ArticlePLoS pathogens2021
Extensive activation, tissue trafficking, turnover and functional impairment of NK cells in COVID-19 patients at disease onset associates with subsequent disease severity.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- [Pulmonary innate immune response in Sars-cov-2 infection]Revista de la Facultad de Ciencias Medicas (Cordoba, Argentina) · 2022Pooled it
- Andes Virus: From Transmission Dynamics to Pandemic Potential.European journal of clinical investigation · 2026Review
- SARS-CoV-2 Infection Associated with HHV-6A Reactivation and an Inhibitory KIR2DL2/HLA-C1 Immunogenetic Profile.Microorganisms · 2026Article
- Digitally Assessed Long COVID Symptomatology Is Associated With Lymphocyte Mitochondrial Dysfunction and Altered Immune Potential.Open forum infectious diseases · 2025Article
- The effect of COVID-19 and sex differences on natural killer cell cytotoxicity.Frontiers in cellular and infection microbiology · 2025Article
- Delineating immune variation between adult and children COVID-19 cases and associations with disease severity.Scientific reports · 2024Article
- CD34Frontiers in immunology · 2024Article
- Elevated levels of cell-free NKG2D-ligands modulate NKG2D surface expression and compromise NK cell function in severe COVID-19 disease.Frontiers in immunology · 2024Article
- Defining the role of natural killer cells in COVID-19.Nature immunology · 2023Review
- Simulation of COVID-19 symptoms in a genetically engineered mouse model: implications for the long haulers.Molecular and cellular biochemistry · 2023Article
- NK cell subsets and dysfunction during viral infection: a new avenue for therapeutics?Frontiers in immunology · 2023Review
- Early expansion of activated adaptive but also exhausted NK cells during acute severe SARS-CoV-2 infection.Frontiers in cellular and infection microbiology · 2023Article
- High baseline frequencies of natural killer cells are associated with asymptomatic SARS-CoV-2 infection.Current research in immunology · 2023Article
- SARS-CoV-2 escapes direct NK cell killing through Nsp1-mediated downregulation of ligands for NKG2D.Cell reports · 2022Article
- Herpes Simplex Virus 1 (HSV-1) Reactivation in Critically Ill COVID-19 Patients: A Brief Narrative Review.Infectious diseases and therapy · 2022Review
- Natural killer cell exhaustion in SARS-CoV-2 infection.Innate immunity · 2022Review
- Lymphocyte Population Changes at Two Time Points during the Acute Period of COVID-19 Infection.Journal of clinical medicine · 2022Article
- Variation in the Humoral Immune Response Induced by the Administration of the BNT162b2 Pfizer/BioNTech Vaccine: A Systematic Review.Vaccines · 2022Review
- Exploring the Utility of NK Cells in COVID-19.Biomedicines · 2022Review
- What we know and still ignore on COVID-19 immune pathogenesis and a proposal based on the experience of allergic disorders.Allergy · 2022Review
Corrections and comments
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Authors and funding
20 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The SARS-CoV-2 infection causes severe respiratory involvement (COVID-19) in 5-20% of patients through initial immune derangement, followed by intense cytokine production and vascular leakage. Evidence of immune involvement point to the participation of T, B, and NK cells in the lack of control of virus replication leading to COVID-19. NK cells contribute to early phases of virus control and to the regulation of adaptive responses. The precise mechanism of NK cell dysregulation is poorly understood, with little information on tissue margination or turnover. We investigated these aspects by multiparameter flow cytometry in a cohort of 28 patients hospitalized with early COVID-19. Relevant decreases in CD56brightCD16+/- NK subsets were detected, with a shift of circulating NK cells toward more mature CD56dimCD16+KIR+NKG2A+ and "memory" KIR+CD57+CD85j+ cells with increased inhibitory NKG2A and KIR molecules. Impaired cytotoxicity and IFN-γ production were associated with conserved expression of natural cytotoxicity receptors and perforin. Moreover, intense NK cell activation with increased HLA-DR and CD69 expression was associated with the circulation of CD69+CD103+ CXCR6+ tissue-resident NK cells and of CD34+DNAM-1brightCXCR4+ inflammatory precursors to mature functional NK cells. Severe disease trajectories were directly associated with the proportion of CD34+DNAM-1brightCXCR4+ precursors and inversely associated with the proportion of NKG2D+ and of CD103+ NK cells. Intense NK cell activation and trafficking to and from tissues occurs early in COVID-19, and is associated with subsequent disease progression, providing an insight into the mechanism of clinical deterioration. Strategies to positively manipulate tissue-resident NK cell responses may provide advantages to future therapeutic and vaccine approaches.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.