Long-Haul COVID-19 and T-Cell Activation

Survivors of severe COVID-19 with long-haul respiratory symptoms display activated T-cell signatures and marked immune perturbations. A cohort study was conducted among a group of patients who had survived severe SARS-CoV-2 infection. Results of the study were presented at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2022 Annual Meeting, held in Phoenix, Arizona, February 25 to 28.

The investigators sought to explore the long-term evolution of T cells following COVID-19 infection among patients with long-haul symptoms. They tracked circulating T cells in a group of 88 individuals who had been hospitalized with COVID-19 and subsequently experienced persistent respiratory symptoms. The T cells were obtained during severe acute COVID-19, at 6 weeks after hospital discharge, and between 6 and 11 months following hospital discharge. High-dimensional immunophenotyping with spectral flow cytometry was used to analyze the participants’ T cells. The Tracking Responders Expanding (T-REX) algorithm was used to identify longitudinal changes in complex T-cell signatures. ImmunoCAP assay was utilized to evaluate patients for antibodies to SARS-CoV-2 proteins.

Participants with long-haul respiratory symptoms who were sampled at 6 weeks following hospital discharge had higher rates of activated and tissue-homing CD4+ and CD8+ T cells, compared with healthy individuals and patients who had experienced a mild acute COVID-19 infection. A higher number of terminally differentiated CD8+ T cells were also detected in these individuals.

The T-REX algorithm identified multiple CD4+ and CD8+ T-cell signatures that expanded or contracted by 95% or more up to 6 months following acute infection, including highly activated subtypes. Fluctuations in T-cell signatures were observed several months following acute infection, even in the presence of decreasing antibodies to SARS-CoV-2 proteins.

The researchers concluded that the activated T-cell signatures and marked immune perturbations detected following severe COVID-19 infection were consistent with trafficking of T cells with dysregulated homeostasis and pathogenic potential. They postulate that activated T cells may contribute to airway inflammation long after an acute illness has resolved.

Reference  

Canderan G, Muehling L, Kadl A, et al. Survivors of COVID-19 with long-haul respiratory symptoms display enhanced activation of circulating T cells. Presented at: American Academy of Allergy, Asthma & Immunology (AAAAI) 2022 Annual Meeting; February 25–28, 2022; Phoenix, AZ. Abstract 175.