Pathophysiological, immunological, and inflammatory features of long COVID

Bohmwald, Karen; Diethelm-Varela, Benjamín; Rodríguez-Guilarte, Linmar; Rivera, Thomas; Riedel, Claudia A.; González, Pablo A.; Kalergis, Alexis M.

doi:10.3389/fimmu.2024.1341600

Cited by 9 publications

(5 citation statements)

References 358 publications

(533 reference statements)

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“…However, we did not cover various phenomena of canonical inflammation related to LC, which can manifest in different organs and tissues of patients suffering from LC. These issues have been addressed in review articles by other authors, including [ 285 , 319 , 320 , 321 , 322 ]. Another aspect of canonical inflammation in LC, which was not included in the aims and objectives of our study, is considering LC as a risk factor for the onset of various inflammatory diseases or the progression of existing inflammatory diseases [ 323 , 324 , 325 , 326 , 327 ].…”

Section: Methodsmentioning

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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Section: Methodsmentioning

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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“…Interestingly, it is involved in innate immunity [419], especially in mucosa [420], and bears similarities to lipopolysaccharide-binding protein (LPS being a molecule that can trigger fibrinaloid formation [191,192,421]). BPIB1 can also inhibit Epstein-Barr virus proliferation [422][423][424] (something of major potential relevance in Long COVID [425][426][427]). Overall, the fact that it is so concentrated in fibrinaloid microclots in the case of Long COVID is thus very notable.…”

Section: Amyloidogenicity Of Proteins 'Entrapped' In Microclotsmentioning

confidence: 99%

Proteomic evidence for amyloidogenic cross-seeding in fibrinaloid microclots

Kell,

Pretorius

2024

Preprint

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In classical amyloidoses, amyloid fibres form through the nucleation and accretion of protein monomers, with protofibrils and fibrils exhibiting a cross-β motif of parallel or antiparallel β-sheets oriented perpendicular to the fibre direction. These protofibrils and fibrils can intertwine to form mature amyloid fibres. Similar phenomena occur in blood from individuals with circulating inflammatory molecules (also those originating from viruses and bacteria). In the presence of inflammagens, pathological clotting can occur, that results in an anomalous amyloid form termed fibrinaloid microclots. Previous proteomic analyses of these microclots have shown the presence of non-fibrin(ogen) proteins, suggesting a more complex mechanism than simple entrapment. We provide evidence against a simple entrapment model, noting that clot pores are too large and centrifugation would have removed weakly bound proteins. Instead, we explore whether co-aggregation into amyloid fibres may involve axial (multiple proteins within the same fibril), lateral (single-protein fibrils contributing to a fibre), or both types of integration. Our analysis of proteomic data from fibrinaloid microclots in different diseases shows no significant overlap with the normal plasma proteome and no correlation between plasma protein abundance and presence in microclots. Notably, abundant plasma proteins like α-2-macroglobulin, fibronectin, and transthyretin are absent from microclots, while less abundant proteins such as adiponectin, periostin, and von Willebrand Factor are well represented. Using bioinformatic tools including AmyloGram and AnuPP, we found that proteins entrapped in fibrinaloid microclots exhibit high amyloidogenic tendencies, suggesting their integration as cross-β elements into amyloid structures. This integration likely contributes to the microclots’ resistance to proteolysis. Our findings underscore the role of cross-seeding in fibrinaloid microclot formation and highlight the need for further investigation into their structural properties and implications in thrombotic and amyloid diseases. These insights provide a foundation for developing novel diagnostic and therapeutic strategies targeting amyloidogenic cross-seeding in blood clotting disorders.

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“…Furthermore, the injury inflicted upon endothelial cells by nucleocapsid and envelope proteins triggers cytokine induction and immune activation. Additionally, the prolonged presence of COVID-19 infection and immune dysregulation may lead to the reactivation of other viruses (Epstein-Barr virus, human herpesvirus 6, and cytomegalovirus) and the onset of bacterial diseases (tuberculosis) [ 60 ]. It is also suggested that the autonomic nervous system may be directly damaged by the SARS-CoV-2 virus or by an autoimmune process, leading to dysautonomia [ 58 ].…”

Section: Introductionmentioning

confidence: 99%

Role of the RAAS in mediating the pathophysiology of COVID-19

Jasiczek,

Doroszko,

Trocha

et al. 2024

Pharmacol. Rep

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The renin-angiotensin-aldosterone system (RAAS) holds a position of paramount importance as enzymatic and endocrine homeostatic regulator concerning the water-electrolyte and acid-base balance. Nevertheless, its intricacy is influenced by the presence of various complementary angiotensins and their specific receptors, thereby modifying the primary RAAS actions. Angiotensin-converting enzyme 2 (ACE2) acts as a surface receptor for SARS-CoV-2, establishing an essential connection between RAAS and COVID-19 infection. Despite the recurring exploration of the RAAS impact on the trajectory of COVID-19 along with the successful resolution of many inquiries, its complete role in the genesis of delayed consequences encompassing long COVID and cardiovascular thrombotic outcomes during the post-COVID phase as well as post-vaccination, remains not fully comprehended. Particularly noteworthy is the involvement of the RAAS in the molecular mechanisms underpinning procoagulant processes throughout COVID-19. These processes significantly contribute to the pathogenesis of organ complications as well as determine clinical outcomes and are discussed in this manuscript.

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Pathophysiological, immunological, and inflammatory features of long COVID

Cited by 9 publications

References 358 publications

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

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

Proteomic evidence for amyloidogenic cross-seeding in fibrinaloid microclots

Role of the RAAS in mediating the pathophysiology of COVID-19

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