Natural killer cell immunotypes related to COVID-19 disease severity

Maucourant, Christopher; Filipovic, Iva; Ponzetta, Andrea; Aleman, Soo; Cornillet, Martin; Hertwig, Laura; Strunz, Benedikt; Lentini, Antonio; Reinius, Björn; Brownlie, Demi; Cuapio, Angélica; Ask, Eivind Heggernes; Hull, Ryan M.; Haroun-Izquierdo, Alvaro; Schaffer, Marie; Klingström, Jonas; Folkesson, Elin; Buggert, Marcus; Sandberg, Johan K.; Eriksson, Lars; Rooyackers, Olav; Ljunggren, Hans‐Gustaf; Malmberg, Karl‐Johan; Michaëlsson, Jakob; Marquardt, Nicole; Hammer, Quirin; Strålin, Kristoffer; Björkström, Niklas K.

doi:10.1126/sciimmunol.abd6832

Cited by 361 publications

(432 citation statements)

References 59 publications

(92 reference statements)

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“…In our cohort, specifically CD56 + NK cells were dramatically decreased during the course of active SARS-CoV-2 viral infections (mild and moderate), while during recovery the numbers were comparable to HC as report by others53. Similarly another recent study suggested the decrease in number of NK cell subsets in COVID-19 patients, with no change in CD56 bright or CD56 dim cells 54 . Thus, these data point to a crucial role of CD56 + NK cells in eliminating SARS-CoV-2 infections 47 .…”

Section: Discussionmentioning

confidence: 68%

SARS-CoV-2 infection paralyzes cytotoxic and metabolic functions of the immune cells

Singh

Trautwein

Fendel³

et al. 2020

Preprint

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The SARS-CoV-2 virus is the causative agent of the global COVID-19 infectious disease outbreak, which can lead to acute respiratory distress syndrome (ARDS). However, it is still unclear how the virus interferes with immune cell and metabolic functions in the human body. In this study, we investigated the immune response in 10 acute or convalescent COVID19 patients. We characterized the peripheral blood mononuclear cells (PBMCs) using flow cytometry and found that CD8+ T cells were significantly subsided in moderate COVID-19 and convalescent patients. Furthermore, characterization of CD8+ T cells suggested that patients with a mild and moderate course of the COVID-19 disease and convalescent patients have significantly diminished expression of both perforin and granzyme B in CD8+ T cells. Using 1H-NMR spectroscopy, we characterized the metabolic status of their autologous PBMCs. We found that fructose, lactate and taurine levels were elevated in infected (mild and moderate) patients compared with control and convalescent patients. Glucose, glutamate, formate and acetate levels were attenuated in COVID-19 (mild and moderate) patients. Our findings reveal patients who suffer from an over activation of the immune system, a change of composition in infusion/intravenous fluids during infection with the aim to lower blood levels of glucose, glutamate, acetate and formate could avoid a life-threatening cytokine storm. In summary, our report suggests that SARS-CoV-2 infection leads to disrupted CD8+ T cytotoxic functions and changes the overall metabolic functions of immune cells.

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Section: Discussionmentioning

confidence: 68%

SARS-CoV-2 infection paralyzes cytotoxic and metabolic functions of the immune cells

Singh

Trautwein

Fendel³

et al. 2020

Preprint

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“…Whether these expansions of adaptive NK cells in HCMV + people were driven by SARS‐CoV‐2, or whether they predated SARS‐CoV‐2 infection, is not known but these data do raise the possibility that adaptive NK cells may contribute to tissue damage in COVID‐19. In support of this hypothesis, in COVID‐19 patients these adaptive cells also express Ksp37, a marker of cytotoxic lymphocytes associated with lung disease, 77 and, despite their lower intrinsic proliferative capacity, also express markers of recent proliferation 74 . This is reminiscent of the increased proliferative capacity of adaptive CD45RO + NK cells in chronic malaria infection as discussed above 61,74 and is also consistent with reports of enrichment of highly differentiated CD56 dim CD57 + NK cells with high proliferative capacity in the peripheral blood in a patient with SARS‐CoV‐2 infection and acute respiratory distress syndrome (ARDS) 78 …”

Section: Emerging Pathogens and Nk Cellsmentioning

confidence: 74%

“…Importantly, HCMV infection and the associated expansion of the subset of adaptive CD56 dim NKG2C + NK cells were associated with severe COVID‐19. Over 90% of severe COVID‐19 cases in this cohort were HCMV + (compared with ~60% of controls and 80% of mild COVID‐19 cases) 74 . More importantly, ~65% of people with severe COVID‐19 had expansion of adaptive NK cells compared with only 10–20% of controls and those with moderate disease 74 .…”

Section: Emerging Pathogens and Nk Cellsmentioning

confidence: 88%

“…As in other viral infections, and irrespective of outcome in terms of disease, innate inflammatory pathways are triggered early in SARS‐CoV‐2 infection. CD56 bright NK cells are activated, and their increased expression of perforin and granzyme B is associated with inflammatory markers of disease severity, in particular with high concentrations of IL‐6 74 . In addition, reduced expression of CD16 on CD56 dim NK cells in people with COVID‐19 75 is consistent with ongoing activation of this subset by SARS‐CoV‐2 antigen/antibody immune complexes 76 .…”

Section: Emerging Pathogens and Nk Cellsmentioning

confidence: 88%

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Regulation of the human NK cell compartment by pathogens and vaccines

Goodier

Riley

2021

Clin & Trans Imm

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Natural killer cells constitute a phenotypically diverse population of innate lymphoid cells with a broad functional spectrum. Classically defined as cytotoxic lymphocytes with the capacity to eliminate cells lacking self-MHC or expressing markers of stress or neoplastic transformation, critical roles for NK cells in immunity to infection in the regulation of immune responses and as vaccineinduced effector cells have also emerged. A crucial feature of NK cell biology is their capacity to integrate signals from pathogen-, tumor-or stress-induced innate pathways and from antigenspecific immune responses. The extent to which innate and acquired immune mediators influence NK cell effector function is influenced by the maturation and differentiation state of the NK cell compartment; moreover, NK cell differentiation is driven in part by exposure to infection. Pathogens can thus mould the NK cell response to maximise their own success and/or minimise the damage they cause. Here, we review recent evidence that pathogen-and vaccine-derived signals influence the differentiation, adaptation and subsequent effector function of human NK cells.

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“… 68 In addition, reduced natural killer (NK) counts and the emergence of adaptive NK subsets are associated with severe disease. 69 Some clinical data suggest that there may be relatively high antibody titers associated with severe COVID-19; 70 while antibodies have a critical role in neutralizing virus to control infections, activation of Fcγ receptors, degranulation of phagocytes, and priming release of cytokines may also contribute to the cytokine storm. Projections from SARS-CoV-1 studies and some reports with COVID-19 patients show elevated levels of complement components in serum and post mortem autopsy lung sections, indicating the potential for complement activation to increase the severity of inflammation and to serve as a host mediator of the resulting ARDS.…”

Section: Infection Inflammation and Host Factors In Covid-19 Pathopmentioning

confidence: 99%

Biomaterials-Based Opportunities to Engineer the Pulmonary Host Immune Response in COVID-19

Jarai

Stillman

Bomb

et al. 2020

ACS Biomater. Sci. Eng.

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The COVID-19 pandemic caused by the global spread of the SARS-CoV-2 virus has led to a staggering number of deaths worldwide and significantly increased burden on healthcare as nations scramble to find mitigation strategies. While significant progress has been made in COVID-19 diagnostics and therapeutics, effective prevention and treatment options remain scarce. Because of the potential for the SARS-CoV-2 infections to cause systemic inflammation and multiple organ failure, it is imperative for the scientific community to evaluate therapeutic options aimed at modulating the causative host immune responses to prevent subsequent systemic complications. Harnessing decades of expertise in the use of natural and synthetic materials for biomedical applications, the biomaterials community has the potential to play an especially instrumental role in developing new strategies or repurposing existing tools to prevent or treat complications resulting from the COVID-19 pathology. Leveraging microparticle- and nanoparticle-based technology, especially in pulmonary delivery, biomaterials have demonstrated the ability to effectively modulate inflammation and may be well-suited for resolving SARS-CoV-2-induced effects. Here, we provide an overview of the SARS-CoV-2 virus infection and highlight current understanding of the host’s pulmonary immune response and its contributions to disease severity and systemic inflammation. Comparing to frontline COVID-19 therapeutic options, we highlight the most significant untapped opportunities in immune engineering of the host response using biomaterials and particle technology, which have the potential to improve outcomes for COVID-19 patients, and identify areas needed for future investigations. We hope that this work will prompt preclinical and clinical investigations of promising biomaterials-based treatments to introduce new options for COVID-19 patients.

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Natural killer cell immunotypes related to COVID-19 disease severity

Cited by 361 publications

References 59 publications

SARS-CoV-2 infection paralyzes cytotoxic and metabolic functions of the immune cells

SARS-CoV-2 infection paralyzes cytotoxic and metabolic functions of the immune cells

Regulation of the human NK cell compartment by pathogens and vaccines

Biomaterials-Based Opportunities to Engineer the Pulmonary Host Immune Response in COVID-19

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