SARS-CoV-2 and Its Bacterial Co- or Super-Infections Synergize to Trigger COVID-19 Autoimmune Cardiopathies DOI Open Access
Robert Root‐Bernstein, Jack Huber,

Alison Ziehl

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12177 - 12177

Published: July 29, 2023

Autoimmune cardiopathies (AC) following COVID-19 and vaccination against SARS-CoV-2 occur at significant rates but are of unknown etiology. This study investigated the possible roles viral bacterial mimicry, as well viral-bacterial co-infections, inducers AC using proteomic methods enzyme-linked immunoadsorption assays. BLAST LALIGN results this demonstrate that shares a significantly greater number high quality similarities to some cardiac protein compared with other viruses; bacteria such Streptococci, Staphylococci Enterococci also display very proteins different set than SARS-CoV-2; importance these is largely validated by ELISA experiments demonstrating polyclonal antibodies COVID-19-associated recognize affinity; account for range targeted autoantibodies in autoimmune myocarditis, both triggers probably required; targets often molecularly complementary antigens actin myosin, laminin collagen, or creatine kinase pyruvate kinase, known bind each other; corresponding recognizing affinity if they have an idiotype-anti-idiotype relationship. These suggest from infections complicated infections. Vaccination infections, Streptococci Haemophilus, may therefore decrease risk, appropriate timely use antibiotics among patients careful screening vaccinees signs infection fever, diarrhea, infected wounds, gum disease, etc.

Language: Английский

Microvascular Thrombosis as a Critical Factor in Severe COVID-19 DOI Open Access
Patricia P. Wadowski, Benjamin Panzer, Alicja Józkowicz

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2492 - 2492

Published: Jan. 27, 2023

Platelet-endothelial interactions have a critical role in microcirculatory function, which maintains tissue homeostasis. The subtle equilibrium between platelets and the vessel wall is disturbed by coronavirus disease 2019 (COVID-19), affects all three components of Virchow's triad (endothelial injury, stasis hypercoagulable state). Endotheliitis, vasculitis, glycocalyx degradation, alterations blood flow viscosity, neutrophil extracellular trap formation microparticle shedding are only few pathomechanisms contributing to endothelial damage microthrombosis resulting capillary plugging ischemia. In following opinion paper, we discuss major pathological processes leading microvascular activation thrombosis as possible adverse factor driving deterioration patient course severe COVID-19.

Language: Английский

Citations

28
From Co-Infections to Autoimmune Disease via Hyperactivated Innate Immunity: COVID-19 Autoimmune Coagulopathies, Autoimmune Myocarditis and Multisystem Inflammatory Syndrome in Children DOI Open Access
Robert Root‐Bernstein

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 3001 - 3001

Published: Feb. 3, 2023

Neutrophilia and the production of neutrophil extracellular traps (NETs) are two many measures increased inflammation in severe COVID-19 that also accompany its autoimmune complications, including coagulopathies, myocarditis multisystem inflammatory syndrome children (MIS-C). This paper integrates currently disparate innate hyperactivation relates these to SARS-CoV-2 activation immunity. Aggregated data include Toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD) receptors, NOD leucine-rich repeat pyrin-domain-containing (NLRPs), retinoic acid-inducible gene I (RIG-I) melanoma-differentiation-associated 5 (MDA-5). mainly activates virus-associated TLR3, TLR7, TLR8, NLRP3, RIG-1 MDA-5. Severe COVID-19, however, is characterized by additional TLR1, TLR2, TLR4, TLR5, TLR6, NOD1 NOD2, which primarily responsive bacterial antigens. The patterns Kawasaki disease, or MIS-C, mimic those rather than alone suggesting autoimmunity follows combined SARS-CoV-2-bacterial infections. Viral known synergize produce required support disease pathology. Additional studies demonstrate anti-bacterial antibodies account for autoantigen targets complications.

Language: Английский

Citations

22
The role of pathogens in diabetes pathogenesis and the potential of immunoproteomics as a diagnostic and prognostic tool DOI Creative Commons
Muhammad Umar Sohail,

Fathima Mashood,

Andreas Oberbach

et al.

Frontiers in Microbiology, Journal Year: 2022, Volume and Issue: 13

Published: Nov. 14, 2022

Diabetes mellitus (DM) is a group of metabolic diseases marked by hyperglycemia, which increases the risk systemic infections. DM patients are at greater hospitalization and mortality from bacterial, viral, fungal Poor glycemic control can result in skin, blood, bone, urinary, gastrointestinal, respiratory tract infections recurrent Therefore, evidence that play critical role progression hazard ratio for person with dying any infection higher. Early diagnosis better help prevent improve treatment outcomes. Perhaps, half (49.7%) people living undiagnosed, resulting higher frequency induced hyperglycemic milieu favors immune dysfunction. Novel diagnostic therapeutic markers prevention desirable. High-throughput blood-based immunoassays screen hyperglycemia required to guide timely interventions efficiently monitor responses. The present review aims collect information on most common associated DM, their origin, pathogenesis, potential immunoproteomics assays early While disease pathogenesis poorly described. Nevertheless, more research identify novel prognostic understand management Precise monitoring diabetic may provide insights into healthy prognosis.

Language: Английский

Citations

15
T Cell Receptor Sequences Amplified during Severe COVID-19 and Multisystem Inflammatory Syndrome in Children Mimic SARS-CoV-2, Its Bacterial Co-Infections and Host Autoantigens DOI Open Access
Robert Root‐Bernstein, Elizabeth F. Churchill, Shelby Oliverio

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1335 - 1335

Published: Jan. 10, 2023

Published hypervariable region V-beta T cell receptor (TCR) sequences were collected from people with severe COVID-19 characterized by having various autoimmune complications, including blood coagulopathies and cardiac autoimmunity, as well patients diagnosed the Kawasaki disease (KD)-like multisystem inflammatory syndrome in children (MIS-C). These compared comparable published v-beta TCR KD healthy individuals. Since are supposed to be complementary antigens that induce clonal expansion, it was surprising only a quarter of derived MIS-C mimicked SARS-CoV-2 proteins. Thirty percent KD-derived coronaviruses other than SARS-CoV-2. In contrast, three individuals those myocarditis displayed similarities any coronavirus. each disease, significant increases found amount TCRs mimicking specific bacterial co-infections (especially Enterococcus faecium, Staphylococcal Streptococcal antigens) host autoantigens targeted diseases myosin, collagen, phospholipid-associated proteins, coagulation proteins). Theoretical explanations for these observations implications unravel causes explored.

Language: Английский

Citations

5
Clostridia and Enteroviruses as Synergistic Triggers of Type 1 Diabetes Mellitus DOI Open Access
Robert Root‐Bernstein, Kaylie Chiles, Jack Huber

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 8336 - 8336

Published: May 6, 2023

What triggers type 1 diabetes mellitus (T1DM)? One common assumption is that are individual microbes mimic autoantibody targets such as insulin (INS). However, most highly associated with T1DM pathogenesis, coxsackieviruses (COX), lack INS mimicry and have failed to induce in animal models. Using proteomic similarity search techniques, we found COX actually mimicked the receptor (INSR). Clostridia were best mimics of INS. antibodies cross-reacted ELISA experiments, confirming mimicry. INSR. further bound idiotype-anti-idiotype pairs conserving INS-INSR complementarity. Ultraviolet spectrometry studies demonstrated INS-like peptides INSR-like peptides. These complementary also recognized antigens by T cell sequences derived from patients. Finally, sera patients strongly inactivated Clostridium sporogenes, while healthy individuals did not; exhibited evidence anti-idiotype against idiotypic INS, glutamic acid decarboxylase, protein tyrosine phosphatase non-receptor (islet antigen-2) antibodies. results suggest triggered combined enterovirus-Clostridium (and possibly Epstein-Barr-virus-Streptococcal) infections, probable rate co-infections approximates new diagnoses.

Language: Английский

Citations

4
SARS-CoV-2 and Its Bacterial Co- or Super-Infections Synergize to Trigger COVID-19 Autoimmune Cardiopathies DOI Open Access
Robert Root‐Bernstein, Jack Huber,

Alison Ziehl

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 12177 - 12177

Published: July 29, 2023

Autoimmune cardiopathies (AC) following COVID-19 and vaccination against SARS-CoV-2 occur at significant rates but are of unknown etiology. This study investigated the possible roles viral bacterial mimicry, as well viral-bacterial co-infections, inducers AC using proteomic methods enzyme-linked immunoadsorption assays. BLAST LALIGN results this demonstrate that shares a significantly greater number high quality similarities to some cardiac protein compared with other viruses; bacteria such Streptococci, Staphylococci Enterococci also display very proteins different set than SARS-CoV-2; importance these is largely validated by ELISA experiments demonstrating polyclonal antibodies COVID-19-associated recognize affinity; account for range targeted autoantibodies in autoimmune myocarditis, both triggers probably required; targets often molecularly complementary antigens actin myosin, laminin collagen, or creatine kinase pyruvate kinase, known bind each other; corresponding recognizing affinity if they have an idiotype-anti-idiotype relationship. These suggest from infections complicated infections. Vaccination infections, Streptococci Haemophilus, may therefore decrease risk, appropriate timely use antibiotics among patients careful screening vaccinees signs infection fever, diarrhea, infected wounds, gum disease, etc.

Language: Английский

Citations

2