An Early Th1 Response Is a Key Factor for a Favorable COVID-19 Evolution

Abstract

The Th1/Th2 balance plays a crucial role in the progression of different pathologies and is a determining factor in the evolution of infectious diseases. This work has aimed to evaluate the early, or on diagnosis, T-cell compartment response, T-helper subsets and anti-SARS-CoV-2 antibody specificity in COVID-19 patients and to classify them according to evolution based on infection severity. A unicenter, randomized group of 146 COVID-19 patients was divided into four groups in accordance with the most critical events during the course of disease. The immunophenotype and T-helper subsets were analyzed by flow cytometry. Asymptomatic SARS-CoV-2 infected individuals showed a potent and robust Th1 immunity, with a lower Th17 and less activated T-cells at the time of sample acquisition compared not only with symptomatic patients, but also with healthy controls. Conversely, severe COVID-19 patients presented with Th17-skewed immunity, fewer Th1 responses and more activated T-cells. The multivariate analysis of the immunological and inflammatory parameters, together with the comorbidities, showed that the Th1 response was an independent protective factor for the prevention of hospitalization (OR 0.17, 95% CI 0.03–0.81), with an AUC of 0.844. Likewise, the Th1 response was found to be an independent protective factor for severe forms of the disease (OR 0.09, 95% CI: 0.01–0.63, p = 0.015, AUC: 0.873). In conclusion, a predominant Th1 immune response in the acute phase of the SARS-CoV-2 infection could be used as a tool to identify patients who might have a good disease evolution.

COVID‐19, obesity, and immune response 2 years after the pandemic: A timeline of scientific advances

“… 126 , 127 Severe COVID‐19, in turn, provokes dampened Th1 and Treg responses, while promoting the Th17 profile. 128 , 129 , 130 Similar to obesity, the IL‐17/IL‐10 ratio is increased in COVID‐19 cases, even in deceased patients, as compared to those who improved. 130 The cytokine milieu in these changes plays an important role.…”

“…The Treg/Th17 ratio is decreased in obesity, and this is related to metabolic health 126,127 . Severe COVID‐19, in turn, provokes dampened Th1 and Treg responses, while promoting the Th17 profile 128–130 . Similar to obesity, the IL‐17/IL‐10 ratio is increased in COVID‐19 cases, even in deceased patients, as compared to those who improved 130 .…”

Effective Natural Killer Cell Degranulation Is an Essential Key in COVID-19 Evolution

“…In the same way, NK cell depletion leads to reduced Th1 responses [ 63 ]. Our group recently described the importance of a strong Th1 response for a positive outcome of COVID-19 [ 14 ]. This fact together with the findings described in this work suggests that adequate NK activity, both as an effector and modulator towards the Th1 response, would be essential to establish a coordinated cytotoxic response of innate and adaptive immunity, which allows for the prompt clearance of SARS-CoV2 infection.…”

“…One possible hypothesis is that immune dysregulation is associated with the presence of comorbidities and with the predominant immune response in the initial moments of the disease [ 12 ]. It has been observed that rapid Th1 responses are associated with lower probabilities for the development of hyperinflammatory complications, which are frequently observed in patients with an initial Th2 and/or Th17 immune response [ 13 , 14 ].…”

COVID-19 imparted immune manifestation can be combated by NLGP: Lessons from cancer research

“…Asymptomatic SARS-CoV-2 infected individuals showed a potent and robust Type 1 immunity with high CD8 + T cell count, having a lower count of Th17 cells [19] . Conversely, severe COVID-19 patients presented with Th17-skewed immunity, fewer Type 1 responses and more antigen experienced T-cells.…”