Studies show that long COVID remodeling of T cell dynamics depends on the severity of SARS-CoV-2.

Recent studies published in Immunology Frontier Functional remodeling of post-coronavirus disease 2019 (COVID-19) T cells It occurs in two steps and results in different convalescent immune states 6 months after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Background

To date, more than 540 million COVID-19 cases have been reported worldwide, accounting for more than 6.3 million deaths. The disease was declared a pandemic in March 2020 and has since evolved with a persistent wave of reinfection caused by a new variant of concern (VOC) of the causative agent, SARS-CoV-2. rice field.

The course of COVID-19 is mild in most patients, but many develop severe symptoms that can be fatal. Many studies report that convalescent individuals suffer from “long COVID” or post-acute COVID syndrome (PACS). PACS is mild and may be associated with fatigue, dyspnea, cognitive dysfunction, and neurological dysfunction. It can also be harmful to your health, including cerebrovascular events such as pulmonary fibrosis and stroke.

Long COVID impairs quality of life and is associated with significant morbidity and can precipitate not only in patients who have had severe illness in the past, but also in mild patients. COVID-19 Symptoms And asymptomatic. However, in patients with asymptomatic SARS-CoV-2 infection and those who have experienced mild symptoms, the immune status and possible predictors and mechanisms of PACS remain unclear.

PACS represents an incomplete recovery from COVID-19, causing ongoing health-related problems in more than 30% of all recovery periods. The long-term outbreak of COVID does not depend on the severity of SARS-CoV-2 infection. The persistent peripheral immune system is involved in the PACS mechanism of patients with asymptomatic infections and those with mild COVID-19 symptoms and may help to understand the symptoms and identify long-term COVID predictors.

the study

In this study, longitudinal studies of mild, moderate, and severe COVID-19 convalescent patients will be conducted at two time points to integrate the symptoms reported by the patients and evaluate the dynamics of the T cell immune landscape. I needed to. Patients were cross-examined 3 and 6 months after diagnosis to assess signs of immune changes after COVID-19. Long-term immune changes were interpreted to explain T cell multifunctionality and plasma inflammation marker levels.

The study included 59 male patients who recovered from COVID-19, and these patients were classified based on the severity of the disease. The severity of the disease was estimated by the size of the lung lesions on a computer tomography (CT) scan and the type of oxygen therapy required. The study cohort was selected from patients admitted to the Central Clinical Hospital of the Polish Ministry of Interior and Administration in Warsaw from June to November 2020, or from March to April 2021.

Survey results

It was noted that most of the studies described long COVIDs 1-3 months after recovery or only reported patients with severe symptoms. There was a lack of sufficient data on T cell subsets from convalescent subjects.

This study shows several immune parameters that may predict long COVID, collected 3 and 6 months after mild, moderate, or severe SARS-CoV-2 infection. .. Functional changes were confirmed after the first 3 months after COVID-19. This renders the aging state of CD4 + and CD8 + T cells and interferes with the CD4 + Treg subset. This suppresses the unstable Th1 / Th17-like Treg phenotype and the inflammatory polarization of CD4 +.

Mild convalescence, on the other hand, shows more naive Tregs rather than polarization of T cells into a depleted state. In addition, many long COVID symptoms, such as fatigue and cognitive dysfunction, were found to be dependent on the severity of the COVID symptoms.

Immune dysregulation also correlated with post-acute COVID-19 stage. Reports suggest that T cell activation and depletion increased after SARS-CoV-2 infection. In addition, T cell depletion played an important role in long COVID. During the severe recovery phase, more depleted aging T cells were also identified. In addition, after the first 3 months of recovery after COVID-19, there was a significant bias towards depleted or aged T cells.

On the other hand, 6 months after recovery of COVID-19, T cell aging was seen in patients with severe symptoms but not in patients with mild or moderate disease. The results show that convalescent individuals with severe COVID-19 may persist long-term dysfunction of T cell responses, and therefore immunity and other infections, cancer, and other. It has been suggested that protection against the disease may be compromised.

In addition, the number of Tregs tended to be significantly reduced in patients with COVID-19, and inhibition of their activity correlated with the severity of COVID-19. The results indicate that the function of Treg cells changed during the recovery of COVID-19. This can affect the elimination of inflammation.

In addition, moderate and severe convalescent individuals showed T cell function types that produce high levels of Th1 and Th17 cytokines. Notably, a long recovery period of 3-6 months, for example, strongly inhibits the co-production of Th1 and Th17 cytokines, as well as tumor necrosis factor (TNF) -α and interleukin (IL) -17. This finding was consistent with previous reports.

Severe recovery was observed to induce an increase in the proportion of CD8 + cells that produce granzyme B along with interferon (IFN) -γ during long-term recovery. In addition, the chronic inflammatory condition persists in the severe recovery phase for a long time after COVID-19. Therefore, pro-resolution strategies and “resolution pharmacology” can be developed to prevent long-term inflammatory conditions after COVID. These modalities may also help prevent long-term COVID in patients who have experienced severe COVID-19 symptoms.

In particular, fatigue and / or cognitive dysfunction are features of long COVID that coexist frequently and affect all convalescent periods. Post-COVID syndrome occurs in 10-35% of cases. However, in patients hospitalized with COVID, the incidence is high, up to 85%. Differences in the severity of long-term COVID symptoms and complications in patients infected with various variants of SARS-CoV-2 have not yet been investigated.

In addition, long COVID symptoms also appear during the mild and moderate recovery phase and are not only associated with T cell depletion / aging or impaired inflammatory dispersal. In fact, the set of mechanisms that cause the severity of COVID-19 may also determine the symptoms of long COVID.

Mild recovery may also indicate long-term changes in the blood cell transcriptome, but different immune end types have been shown with different long COVID symptoms. Therefore, different immune cells can cause different long COVID symptoms. In addition, continuous long-term immune response remodeling occurs 3-6 months after COVID.

Fatigue and cognitive dysfunction, on the other hand, are severity-independent and may not be associated with T cell depletion / aging. Long-term studies of all severity stages of COVID-19 are guaranteed to delineate the association characteristics of long COVID symptoms and immune responses in populations of different age groups and genders. This helps explain the metabolic changes in immune cells and the neurological symptoms after COVID-19.