Inflammation, immunity, and antigen persistence in post-acute sequelae of SARS-CoV-2 infection

Newell, Krista L; Waickman, Adam T.

doi:10.1016/j.coi.2022.102228

Cited by 21 publications

(15 citation statements)

References 53 publications

(63 reference statements)

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“…As for the mechanism, Dani et al ( 77 ) proposed that long COVID may be associated with viral or immune-mediated disruption of the autonomic nervous system, leading to orthostatic intolerance syndrome. Newell et al ( 78 ) concluded that immunological misfiring, inflammatory storms, and persistent inflammation played a key role in long COVID. However, there is a lack of concrete and consistently definition and characterization of “long COVID”.…”

Section: Discussionmentioning

confidence: 99%

A bibliometric analysis of COVID-19 publications in neurology by using the visual mapping method

Zhang

Weng

2022

Front. Public Health

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BackgroundThe characteristic symptom of coronavirus disease 2019 (COVID-19) is respiratory distress, but neurological symptoms are the most frequent extra-pulmonary symptoms. This study aims to explore the current status and hot topics of neurology-related research on COVID-19 using bibliometric analysis.MethodsPublications regarding neurology and COVID-19 were retrieved from the Web of Science Core Collection (WoSCC) on March 28 2022. The Advanced search was conducted using “TS = (‘COVID 19’ or ‘Novel Coronavirus 2019’ or ‘Coronavirus disease 2019’ or ‘2019-nCOV’ or ‘SARS-CoV-2’ or ‘coronavirus-2’) and TS = (‘neurology’or ‘neurological’ or ‘nervous system’ or ‘neurodegenerative disease’ or ‘brain’ or ‘cerebra’ or ‘nerve’)”. Microsoft Excel 2010 and VOSviewer were used to characterize the largest contributors, including the authors, journals, institutions, and countries. The hot topics and knowledge network were analyzed by CiteSpace and VOSviewer.ResultsA total of 5,329 publications between 2020 and 2022 were retrieved. The United States, Italy, and the United Kingdom were three key contributors to this field. Harvard Medical School, the Tehran University of Medical Sciences, and the UCL Queen Square Institute of Neurology were the major institutions with the largest publications. Josef Finsterer from the University of São Paulo (Austria) was the most prolific author. Tom Solomon from the University of Liverpool (UK) was the most cited author. Neurological Sciences and Frontiers in Neurology were the first two most productive journals, while Journal of Neurology held the first in terms of total citations and citations per publication. Cerebrovascular diseases, neurodegenerative diseases, encephalitis and encephalopathy, neuroimmune complications, neurological presentation in children, long COVID and mental health, and telemedicine were the central topics regarding the neurology-related research on COVID-19.ConclusionNeurology-related research on COVID-19 has attracted considerable attention worldwide. Research topics shifted from “morality, autopsy, and telemedicine” in 2020 to various COVID-19-related neurological symptoms in 2021, such as “stroke,” “Alzheimer's disease,” “Parkinson's disease,” “Guillain–Barre syndrome,” “multiple sclerosis,” “seizures in children,” and “long COVID.” “Applications of telemedicine in neurology during COVID-19 pandemic,” “COVID-19-related neurological complications and mechanism,” and “long COVID” require further study.

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Section: Discussionmentioning

confidence: 99%

A bibliometric analysis of COVID-19 publications in neurology by using the visual mapping method

Zhang

Weng

2022

Front. Public Health

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Section: Long Covidmentioning

confidence: 99%

“…Several studies have subsequently shown similar findings in patients with long COVID at various timepoints. 35,41,121,177,[179][180][181][182][183][184][185][186][187][188] Galan et al 180 observed increased levels of functional memory CD8 + T cells, increased CD4 + regulatory T cells, and increased expression of PD1 on T cells in long COVID patients 7month post-infection. Similarly, Peluso et al 177 noted increased SARS-CoV-2-specific adaptive immune responses in long COVID patients, regardless of their initial disease severity, as far as 9-month post-infection.…”

Section: Adaptive Immunity During Long Covidmentioning

confidence: 99%

“…In line with these organ-specific findings, SARS-CoV-2 antigen has been recovered from multiple body sites including the gastrointestinal tract, hepatic tissues, the brain, lymphoid tissues, and in circulation up to 7-month postinfection 34,40,207,208 Some groups proposed that, much like other chronic infections, persistent antigen exposure leads to chronic immune activation and subsequent systemic and compartmentalized inflammation, contributing to the wide array of clinical manifestations seen in long COVID. 105,165,177,178,181,183,[189][190][191][192][193][209][210][211][212] Post-acute sequalae due to antigen persistence Antigen persistence and subsequent clinical sequelae postinfection are not novel to SARS-CoV-2 as infectious causes of chronic autoimmune and inflammatory disorders have been explored for decades. 12,[213][214][215][216][217] Chronic infections such as HIV, CMV, and EBV are associated with viral latency and persistence, leading to chronic exposure to viral antigens and subsequent immune activation and inflammation, contributing to the various sequelae of these infections.…”

Section: Localized Immune Responses During Long Covidmentioning

confidence: 99%

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The role of immune activation and antigen persistence in acute and long COVID

Opsteen

Files

Fram

et al. 2023

Journal of Investigative Medicine

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In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered the global coronavirus disease 2019 (COVID-19) pandemic. Although most infections cause a self-limited syndrome comparable to other upper respiratory viral pathogens, a portion of individuals develop severe illness leading to substantial morbidity and mortality. Furthermore, an estimated 10%–20% of SARS-CoV-2 infections are followed by post-acute sequelae of COVID-19 (PASC), or long COVID. Long COVID is associated with a wide variety of clinical manifestations including cardiopulmonary complications, persistent fatigue, and neurocognitive dysfunction. Severe acute COVID-19 is associated with hyperactivation and increased inflammation, which may be an underlying cause of long COVID in a subset of individuals. However, the immunologic mechanisms driving long COVID development are still under investigation. Early in the pandemic, our group and others observed immune dysregulation persisted into convalescence after acute COVID-19. We subsequently observed persistent immune dysregulation in a cohort of individuals experiencing long COVID. We demonstrated increased SARS-CoV-2-specific CD4+ and CD8+ T-cell responses and antibody affinity in patients experiencing long COVID symptoms. These data suggest a portion of long COVID symptoms may be due to chronic immune activation and the presence of persistent SARS-CoV-2 antigen. This review summarizes the COVID-19 literature to date detailing acute COVID-19 and convalescence and how these observations relate to the development of long COVID. In addition, we discuss recent findings in support of persistent antigen and the evidence that this phenomenon contributes to local and systemic inflammation and the heterogeneous nature of clinical manifestations seen in long COVID.

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“…Despite the increasing awareness of Long-COVID, the potential pathophysiological mechanisms of it remain poorly characterized, and may correlate with several factors ( 120 , 121 ). Proposed causes include lingering viruses, chronic inflammation, or microscopic thrombi ( 122 , 123 ).…”

Section: Long Covidmentioning

confidence: 99%

Pathophysiological mechanisms of thrombosis in acute and long COVID-19

Jing

Xiang

et al. 2022

Front. Immunol.

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COVID-19 patients have a high incidence of thrombosis, and thromboembolic complications are associated with severe COVID-19 and high mortality. COVID-19 disease is associated with a hyper-inflammatory response (cytokine storm) mediated by the immune system. However, the role of the inflammatory response in thrombosis remains incompletely understood. In this review, we investigate the crosstalk between inflammation and thrombosis in the context of COVID-19, focusing on the contributions of inflammation to the pathogenesis of thrombosis, and propose combined use of anti-inflammatory and anticoagulant therapeutics. Under inflammatory conditions, the interactions between neutrophils and platelets, platelet activation, monocyte tissue factor expression, microparticle release, and phosphatidylserine (PS) externalization as well as complement activation are collectively involved in immune-thrombosis. Inflammation results in the activation and apoptosis of blood cells, leading to microparticle release and PS externalization on blood cells and microparticles, which significantly enhances the catalytic efficiency of the tenase and prothrombinase complexes, and promotes thrombin-mediated fibrin generation and local blood clot formation. Given the risk of thrombosis in the COVID-19, the importance of antithrombotic therapies has been generally recognized, but certain deficiencies and treatment gaps in remain. Antiplatelet drugs are not in combination with anticoagulant treatments, thus fail to dampen platelet procoagulant activity. Current treatments also do not propose an optimal time for anticoagulation. The efficacy of anticoagulant treatments depends on the time of therapy initiation. The best time for antithrombotic therapy is as early as possible after diagnosis, ideally in the early stage of the disease. We also elaborate on the possible mechanisms of long COVID thromboembolic complications, including persistent inflammation, endothelial injury and dysfunction, and coagulation abnormalities. The above-mentioned contents provide therapeutic strategies for COVID-19 patients and further improve patient outcomes.

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Inflammation, immunity, and antigen persistence in post-acute sequelae of SARS-CoV-2 infection

Cited by 21 publications

References 53 publications

A bibliometric analysis of COVID-19 publications in neurology by using the visual mapping method

A bibliometric analysis of COVID-19 publications in neurology by using the visual mapping method

The role of immune activation and antigen persistence in acute and long COVID

Pathophysiological mechanisms of thrombosis in acute and long COVID-19

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