Killer immunoglobulin‑like receptor 2DS5 is associated with recovery from coronavirus disease 2019 Vadim Lesan 1* , Moritz Bewarder 1 , Carlos Metz 2 , André Becker 2 , Sebastian Mang 2 , Evi Regitz 1 , Lorenz Thurner 1 , Frank Neumann 1 , Igor Kos 1 , Konstantinos Christofyllakis 1 , Guy Danziger 2 , Stephan Stilgenbauer 1 , Robert Bals 2 , Philipp M. Lepper 2 , Dominic Kaddu‑Mulindwa 1† and Torben Rixecker 2† Abstract Background: Despite numerous advances in the identifcation 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 moder‑ ate 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 infuence of KIR genotype on outcome of patients with COVID‑19 has not been investigated so far. We retrospectively analyzed the outcome associa‑ tions 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 fndings in an independent validation cohort of patients with moderate COVID‑19 admitted to our tertiary medical center. Results: 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 recov‑ ered from COVID‑19 had signifcantly 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 signif‑ cantly associated with shorter time to recovery (21.6 ± 2.8 days vs. 44.6 ± 2.2 days, p‑value = 0.01). KIR2DS5 positivity was signifcantly 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. Conclusion: NK cells and KIR genotype might have an impact on recovery from COVID‑19. Keywords: KIR, NK cells, SARS‑CoV‑2, COVID‑19, ARDS, Intensive care unit Open Access © The Author(s), 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the mate‑ rial. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creativecommons.org/licenses/by/4.0/. RESEARCH ARTICLES Lesan et al. ICMx (2021) 9:45 https://doi.org/10.1186/s40635‑021‑00409‑4 Intensive Care Medicine Experimental *Correspondence: vadim.lesan@uks.eu † Dominic Kaddu‑Mulindwa and Torben Rixecker contributed equally to this work 1 Department of Internal Medicine I (Oncology, Hematology, Clinical Immunology, Rheumatology), Saarland University Medical Center, University Hospital, Saarland, 66421 Homburg, Germany Full list of author information is available at the end of the article