Lymphocytes were examined during COVID-19 and at up to 6 months of convalescence
B cell changes seen during acute COVID-19 were largely restored in convalescence
T cells from convalescent COVID-19 patients displayed persistent changes
Lymphocyte signatures defined 3 convalescent patient groups, one with poorer outcomes
Context and significance
The coronavirus disease 2019 (COVID-19) pandemic, caused by a novel coronavirus strain, has resulted in >100 million infections worldwide. Emerging evidence suggests that some COVID-19 patients suffer persistent symptoms, including fatigue, fibrotic lung disease, and myalgia; however, the long-term immune response in these patients remains ill-defined. Here, we conducted an observational study examining lymphocyte populations in COVID-19 patients during hospitalization and at up to 6 months of convalescence. We identified a number of lymphocyte alterations that persisted in convalescent patients. Moreover, the compilation of lymphocyte parameters in convalescent COVID-19 patients identified 3 distinct patient subgroups, with 1 subgroup associated with poorer clinical outcome. Our study outlines lymphocyte changes in convalescent COVID-19 patients associated with negative effects on subsequent health.
Summary
Background
Emerging studies indicate that some coronavirus disease 2019 (COVID-19) patients suffer from persistent symptoms, including breathlessness and chronic fatigue; however, the long-term immune response in these patients presently remains ill-defined.
Methods
Here, we describe the phenotypic and functional characteristics of B and T cells in hospitalized COVID-19 patients during acute disease and at 3–6 months of convalescence.
Findings
We report that the alterations in B cell subsets observed in acute COVID-19 patients were largely recovered in convalescent patients. In contrast, T cells from convalescent patients displayed continued alterations with persistence of a cytotoxic program evident in CD8+ T cells as well as elevated production of type 1 cytokines and interleukin-17 (IL-17). Interestingly, B cells from patients with acute COVID-19 displayed an IL-6/IL-10 cytokine imbalance in response to Toll-like receptor activation, skewed toward a pro-inflammatory phenotype. Whereas the frequency of IL-6+ B cells was restored in convalescent patients irrespective of clinical outcome, the recovery of IL-10+ B cells was associated with the resolution of lung pathology.
Conclusions
Our data detail lymphocyte alterations in previously hospitalized COVID-19 patients up to 6 months following hospital discharge and identify 3 subgroups of convalescent patients based on distinct lymphocyte phenotypes, with 1 subgroup associated with poorer clinical outcome. We propose that alterations in B and T cell function following hospitalization with COVID-19 could affect longer-term immunity and contribute to some persistent symptoms observed in convalescent COVID-19 patients.
Funding
Provided by UKRI, Lister Institute of Preventative Medicine, the Wellcome Trust, The Kennedy Trust for Rheumatology Research, and 3M Global Giving.
