Remodeling of T Cell Dynamics During Long COVID Is Dependent on Severity of SARS-CoV-2 Infection, 2022, Wiech et al

[Andy]

Several COVID-19 convalescents suffer from the post-acute COVID-syndrome (PACS)/long COVID, with symptoms that include fatigue, dyspnea, pulmonary fibrosis, cognitive dysfunctions or even stroke. Given the scale of the worldwide infections, the long-term recovery and the integrative health-care in the nearest future, it is critical to understand the cellular and molecular mechanisms as well as possible predictors of the longitudinal post-COVID-19 responses in convalescent individuals. The immune system and T cell alterations are proposed as drivers of post-acute COVID syndrome. However, despite the number of studies on COVID-19, many of them addressed only the severe convalescents or the short-term responses.

Here, we performed longitudinal studies of mild, moderate and severe COVID-19-convalescent patients, at two time points (3 and 6 months from the infection), to assess the dynamics of T cells immune landscape, integrated with patients-reported symptoms. We show that alterations among T cell subsets exhibit different, severity- and time-dependent dynamics, that in severe convalescents result in a polarization towards an exhausted/senescent state of CD4+ and CD8+ T cells and perturbances in CD4+ Tregs. In particular, CD8+ T cells exhibit a high proportion of CD57+ terminal effector cells, together with significant decrease of naïve cell population, augmented granzyme B and IFN-γ production and unresolved inflammation 6 months after infection. Mild convalescents showed increased naïve, and decreased central memory and effector memory CD4+ Treg subsets. Patients from all severity groups can be predisposed to the long COVID symptoms, and fatigue and cognitive dysfunctions are not necessarily related to exhausted/senescent state and T cell dysfunctions, as well as unresolved inflammation that was found only in severe convalescents.

In conclusion, the post-COVID-19 functional remodeling of T cells could be seen as a two-step process, leading to distinct convalescent immune states at 6 months after infection. Our data imply that attenuation of the functional polarization together with blocking granzyme B and IFN-γ in CD8+ cells might influence post-COVID alterations in severe convalescents. However, either the search for long COVID predictors or any treatment to prevent PACS and further complications is mandatory in all patients with SARS-CoV-2 infection, and not only in those suffering from severe COVID-19.

Open access, https://www.frontiersin.org/articles/10.3389/fimmu.2022.886431/full

 

[SNT Gatchaman]

A total of 59 male COVID-19 recovered patients between 27-64 years of age were included in the study and divided into three age-matched groups according to the severity of disease measured by the size of lung lesions confirmed by computed tomography scan and the type of applied oxygen therapy. All patients were hospitalized over the period of 25th June - 3rd November 2020 or 13th March – 23rd April 2021

Hopefully they go on with:

Future deep, long-lasting studies of COVID-19 of all severity stages, together with selected age-related and male/female groups are needed to better understand the nature of association of the long-term defects in the immune system with prolonged responses that include metabolic changes of immune cells, as well as emerging neurological manifestations.

In any case, either the search for long COVID predictors or any treatment to prevent the post-COVID syndrome and further possible complications is mandatory in all patients with SARS-CoV-2 infection, and not only in those suffering from severe/acute COVID-19.