SARS-CoV-2 specific T cells play an important role in reducing COVID-19 mortality

Recent US research, now medRxiv* The preprint server supports a beneficial role rather than an immunopathological role of effector T cells in severe infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus It provides some important insights into the fight against disease 2019 (COVID-19). ).

The ongoing devastating COVID-19 pandemic caused by the betacoronavirus SARS-CoV-2 has shaken the global health system and economy, killing more than 2.22 million people in the year since its emergence. It was.

The human adaptive immune system is composed of cellular (T cell) and humoral (B cell) immunity and plays an important role in defense against SARS-CoV-2. And while the coordinated interactions between the cellular and humoral arms appear to be essential for effective control, T cells If the B cell response is inadequate, the infection seems to be resolved.

A consistent feature of severe COVID-19 is T-cell lymphopenia (ie, an abnormal decrease in blood lymphocyte levels), which is unlikely to simply indicate T cell sequestration in infected lungs. We know.

T cells as the “most valuable player”?

T cells may be a major contributor to SARS-CoV-2 immunity. However, little is known about the phenotypic characteristics of SARS-CoV-2 specific T cells associated with recovery from severe COVID-19. Nonetheless, some new studies have analyzed the characteristics of T cells that recognize the SARS-CoV-2 epitope.

Considering these antigen-Specific cells can recognize virus-infected cells and directly produce specific antibodies, most likely to have a beneficial effect on recovery from the disease. They are also the main target of vaccination efforts.

In this study, a research group led by Gladstone Institutes and Dr. Jason Nadleman of the University of California, San Francisco (USA) aimed to characterize T cells in individuals admitted to the ICU for COVID-19. It was made. It recovered successfully and some succumbed to illness.

Deep phenotypic approach

In this study, researchers compared total T cells with SARSCoV-2 specific T cells in mild, moderate, and severe cases of COVID-19. In addition, in severe cases, a detailed analysis of longitudinal specimens was performed to identify predictive features associated with survival.

A total of 48 blood samples from 34 individuals infected with SARS-CoV-2 were analyzed along with samples from 11 uninfected controls. Samples were taken from ICU patients classified as “severe cases” (68.8%) and inpatients who did not require ICUs classified as “moderate cases” (31.2%).

Scientists used a 38-parameter CyTOF to implement deep phenotypes for both total T cells and SARS-CoV-2 specific T cells. This is a recently introduced technique for characterization of T cells from convalescent individuals.

This allows us to identify virus-specific and bystander T cell unique phenotypic features associated with recovery from severe disease and include a comprehensive set of T cell features present in the lungs of COVID-19 patients. Combined with a typical test.

Role of SARS-CoV-2 specific T cells

Individuals in this study who recovered from a severe form of COVID-19 compared to deceased patients had an increased number of SARS-CoV-2 specific T cells that could polish a physiological response known as homeostatic proliferation. Was shown.

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

Conversely, in fatal cases of COVID-19, the number of SARS-CoV-2 specific regulatory T cells increased and activated bystander CXCR4 + T cells proliferated in a time-dependent manner (the latter). Cell subsets of “extrafollic” helper T cells).

Taking all results into account, this study found that lung homing T cells activated through the bystander effect contribute to immunopathology, while being non-suppressive and robust SARS-CoV-2 specific. The T cell response represents a model that controls the etiology and stimulates recovery from severe COVID-19.

Impact on vaccination efforts

In a nutshell, the findings of this study facilitate recovery from COVID-19 and support a preferred rather than immunopathological role for effector SARS-CoV-2 specific T cells during severe acute infections. To do.

“Given the longevity of SARS-CoV-2 specific T cells, it is suggested that strategies to enhance the effector function of SARS-CoV-2 specific T cells, including vaccination, may be beneficial in reducing COVID-19. Helps end the mortality and this catastrophic pandemic, “says the author of this. medRxiv Research.

In any case, the study was correlative and phenotypic in nature, requiring a follow-up function assay to establish the causative effect and a study of a larger cohort of infected individuals.

*Important Notices

medRxiv Publish preliminary scientific reports that should not be considered definitive as they are not peer-reviewed, guide clinical / health-related behaviors, and should not be treated as established information.