Friends or foes? The knowns and unknowns of natural killer cell biology in COVID-19 and other coronaviruses in July 2020

Manickam, Cordelia; Sugawara, Sho K.; Reeves, R. Keith

doi:10.1371/journal.ppat.1008820

Cited by 29 publications

(26 citation statements)

References 89 publications

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“…Without the support of healthy phagocytes ADCC may increase inflammation (e.g. through DAMP release), however, reports of this and unassisted NK cell lysis of virally infected cells are mostly absent in COVID-19 [ 51 ], including peptide-loaded MHC-1 presentation and recognition. SARS-CoV-2 ORF8-mediated downregulation of MHC-I in infected cells [ 52 ] could also either promote or inhibit NK cell-mediated lysis, though this is also not known in COVID-19.…”

Section: Introductionmentioning

confidence: 99%

Innate immunology in COVID-19—a living review. Part II: dysregulated inflammation drives immunopathology

Prs.

Alrubayyi

Pring

et al. 2020

Oxford Open Immunology

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The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a global health crisis and will likely continue to impact public health for years. As the effectiveness of the innate immune response is crucial to patient outcome, huge efforts have been made to understand how dysregulated immune responses may contribute to disease progression. Here we have reviewed current knowledge of cellular innate immune responses to SARS-CoV-2 infection, highlighting areas for further investigation and suggesting potential strategies for intervention. We conclude that in severe COVID-19 initial innate responses, primarily type I interferon, are suppressed or sabotaged which results in an early interleukin (IL)-6, IL-10 and IL-1β-enhanced hyperinflammation. This inflammatory environment is driven by aberrant function of innate immune cells: monocytes, macrophages and natural killer cells dispersing viral pathogen-associated molecular patterns and damage-associated molecular patterns into tissues. This results in primarily neutrophil-driven pathology including fibrosis that causes acute respiratory distress syndrome. Activated leukocytes and neutrophil extracellular traps also promote immunothrombotic clots that embed into the lungs and kidneys of severe COVID-19 patients, are worsened by immobility in the intensive care unit and are perhaps responsible for the high mortality. Therefore, treatments that target inflammation and coagulation are promising strategies for reducing mortality in COVID-19.

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Section: Introductionmentioning

confidence: 99%

Innate immunology in COVID-19—a living review. Part II: dysregulated inflammation drives immunopathology

Prs.

Alrubayyi

Pring

et al. 2020

Oxford Open Immunology

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“…67 Activation, immunotyping, reduction in number of circulating NK cells, alteration in subsets and exhaustion in phenotypes following coronavirus infection indicates their involvement in immunopathology of COVID-19. 73,74 As exaggerated inflammation is hall mark of COVID-19 severity 75 and NK cells have prominent role in inflammatory cascade hence immunomodulation by NK cells can prove beneficial for COVID-19 patients. 11,74 In one clinical trial, application of NK cells for treatment of COVID-19 patients has evaluated safety and efficiency of NK cell therapy in combination with standard therapy.…”

Section: Natural Killer (Nk) Cell-based Therapiesmentioning

confidence: 99%

Immunotherapies and immunomodulatory approaches in clinical trials - a mini review

Yatoo

Hamid

Rather

et al. 2021

Human Vaccines & Immunotherapeutics

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The coronavirus disease (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created havoc worldwide. Due to the non-availability of any vaccine or drugs against COVID-19, immunotherapies involving convalescent plasma, immunoglobulins, antibodies (monoclonal or polyclonal), and the use of immunomodulatory agents to enhance immunity are valuable alternative options. Cell-based therapies including natural killer cells, T cells, stem cells along with cytokines and toll-like receptors (TLRs) based therapies are also being exploited potentially against COVID-19. Future research need to strengthen the field of developing effective immunotherapeutics and immunomodulators with a thrust of providing appropriate, affordable, convenient, and cost-effective prophylactic and treatment regimens to combat global COVID-19 crisis that has led to a state of medical emergency enforcing entire countries of the world to devote their research infrastructure and manpower in tackling this pandemic.

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“…On contrary, regulation of epidemic virus infection is nowadays crucial, in context of covid-19, because we do not have any specific weapons against its pandemic. Covid-19 that anyone does not yet have immunity may be recognized as non-self pathogen and theoretically eliminated by NK cells [46]. As outcome of Covid-19 patients with preexisting CKD and HD is significantly poor [47], restoring the viral elimination mechanism of NK cells in uremic status may be effective in improving their prognosis.…”

Section: Clinical Significance Of Nk Cell Dysfunction In Endstage Kidmentioning

confidence: 99%

Dysfunction of natural killer cells in end-stage kidney disease on hemodialysis

Nagai

2021

Ren Replace Ther

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Natural killer (NK) cells are known to play an important role in defense against infection and tumors. Although there is no clear consensus, most studies have shown that the number and cytotoxicity of NK cells decreases in end-stage kidney disease (ESKD) patients undergoing hemodialysis. Uremic patients chronically suffer from oxidative stress, which could be responsible for downregulation of the activating receptors on NK cells and modulation of ligand expression for activating receptors. Theoretically, the reduced number of NK cells and decreased function might increase susceptibility to viral infections and cancer development in patients with ESKD. There is emerging evidence that NK cell numbers may be an outcome predictor in renal transplantation; however, the clinical significance of NK cell dysfunction in dialysis patients requires clarification. In this review, I describe NK cell number, cytotoxic activity, and activating mechanisms in the context of uremia and oxidative stress, which is anticipated to assist in elucidating the mechanisms underlying immunodeficiency in dialysis patients.

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Friends or foes? The knowns and unknowns of natural killer cell biology in COVID-19 and other coronaviruses in July 2020

Cited by 29 publications

References 89 publications

Innate immunology in COVID-19—a living review. Part II: dysregulated inflammation drives immunopathology

Innate immunology in COVID-19—a living review. Part II: dysregulated inflammation drives immunopathology

Immunotherapies and immunomodulatory approaches in clinical trials - a mini review

Dysfunction of natural killer cells in end-stage kidney disease on hemodialysis

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