Early stimulated immune responses predict clinical disease severity in hospitalized COVID-19 patients.

Background: The immune pathogenesis underlying the diverse clinical course of COVID-19 is poorly understood. Currently, there is an unmet need in daily clinical practice for early biomarkers and improved risk stratification tools to help identify and monitor COVID-19 patients at risk of severe disease. Methods: We performed longitudinal assessment of stimulated immune responses in 30 patients hospitalized with COVID-19. We used the TruCulture whole-blood ligand-stimulation assay applying standardized stimuli to activate distinct immune pathways, allowing quantification of cytokine responses. We further characterized immune cell subsets by flow cytometry and used this deep immunophenotyping data to map the course of clinical disease within and between patients. Results: Here we demonstrate impairments in innate immune response pathways at time of COVID-19 hospitalization that are associated with the development of severe disease. We show that these impairments are transient in those discharged from hospital, as illustrated by functional and cellular immune reconstitution. Specifically, we identify lower levels of LPS-stimulated IL-1ß, and R848-stimulated IL-12 and IL-17A, at hospital admission to be significantly associated with increasing COVID-19 disease severity during hospitalization. Furthermore, we propose a stimulated immune response signature for predicting risk of developing severe or critical COVID-19 disease at time of hospitalization, to validate in larger cohorts. Conclusions: We identify early impairments in innate immune responses that are associated with subsequent COVID-19 disease severity. Our findings provide basis for early identification of patients at risk of severe disease which may have significant implications for the early management of patients hospitalized with COVID-19.

Patients with CLL have a lower risk of death from COVID-19 in the Omicron era.

Previous studies have shown that patients with chronic lymphocytic leukemia (CLL) and coronavirus disease 2019 (COVID-19) have high mortality rates. Infection with the Omicron variant has been described as a milder disease course in the general population. However, the outcome for immunocompromised patients has not previously been reported. In a cohort of patients with CLL tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at hospital test sites in the time periods before and after dominance of the Omicron variant, rates of hospitalizations and intensive care unit admissions declined significantly, whereas 30-day mortality remained as high as 23% in the period with dominance of the Omicron sublineage BA.2 variant. However, for a larger population-based cohort of patients with CLL (including the hospital cohort), 30-day mortality was 2%. Thus, patients with CLL with close hospital contacts and, in particular, those >70 years of age with 1 or more comorbidities should be considered for closer monitoring and preemptive antiviral therapy upon a positive SARS-CoV-2 test.