Lesan Vadim, Bewarder Moritz, Metz Carlos, Becker André, Mang Sebastian, Regitz Evi, Thurner Lorenz, Neumann Frank, Kos Igor, Christofyllakis Konstantinos, Danziger Guy, Stilgenbauer Stephan, Bals Robert, Lepper Philipp M, Kaddu-Mulindwa Dominic, Rixecker Torben
Department of Internal Medicine I (Oncology, Hematology, Clinical Immunology, Rheumatology), Saarland University Medical Center, University Hospital, Saarland, 66421, Homburg, Germany.
Department of Internal Medicine V (Pneumology, Allergology and Critical Care Medicine), Interdisciplinary COVID-19 Center, University Hospital, Saarland, Homburg, Germany.
Intensive Care Med Exp. 2021 Sep 3;9(1):45. doi: 10.1186/s40635-021-00409-4.
Despite numerous advances in the identification of risk factors for the development of severe coronavirus disease 2019 (COVID-19), factors that promote recovery from COVID-19 remain unknown. Natural killer (NK) cells provide innate immune defense against viral infections and are known to be activated during moderate and severe COVID-19. Killer immunoglobulin-like receptors (KIR) mediate NK cell cytotoxicity through recognition of an altered MHC-I expression on infected target cells. However, the influence of KIR genotype on outcome of patients with COVID-19 has not been investigated so far. We retrospectively analyzed the outcome associations of NK cell count and KIR genotype of patients with COVID-19 related severe ARDS treated on our tertiary intensive care unit (ICU) between February and June 2020 and validated our findings in an independent validation cohort of patients with moderate COVID-19 admitted to our tertiary medical center.
Median age of all patients in the discovery cohort (n = 16) was 61 years (range 50-71 years). All patients received invasive mechanical ventilation; 11 patients (68%) required extracorporeal membrane oxygenation (ECMO). Patients who recovered from COVID-19 had significantly higher median NK cell counts during the whole observational period compared to patients who died (121 cells/µL, range 16-602 cells/µL vs 81 cells/µL, range 6-227 cells/µL, p-value = 0.01). KIR2DS5 positivity was significantly associated with shorter time to recovery (21.6 ± 2.8 days vs. 44.6 ± 2.2 days, p-value = 0.01). KIR2DS5 positivity was significantly associated with freedom from transfer to ICU (0% vs 9%, p-value = 0.04) in the validation cohort which consisted of 65 patients with moderate COVID-19.
NK cells and KIR genotype might have an impact on recovery from COVID-19.
尽管在识别2019年冠状病毒病（COVID-19）重症发展的风险因素方面取得了诸多进展，但促进COVID-19康复的因素仍然未知。自然杀伤（NK）细胞提供针对病毒感染的固有免疫防御，并且已知在中度和重度COVID-19期间被激活。杀伤细胞免疫球蛋白样受体（KIR）通过识别感染靶细胞上改变的MHC-I表达来介导NK细胞的细胞毒性。然而，迄今为止尚未研究KIR基因型对COVID-19患者预后的影响。我们回顾性分析了2020年2月至6月在我们的三级重症监护病房（ICU）接受治疗的COVID-19相关重症急性呼吸窘迫综合征患者的NK细胞计数和KIR基因型与预后的关联，并在我们三级医疗中心收治的中度COVID-19患者的独立验证队列中验证了我们的发现。
发现队列中的所有患者（n = 16）的中位年龄为61岁（范围50 - 71岁）。所有患者均接受有创机械通气；11名患者（68%）需要体外膜肺氧合（ECMO）。与死亡患者相比，从COVID-19康复的患者在整个观察期内的中位NK细胞计数显著更高（121个细胞/µL，范围16 - 602个细胞/µL vs 81个细胞/µL，范围6 - 227个细胞/µL，p值 = 0.01）。KIR2DS5阳性与恢复时间较短显著相关（21.6 ± 2.8天 vs. 44.6 ± 2.2天，p值 = 0.01）。在由65名中度COVID-19患者组成的验证队列中，KIR2DS5阳性与无需转入ICU显著相关（0% vs 9%，p值 = 0.04）。
NK细胞和KIR基因型可能对COVID-19的康复有影响。
