ABSTRACT
Objectives: The role of innate lymphoid cells (ILCs) in coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is unknown. Understanding the immune response in COVID-19 could contribute to unravel the pathogenesis and identification of treatment targets. To describe the phenotypic landscape of circulating ILCs in COVID-19 patients and to identify ILC phenotypes correlated to serum biomarkers, clinical markers, and laboratory parameters relevant in COVID-19. Methods: Blood samples collected from moderately (n=11) and severely ill (n=12) COVID-19 patients as well as healthy control donors (n=16), were analyzed with 18-parameter flow cytometry. Using supervised and unsupervised approaches, we examined the ILC activation status and homing profile. Clinical and laboratory parameters were obtained from all COVID-19 patients and serum biomarkers were analyzed with multiplex immunoassays. Results: ILCs were largely depleted from the circulation of COVID-19 patients compared with healthy controls. Remaining circulating ILCs from patients revealed increased frequencies of ILC2 in moderate COVID-19, with a concomitant decrease of ILC precursors (ILCp), as compared with controls. ILC2 and ILCp showed an activated phenotype with increased CD69 expression, whereas expression levels of the chemokine receptors CXCR3 and CCR4 were significantly altered in ILC2 and ILCp, and ILC1, respectively. The activated ILC profile of COVID-19 patients was associated with soluble inflammatory markers, while frequencies of ILC subsets were correlated with laboratory parameters that reflect the disease severity. Conclusion: This study provides insights into the potential role of ILCs in immune responses against SARS-CoV-2, particularly linked to the severity of COVID-19.
Subject(s)
COVID-19ABSTRACT
Understanding innate immune responses in COVID-19 is important for deciphering mechanisms of host responses and interpreting disease pathogenesis. Natural killer (NK) cells are innate effector lymphocytes that respond to acute viral infections, but might also contribute to immune pathology. Here, using 28-color flow cytometry, we describe a state of strong NK cell activation across distinct subsets in peripheral blood of COVID-19 patients, a pattern mirrored in scRNA-seq signatures of lung NK cells. Unsupervised high-dimensional analysis identified distinct immunophenotypes that were linked to disease severity. Hallmarks of these immunophenotypes were high expression of perforin, NKG2C, and Ksp37, reflecting a high presence of adaptive NK cell expansions in circulation of patients with severe disease. Finally, arming of CD56bright NK cells was observed in course of COVID-19 disease states, driven by a defined protein-protein interaction network of inflammatory soluble factors. This provides a detailed map of the NK cell activation-landscape in COVID-19 disease.