Persistent serum protein signatures define an inflammatory subset of long COVID

Talla, Aarthi; Vasaikar, Suhas; Szeto, Gregory L.; Lemos, Maria P.; Czartoski, Julie; Macmillan, Hugh; Moodie, Zoe; Cohen, Kristen W.; Ballweber-Fleming, Lamar; Thomson, Zachary; Okada, Lauren; Becker, Lynne A.; Coffey, Ernest M.; Rosa, Stephen C. De; Newell, Evan W.; Skene, Peter J.; Li, Xiaojun; Bumol, Thomas F.; McElrath, M. Juliana; Torgerson, Troy R.

doi:10.1101/2022.05.09.491196

Cited by 14 publications

(18 citation statements)

References 28 publications

(33 reference statements)

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“…However, progress has been hindered by nonuniform definitions of PASC, the heterogeneity of PASC clinical phenotypes, and the advent of novel treatments and viral variants that can alter the underlying pathobiology. A number of candidate biomarkers are purported to predict or diagnose PASC, including persistence of viral antigens, auto‐antibodies, dysregulated T/NK cell signaling, amyloid deposits (“microclots”), and endothelial proteins, such as angiopoietin‐2, but findings vary across cohort studies 8,15–17 . Here, there was no difference in plasma biomarkers of systemic inflammation, epithelial injury, or activated coagulation between groups, but we observed increased endothelial proteins, although only NEDD9 maintained significance when adjusting for multiple comparisons.…”

Section: Discussionmentioning

confidence: 57%

Plasma NEDD9 is increased following SARS‐CoV‐2 infection and associates with indices of pulmonary vascular dysfunction

Alba,

Zhou,

Mascia

et al. 2024

Pulm. circ.

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Section: Discussionmentioning

confidence: 57%

Plasma NEDD9 is increased following SARS‐CoV‐2 infection and associates with indices of pulmonary vascular dysfunction

Alba,

Zhou,

Mascia

et al. 2024

Pulm. circ.

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“…As shown in Table 2 , we also investigated the pathways, biological processes, molecular functions, and cellular components that occur most frequently in each of the individual symptoms (Talla et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Long COVID: G Protein-Coupled Receptors (GPCRs) responsible for persistent post-COVID symptoms

Das

Kumar

2022

Preprint

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As of early December 2022, COVID-19 had a significant impact on the lives of people all around the world, with over 630 million documented cases and over 6 million deaths. A recent clinical analysis revealed that under certain conditions, a patient's disease symptoms are more likely to persist. Long COVID is characterised by many symptoms that continue long after the SARS-CoV-2 infection has resolved. This work utilised computational methods to analyse the persistence of COVID symptoms after recovery and to identify the relevant genes. Based on functional similarity, differentially expressed genes (DEGs) of SARS-CoV-2 infection and 255 symptoms of long covid were examined, and potential genes were identified based on the rank of functional similarity. Then, hub genes were identified by analysing the interactions between proteins. Using the identified key genes and the drug-gene interaction score, FDA drugs with potential for possible alternatives were identified. Also discovered were the gene ontology and pathways for 255 distinct symptoms. A website (https://longcovid.omicstutorials.com/) with a list of significant genes identified as biomarkers and potential treatments for each symptom was created. All of the hub genes associated with the symptoms, GNGT1, GNG12, GNB3, GNB4, GNG13, GNG8, GNG3, GNG7, GNG10, and GNAI1, were discovered to be associated with G-protein coupled receptors. This demonstrates that persistent COVID infection affects various organ systems and promotes chronic inflammation following infection. CTLA4, PTPN22, KIT, KRAS, NF1, RET, and CTNNB1 were identified as the common genes that regulate T-cell immunity via GPCR and cause a variety of symptoms, including autoimmunity, cardiovascular, dermatological, general symptoms, gastrointestinal, pulmonary, reproductive, genitourinary, and endocrine symptoms (RGEM). Among other functions, they were found to be involved in the positive regulation of protein localization to the cell cortex, the regulation of triglyceride metabolism, the binding of G protein-coupled receptors, the binding of G protein-coupled serotonin receptors, the heterotrimeric G-protein complex, and the cell cortex region. These biomarker data, together with the gene ontology and pathway information that accompanies them, are intended to aid in determining the cause and improving the efficacy of treatment.

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“…However, it is essential to note that this interpretation may oversimplify PASC conditions. The studies summarized here include several distinct mechanisms, depending on the organ system affected, the specific individuals' PASC immune profiles (148,149), and whether the studies focused on unique organ systems, such as neurologic or pulmonary PASC (150,151). For example, neurologic PASC was associated with high levels of glial fibrillary acidic but not neurofilament light chain proteins, together with increases in more general activation markers (i.e., TNF, IL-6, MCP-1) (150).…”

Section: Closing Remarksmentioning

confidence: 99%

Tissue injury and leukocyte changes in post-acute sequelae of SARS-CoV-2: review of 2833 post-acute patient outcomes per immune dysregulation and microbial translocation in long COVID

Islam¹,

Wang²,

Abdel‐Mohsen

et al. 2023

Journal of Leukocyte Biology

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A significant number of persons with coronavirus disease 2019 (COVID-19) experience persistent, recurrent, or new symptoms several months after the acute stage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This phenomenon, termed post-acute sequelae of SARS-CoV-2 (PASC) or long COVID, is associated with high viral titers during acute infection, a persistently hyperactivated immune system, tissue injury by NETosis-induced micro-thrombofibrosis (NETinjury), microbial translocation, complement deposition, fibrotic macrophages, the presence of autoantibodies, and lymphopenic immune environments. Here, we review the current literature on the immunological imbalances that occur during PASC. Specifically, we focus on data supporting common immunopathogenesis and tissue injury mechanisms shared across this highly heterogenous disorder, including NETosis, coagulopathy, and fibrosis. Mechanisms include changes in leukocyte subsets/functions, fibroblast activation, cytokine imbalances, lower cortisol, autoantibodies, co-pathogen reactivation, and residual immune activation driven by persistent viral antigens and/or microbial translocation. Taken together, we develop the premise that SARS-CoV-2 infection results in PASC as a consequence of acute and/or persistent single or multiple organ injury mediated by PASC determinants to include the degree of host responses (inflammation, NETinjury), residual viral antigen (persistent antigen), and exogenous factors (microbial translocation). Determinants of PASC may be amplified by comorbidities, age, and sex.

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Persistent serum protein signatures define an inflammatory subset of long COVID

Cited by 14 publications

References 28 publications

Plasma NEDD9 is increased following SARS‐CoV‐2 infection and associates with indices of pulmonary vascular dysfunction

Plasma NEDD9 is increased following SARS‐CoV‐2 infection and associates with indices of pulmonary vascular dysfunction

Long COVID: G Protein-Coupled Receptors (GPCRs) responsible for persistent post-COVID symptoms

Tissue injury and leukocyte changes in post-acute sequelae of SARS-CoV-2: review of 2833 post-acute patient outcomes per immune dysregulation and microbial translocation in long COVID

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