The Study of the Immune Status in Post-Covid Syndrome by Flow Cytometry

A novel coronavirus infection was described in 2019 in Wuhan, China. From the first months of the spread of the infection around the world, evidence began to appear that patients after recovery had various symptoms. Duration, intensity, and variability of symptoms vary among patients and are often not associated with the severity of the most acute illness. Recently the concept of post-COVID syndrome (postCOVID or long-COVID in the English-language literature) has acquired increasingly clear diagnostic criteria. Persistent symptoms and / or the appearance of delayed complications after 4 weeks or more from the onset of symptoms of an acute illness are commonly called post-COVID syndrome. The wide range of symptoms that can occur in patients with post-COVID syndrome is now a major health concern worldwide. A proper clinical evaluation will help determine the etiology and build a treatment plan. Longer studies aimed at identifying the effects of COVID-19, possible risk factors for their development, a detailed study of the pathogenetic mechanisms of SARS-CoV-2, and the development of treatment and rehabilitation methods to improve the mental and physical health of surviving patients are relevant elements of study for the foreseeable future. T-lymphocytes are a poorly studied population of T lymphocytes. These cells are more often localized in the mucous membranes of the body which have the properties of innate and acquired immunity. The main biological functions are cytolysis, immunoregulation which indicates an important immunocompetent role of this type of cell population in severe infectious diseases. This article provides information on the fraction of T-lymphocytes during the formation of adaptive immunity in patients with post-COVID syndrome.

γδ T Cells in Emerging Viral Infection: An Overview.

New emerging viruses belonging to the Coronaviridae, Flaviviridae, and Filoviridae families are serious threats to public health and represent a global concern. The surveillance to monitor the emergence of new viruses and their transmission is an important target for public health authorities. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an excellent example of a pathogen able to cause a pandemic. In a few months, SARS-CoV-2 has spread globally from China, and it has become a world health problem. Gammadelta (γδ) T cell are sentinels of innate immunity and are able to protect the host from viral infections. They enrich many tissues, such as the skin, intestines, and lungs where they can sense and fight the microbes, thus contributing to the protective immune response. γδ T cells perform their direct antiviral activity by cytolytic and non-cytolytic mechanisms against a wide range of viruses, and they are able to orchestrate the cellular interplay between innate and acquired immunity. For their pleiotropic features, γδ T cells have been proposed as a target for immunotherapies in both cancer and viral infections. In this review, we analyzed the role of γδ T cells in emerging viral infections to define the profile of the response and to better depict their role in the host protection.

Comprehensive Analysis of the ILCs and Unconventional T Cells in Virus Infection: Profiling and Dynamics Associated with COVID-19 Disease for a Future Monitoring System and Therapeutic Opportunities.

This review is a comprehensive analysis of the effects of SARS-CoV-2 infection on Unconventional T cells and innate lymphoid cells (ILCs). COVID-19 affected patients show dysregulation of their adaptive immune systems, but many questions remain unsolved on the behavior of Unconventional cells and ILCs during infection, considering their role in maintaining homeostasis in tissue. Therefore, we highlight the differences that exist among the studies in cohorts of patients who in general were categorized considering symptoms and hospitalization. Moreover, we make a critical analysis of the presence of particular clusters of cells that express activation and exhausted markers for each group in order to bring out potential diagnostic factors unconsidered before now. We also focus our attention on studies that take into consideration recovered patients. Indeed, it could be useful to determine Unconventional T cells' and ILCs' frequencies and functions in longitudinal studies because it could represent a way to monitor the immune status of SARS-CoV-2-infected subjects. Possible changes in cell frequencies or activation profiles could be potentially useful as prognostic biomarkers and for future therapy. Currently, there are no efficacious therapies for SARS-CoV-2 infection, but deep studies on involvement of Unconventional T cells and ILCs in the pathogenesis of COVID-19 could be promising for targeted therapies.

Single-Cell RNAseq Profiling of Human γδ T Lymphocytes in Virus-Related Cancers and COVID-19 Disease.

The detailed characterization of human γδ T lymphocyte differentiation at the single-cell transcriptomic (scRNAseq) level in tumors and patients with coronavirus disease 2019 (COVID-19) requires both a reference differentiation trajectory of γδ T cells and a robust mapping method for additional γδ T lymphocytes. Here, we incepted such a method to characterize thousands of γδ T lymphocytes from (n = 95) patients with cancer or adult and pediatric COVID-19 disease. We found that cancer patients with human papillomavirus-positive head and neck squamous cell carcinoma and Epstein-Barr virus-positive Hodgkin's lymphoma have γδ tumor-infiltrating T lymphocytes that are more prone to recirculate from the tumor and avoid exhaustion. In COVID-19, both TCRVγ9 and TCRVγnon9 subsets of γδ T lymphocytes relocalize from peripheral blood mononuclear cells (PBMC) to the infected lung tissue, where their advanced differentiation, tissue residency, and exhaustion reflect T cell activation. Although severe COVID-19 disease increases both recruitment and exhaustion of γδ T lymphocytes in infected lung lesions but not blood, the anti-IL6R therapy with Tocilizumab promotes γδ T lymphocyte differentiation in patients with COVID-19. PBMC from pediatric patients with acute COVID-19 disease display similar γδ T cell lymphopenia to that seen in adult patients. However, blood γδ T cells from children with the COVID-19-related multisystem inflammatory syndrome are not lymphodepleted, but they are differentiated as in healthy PBMC. These findings suggest that some virus-induced memory γδ T lymphocytes durably persist in the blood of adults and could subsequently infiltrate and recirculate in tumors.

Gamma Delta T Cells and Their Involvement in COVID-19 Virus Infections.

The global outbreak of the SARS-Cov-2 virus in 2020 has killed millions of people worldwide and forced large parts of the world into lockdowns. While multiple vaccine programs are starting to immunize the global population, there is no direct cure for COVID-19, the disease caused by the SARS-Cov-2 infection. A common symptom in patients is a decrease in T cells, called lymphopenia. It is as of yet unclear what the exact role of T cells are in the immune response to COVID-19. The research so far has mainly focused on the involvement of classical αß T cells. However, another subset of T cells called γδ T cells could have an important role to play. As part of the innate immune system, γδ T cells respond to inflammation and stressed or infected cells. The γδ T cell subset appears to be particularly affected by lymphopenia in COVID-19 patients and commonly express activation and exhaustion markers. Particularly in children, this subset of T cells seems to be most affected. This is interesting and relevant because γδ T cells are more prominent and active in early life. Their specific involvement in this group of patients could indicate a significant role for γδ T cells in this disease. Furthermore, they seem to be involved in other viral infections and were able to kill SARS infected cells in vitro. γδ T cells can take up, process and present antigens from microbes and human cells. As e.g. tumour-associated antigens are presented by MHC on γδ T cells to classical T-cells, we argue here that it stands to reason that also viral antigens, such as SARS-Cov-2-derived peptides, can be presented in the same way. γδ T cells are already used for medical purposes in oncology and have potential in cancer therapy. As γδ T cells are not necessarily able to distinguish between a transformed and a virally infected cell it could therefore be of great interest to investigate further the relationship between COVID-19 and γδ T cells.