), to severe COVID-19 patients may provide an effective cure especially in cases suffering from cytokine storms. More intriguingly, the ongoing evidence for persistent clonal expansion of NK memory cells characterized by an activating phenotype in response to viral infections, can benefit the future studies on vaccine development and adoptive NK cell therapy in COVID-19. Whether vaccinated volunteers or recovered patients can also be considered as suitable candidates for cell donation could be the subject of future research. |
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Keywords: | Adoptive cell therapy Coronavirus disease 2019 (COVID-19) Cytokine storm Innate immune response Memory cells NK cell SARS-CoV-2 Vaccine ACE" },{" #name" :" keyword" ," $" :{" id" :" k0035" }," $$" :[{" #name" :" text" ," _" :" Angiotensin converting enzyme ADCC" },{" #name" :" keyword" ," $" :{" id" :" k0045" }," $$" :[{" #name" :" text" ," _" :" Antibody-dependent cellular cytotoxicity ARDS" },{" #name" :" keyword" ," $" :{" id" :" k0055" }," $$" :[{" #name" :" text" ," _" :" Acute respiratory distress syndrome CAR-NK" },{" #name" :" keyword" ," $" :{" id" :" k0065" }," $$" :[{" #name" :" text" ," _" :" Chimeric antigen receptor-NK COVID-19" },{" #name" :" keyword" ," $" :{" id" :" k0075" }," $$" :[{" #name" :" text" ," _" :" Corona virus disease 2019 CRS" },{" #name" :" keyword" ," $" :{" id" :" k0085" }," $$" :[{" #name" :" text" ," _" :" cytokine release syndrome DCs" },{" #name" :" keyword" ," $" :{" id" :" k0095" }," $$" :[{" #name" :" text" ," _" :" Dendritic cells DNAM" },{" #name" :" keyword" ," $" :{" id" :" k0105" }," $$" :[{" #name" :" text" ," _" :" DNAX Accessory Molecule G-CSF" },{" #name" :" keyword" ," $" :{" id" :" k0115" }," $$" :[{" #name" :" text" ," _" :" Granulocyte-colony stimulating factor GM-CSF" },{" #name" :" keyword" ," $" :{" id" :" k0125" }," $$" :[{" #name" :" text" ," _" :" Granulocyte macrophage colony-stimulating factor HLA" },{" #name" :" keyword" ," $" :{" id" :" k0135" }," $$" :[{" #name" :" text" ," _" :" Human leukocyte antigen ICAM" },{" #name" :" keyword" ," $" :{" id" :" k0145" }," $$" :[{" #name" :" text" ," _" :" Intercellular Adhesion Molecule ICU" },{" #name" :" keyword" ," $" :{" id" :" k0155" }," $$" :[{" #name" :" text" ," _" :" Intensive care unit IFN" },{" #name" :" keyword" ," $" :{" id" :" k0165" }," $$" :[{" #name" :" text" ," _" :" Interferon IL" },{" #name" :" keyword" ," $" :{" id" :" k0175" }," $$" :[{" #name" :" text" ," _" :" Interleukin IP-10" },{" #name" :" keyword" ," $" :{" id" :" k0185" }," $$" :[{" #name" :" text" ," _" :" IFN-γ-inducible protein 10 KIRs" },{" #name" :" keyword" ," $" :{" id" :" k0195" }," $$" :[{" #name" :" text" ," _" :" Killer immunoglobulin-like receptors MCP" },{" #name" :" keyword" ," $" :{" id" :" k0205" }," $$" :[{" #name" :" text" ," _" :" Monocyte chemoattractant protein MDA" },{" #name" :" keyword" ," $" :{" id" :" k0215" }," $$" :[{" #name" :" text" ," _" :" Melanoma differentiation-associated protein MERS" },{" #name" :" keyword" ," $" :{" id" :" k0225" }," $$" :[{" #name" :" text" ," _" :" Middle East respiratory syndrome MHC" },{" #name" :" keyword" ," $" :{" id" :" k0235" }," $$" :[{" #name" :" text" ," _" :" Major histocompatibility MIG" },{" #name" :" keyword" ," $" :{" id" :" k0245" }," $$" :[{" #name" :" text" ," _" :" Monokine induced by gamma interferon MIP" },{" #name" :" keyword" ," $" :{" id" :" k0255" }," $$" :[{" #name" :" text" ," _" :" Macrophage inflammatory protein NCRs" },{" #name" :" keyword" ," $" :{" id" :" k0265" }," $$" :[{" #name" :" text" ," _" :" Natural cytotoxicity receptors NK" },{" #name" :" keyword" ," $" :{" id" :" k0275" }," $$" :[{" #name" :" text" ," _" :" Natural killer NKD" },{" #name" :" keyword" ," $" :{" id" :" k0285" }," $$" :[{" #name" :" text" ," _" :" NK cell deficiency PAMPs" },{" #name" :" keyword" ," $" :{" id" :" k0295" }," $$" :[{" #name" :" text" ," _" :" Pathogen associated molecular patterns PBMCs" },{" #name" :" keyword" ," $" :{" id" :" k0305" }," $$" :[{" #name" :" text" ," _" :" Peripheral blood mononuclear cells PRRs" },{" #name" :" keyword" ," $" :{" id" :" k0315" }," $$" :[{" #name" :" text" ," _" :" Pattern recognition receptors RANTES" },{" #name" :" keyword" ," $" :{" id" :" k0325" }," $$" :[{" #name" :" text" ," _" :" Regulated upon Activation, Normal T Cell Expressed and Presumably Secreted RIG" },{" #name" :" keyword" ," $" :{" id" :" k0335" }," $$" :[{" #name" :" text" ," _" :" Retinoic acid-inducible gene SARS-CoV" },{" #name" :" keyword" ," $" :{" id" :" k0345" }," $$" :[{" #name" :" text" ," _" :" Severe acute respiratory syndrome-coronavirus TGF" },{" #name" :" keyword" ," $" :{" id" :" k0355" }," $$" :[{" #name" :" text" ," _" :" Transforming growth factor TLR" },{" #name" :" keyword" ," $" :{" id" :" k0365" }," $$" :[{" #name" :" text" ," _" :" Toll-like receptor TNF" },{" #name" :" keyword" ," $" :{" id" :" k0375" }," $$" :[{" #name" :" text" ," _" :" Tumor necrosis factor |
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