Innate lymphoid cell composition associates with COVID-19 disease severity

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.

High-dimensional profiling reveals phenotypic heterogeneity and disease-specific alterations of granulocytes in COVID-19

“…To provide an in-depth characterization of the granulocyte compartment in patients with moderate or severe COVID-19, we designed a strategy based on the integrated analysis of high dimensional flow cytometry data from whole blood cells, extensive proteomic screening in serum and plasma, and detailed clinical and laboratory information from patients included in the study (Figure 1A). Twenty-six hospitalized COVID-19 patients (10 moderate and 16 severe) and age-matched healthy controls were recruited at Karolinska University Hospital as part of the Karolinska KI/K COVID-19 Immune Atlas effort (25-28) (Figure 1B, Supplemental Tables 1-3). No differences in age, sex, body-mass index (BMI) or time from symptom debut until hospital admission, were present between moderate and severe patients (Figure 1B, Supplemental Table 2).…”

Longitudinal characterization of humoral and cellular immunity in hospitalized COVID-19 patients reveal immune persistence up to 9 months after infection

“…Twenty-six hospitalized COVID-19 patients were included in this study, ten of whom were treated at the infectious disease unit (IDU) and are referred to as moderate, while sixteen patients were treated at the intensive care unit (ICU) and are referred to as severe (Figure 1A; Table 1). The present patient cohorts were part of the Karolinska KI/K COVID-19 Immune Atlas project, where characterizations of other immune cell subsets during acute COVID-19 have been described 16–21 . When possible, these patients were sampled longitudinally at 5- and 9-months after symptom onset (Figure 1A; Table 1).…”

“…In addition, 17 patients were followed up at 5months and 13 patients were followed up at 9-months since symptom onset ( Figure 1A). This COVID-19 patient cohort is part of the Karolinska KI/K COVID-19 Immune Atlas project [16][17][18][19][20][21] . More clinical information and other related data can be found at covid19cellatlas.com.…”

Life-long passion for antiviral research and drug development: 80th birthday of Prof. Dr. Erik De Clercq

“…With the support of our esteemed professor, we presented a multi-country survey of COVID-19 to characterize mortality-associated factors in elderly males with comorbidities [111] . In addition to remdesivir and dexamethasone, many strategies are still under development to treat COVID-19 [113] , [114] , [115] , [116] , [117] , [118] , [119] , [120] , [121] , [122] , [123] , [124] , [125] , [126] , [127] .…”