Abnormality in the NK cell population is prolonged in severe COVID-19 patients

Leem, Galam; Cheon, Shinhye; Lee, Hoyoung; Choi, Seong Jin; Jeong, Seongju; Kim, Eui-Soon; Jeong, Hye Won; Jeong, Hyeongseok; Park, Su-Hyung; Kim, Yeon-Sook; Shin, Eui-Cheol

Background Our understanding of adaptive immune responses in COVID-19 patients is rapidly evolving, but information on the innate immune responses by natural killer (NK) cells is still insufficient. Objective We aimed to examine the phenotypic and functional status of NK cells and their changes during the course of mild and severe COVID-19. Methods We performed RNA sequencing (RNA-seq) and flow cytometric analysis of NK cells from patients with mild and severe COVID-19 at multiple time points in the course of the disease using cryopreserved peripheral blood mononuclear cells (PBMCs). Results In RNA-seq analysis, the NK cells exhibited distinctive features compared to healthy donors, with significant enrichment of pro-inflammatory cytokine-mediated signaling pathways. Intriguingly, we found that the unconventional CD56dimCD16neg (uCD56dim) NK cell population expanded in cryopreserved PBMCs from COVID-19 patients regardless of disease severity, accompanied by decreased NK cell cytotoxicity. The NK cell population was rapidly normalized alongside the disappearance of uCD56dim NK cells and the recovery of NK cell cytotoxicity in mild COVID-19 patients, but this occurred slowly in severe COVID-19 patients. Conclusion The current longitudinal study provides a deep understanding of the NK cell biology in COVID-19.