RESUMEN
BACKGROUND: Natural killer (NK) cells are innate lymphoid cells that mediate antitumour and antiviral responses. However, very little is known about how ageing influences human NK cells, especially at the single-cell level. METHODS: We applied single-cell sequencing (scRNA-seq) to human lymphocytes and NK cells from 4 young and 4 elderly individuals and then analysed the transcriptome data using Seurat. We detected the proportion and phenotype of NK cell subsets in peripheral blood samples from a total of 62 young and 52 elderly healthy donors by flow cytometry. We also used flow cytometry to examine the effector functions of NK cell subsets upon IFN-α/IL-12+IL-15/K562/IL-2 stimulation in vitro in peripheral blood samples from a total of 64 young and 63 elderly healthy donors. We finally studied and integrated single-cell transcriptomes of NK cells from 15 young and 41 elderly COVID-19 patients with those from 12 young and 6 elderly healthy control individuals to investigate the impacts of ageing on NK cell subsets in COVID-19 disease. RESULTS: We discovered a memory-like NK subpopulation (NK2) exhibiting the largest distribution change between elderly and young individuals among lymphocytes. Notably, we discovered a unique NK subset that was predominantly CD52+ NK2 cells (NK2.1). These memory-like NK2.1 cells accumulated with age, exhibited proinflammatory characteristics, and displayed a type I interferon response state. Integrative analyses of a large-cohort COVID-19 dataset and our datasets revealed that NK2.1 cells from elderly COVID-19 patients are enriched for type I interferon signalling, which is positively correlated with disease severity in COVID-19. CONCLUSIONS: We identified a unique memory-like NK cell subset that accumulates with ageing and correlates with disease severity in COVID-19. Our results identify memory-like NK2.1 cells as a potential target for developing immunotherapies for infectious diseases and for addressing age-related dysfunctions of the immune system.
Asunto(s)
COVID-19 , Transcriptoma , Anciano , Envejecimiento/genética , Humanos , Inmunidad Innata , Células Asesinas Naturales/metabolismo , Índice de Severidad de la EnfermedadAsunto(s)
Células Productoras de Anticuerpos/inmunología , Betacoronavirus/fisiología , Infecciones por Coronavirus/inmunología , Inflamación/inmunología , Neumonía Viral/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Anticuerpos Antivirales/sangre , COVID-19 , Progresión de la Enfermedad , Interacciones Huésped-Patógeno , Humanos , Inmunidad Humoral , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Interleucina-6/metabolismo , Pandemias , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Glicoproteína de la Espiga del Coronavirus/inmunologíaRESUMEN
SARS-CoV-2 outbreak has attracted global attention. Verifying the presence of viral RNA is the gold standard for the diagnosis of COVID-19. However, RT-qPCR diagnosis often fails to catch infected patients, because of inconsistent swab sample collection. Here we report a case that showed 5 consecutive negative and 1 low-viral- dose RT-qPCR results during illness spanning over 20 days. Clinical symptoms suggest SARS-CoV-2 infection with typical ground glass like a lung in computed tomography. SARS-CoV-2 infection was serologically confirmed by the presence of anti-SARS-CoV-2 specific antibodies in patients' serum. Finally, a high level of protective IgG was produced after the patient recovered. Surprisingly, as a barber and a housewife staying at home for the first 2 weeks after the onset of illness, none of the close contacts were infected, showing a case of low viral load and low infectivity in this patient.