SARS-CoV-2-specific T cells are key players in decreasing COVID-19 mortality

A recent US study, currently available on medRxiv* preprint server, supports a beneficial rather than immunopathologic role for effector T-cells during serious infections with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – and provides several important insights for our battle against coronavirus disease 2019 (COVID-19).

The ongoing and disruptive COVID-19 pandemic, caused by the beta-coronavirus SARS-CoV-2, has shaken the world's healthcare systems and economy and claimed more than 2.22 million lives a year after its emergence.

Human adaptive immune system consists of cellular (T cell) and humoral (B cell) immunity and plays a crucial role in our defense against SARS-CoV-2. And while a coordinated interplay between the cellular and humoral arms seems to be indispensable for effective control, T cells appear to be capable of resolving the infection when B cell responses are deficient.

We know that a consistent feature of severe COVID-19 is T cell lymphopenia (i.e., an abnormally decreased level of lymphocytes in the blood), which is unlikely to merely indicate T cell sequestration in the infected lungs.

T cells as 'the most valuable players'?

T cells are likely key contributors to SARS-CoV-2 immunity; however, not much is known about the phenotypic features of SARS-CoV-2-specific T cells related to recovery from severe COVID-19. That said, some newer studies have analyzed the features of T cells recognizing SARS-CoV-2 epitopes.

Considering that these antigen-specific cells can recognize virally-infected cells and generate specific antibodies directly, they hold the most potential to show a beneficial effect on recovery from disease. They are also principal targets of vaccination endeavors.

In this study, a research group led by Dr. Jason Neidleman from the Gladstone Institutes and the University of California in San Francisco (USA) aimed to define the features of T cells from individuals hospitalized in the ICU due to COVID-19 – including some that successfully recovered and some that succumbed to the disease.

A deep phenotyping approach

In this study, the researchers have compared total and SARS CoV-2-specific T cells in mild, moderate and severe cases of COVID-19. Moreover, within the severe cases, an in-depth analysis of longitudinal specimens was conducted to pinpoint any predictive features linked to survival.

A total of 48 blood specimens from 34 individuals infected with SARS-CoV-2 have been analyzed, together with samples from 11 uninfected controls. Samples were taken from ICU patients classified as "severe cases" (68.8%), and from hospitalized patients without the need for the ICU, classified as "moderate cases" (31.2%).

The scientists implemented deep phenotyping of both total and SARS-CoV-2-specific T cells using 38-parameter CyTOF – a recently introduced technique for the characterization of T cells from convalescent individuals.

This enabled the identification of unique phenotypic characteristics of viral-specific and bystander T cells associated with recovery from severe disease, which was then paired with a comprehensive examination of the features of T cells present in the lungs of COVID-19 patients.

The role of SARS-CoV-2-specific T cells

Relative to patients who have died, individuals in this study that recovered from severe forms of COVID-19 presented with elevated numbers of SARS-CoV-2-specific T cells capable of honing a physiological response known as homeostatic proliferation.

More specifically, the researchers observed an increased number of CD8-positive transitional memory T-cells in patients with mild symptoms and a higher number of activated, PD1-expressing T-cells in patients with severe symptoms.

Conversely, in fatal cases of COVID-19, there was an elevated number of SARS-CoV-2-specific regulatory T cells and a time-dependent upsurge in activated bystander CXCR4+ T-cells (the latter subset of cells is also regarded as "extrafollicular" helper T cells).

When all results are taken into account, this study represents a model in which lung-homing T cells activated via bystander effect contribute to immunopathology, whereas a non-suppressive and robust SARS-CoV-2-specific T cell response controls pathogenesis and stimulates recovery from severe COVID-19.

Implications for vaccination efforts

In a nutshell, this study's findings support a favorable rather than immunopathologic role for effector SARS-CoV-2-specific T cells during the severe acute infection, together with promoting recovery from COVID-19.

"Taking into consideration the longevity of SARS-CoV-2-specific T cells, our results suggest that strategies to boost the effector functions of SARS-CoV-2-specific T cells, including by vaccination, will be beneficial for decreasing COVID-19 mortality and helping to end this devastating pandemic", say the authors of this medRxiv study.

In any case, since this study was correlative and phenotypical in nature, follow-up functional assays will be needed to establish any causal effect, as well as studies on larger cohorts of infected individuals.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal references:
Dr. Tomislav Meštrović

Written by

Dr. Tomislav Meštrović

Dr. Tomislav Meštrović is a medical doctor (MD) with a Ph.D. in biomedical and health sciences, specialist in the field of clinical microbiology, and an Assistant Professor at Croatia's youngest university - University North. In addition to his interest in clinical, research and lecturing activities, his immense passion for medical writing and scientific communication goes back to his student days. He enjoys contributing back to the community. In his spare time, Tomislav is a movie buff and an avid traveler.

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