Elevated Th17 cells associated with increased risk of critical COVID

By Shanet Susan AlexJun 14 2022Reviewed by Aimee Molineux

In a recent article published in the European Journal of Internal Medicine, researchers in France indicated that T cell immune reaction correlates possibly with the chance of critical severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among hospitalized patients.

Study: T-cell immune response predicts the risk of critical SARS-Cov2 infection in hospitalized COVID-19 patients. ​​​​​​​Image Credit : fusebulb / Shuttterstock

Background

The coronavirus disease 2019 (COVID-19) pandemic that started in late December 2019 has infected approximately 540 million individuals worldwide and claimed the lives of over 6.3 million people. The SARS-CoV-2 infection has been better managed since its emergence, initially using dexamethasone and more recently with biologics that suppress the interleukin 6 (IL-6) or IL-1β signaling routes.

Although the exact pathophysiology of COVID-19 is unknown, investigations have demonstrated that infection with SARS-CoV-2 results in a cytokine storm with high IL-6 secretion. Based on these findings, a monoclonal antibody, tocilizumab, aimed against IL-6 membranous and soluble receptors, has emerged as a viable therapy for individuals with severe COVID-19.

According to the latest randomized controlled studies, if the infection progresses in hospitalized SARS-CoV-2 patients, tocilizumab is given to help control the cytokine storm. On the other hand, clinicians lack a reliable indicator for predicting the probability of illness deteriorating. Tocilizumab therapy can be started sooner and possibly lessen the requirement for mechanical breathing if people at greater risk of progressing to severe disease could be better identified.

About the study

The goal of the present study was to find markers of illness progression in hospitalized SARS-CoV-2-infected individuals. The authors anticipated that examining the T-cell immune reaction in SARS-CoV-2 patients in hospitals could indicate the likelihood of disease deterioration.

The research prospectively included individuals hospitalized for severe recent-onset COVID-19, i.e., less than a week, with reverse transcription-polymerase chain reaction (RT-PCR)-validated SARS-CoV-2 infection. All subjects were enrolled following the submission of written informed consent. This study excluded pregnant women, patients less than 18 years, and individuals who were incapable of giving consent to the research.

Fresh peripheral blood mononuclear cells (PBMCs) were isolated for flow cytometry analysis (FACS) from blood samples taken at enrollment and before commencing corticosteroid therapy. On paper case report forms, clinical, demographical, radiological, biological, and outcome data were documented prospectively. The subjects' National Early Warning 2 (NEWS2) score was determined at the time of insertion. Admission to the intensive care unit or mortality, whichever came first, was considered a critical SARS-CoV-2 infection.

The SARS-CoV-2 patients remained stable, and individuals who advanced to severe disease were compared on the proportion of plasma IL-6 and T-cell subsets at admission, preceding any steroid medication.

Results

The study results demonstrated that among the 37 COVID-19 patients comprising 19 women and 18 men included in the research, 11, i.e., 30%, developed severe SARS-CoV-2 infection. Chronic medical conditions like diabetes, hypertension, cardiovascular diseases, obesity, chronic respiratory diseases, or elevated NEWS2 scores were not strongly correlated with advancement to critical COVID-19 in the current study, contrary to previous investigations. This could be due to the research's small sample size.

Critical COVID-19 patients were older, had elevated creatinine levels, and lower proportions of circulating B cells, T cells, and CD4+ T cells at the time of admission than those who experienced a better prognosis. Besides the T helper 17 (Th17) cells proportion, which was two times greater in patients who advanced to critical SARS-CoV-2 infection, there was no substantial distinction between the two cohorts across T cell subsets. The severe COVID-19 group also had superior plasma IL-6 levels during admission.

Further, the proportion of circulating Th17 cells at hospital admission was the sole predictor correlated with a greater probability of progressing to severe SARS-CoV-2 infection in multivariate analysis. Hence, the team stated that Th17 cell analysis could aid in identifying patients who require anti-IL6R therapy, such as tocilizumab. 

Indeed, the authors found that Th17 cells accounting for more than 0.435% of CD4 T cells in severe SARS-CoV-2 infection were linked to a worse chance of survival. They noted that the excess of Th1 cells in COVID-19 was probably associated with more adverse consequences and might cause an exaggerated inflammatory reaction counterproductive to viral clearance.

Conclusions

Overall, the study findings depicted that an increased proportion of Th17 cells in hospitalized SARS-CoV-2 patients was linked to a higher risk of catastrophic illness progression. 

The team discovered that individuals who advanced to critical COVID-19 had a prominent percentage of Th17 cells at baseline. Since a meaningful result was achieved amidst the limited number of subjects enrolled, this marker may be beneficial in predicting the probability of escalation to severe SARS CoV-2 infection in hospitalized COVID-19 patients. If these findings were validated in a larger trial, the authors believe that this marker can be used to efficiently target the patient base for whom tocilizumab could reduce the likelihood of advancement to critical COVID-19.

Moreover, since the proportion of Th17 lymphocytes corresponds with the CD4+CCR6+CD161+ T lymphocytes percentage, which can be measured quickly in routine hematology laboratories, the scientists believe that it may be possible to avoid the complexity and time required to obtain Th17 levels in routine practice. Unfortunately, this subset was not measured in the current study, but the subject merits additional investigation.

Source

Samson M, Nicolas B, Ciudad M, Greigert H, Guilhem A, Cladiere C et al. T-cell immune response predicts the risk of critical SARS-Cov2 infection in hospitalized COVID-19 patients. European Journal of Internal Medicine. 2022, DOI: https://doi.org/10.1016/j.ejim.2022.06.001, https://www.ejinme.com/article/S0953-6205(22)00213-8/