Spontaneous, persistent T-cell dependent IFN-γ release in patients who progress to Long COVID

Krishna, Benjamin A.; Lim, Eleanor; Mactavous, Lenette; Jackson, Sarah E.; Team, NIHR BioResource; Lyons, Paul; Döffinger, Rainer; Bradley, John R.; Smith, Kenneth; Matheson, Nicholas J; Lehner, Paul J.; Sithole, Nyaradzai; Wills, Mark R.

doi:10.21203/rs.3.rs-2034285/v1

Cited by 3 publications

(6 citation statements)

References 39 publications

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“…Krishna et al investigated the levels of IFN-γ from PBMCs of patients with LC and from patients who had recovered from acute COVID-19 infection [55].…”

Section: Testing-defined Clusters Of Lcmentioning

confidence: 99%

“…54 unexposed donor samples were recruited by the National Institute for Health Research BioResource Cambridge through the Anti-viral Responses in Ageing study before October 2019, so these patients were not exposed to SARS-CoV-2. 55 LC patients were recruited for the study based on LC symptoms that persisted for at least five months after acute COVID-19 [55].…”

Section: Testing-defined Clusters Of Lcmentioning

confidence: 99%

“…No scRNA sequencing data, however, were performed to analyze this population of CD8+ T cells in patients with long COVID. This could have helped to characterize the activation profiles of these cells more fully [55]. A considerable number of the LC patients had symptoms resolve spontaneously or after vaccination.…”

Section: Testing-defined Clusters Of Lcmentioning

confidence: 99%

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Long COVID: Long-Term Impact of SARS-CoV2

Makhluf,

Madany,

Kim

2024

Diagnostics

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Four years post-pandemic, SARS-CoV-2 continues to affect many lives across the globe. An estimated 65 million people suffer from long COVID, a term used to encapsulate the post-acute sequelae of SARS-CoV-2 infections that affect multiple organ systems. Known symptoms include chronic fatigue syndrome, brain fog, cardiovascular issues, autoimmunity, dysautonomia, and clotting due to inflammation. Herein, we review long COVID symptoms, the proposed theories behind the pathology, diagnostics, treatments, and the clinical trials underway to explore treatments for viral persistence, autonomic and cognitive dysfunctions, sleep disturbances, fatigue, and exercise intolerance.

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“…Krishna et al investigated the levels of IFN-γ from PBMCs of patients with LC and from patients who had recovered from acute COVID-19 infection [55].…”

Section: Testing-defined Clusters Of Lcmentioning

confidence: 99%

Section: Testing-defined Clusters Of Lcmentioning

confidence: 99%

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Long COVID: Long-Term Impact of SARS-CoV2

Makhluf,

Madany,

Kim

2024

Diagnostics

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“…This persistence is critical as studies have shown that while antibody titers against SARS-CoV-2 decrease over time, the T-cell response, particularly memory T cells, remains more robust [155,158]. Interestingly, a significant proportion of LC patients retain T-cell responses to SARS-CoV-2 antigens months after recovery, even when antibodies are undetectable [159]. Also, no relationship was found between antibodies against the SARS-CoV-2 nucleocapsid antigen (protein N) and clinical LC symptomatology in a studied Danish population [160].…”

Section: The Relationship Of Long Covid To Systemic Low-grade Inflamm...mentioning

confidence: 99%

Exploring the Pathophysiology of Long COVID: The Central Role of Low-Grade Inflammation and Multisystem Involvement

Gusev,

Sarapultsev

2024

IJMS

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Long COVID (LC), also referred to as Post COVID-19 Condition, Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), and other terms, represents a complex multisystem disease persisting after the acute phase of COVID-19. Characterized by a myriad of symptoms across different organ systems, LC presents significant diagnostic and management challenges. Central to the disorder is the role of low-grade inflammation, a non-classical inflammatory response that contributes to the chronicity and diversity of symptoms observed. This review explores the pathophysiological underpinnings of LC, emphasizing the importance of low-grade inflammation as a core component. By delineating the pathogenetic relationships and clinical manifestations of LC, this article highlights the necessity for an integrated approach that employs both personalized medicine and standardized protocols aimed at mitigating long-term consequences. The insights gained not only enhance our understanding of LC but also inform the development of therapeutic strategies that could be applicable to other chronic conditions with similar pathophysiological features.

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“…At present the cause of PASC remains elusive. However, there is a growing of evidence that PASC is associated with chronic inflammation [4][5][6][7][8][9][10][11][12] . For example, recently Cervia-Hasler 10 and colleagues demonstrated that at six months post-infection there was increased complement activation in PASC patients.…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular symptoms of PASC are associated with trace-level cytokines that affect the function of human pluripotent stem cell derived cardiomyocytes

Sinclair,

Vedelago,

Ryan

et al. 2024

Preprint

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Globally, over 65 million individuals are estimated to suffer from post-acute sequelae of COVID-19 (PASC). A large number of individuals living with PASC experience cardiovascular symptoms (i.e. chest pain and heart palpitations) (PASC-CVS). The role of chronic inflammation in these symptoms, in particular in individuals with symptoms persisting for >1 year after SARS-CoV-2 infection, remains to be clearly defined. In this cross-sectional study, blood samples were obtained from three different sites in Australia from individuals with i) a resolved SARS-CoV-2 infection (and no persistent symptoms i.e. Recovered), ii) individuals with prolonged PASC-CVS and iii) SARS-CoV-2 negative individuals. Individuals with PASC-CVS, relative to Recovered individuals, had a blood transcriptomic signature associated with inflammation. This was accompanied by elevated levels of pro-inflammatory cytokines (IL-12, IL-1beta;, MCP-1 and IL-6) at approximately 18 months post-infection. These cytokines were present in trace amounts, such that they could only be detected with the use of novel nanotechnology. Importantly, these trace-level cytokines had a direct effect on the functionality of pluripotent stem cell derived cardiomyocytes in vitro. This effect was not observed in the presence of dexamethasone. Plasma proteomics demonstrated further differences between PASC-CVS and Recovered patients at approximately 18 months post-infection including enrichment of complement and coagulation associated proteins in those with prolonged cardiovascular symptoms. Together, these data provide a new insight into the role of chronic inflammation in PASC-CVS and present nanotechnology as a possible novel diagnostic approach for the condition.

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Spontaneous, persistent T-cell dependent IFN-γ release in patients who progress to Long COVID

Cited by 3 publications

References 39 publications

Long COVID: Long-Term Impact of SARS-CoV2

Long COVID: Long-Term Impact of SARS-CoV2

Exploring the Pathophysiology of Long COVID: The Central Role of Low-Grade Inflammation and Multisystem Involvement

Cardiovascular symptoms of PASC are associated with trace-level cytokines that affect the function of human pluripotent stem cell derived cardiomyocytes

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