A scoping review of regulatory T cell dynamics in convalescent COVID-19 patients – indications for their potential involvement in the development of Long COVID?

Abstract

BackgroundRecovery from coronavirus disease 2019 (COVID-19) can be impaired by the persistence of symptoms or new-onset health complications, commonly referred to as Long COVID. In a subset of patients, Long COVID is associated with immune system perturbations of unknown etiology, which could be related to compromised immunoregulatory mechanisms.ObjectiveThe objective of this scoping review was to summarize the existing literature regarding the frequency and functionality of Tregs in convalescent COVID-19 patients and to explore indications for their potential involvement in the development of Long COVIDDesignA systematic search of studies investigating Tregs during COVID-19 convalescence was conducted on MEDLINE (via Pubmed) and Web of Science.ResultsThe literature search yielded 17 relevant studies, of which three included a distinct cohort of patients with Long COVID. The reviewed studies suggest that the Treg population of COVID-19 patients can reconstitute quantitatively and functionally during recovery. However, the comparison between recovered and seronegative controls revealed that an infection-induced dysregulation of the Treg compartment can be sustained for at least several months. The small number of studies investigating Tregs in Long COVID allowed no firm conclusions to be drawn about their involvement in the syndrome’s etiology. Yet, even almost one year post-infection Long COVID patients exhibit significantly altered proportions of Tregs within the CD4+ T cell population.ConclusionsPersistent alterations in cell frequency in Long COVID patients indicate that Treg dysregulation might be linked to immune system-associated sequelae. Future studies should aim to address the association of Treg adaptations with different symptom clusters and blood parameters beyond the sole quantification of cell frequencies while adhering to consensualized phenotyping strategies.

Regulatory T Cells (Tregs) and COVID-19: Unveiling the Mechanisms, and Therapeutic Potentialities with a Special Focus on Long COVID

“…Apart from the above-mentioned manifestations of the COVID-19 disease, severe immunopathology has been considered an important characteristic in various cases. The poor prognosis of the SARS-CoV-2 infection or the multiple organ damage is specifically associated with defective T-cell-mediated immune response, which is characterized by excessive proinflammatory cytokines, reduced number of lymphocytes, and newly developed or worsened autoimmune response [ 23 , 106 ]. According to a recent observational cohort research, one in eight individuals who caught COVID-19 is thought to have symptoms that last longer than the acute symptomatic period [ 107 ].…”

“…The World Health Organization (WHO) describes these sequelae, also known as “long COVID” in common usage today, as a post-COVID-19 condition that typically manifests three months following a confirmed or suspected SARS-CoV-2 infection and includes a group of new-onset, prolonged, or varying ailments that persists for at least two months [ 108 ]. According to several studies, the most prevalent symptoms in this situation include exhaustion, breathlessness, post-exertional malaise, chronic cough, headache, muscle aches, tachycardia, concentration deficits, and a decreased quality of life [ 23 , 109 , 110 , 111 ].…”

“…But the interesting fact is that only a few studies have been done on the involvement of Tregs in patients suffering from long COVID or recovering patients from long COVID. Tregs can be important components of the immune system that may control and fine-tune autoimmune responses, promoting immunological homeostasis in the long COVID [ 23 ].…”

“…Furthermore, insufficient research has been conducted on regulatory T cells (Tregs) in patients with long COVID and recovering COVID-19 patients [ 20 ]. Aspects of Treg function, such as cytokine production or suppressive efficacy in long COVID, have not been investigated in any of the current clinical studies [ 23 ]. Due to a dearth of studies addressing Tregs in these aspects, it is hard to draw clear conclusions on the kind of Treg adaptations in long COVID and their potential therapeutic involvement in long COVID management.…”

Folgen nach SARS-CoV-2-Infektion einschließlich Post-COVID-Syndrom

“…Während das akute Krankheitsbild COVID-19 mittlerweile gut verstanden wird, sind die genauen pathophysiologischen Mechanismen und Langzeitfolgen, die zur Entstehung von Post-COVID-Syndromen führen, zurzeit noch unzureichend verstanden. Aktuell diskutierte Mechanismen beinhalten unter anderem eine Viruspersistenz, eine andauernde (systemische) Inflammation [11], die Entwicklung von agonistischen Autoantikörpern gegen G-Proteingekoppelte Rezeptoren [12], eine Veränderung in regulatorischen T-Zellen [13], mikrovaskuläre Veränderungen im Sinne einer "Endotheliitis" [14] und eine intestinale Dysbiose [15]. Dabei ist zu beachten, dass es zu keinem der diskutierten pathophysiologischen Mechanismen eindeutige Beweise gibt und auch eine multifaktorielle Genese aktuell nicht auszuschließen ist.…”