IPAK Impact on Biomedical and Clinical Science: Pathogenic Priming by SCV2 Protein Epitopes is Now Mainstream Science
This number of studies inspired by our April 2020 - wide in scope and impact. IPAK research is 100% funded by YOU, the public.
These studies cite our April 2020 study - the first to warn of unsafe B-cell epitopes in SARS-CoV-2 proteins. (J Transl Autoimmun. 2020 Apr 9;3:100051. doi: 10.1016/j.jtauto.2020.100051. eCollection 2020).
The study that started it:
Pathogenic priming likely contributes to serious and critical illness and mortality in COVID-19 via autoimmunity
Affiliations expand
PMID: 32292901
PMCID: PMC7142689
Free PMC article
Abstract
Homology between human and viral proteins is an established factor in viral- or vaccine-induced autoimmunity. Failure of SARS and MERS vaccines in animal trials involved pathogenesis consistent with an immunological priming that could involve autoimmunity in lung tissues due to previous exposure to the SARS and MERS spike protein. Exposure pathogenesis to SARS-CoV-2 in COVID-19 likely will lead to similar outcomes. Immunogenic peptides in viruses or bacteria that match human proteins are good candidates for pathogenic priming peptides (similar to the more diffuse idea of "immune enhancement"). Here I provide an assessment of potential for human pathogenesis via autoimmunity via exposure, via infection or injection. SAR-CoV-2 spike proteins, and all other SARS-CoV-2 proteins, immunogenic epitopes in each SARS-CoV-2 protein were compared to human proteins in search of high local homologous matching. Only one immunogenic epitope in a SARS-CoV-2 had no homology to human proteins. If all of the parts of the epitopes that are homologous to human proteins are excluded from consideration due to risk of pathogenic priming, the remaining immunogenic parts of the epitopes may be still immunogenic and remain as potentially viable candidates for vaccine development. Mapping of the genes encoding human protein matches to pathways point to targets that could explain the observed presentation of symptoms in COVID-19 disease. It also strongly points to a large number of opportunities for expected disturbances in the immune system itself, targeting elements of MHC Class I and Class II antigen presentation, PD-1 signaling, cross-presentation of soluble exogenous antigens and the ER-Phagosome pathway. Translational consequences of these findings are explored.
Keywords: Autoimmunity; COVID-19; Immune Enhancement; Pathogenic priming; SARS-CoV-2.
© 2020 The Author(s).
Conflict of interest statement
Dr. Lyons-Weiler has, in the past, served as expert witness in the National Vaccine Injury Compensation Program.
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2 Antibodies (Basel) . 2022 Oct 25;11(4):68. doi: 10.3390/antib11040068.
The study that validated Lyons-Weiler (2020):
ront Immunol
. 2021 Jan 19;11:617089.
doi: 10.3389/fimmu.2020.617089. eCollection 2020.
Reaction of Human Monoclonal Antibodies to SARS-CoV-2 Proteins With Tissue Antigens: Implications for Autoimmune Diseases
Aristo Vojdani 1 2, Elroy Vojdani 3, Datis Kharrazian 2 4 5
Affiliations expand
PMID: 33584709
PMCID: PMC7873987
Free PMC article
Abstract
We sought to determine whether immune reactivity occurs between anti-SARS-CoV-2 protein antibodies and human tissue antigens, and whether molecular mimicry between COVID-19 viral proteins and human tissues could be the cause. We applied both human monoclonal anti-SARS-Cov-2 antibodies (spike protein, nucleoprotein) and rabbit polyclonal anti-SARS-Cov-2 antibodies (envelope protein, membrane protein) to 55 different tissue antigens. We found that SARS-CoV-2 antibodies had reactions with 28 out of 55 tissue antigens, representing a diversity of tissue groups that included barrier proteins, gastrointestinal, thyroid and neural tissues, and more. We also did selective epitope mapping using BLAST and showed similarities and homology between spike, nucleoprotein, and many other SARS-CoV-2 proteins with the human tissue antigens mitochondria M2, F-actin and TPO. This extensive immune cross-reactivity between SARS-CoV-2 antibodies and different antigen groups may play a role in the multi-system disease process of COVID-19, influence the severity of the disease, precipitate the onset of autoimmunity in susceptible subgroups, and potentially exacerbate autoimmunity in subjects that have pre-existing autoimmune diseases. Very recently, human monoclonal antibodies were approved for use on patients with COVID-19. The human monoclonal antibodies used in this study are almost identical with these approved antibodies. Thus, our results can establish the potential risk for autoimmunity and multi-system disorders with COVID-19 that may come from cross-reactivity between our own human tissues and this dreaded virus, and thus ensure that the badly-needed vaccines and treatments being developed for it are truly safe to use against this disease.
Keywords: COVID-19; SARS-CoV-2; autoimmunity; cross-reactivity; molecular mimicry.
Copyright © 2021 Vojdani, Vojdani and Kharrazian.
Other studies citing Lyons-Weiler (2020):
Shared 6mer Peptides of Human and Omicron (21K and 21L) at SARS-CoV-2 Mutation Sites
Yekbun Adiguzel 1, Yehuda Shoenfeld 2
Affiliations expand
PMID: 36412834
PMCID: PMC9680445
Free PMC article
Abstract
We investigated the short sequences involving Omicron 21K and Omicron 21L variants to reveal any possible molecular mimicry-associated autoimmunity risks and changes in those. We first identified common 6mers of the viral and human protein sequences present for both the mutant (Omicron) and nonmutant (SARS-CoV-2) versions of the same viral sequence and then predicted the binding affinities of those sequences to the HLA supertype representatives. We evaluated change in the potential autoimmunity risk, through comparative assessment of the nonmutant and mutant viral sequences and their similar human peptides with common 6mers and affinities to the same HLA allele. This change is the lost and the new, or de novo, autoimmunity risk, associated with the mutations in the Omicron 21K and Omicron 21L variants. Accordingly, e.g., the affinity of virus-similar sequences of the Ig heavy chain junction regions shifted from the HLA-B*15:01 to the HLA-A*01:01 allele at the mutant sequences. Additionally, peptides of different human proteins sharing 6mers with SARS-CoV-2 proteins at the mutation sites of interest and with affinities to the HLA-B*07:02 allele, such as the respective SARS-CoV-2 sequences, were lost. Among all, any possible molecular mimicry-associated novel risk appeared to be prominent in HLA-A*24:02 and HLA-B*27:05 serotypes upon infection with Omicron 21L. Associated disease, pathway, and tissue expression data supported possible new risks for the HLA-B*27:05 and HLA-A*01:01 serotypes, while the risks for the HLA-B*07:02 serotypes could have been lost or diminished, and those for the HLA-A*03:01 serotypes could have been retained, for the individuals infected with Omicron variants under study. These are likely to affect the complications related to cross-reactions influencing the relevant HLA serotypes upon infection with Omicron 21K and Omicron 21L.
Keywords: COVID-19; HLA class I; SARS-CoV-2; autoimmunity; disease susceptibility; peptide similarity.
Conflict of interest statement
The authors declare no conflict of interest.
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3 Arab J Gastroenterol. 2022 Nov;23(4):241-245.
doi: 10.1016/j.ajg.2022.07.001. Epub 2022 Jul 25.
Anti-Saccharomyces cerevisiae antibodies in patients with COVID-19
Sarra Melayah 1, Amani Mankaï 2, Malek Jemni 3, Arij Ben Chaben 4, Mariam Ghozzi 3, Asma Ben Abdelkrim 5, Kousay Ach 5, Nadia Ghariani 6, Mohamed Denguezli 6, Wafa Benzarti 7, Mohamed Benzarti 7, Salma Melayah 8, Walid Naija 8, Ibtissem Ghedira 3
Affiliations expand
PMID: 36351870
PMCID: PMC9309156
Free PMC article
Abstract
Background and study aim: Anti-Saccharomyces cerevisiae antibodies (ASCA) have been described in many autoimmune diseases (AIDs). Coronavirus disease 2019 (COVID-19) could trigger AIDs. This study aimed to determine the frequency of ASCA in patients with COVID-19.
Patients and methods: This study included 88 adult patients with severe COVID-19, 51 mild COVID-19, and 160 healthy blood donors. ASCA of isotype immunoglobulin (Ig)G and IgA were detected by enzyme-linked immunosorbent assay.
Results: The frequency of ASCA (IgG or IgA) was significantly higher in patients with severe COVID-19 (21.6 % vs 3.7 %, p < 10-3) and in patients with mild COVID-19 than in the healthy controls (13.7 % vs 3.7 %, p = 0.03). ASCA-IgA was significantly more frequent in patients with severe COVID-19 than in healthy controls (15.9 % vs 0.6 %, p < 10-3). ASCA-IgG was significantly more frequent in patients with mild COVID-19 than in healthy controls (13.7 % vs 3.1 %, p = 0.02). ASCA (IgG or IgA) were more frequent in severe than in mild COVID-19, but the difference was not statistically significant (21.6 % vs 13.7 %). ASCA-IgA was significantly more frequent in patients with severe than those with mild COVID-19 (15.9 % vs 0 %, p = 0.003). The mean ASCA-IgG and ASCA-IgA levels were significantly higher in patients with severe COVID-19 than in healthy controls (5.8 U/mL ± 11.8 vs 2.3 U/mL ± 2.8, p < 10-3 and 9.2 U/mL ± 21.5 vs 3.4 U/mL ± 1.7, respectively, p < 10-3). The mean ASCA-IgG levels were significantly higher in patients with mild COVID-19 than in healthy controls (6.2 U/mL ± 12.9 vs 2.3 U/mL ± 2.8, p < 10-3). The mean ASCA-IgA levels were significantly higher in patients with severe than in those with mild COVID-19 (9.2 U/mL ± 21.5 vs 2.6 U/mL ± 1.2, p = 0.03).
Conclusion: ASCA was more frequent in patients with COVID-19 than in healthy controls.
Keywords: Adults; Anti-Saccharomyces cerevisiae antibodies; mild COVID-19; severe COVID-19.
Copyright © 2022 Pan-Arab Association of Gastroenterology. Published by Elsevier B.V. All rights reserved.
Conflict of interest statement
Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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4
Front Bioinform. 2021 Aug 19;1:709533.
doi: 10.3389/fbinf.2021.709533. eCollection 2021.
Predicted B Cell Epitopes Highlight the Potential for COVID-19 to Drive Self-Reactive Immunity
Rhiane Moody 1, Kirsty L Wilson 1, Jennifer C Boer 1, Jessica K Holien 2, Katie L Flanagan 1 3 4 5, Anthony Jaworowski 1, Magdalena Plebanski 1
Affiliations expand
PMID: 36303764
PMCID: PMC9581003
Free PMC article
Abstract
COVID-19, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), whilst commonly characterised as a respiratory disease, is reported to have extrapulmonary manifestations in multiple organs. Extrapulmonary involvement in COVID-19 includes autoimmune-like diseases such as Guillain-Barré syndrome and Kawasaki disease, as well as the presence of various autoantibodies including those associated with autoimmune diseases such a systemic lupus erythematosus (e.g. ANA, anti-La). Multiple strains of SARS-CoV-2 have emerged globally, some of which are found to be associated with increased transmissibility and severe disease. We performed an unbiased comprehensive mapping of the potential for cross-reactivity with self-antigens across multiple SARS-CoV-2 proteins and compared identified immunogenic regions across multiples strains. Using the Immune Epitope Database (IEDB) B cell epitope prediction tool, regions predicted as antibody epitopes with high prediction scores were selected. Epitope sequences were then blasted to eight other global strains to identify mutations within these regions. Of the 15 sequences compared, eight had a mutation in at least one other global strain. Predicted epitopes were then compared to human proteins using the NCBI blast tool. In contrast to studies focusing on short sequences of peptide identity, we have taken an immunological approach to selection criteria for further analysis and have identified 136 alignments of 6-23 amino acids (aa) in 129 human proteins that are immunologically likely to be cross-reactive with SARS-CoV-2. Additionally, to identify regions with significant potential to interfere with host cell function-or promote immunopathology, we identified epitope regions more likely to be accessible to pathogenic autoantibodies in the host, selected using a novel combination of sequence similarity, and modelling protein and alignment localization with a focus on extracellular regions. Our analysis identified 11 new predicted B-cell epitopes in host proteins, potentially capable of explaining key aspects of COVID-19 extrapulmonary pathology, and which were missed in other in silico studies which used direct identity rather than immunologically related functional criteria.
Keywords: COVID-19; autoimmunity; epitope mapping; molecular-mimicry; peptides; self-reactivity.
Copyright © 2021 Moody, Wilson, Boer, Holien, Flanagan, Jaworowski and Plebanski.
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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5
Viruses. 2022 Oct 16;14(10):2270.
doi: 10.3390/v14102270.
Systems Bioinformatics Reveals Possible Relationship between COVID-19 and the Development of Neurological Diseases and Neuropsychiatric Disorders
Anna Onisiforou 1, George M Spyrou 1
Affiliations expand
PMID: 36298824
PMCID: PMC9611753
DOI: 10.3390/v14102270
Free PMC article
Abstract
Coronavirus Disease 2019 (COVID-19) is associated with increased incidence of neurological diseases and neuropsychiatric disorders after infection, but how it contributes to their development remains under investigation. Here, we investigate the possible relationship between COVID-19 and the development of ten neurological disorders and three neuropsychiatric disorders by exploring two pathological mechanisms: (i) dysregulation of host biological processes via virus-host protein-protein interactions (PPIs), and (ii) autoreactivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epitopes with host "self" proteins via molecular mimicry. We also identify potential genetic risk factors which in combination with SARS-CoV-2 infection might lead to disease development. Our analysis indicated that neurodegenerative diseases (NDs) have a higher number of disease-associated biological processes that can be modulated by SARS-CoV-2 via virus-host PPIs than neuropsychiatric disorders. The sequence similarity analysis indicated the presence of several matching 5-mer and/or 6-mer linear motifs between SARS-CoV-2 epitopes with autoreactive epitopes found in Alzheimer's Disease (AD), Parkinson's Disease (PD), Myasthenia Gravis (MG) and Multiple Sclerosis (MS). The results include autoreactive epitopes that recognize amyloid-beta precursor protein (APP), microtubule-associated protein tau (MAPT), acetylcholine receptors, glial fibrillary acidic protein (GFAP), neurofilament light polypeptide (NfL) and major myelin proteins. Altogether, our results suggest that there might be an increased risk for the development of NDs after COVID-19 both via autoreactivity and virus-host PPIs.
Keywords: COVID-19; SARS-CoV-2; autoimmunity; epitopes; molecular mimicry; network biology; neurodegenerative diseases; neurological diseases; neuropsychiatric disorders; systems bioinformatics.
Conflict of interest statement
The authors declare no conflict of interest.
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6
Review
Iran J Pharm Res. 2022 Jan 24;21(1):e124228.
doi: 10.5812/ijpr.124228. eCollection 2022 Dec.
Review on Approved and Inprogress COVID-19 Vaccines
Amir Farnudian-Habibi 1 2, Mobina Mirjani 1 2, Vahideh Montazer 3, Shima Aliebrahimi 4, Iman Katouzian 5, Saeed Abdolhosseini 6, Ali Rahmani 1 2, Hossein Keyvani 7, Seyed Nasser Ostad 8, Mazda Rad-Malekshahi 1 2
Affiliations expand
PMID: 36060923
PMCID: PMC9420219
DOI: 10.5812/ijpr.124228
Free PMC article
Abstract
The last generation of Coronavirus named COVID-19 is responsible for the recent worldwide outbreak. Concerning the widespread and quick predominance, there is a critical requirement for designing appropriate vaccines to surmount this grave problem. Correspondingly, in this revision, COVID-19 vaccines (which are being developed until March 29th, 2021) are classified into specific and non-specific categories. Specific vaccines comprise genetic-based vaccines (mRNA, DNA), vector-based, protein/recombinant protein vaccines, inactivated viruses, live-attenuated vaccines, and novel strategies including microneedle arrays (MNAs), and nanoparticles vaccines. Moreover, specific vaccines such as BCG, MRR, and a few other vaccines are considered Non-specific. What is more, according to the significance of Bioinformatic sciences in the cutting-edge vaccine design and rapid outbreak of COVID-19, herein, Bioinformatic principles including reverse vaccinology, epitopes prediction/selection and, their further applications in the design of vaccines are discussed. Last but not least, safety, challenges, advantages, and future prospects of COVID-19 vaccines are highlighted.
Keywords: Bioinformatic; COVID-19; Epitope Prediction; Reverse Vaccinology; mRNA Vaccine.
Copyright © 2022, Author(s).
Conflict of interest statement
Conflict of Interests: There is no conflict of interests in this paper.
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7
Review
Pathophysiology. 2022 Jul 28;29(3):414-425.
doi: 10.3390/pathophysiology29030033.
Autoimmune Autonomic Dysfunction Syndromes: Potential Involvement and Pathophysiology Related to Complex Regional Pain Syndrome, Fibromyalgia, Chronic Fatigue Syndrome, Silicone Breast Implant-Related Symptoms and Post-COVID Syndrome
Naim Mahroum 1, Yehuda Shoenfeld 2
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PMID: 35997389
PMCID: PMC9396987
Free PMC article
Abstract
The pathophysiological mechanisms involved in chronic disorders such as complex regional pain syndrome, fibromyalgia, chronic fatigue syndrome, silicone breast implant-related symptoms, and post-COVID syndrome have not been clearly defined. The course of the pain in some of the syndromes, the absence of evident tissue damage, and the predominance of alterations in the autonomic nervous system are shared similarities between them. The production of autoantibodies following a trigger in the syndromes was previously described, for instance, trauma in complex regional pain syndrome, infectious agents in fibromyalgia, chronic fatigue syndrome, and post-COVID syndrome, and the immune stimulation by silicone in women with breast implants. In fact, the autoantibodies produced were shown to be directed against the autonomic nervous system receptors, leading to the amplification of the perception of pain alongside various clinical symptoms seen during the clinical course of the syndromes. Therefore, we viewed autoantibodies targeting the autonomic nervous system resulting in autonomic dysfunction as likely the most comprehensive explanation of the pathophysiology of the disorders mentioned. Based on this, we aimed to introduce a new concept uniting complex regional pain syndrome, fibromyalgia, chronic fatigue syndrome, silicone breast implant-related symptoms, and post-COVID syndrome, namely "autoimmune autonomic dysfunction syndromes". Due to its etiological, pathophysiological, and clinical implications, the suggested term would be more precise in classifying the syndromes under one title. The new title would doubtlessly facilitate both laboratory and clinical studies aimed to improve diagnosis and make treatment options more directed and precise.
Keywords: autonomic nervous system; chronic fatigue syndrome; complex regional pain syndrome; fibromyalgia; post-COVID syndrome; silicone breast implants.
Conflict of interest statement
The authors declare no conflict of interest.
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8
Case Reports
Front Med (Lausanne). 2022 Jul 22;9:918721.
doi: 10.3389/fmed.2022.918721. eCollection 2022.
Case Report: Subacute thyroiditis after receiving inactivated SARS-CoV-2 vaccine (BBIBP-CorV)
Linhua Pi 1 2 3, Jian Lin 1 2 3, Ying Zheng 4, Zhen Wang 1 2 3, Zhiguang Zhou 1 2 3
Affiliations expand
PMID: 35935798
PMCID: PMC9355607
Free PMC article
Abstract
Background: Subacute thyroiditis, an inflammatory disease, has been reported caused by vaccines in rare cases. In the context of the coronavirus disease 19 pandemic, various SARS-CoV-2 vaccines have been developed and may be potential triggers for subacute thyroiditis.
Case presentation: We report a case of subacute thyroiditis 3 days after receiving the second dose of inactivated SARS-CoV-2 vaccine (BBIBP-CorV). The patient did not report a previous history of thyroid disease, upper respiratory tract infection, or COVID-19. Physical examination, laboratory testing, ultrasonography, and radioactive iodine uptake were consistent with subacute thyroiditis. During follow-up, the patient recovered from symptoms and signs, and imaging changes except for hypothyroidism, requiring an ongoing thyroxine replacement.
Conclusions: Inactivated SARS-CoV-2 vaccine may be a causal trigger leading to subacute thyroiditis. Clinicians should be aware of subacute thyroiditis as a possible thyroid-related side effect of an inactivated SARS-CoV-2 vaccine.
Keywords: BBIBP-CorV; coronavirus disease 2019; severe acute respiratory syndrome coronavirus 2; subacute thyroiditis; vaccine.
Copyright © 2022 Pi, Lin, Zheng, Wang and Zhou.
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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9
Hosp Pharm. 2022 Aug;57(4):575-587.
doi: 10.1177/00185787211066463. Epub 2022 Jan 19.
Narrative Review: Addressing Covid-19 Vaccine Concerns in Special and Vulnerable Populations
Kent A Owusu 1 2, Muhammad K Effendi 3, Melissa L Thompson Bastin 4, Samad Tirmizi 2, Ishaq Lat 5, Mahmoud A Ammar 2
Affiliations expand
PMID: 35898240
PMCID: PMC9310301 (available on 2023-08-01)
Abstract
Public health advocates and healthcare professionals (HCPs) have been challenged with vaccine hesitancy and addressing misinformation. In order for HCPs and pharmacists, in particular, to serve as effective stewards of COVID-19 vaccine science in the interest of the public good, it is imperative for HCPs to appreciate the various factors contributing to vaccine hesitancy and vaccine distrust. A PubMed search was performed and relevant articles on COVID-19 vaccine in populations of interest were included. Information from health agencies, such as the Centers for Disease Control and Prevention (CDC) as well as established professional health societies was incorporated for guidance. This review focuses on COVID-19 vaccine concerns in the populations of children, pregnancy and lactation, immunocompromised, and religious and ethnic disparities. We also discuss post emergency use authorization experience with respect to vaccine safety including annotations on Guillain-Barré Syndrome, myocarditis and pericarditis, and thrombosis with thrombocytopenia syndrome.
Keywords: education; infectious diseases; pediatrics; pharmacists; pregnancy/lactation; vaccines.
© The Author(s) 2022.
Conflict of interest statement
Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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10
Clin Auton Res. 2022 Aug;32(4):307-311.
doi: 10.1007/s10286-022-00880-3. Epub 2022 Jul 23.
Postural orthostatic tachycardia syndrome after mRNA COVID-19 vaccine
Ahmed M Eldokla 1 2, Mohammed T Numan 3
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PMID: 35870086
PMCID: PMC9308031
Free PMC article
No abstract available
Conflict of interest statement
On behalf of all authors, the corresponding author states that there is no conflict of interest.
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11
Case Reports
Respir Med Case Rep. 2022 Jul 14;38:101702.
doi: 10.1016/j.rmcr.2022.101702. eCollection 2022.
Eosinophilic granulomatosis with polyangiitis after COVID-19: A case report
Sajad Karampoor 1 2, Fatemeh Afrashteh 3, Shahrzad Rahmani 4, Azadeh Laali 5
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PMID: 35854792
PMCID: PMC9279185
Free PMC article
Abstract
COVID-19 can damage the endothelial cells of every organ in the body and lead to vasculopathy and vasculitis. It has been shown that various types of vasculitis could be a new manifestation of COVID-19. Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic necrotizing vasculitis that affects small vessels. Here we report our experience with a 42-year-old man with a 3-weeks history of fever of unknown origin after two months from COVID-19 recovery presented with loss of appetite, loss of weight, and paresthesia in his lower extremities. After required evaluations including nerve biopsy, EGPA was diagnosed for him.
Keywords: COVID-19; Eosinophilic granulomatosis with polyangiitis; Fever of unknown origin; Leucocytoclastic vasculitis.
© 2022 The Authors.
Conflict of interest statement
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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12
Review
Pathophysiology. 2022 Jun 3;29(2):243-280.
doi: 10.3390/pathophysiology29020020.
The Role of Exposomes in the Pathophysiology of Autoimmune Diseases II: Pathogens
Aristo Vojdani 1 2, Elroy Vojdani 3, Avi Z Rosenberg 4, Yehuda Shoenfeld 5 6 7
Affiliations expand
PMID: 35736648
PMCID: PMC9231084
Free PMC article
Abstract
In our continuing examination of the role of exposomes in autoimmune disease, we use this review to focus on pathogens. Infections are major contributors to the pathophysiology of autoimmune diseases through various mechanisms, foremost being molecular mimicry, when the structural similarity between the pathogen and a human tissue antigen leads to autoimmune reactivity and even autoimmune disease. The three best examples of this are oral pathogens, SARS-CoV-2, and the herpesviruses. Oral pathogens reach the gut, disturb the microbiota, increase gut permeability, cause local inflammation, and generate autoantigens, leading to systemic inflammation, multiple autoimmune reactivities, and systemic autoimmunity. The COVID-19 pandemic put the spotlight on SARS-CoV-2, which has been called "the autoimmune virus." We explore in detail the evidence supporting this. We also describe how viruses, in particular herpesviruses, have a role in the induction of many different autoimmune diseases, detailing the various mechanisms involved. Lastly, we discuss the microbiome and the beneficial microbiota that populate it. We look at the role of the gut microbiome in autoimmune disorders, because of its role in regulating the immune system. Dysbiosis of the microbiota in the gut microbiome can lead to multiple autoimmune disorders. We conclude that understanding the precise roles and relationships shared by all these factors that comprise the exposome and identifying early events and root causes of these disorders can help us to develop more targeted therapeutic protocols for the management of this worldwide epidemic of autoimmunity.
Keywords: autoantibodies; autoimmunity; bystander activation; environmental trigger; epitope spreading; exposome; infection; molecular mimicry; pathogen; pathophysiology.
Conflict of interest statement
A.V. is co-owner, CEO, and technical director of Immunosciences Lab., Inc. E.V. is the owner and founder of Regenera Medical. A.Z.R. and Y.S. declare no conflict of interest.
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13
Med Sci Monit. 2022 Mar 8;28:e936292.
doi: 10.12659/MSM.936292.
A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Management of Mild-to-Moderate Symptomatic COVID-19
Serafino Fazio 1, Flora Affuso 2, Paolo Bellavite 3
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PMID: 35256581
PMCID: PMC8917781
DOI: 10.12659/MSM.936292
Free PMC article
Abstract
In the past 2 years, the coronavirus disease 2019 (COVID-19) pandemic has driven investigational studies and controlled clinical trials on antiviral treatments and vaccines that have undergone regulatory approval. Now that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants may become endemic over time, there remains a need to identify drugs that treat the symptoms of COVID-19 and prevent progression toward severe cases, hospitalization, and death. Understanding the molecular mechanisms of SARS-CoV-2 infection is extremely important for the development of effective therapies against COVID-19. This review outlines the key pathways involved in the host response to SARS-CoV-2 infection and discusses the potential role of antioxidant and anti-inflammatory pharmacological approaches for the management of early mild-to-moderate COVID-19, using the examples of combined indomethacin, low-dose aspirin, omeprazole, hesperidin, quercetin, and vitamin C. The pharmacological targets of these substances are described here for their possible synergism in counteracting SARS-CoV-2 replication and progression of the infection from the upper respiratory airways to the blood, avoiding vascular complications and cytokine and bradykinin storms.
Conflict of interest statement
Conflict of interest: Paolo Bellavite has a consultancy agreement with Vanda s.r.l. (Frascati, Rome). The other authors have no competing interests to declare
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14
Review
J Clin Med. 2022 Feb 11;11(4):934.
doi: 10.3390/jcm11040934.
A Comprehensive Review of Neuromuscular Manifestations of COVID-19 and Management of Pre-Existing Neuromuscular Disorders in Children
Daniel J Goetschius 1, Yunsung Kim 1, Ashutosh Kumar 2, Dustin Paul 3, Sunil Naik 2
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PMID: 35207206
PMCID: PMC8876161
DOI: 10.3390/jcm11040934
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Abstract
Since the emergence of SARS-CoV-2, several studies have been published describing neuromuscular manifestations of the disease, as well as management of pre-existing pediatric neuromuscular disorders during the COVID-19 pandemic. These disorders include muscular dystrophies, myasthenic syndromes, peripheral nerve disorders, and spinal muscular atrophy. Such patients are a vulnerable population due to frequent complications such as scoliosis, cardiomyopathy, and restrictive lung disease that put them at risk of severe complications of COVID-19. In this review, neuromuscular manifestations of COVID-19 in children and the management of pre-existing pediatric neuromuscular disorders during the COVID-19 pandemic are discussed. We also review strategies to alleviate pandemic-associated disruptions in clinical care and research, including the emerging role of telemedicine and telerehabilitation to address the continued special needs of these patients.
Keywords: COVID-19; MIS-C; SARS-CoV-2; children; muscular dystrophy; neuromuscular; pediatric; spinal muscular atrophy; telemedicine; treatment.
Conflict of interest statement
The authors declare no conflict of interest.
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15
QRB Discov. 2021 Dec 13;3:e1.
doi: 10.1017/qrd.2021.13. eCollection 2022.
A novel statistical method predicts mutability of the genomic segments of the SARS-CoV-2 virus
Amir Hossein Darooneh 1, Michelle Przedborski 1, Mohammad Kohandel 1
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PMID: 35106478
PMCID: PMC8795775
DOI: 10.1017/qrd.2021.13
Free PMC article
Abstract
The SARS-CoV-2 virus has made the largest pandemic of the 21st century, with hundreds of millions of cases and tens of millions of fatalities. Scientists all around the world are racing to develop vaccines and new pharmaceuticals to overcome the pandemic and offer effective treatments for COVID-19 disease. Consequently, there is an essential need to better understand how the pathogenesis of SARS-CoV-2 is affected by viral mutations and to determine the conserved segments in the viral genome that can serve as stable targets for novel therapeutics. Here, we introduce a text-mining method to estimate the mutability of genomic segments directly from a reference (ancestral) whole genome sequence. The method relies on calculating the importance of genomic segments based on their spatial distribution and frequency over the whole genome. To validate our approach, we perform a large-scale analysis of the viral mutations in nearly 80,000 publicly available SARS-CoV-2 predecessor whole genome sequences and show that these results are highly correlated with the segments predicted by the statistical method used for keyword detection. Importantly, these correlations are found to hold at the codon and gene levels, as well as for gene coding regions. Using the text-mining method, we further identify codon sequences that are potential candidates for siRNA-based antiviral drugs. Significantly, one of the candidates identified in this work corresponds to the first seven codons of an epitope of the spike glycoprotein, which is the only SARS-CoV-2 immunogenic peptide without a match to a human protein.
Keywords: Mutability; SARS-CoV2; Statistical Analysis; Word Ranking.
© The Author(s) 2021.
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16
Multicenter Study
Gut. 2022 Mar;71(3):544-552.
doi: 10.1136/gutjnl-2021-325989. Epub 2022 Jan 26.
Gut microbiota dynamics in a prospective cohort of patients with post-acute COVID-19 syndrome
Qin Liu # 1 2 3 4, Joyce Wing Yan Mak # 1 2 3, Qi Su # 1 2 3 4, Yun Kit Yeoh 1 4 5, Grace Chung-Yan Lui 2 6, Susanna So Shan Ng 2, Fen Zhang 1 2 3 4, Amy Y L Li 1 2 3, Wenqi Lu 1 2 3 4, David Shu-Cheong Hui 6, Paul Ks Chan 1 5, Francis K L Chan 1 2 3 4, Siew C Ng 7 2 3 4
Affiliations expand
PMID: 35082169
PMCID: PMC8814432
Free PMC article
Abstract
Background: Long-term complications after COVID-19 are common, but the potential cause for persistent symptoms after viral clearance remains unclear.
Objective: To investigate whether gut microbiome composition is linked to post-acute COVID-19 syndrome (PACS), defined as at least one persistent symptom 4 weeks after clearance of the SARS-CoV-2 virus.
Methods: We conducted a prospective study of 106 patients with a spectrum of COVID-19 severity followed up from admission to 6 months and 68 non-COVID-19 controls. We analysed serial faecal microbiome of 258 samples using shotgun metagenomic sequencing, and correlated the results with persistent symptoms at 6 months.
Results: At 6 months, 76% of patients had PACS and the most common symptoms were fatigue, poor memory and hair loss. Gut microbiota composition at admission was associated with occurrence of PACS. Patients without PACS showed recovered gut microbiome profile at 6 months comparable to that of non-COVID-19 controls. Gut microbiome of patients with PACS were characterised by higher levels of Ruminococcus gnavus, Bacteroides vulgatus and lower levels of Faecalibacterium prausnitzii. Persistent respiratory symptoms were correlated with opportunistic gut pathogens, and neuropsychiatric symptoms and fatigue were correlated with nosocomial gut pathogens, including Clostridium innocuum and Actinomyces naeslundii (all p<0.05). Butyrate-producing bacteria, including Bifidobacterium pseudocatenulatum and Faecalibacterium prausnitzii showed the largest inverse correlations with PACS at 6 months.
Conclusion: These findings provided observational evidence of compositional alterations of gut microbiome in patients with long-term complications of COVID-19. Further studies should investigate whether microbiota modulation can facilitate timely recovery from post-acute COVID-19 syndrome.
Keywords: COVID-19; intestinal microbiology.
© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.
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Competing interests: None declared.
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17
Review
J Pers Med. 2021 Nov 25;11(12):1253.
doi: 10.3390/jpm11121253.
Nature of Acquired Immune Responses, Epitope Specificity and Resultant Protection from SARS-CoV-2
Reginald M Gorczynski 1, Robyn A Lindley 2 3, Edward J Steele 4 5, Nalin Chandra Wickramasinghe 6 7 8
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PMID: 34945725
PMCID: PMC8708741
DOI: 10.3390/jpm11121253
Free PMC article
Abstract
The primary global response to the SARS-CoV-2 pandemic has been to bring to the clinic as rapidly as possible a number of vaccines that are predicted to enhance immunity to this viral infection. While the rapidity with which these vaccines have been developed and tested (at least for short-term efficacy and safety) is commendable, it should be acknowledged that this has occurred despite the lack of research into, and understanding of, the immune elements important for natural host protection against the virus, making this endeavor a somewhat unique one in medical history. In contrast, as pointed out in the review below, there were already important past observations that suggested that respiratory infections at mucosal surfaces were susceptible to immune clearance by mechanisms not typical of infections caused by systemic (blood-borne) pathogens. Accordingly, it was likely to be important to understand the role for both innate and acquired immunity in response to viral infection, as well as the optimum acquired immune resistance mechanisms for viral clearance (B cell or antibody-mediated, versus T cell mediated). This information was needed both to guide vaccine development and to monitor its success. We have known that many pathogens enter into a quasi-symbiotic relationship with the host, with each undergoing sequential change in response to alterations the other makes to its presence. The subsequent evolution of viral variants which has caused such widespread concern over the last 3-6 months as host immunity develops was an entirely predictable response. What is still not known is whether there will be other unexpected side-effects of the deployment of novel vaccines in humans which have yet to be characterized, and, if so, how and if these can be avoided. We conclude by remarking that to ignore a substantial body of well-attested immunological research in favour of expediency is a poor way to proceed.
Keywords: SARS-CoV-2; acquired immunity; host resistance; innate immunity; mucosal immunity; vaccination.
Conflict of interest statement
The authors declare no conflict of interest.
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18
Review
Front Immunol. 2021 Sep 17;12:733418.
doi: 10.3389/fimmu.2021.733418. eCollection 2021.
To Be or Not To Be Vaccinated: That Is a Question in Myasthenia Gravis
Qian Zhou 1, Ran Zhou 1, Haojun Yang 1, Huan Yang 1
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PMID: 34603311
PMCID: PMC8485039
Free PMC article
Abstract
Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and abnormal fatigability due to the antibodies against postsynaptic receptors. Despite the individual discrepancy, patients with MG share common muscle weakness, autoimmune dysfunction, and immunosuppressive treatment, which predispose them to infections that can trigger or exacerbate MG. Vaccination, as a mainstay of prophylaxis, is a major management strategy. However, the past years have seen growth in vaccine hesitancy, owing to safety and efficacy concerns. Ironically, vaccines, serving as an essential and effective means of defense, may induce similar immune cross-reactivity to what they are meant to prevent. Herein, we outline the progress in vaccination, review the current status, and postulate the clinical association among MG, vaccination, and immunosuppression. We also address safety and efficacy concerns of vaccination in MG, in relation to COVID-19. Since only a handful of studies have reported vaccination in individuals with MG, we further review the current clinical studies and guidelines in rheumatic diseases. Overall, our reviews offer a reference to guide future vaccine clinical decision-making and improve the management of MG patients.
Keywords: COVID-19; SARS-CoV-2; autoimmune; immunosuppression; infection prophylaxis; myasthenia gravis; neuromuscular disease; vaccines.
Copyright © 2021 Zhou, Zhou, Yang and Yang.
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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19
Review
Rheumatol Int. 2021 Nov;41(11):2031-2039.
doi: 10.1007/s00296-021-04998-x. Epub 2021 Sep 22.
Reactive arthritis after COVID-19: a case-based review
Burhan Fatih Kocyigit 1, Ahmet Akyol 2
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PMID: 34550429
PMCID: PMC8456072
Free PMC article
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 19 (COVID-19) pandemic, which is deeply affecting the whole world. In this new case for the scientific world, scientists are investigating the etiopathogenesis of viral infection-induced damage and have started to focus on the short and long-term immune system effects and alterations after SARS-CoV-2 infection. The case is here reported of a 53-year-old female patient with acute monoarthritis after SARS-CoV-2 infection, who responded adequately to 150 mg/day diclofenac treatment, and the available case reports are comprehensively reviewed. With the focus on arthritis after SARS-CoV2 infection, which emerges as a new pathological condition associated with COVID-19, it was aimed to examine the possible immunological mechanisms of post-COVID-19 arthritis based on the current data on SARS-CoV-2 and the known pathogenetic background of viral arthritis.
Keywords: Acute arthritis; COVID-19; Reactive arthritis; SARS-CoV-2; Viral arthritis.
© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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The authors have no conflict of interest to declare.
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20
Int J Immunopathol Pharmacol. 2021 Jan-Dec;35:20587384211042115.
doi: 10.1177/20587384211042115.
A retrospective study on the prevalence of anti-phospholipid antibodies, thrombotic events and cutaneous signs of vasculopathy in 173 hospitalized COVID-19 patients
Giulia Gasparini 1 2 3, Paola Canepa 1, Simonetta Verdiani 1, Luca Carmisciano 4, Emanuele Cozzani 1 2, Denise De Grazia 1, Orsi Andrea 5 6, Giancarlo Icardi 5 6, Aurora Parodi 1 2
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PMID: 34541915
PMCID: PMC8460963
Free PMC article
Abstract
Background: Hypercoagulability is a risk factor of thromboembolic events in COVID-19. Anti-phospholipid (aPL) antibodies have been hypothesized to be involved. Typical COVID-19 dermatological manifestations of livedo reticularis and digital ischemia may resemble cutaneous manifestations of anti-phospholipid syndrome (APS).
Objectives: To investigate the association between aPL antibodies and thromboembolic events, COVID-19 severity, mortality, and cutaneous manifestations in patients with COVID-19.
Methods: aPL antibodies [anti-beta2-glycoprotein-1 (B2GP1) and anti-cardiolipin (aCL) antibodies] were titered in frozen serum samples from hospitalized COVID-19 patients and the patients' clinical records were retrospectively analyzed.
Results: 173 patients were enrolled. aPL antibodies were detected in 34.7% of patients, anti-B2GP1 antibodies in 30.1%, and aCL antibodies in 10.4%. Double positivity was observed in 5.2% of patients. Thromboembolic events occurred in 9.8% of patients, including 11 pulmonary embolisms, 1 case of celiac tripod thrombosis, and six arterial ischemic events affecting the cerebral, celiac, splenic, or femoral-popliteal arteries or the aorta. aPL antibodies were found in 52.9% of patients with vascular events, but thromboembolic events were not correlated to aPL antibodies (adjusted OR = 1.69, p = 0.502). Ten patients (5.8%) had cutaneous signs of vasculopathy: nine livedo reticularis and one acrocyanosis. No significant association was observed between the presence of cutaneous vasculopathy and aPL antibodies (p = 0.692).
Conclusions: Anti-phospholipid antibodies cannot be considered responsible for hypercoagulability and thrombotic events in COVID-19 patients. In COVID-19 patients, livedo reticularis and acrocyanosis do not appear to be cutaneous manifestations of APS.
Keywords: COVID-19; SARS-CoV-2; acrocyanosis; anti-phospholipid antibodies; anti-phospholipid syndrome; hypercoagulation; livedo reticularis; vasculopathy.
Conflict of interest statement
Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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21
Review
Int J Mol Sci. 2021 Aug 20;22(16):8965.
doi: 10.3390/ijms22168965.
Adaptive Immunity and the Risk of Autoreactivity in COVID-19
Rhiane Moody 1, Kirsty Wilson 1, Katie L Flanagan 1 2 3 4, Anthony Jaworowski 1, Magdalena Plebanski 1
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PMID: 34445670
PMCID: PMC8396528
DOI: 10.3390/ijms22168965
Free PMC article
Abstract
While first and foremost considered a respiratory infection, COVID-19 can result in complications affecting multiple organs. Immune responses in COVID-19 can both protect against the disease as well as drive it. Insights into these responses, and specifically the targets being recognised by the immune system, are of vital importance in understanding the side effects of COVID-19 and associated pathologies. The body's adaptive immunity recognises and responds against specific targets (antigens) expressed by foreign pathogens, but not usually to target self-antigens. However, if the immune system becomes dysfunctional, adaptive immune cells can react to self-antigens, which can result in autoimmune disease. Viral infections are well reported to be associated with, or exacerbate, autoimmune diseases such as multiple sclerosis (MS) and systemic lupus erythematosus (SLE). In COVID-19 patients, both new onset MS and SLE, as well as the occurrence of other autoimmune-like pathologies, have been reported. Additionally, the presence of autoantibodies, both with and without known associations to autoimmune diseases, have been found. Herein we describe the mechanisms of virally induced autoimmunity and summarise some of the emerging reports on the autoimmune-like diseases and autoreactivity that is reported to be associated with SARS-CoV-2 infection.
Keywords: COVID-19; SARS-CoV-2; autoantibodies; autoimmunity; molecular mimicry.
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The authors declare no conflict of interest.
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22
Biomedicines. 2021 Aug 12;9(8):1003.
doi: 10.3390/biomedicines9081003.
Multiple-Organ Complement Deposition on Vascular Endothelium in COVID-19 Patients
Paolo Macor 1, Paolo Durigutto 2, Alessandro Mangogna 3, Rossana Bussani 4, Luca De Maso 1, Stefano D'Errico 4, Martina Zanon 4, Nicola Pozzi 5, Pier Luigi Meroni 2, Francesco Tedesco 2
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PMID: 34440207
PMCID: PMC8394811
Free PMC article
Abstract
Increased levels of circulating complement activation products have been reported in COVID-19 patients, but only limited information is available on complement involvement at the tissue level. The mechanisms and pathways of local complement activation remain unclear. The aim of this study was to investigate the deposition of complement components in the lungs, kidneys, and liver in patients with COVID-19 patients and to determine the pathway/s of complement activation. We performed immunofluorescence analyses of autopsy specimens of lungs, kidney, and liver from 12 COVID-19 patients who died of acute respiratory failure. Snap-frozen samples embedded in OCT were stained with antibodies against complement components and activation products, IgG, and spike protein of SARS-CoV-2. Lung deposits of C1q, C4, C3, and C5b-9 were localized in the capillaries of the interalveolar septa and on alveolar cells. IgG displayed a similar even distribution, suggesting classical pathway activation. The spike protein is a potential target of IgG, but its uneven distribution suggests that other viral and tissue molecules may be targeted by IgG. FB deposits were also seen in COVID-19 lungs and are consistent with activation of the alternative pathway, whereas MBL and MASP-2 were hardly detectable. Analysis of kidney and liver specimens mirrored findings observed in the lung. Complement deposits were seen on tubules and vessels of the kidney with only mild C5b-9 staining in glomeruli, and on the hepatic artery and portal vein of the liver. Complement deposits in different organs of deceased COVID-19 patients caused by activation of the classical and alternative pathways support the multi-organ nature of the disease and the contribution of the complement system to inflammation and tissue damage.
Keywords: COVID-19; classical pathway; complement activation; multi-organ deposition; spike protein.
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Update of
Multi-organ complement deposition in COVID-19 patients.Macor P, Durigutto P, Mangogna A, Bussani R, D'Errico S, Zanon M, Pozzi N, Meroni P, Tedesco F.medRxiv. 2021 Jan 8:2021.01.07.21249116. doi: 10.1101/2021.01.07.21249116. Preprint.PMID: 33442701 Free PMC article. Updated.
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23
Review
J Clin Med. 2021 Aug 2;10(15):3441.
doi: 10.3390/jcm10153441.
SARS-CoV-2 and the Brain: What Do We Know about the Causality of 'Cognitive COVID?
Hashir Ali Awan 1, Mufaddal Najmuddin Diwan 1, Alifiya Aamir 1, Muneeza Ali 1, Massimo Di Giannantonio 2, Irfan Ullah 3, Sheikh Shoib 4, Domenico De Berardis 2 4 5
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PMID: 34362224
PMCID: PMC8347421
DOI: 10.3390/jcm10153441
Free PMC article
Abstract
The second year of the COVID-19 (coronavirus disease) pandemic has seen the need to identify and assess the long-term consequences of a SARS-CoV-2 infection on an individual's overall wellbeing, including adequate cognitive functioning. 'Cognitive COVID' is an informal term coined to interchangeably refer to acute changes in cognition during COVID-19 and/or cognitive sequelae with various deficits following the infection. These may manifest as altered levels of consciousness, encephalopathy-like symptoms, delirium, and loss of various memory domains. Dysexecutive syndrome is a peculiar manifestation of 'Cognitive COVID' as well. In the previous major outbreaks of viruses like SARS-CoV, MERS-CoV and Influenza. There have been attempts to understand the underlying mechanisms describing the causality of similar symptoms following SARS-CoV-2 infection. This review, therefore, is attempting to highlight the current understanding of the various direct and indirect mechanisms, focusing on the role of neurotropism of SARS-CoV-2, the general pro-inflammatory state, and the pandemic-associated psychosocial stressors in the causality of 'Cognitive COVID.' Neurotropism is associated with various mechanisms including retrograde neuronal transmission via olfactory pathway, a general hematogenous spread, and the virus using immune cells as vectors. The high amounts of inflammation caused by COVID-19, compounded with potential intubation, are associated with a deleterious effect on the cognition as well. Finally, the pandemic's unique psychosocial impact has raised alarm due to its possible effect on cognition. Furthermore, with surfacing reports of post-COVID-vaccination cognitive impairments after vaccines containing mRNA encoding for spike glycoprotein of SARS-CoV-2, we hypothesize their causality and ways to mitigate the risk. The potential impact on the quality of life of an individual and the fact that even a minor proportion of COVID-19 cases developing cognitive impairment could be a significant burden on already overwhelmed healthcare systems across the world make it vital to gather further evidence regarding the prevalence, presentation, correlations, and causality of these events and reevaluate our approach to accommodate early identification, management, and rehabilitation of patients exhibiting cognitive symptoms.
Keywords: COVID-19; SARS-CoV-2; brain; cognitive; diagnosis; neurotropism; prevention.
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The authors declare no conflict of interest.
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24
Eur J Dermatol. 2021 Jun 1;31(3):415-417.
doi: 10.1684/ejd.2021.4043.
Considerations on SARS-Cov-2 vaccines in patients with autoimmune blistering diseases
Emanuele Cozzani 1, Giulia Gasparini 2, Laura Sticchi 3, Roberto Russo 1, Giancarlo Icardi 3, Aurora Parodi 1
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PMID: 34309530
PMCID: PMC8354837
Free PMC article
No abstract available
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25
Review
J Immunother Cancer. 2021 Jul;9(7):e002835.
doi: 10.1136/jitc-2021-002835.
Clinical and immunologic implications of COVID-19 in patients with melanoma and renal cell carcinoma receiving immune checkpoint inhibitors
Benjamin Switzer 1, John Haanen 2, Paul C Lorigan 3 4, Igor Puzanov # 5, Samra Turajlic # 6 7
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PMID: 34272309
PMCID: PMC8288220
Free PMC article
Abstract
The clinical and immunologic implications of the SARS-CoV-2 pandemic for patients with cancer receiving systemic anticancer therapy have introduced a multitude of clinical challenges and academic controversies. This review summarizes the current evidence, discussion points, and recommendations regarding the use of immune checkpoint inhibitors (ICIs) in patients with cancer during the SARS-CoV-2 pandemic, with a focus on patients with melanoma and renal cell carcinoma (RCC). More specifically, we summarize the theoretical concepts and available objective data regarding the relationships between ICIs and the antiviral immune response, along with recommended clinical approaches to the management of melanoma and RCC patient cohorts receiving ICIs throughout the course of the COVID-19 pandemic. Additional insights regarding the use of ICIs in the setting of current and upcoming COVID-19 vaccines and broader implications toward future pandemics are also discussed.
Keywords: COVID-19; immunotherapy; kidney neoplasms; melanoma; vaccination.
© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Conflict of interest statement
Competing interests: JH reports research funding from Amgen, BioNTech, BMS, MSD, and Novartis, received institutional advisory fees from Achilles Tx, BioNTech, BMS, Ipsen, Immunocore, MSD, Merck Serono, Molecular Partners, Novartis, Pfizer, PokeAcell, Roche, Sanofi, Seattle Genetics, T-Knife, and Third Rock Ventures, and reports personal fees and stock options with Neogene Therapeutics. PCL reports research funding from Bristol Myers Squibb and JP Moulton Foundation and received personal fees from Bristol Myers Squibb, Merck, MSD, Novartis, Pierre Fabre, Amgen, and Nektar. IP reports consulting fees from Amgen, Iovance, Nouscom, Oncosec, Oncorus, Merck, and Nektar. ST reports research funding from Cancer Research UK (grant reference number A29911), the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC10988), the UK Medical Research Council (FC10988), and the Wellcome Trust (FC10988), the National Institute for Health Research (NIHR) Biomedical Research Centre at the Royal Marsden Hospital and Institute of Cancer Research (grant reference number A109), the Royal Marsden Cancer Charity, the Rosetrees Trust (grant reference number A2204), Ventana Medical Systems, Inc. (grant reference numbers 10467 and 10530), the National Institute of Health ((U01 CA247439), and Melanoma Research Alliance (Award Ref no 686061), received speaking fees from Roche, Astra Zeneca, Novartis, and Ipsen, and has the following patents filed: Indel mutations as a therapeutic target and predictive biomarker PCTGB2018/051892 and PCTGB2018/051893 and Clear Cell Renal Cell Carcinoma Biomarkers P113326GB.
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26
Acta Trop. 2021 Sep;221:106013.
doi: 10.1016/j.actatropica.2021.106013. Epub 2021 Jun 17.
Peptides of H. sapiens and P. falciparum that are predicted to bind strongly to HLA-A*24:02 and homologous to a SARS-CoV-2 peptide
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PMID: 34146538
PMCID: PMC8255030
Free PMC article
Abstract
Aim: This study is looking for a common pathogenicity between SARS-CoV-2 and Plasmodium species, in individuals with certain HLA serotypes.
Methods: 1. Tblastx searches of SARS-CoV-2 are performed by limiting searches to five Plasmodium species that infect humans. 2. Aligned sequences in the respective organisms' proteomes are searched with blastp. 3. Binding predictions of the identified SARS-CoV-2 peptide to HLA supertype representatives are performed. 4. Blastp searches of predicted epitopes that bind strongly to the identified HLA allele are performed by limiting searches to H. sapiens and Plasmodium species, separately. 5. Peptides with minimum 60% identity to the predicted epitopes are found in results. 6. Peptides among those, which bind strongly to the same HLA allele, are predicted. 7. Step-4 is repeated by limiting searches to H. sapiens, followed by the remaining steps until step-7, for peptides sourced by Plasmodium species after step-6.
Results: SARS-CoV-2 peptide with single letter amino acid code CFLGYFCTCYFGLFC has the highest identity to P. vivax. Its YFCTCYFGLF part is predicted to bind strongly to HLA-A*24:02. Peptides in the human proteome both homologous to YFCTCYFGLF and with a strong binding affinity to HLA-A*24:02 are YYCARRFGLF, YYCHCPFGVF, and YYCQQYFFLF. Such peptides in the Plasmodium species' proteomes are FFYTFYFELF, YFVACLFILF, and YFPTITFHLF. The first one belonging to P. falciparum has a homologous peptide (YFYLFSLELF) in the human proteome, which also has a strong binding affinity to the same HLA allele.
Conclusion: Immune responses to the identified-peptides with similar sequences and strong binding affinities to HLA-A*24:02 can be related to autoimmune response risk in individuals with HLA-A*24:02 serotypes, upon getting infected with SARS-CoV-2 or P. falciparum.
Keywords: Plasmodium; SARS-CoV-2; autoimmunity; disease susceptibility; human leukocyte antigen; molecular mimicry.
Copyright © 2021. Published by Elsevier B.V.
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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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27
Biomed Pharmacother. 2021 Sep;141:111722.
doi: 10.1016/j.biopha.2021.111722. Epub 2021 Jun 5.
Identification of oligopeptides from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) non structural protein 8 (NSP8) and their similarities with type 1 angiotensin II receptor key sites
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PMID: 34144455
PMCID: PMC8179057
Free PMC article
Abstract
Coronavirus disease 2019 is associated with clinical symptoms including severe inflammatory syndrome and a higher expression of angiotensin II. As a pro-inflammatory mediator, the physiologic effects of angiotensin II are mediated by a G-protein coupled receptor, termed AT1R. Following binding, AT1R initiates the process of signal desensitization necessary to maintain cellular homeostasis. At the cellular level, this function occurs via the G protein-dependent signaling and the phosphorylation. We describe amino acids similarities between SARS COV-2 nonstructural protein (NSP8) which is associated with intracellular membranes and AT1R key sites. Since abnormal activation of AT1R receptor leads to a number of physiological disorders, we hypothesize that SARS COV-2 might further interfere with the angiotensin II receptor functions.
Keywords: AT(1)R; G protein; NSP8; Peptides; Sarscov-2; Similarity angiotensin II.
Copyright © 2021. Published by Elsevier Masson SAS.
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The author has no conflict of interest to declare.
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28
Cells. 2021 May 5;10(5):1111.
doi: 10.3390/cells10051111.
Cross-Reactivity and Sequence Homology Between Alpha-Synuclein and Food Products: A Step Further for Parkinson's Disease Synucleinopathy
Aristo Vojdani 1 2 3, Aaron Lerner 4, Elroy Vojdani 5
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PMID: 34063062
PMCID: PMC8147930
Free PMC article
Abstract
Introduction: Parkinson's disease is characterized by non-motor/motor dysfunction midbrain neuronal death and α-synuclein deposits. The accepted hypothesis is that unknown environmental factors induce α-synuclein accumulation in the brain via the enteric nervous system.
Material and methods: Monoclonal antibodies made against recombinant α-synuclein protein or α-synuclein epitope 118-123 were applied to the antigens of 180 frequently consumed food products. The specificity of those antibody-antigen reactions was confirmed by serial dilution and inhibition studies. The Basic Local Alignment Search Tool sequence matching program was used for sequence homologies.
Results: While the antibody made against recombinant α-synuclein reacted significantly with 86/180 specific food antigens, the antibody made against α-synuclein epitope 118-123 reacted with only 32/180 tested food antigens. The food proteins with the greatest number of peptides that matched with α-synuclein were yeast, soybean, latex hevein, wheat germ agglutinin, potato, peanut, bean agglutinin, pea lectin, shrimp, bromelain, and lentil lectin. Conclusions: The cross-reactivity and sequence homology between α-synuclein and frequently consumed foods, reinforces the autoimmune aspect of Parkinson's disease. It is hypothesized that luminal food peptides that share cross-reactive epitopes with human α-synuclein and have molecular similarity with brain antigens are involved in the synucleinopathy. The findings deserve further confirmation by extensive research.
Keywords: BLAST; Parkinson’s disease; antibodies; antigen; cross-reactivity; food; gut-brain axis; sequence homology; synucleinopathy; α-synuclein.
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The authors declare no conflict of interest.
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29
Case Reports
Hum Vaccin Immunother. 2021 Sep 2;17(9):2954-2956.
doi: 10.1080/21645515.2021.1920274. Epub 2021 May 25.
Reactive arthritis after COVID-19 vaccination
Qi-Jun An 1, De-An Qin 1, Jin-Xian Pei 2
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PMID: 34033732
PMCID: PMC8381833
Free PMC article
Abstract
The severe acute respiratory syndrome coronavirus 2-induced coronavirus disease 2019 (COVID-19) has had a global spread. Vaccines play an essential role in preventing the spread. However, almost all types of vaccines have been reported to be associated with adverse events. Reactive arthritis (ReA) after vaccination has been reported; however, ReA after COVID-19 vaccination has not been reported. We reported a 23-year-old woman who suffered from an acute ReA on her left knee joint after COVID-19 vaccination and discussed the etiology and preventive strategy. She presented with swollen, painful left knee joint for 18 d. She had been inoculated 0.5 ml CoronaVac vaccine on 0 d and the 14th day with deltoid intramuscular injection. Finally, she was diagnosed as ReA after CoronaVac vaccination and was administered a single intra-articular injection of 1 ml compound betamethasone. The swelling and pain nearly disappeared after 2 d. On 1month follow-up, her condition was normal. ReA after COVID-19 vaccination is rare. The benefits of vaccination far outweigh its potential risks and vaccination should be administered according to the current recommendations. Further attentions should be put to determine which individual is at higher risk for developing autoimmune diseases after COVID-19 vaccination. More versatile and safer vaccines should be explored.
Keywords: CoronaVac vaccine; adverse event; reactive arthritis.
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30
Adv Exp Med Biol. 2021;1318:149-167.
doi: 10.1007/978-3-030-63761-3_9.
Potential Antiviral Immune Response Against COVID-19: Lessons Learned from SARS-CoV
Mahzad Akbarpour 1 2 3, Laleh Sharifi # 4 5, Amir Reza Safdarian # 6 7 8 9, Pooya Farhangnia # 4 6 10, Mahdis Borjkhani 6 11, Nima Rezaei 4 12 13
Affiliations expand
PMID: 33973177
Abstract
Virus and host innate immune system interaction plays a significant role in forming the outcome of viral diseases. Host innate immunity initially recognizes the viral invasion and induces a rapid inflammatory response, and this recognition activates signaling cascades that trigger the release of antiviral mediators. This chapter aims to explore the mechanisms by which newly emerged coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activates the host immune system. Since SARS-CoV-2 shares similarities with SARS-CoV that caused the epidemic of SARS in 2003, the pathogenesis of both viruses could be at least very similar. For this, this chapter provides a synthesis of literature concerning antiviral immunity in SARS-CoV and SARS-CoV-2. It includes the presentation of epitopes linked to SARS-CoV-2 as well as the ability of SARS-CoV-2 to cause proteolytic activation and interact with angiotensin-converting enzyme 2 (ACE2) via molecular mimicry. This chapter characterizes various mechanisms that this virus may engage in escaping the host immunity, ended by a discussion of humoral immune responses against SARS-CoV-2.
Keywords: COVID-19; Epitope spreading; Humoral response; Innate immunity; SARS-CoV- 2.
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31
J Transl Autoimmun. 2021;4:100100.
doi: 10.1016/j.jtauto.2021.100100. Epub 2021 Apr 16.
Functional autoantibodies against G-protein coupled receptors in patients with persistent Long-COVID-19 symptoms
Gerd Wallukat 1 2, Bettina Hohberger 3, Katrin Wenzel 2, Julia Fürst 4, Sarah Schulze-Rothe 2, Anne Wallukat 2, Anne-Sophie Hönicke 2, Johannes Müller 2
Affiliations expand
PMID: 33880442
PMCID: PMC8049853
Free PMC article
Abstract
Impairment of health after overcoming the acute phase of COVID-19 is being observed more and more frequently. Here different symptoms of neurological and/or cardiological origin have been reported. With symptoms, which are very similar to the ones reported but are not caused by SARS-CoV-2, the occurrence of functionally active autoantibodies (fAABs) targeting G-protein coupled receptors (GPCR-fAABs) has been discussed to be involved. We, therefore investigated, whether GPCR-fAABs are detectable in 31 patients suffering from different Long-COVID-19 symptoms after recovery from the acute phase of the disease. The spectrum of symptoms was mostly of neurological origin (29/31 patients), including post-COVID-19 fatigue, alopecia, attention deficit, tremor and others. Combined neurological and cardiovascular disorders were reported in 17 of the 31 patients. Two recovered COVID-19 patients were free of follow-up symptoms. All 31 former COVID-19 patients had between 2 and 7 different GPCR-fAABs that acted as receptor agonists. Some of those GPCR-fAABs activate their target receptors which cause a positive chronotropic effect in neonatal rat cardiomyocytes, the read-out in the test system for their detection (bioassay for GPCR-fAAB detection). Other GPCR-fAABs, in opposite, cause a negative chronotropic effect on those cells. The positive chronotropic GPCR-fAABs identified in the blood of Long-COVID patients targeted the β2-adrenoceptor (β2-fAAB), the α1-adrenoceptor (α1-fAAB), the angiotensin II AT1-receptor (AT1-fAAB), and the nociceptin-like opioid receptor (NOC-fAAB). The negative chronotropic GPCR-fAABs identified targeted the muscarinic M2-receptor (M2-fAAB), the MAS-receptor (MAS-fAAB), and the ETA-receptor (ETA-fAAB). It was analysed which of the extracellular receptor loops was targeted by the autoantibodies.
Keywords: ACE2, Angiotensin-converting enzyme 2 receptors; AT1-fAAB, Autoantibody targeting the angiotensin II AT1 receptor; Autoantibody; Autoimmunity; COVID-19; CRPS, Complex regional pain syndrome; ETA-fAAB, Autoantibody targeting the endothelin receptor; Fatigue; GPCR, G-protein coupled receptors; Long-COVID; M2-fAAB, Autoantibody targeting the muscarinic receptor; MAS-fAAB, Autoantibody targeting the MAS receptor; NOC-fAAB, Functionally active autoantibody against the nociceptin receptor; PoTS, Postural orthostatic tachycardia syndrome; Post-covid-19 symptom; RAS, Renin angiotensin system; SARS, Severe acute respiratory syndrome; fAAB, Functional autoantibody; α1-fAAB, Autoantibody targeting the alpha1-adrenoceptor; β2-fAAB, Autoantibody targeting the beta2-adrenoceptor.
© 2021 The Author(s).
Conflict of interest statement
The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. G. Wallukat, K. Wenzel, S. Schulze-Rothe, A. Wallukat, A.S. Hönicke, and J. Müller are employed by the Berlin Cures GmbH. G. Wallukat and J. Müller are shareholders of the Berlin Cures Holding AG, the holding company of Berlin Cures. The authors declare no competing interests. All other authors have nothing to declare. The authors have no other relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject or materials discussed in the manuscript apart from those which are disclosed.
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32
Review
Curr Opin Toxicol. 2021 Mar;25:49-56.
doi: 10.1016/j.cotox.2021.03.004. Epub 2021 Mar 29.
Current opinion in neurological manifestations of SARS-CoV-2 infection
Ayse Basak Engin 1, Evren Doruk Engin 2, Atilla Engin 3
Affiliations expand
PMID: 33817451
PMCID: PMC8006515
Free PMC article
Abstract
Neurological symptoms occur in approximately one-third of hospitalized patients with coronavirus disease 2019 (COVID-19). Among these symptoms, hypoxic encephalopathy develops in one-fifth of severe cases, while ischemic strokes due to thrombotic complications are common in one-third of COVID-19 intensive care patients. Brain involvement of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is eventuated by several routes, including hematogenous spread, transsynaptic entry through infected neurons, olfactory nerve, ocular epithelium, vascular endothelium, and impaired blood-brain barrier. Besides the high angiotensin-converting enzyme-2 (ACE2) binding affinity, and FURIN preactivation, SARS-CoV-2 maintains efficient neuronal entry while evading immune surveillance by using basigin and neuropilin-1 receptors. However, the neurological manifestations and their pathogenic mechanisms are still debated in COVID-19 patients.
Keywords: ACE2; Blood–brain barrier; COVID-19; IL-6; Neuropilin-1; Thromboembolic complications.
© 2021 Elsevier B.V. All rights reserved.
Conflict of interest statement
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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33
Review
Cells. 2021 Mar 30;10(4):756.
doi: 10.3390/cells10040756.
"Let Food Be Thy Medicine": Gluten and Potential Role in Neurodegeneration
Aaron Lerner 1, Carina Benzvi 1
Affiliations expand
PMID: 33808124
PMCID: PMC8065505
Free PMC article
Abstract
Wheat is a most favored staple food worldwide and its major protein is gluten. It is involved in several gluten dependent diseases and lately was suggested to play a role in non-celiac autoimmune diseases. Its involvement in neurodegenerative conditions was recently suggested but no cause-and-effect relationship were established. The present narrative review expands on various aspects of the gluten-gut-brain axes events, mechanisms and pathways that connect wheat and gluten consumption to neurodegenerative disease. Gluten induced dysbiosis, increased intestinal permeabillity, enteric and systemic side effects, cross-reactive antibodies, and the sequence of homologies between brain antigens and gluten are highlighted. This combination may suggest molecular mimicry, alluding to some autoimmune aspects between gluten and neurodegenerative disease. The proverb of Hippocrates coined in 400 BC, "let food be thy medicine," is critically discussed in the frame of gluten and potential neurodegeneration evolvement.
Keywords: BLAST; brain; cross-reactivity; gluten; gut-brain axis; intestine; neurodegeneration; nutrients; sequence homology.
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.
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34
Review
Medicina (Kaunas). 2021 Mar 9;57(3):253.
doi: 10.3390/medicina57030253.
Does COVID-19 Vaccination Warrant the Classical Principle " ofelein i mi vlaptin"?
Michael Doulberis 1, Apostolis Papaefthymiou 1 2, Georgios Kotronis 3, Dimitra Gialamprinou 4, Elpidoforos S Soteriades 5 6, Anthony Kyriakopoulos 7, Eleftherios Chatzimichael 8, Kyriaki Kafafyllidou 9, Christos Liatsos 10, Ioannis Chatzistefanou 11, Paul Anagnostis 12, Vitalii Semenin 13, Smaragda Ntona 14, Ioanna Gkolia 15, Dimitrios David Papazoglou 16, Nikolaos Tsinonis 17, Spyros Papamichos 1, Hristos Kirbas 18, Petros Zikos 19, Dionisios Niafas 20, Jannis Kountouras 1
Affiliations expand
PMID: 33803295
PMCID: PMC7999356
Free PMC article
Abstract
The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic warrants an imperative necessity for effective and safe vaccination, to restrain Coronavirus disease 2019 (COVID-19) including transmissibility, morbidity, and mortality. In this regard, intensive medical and biological research leading to the development of an arsenal of vaccines, albeit incomplete preconditioned evaluation, due to emergency. The subsequent scientific gap raises some concerns in the medical community and the general public. More specifically, the accelerated vaccine development downgraded the value of necessary pre-clinical studies to elicit medium- and long-term beneficial or harmful consequences. Previous experience and pathophysiological background of coronaviruses' infections and vaccine technologies, combined with the global vaccines' application, underlined the obligation of a cautious and qualitative approach, to illuminate potential vaccination-related adverse events. Moreover, the high SARS-CoV-2 mutation potential and the already aggregated genetical alterations provoke a rational vagueness and uncertainty concerning vaccines' efficacy against dominant strains and the respective clinical immunity. This review critically summarizes existing evidence and queries regarding SARS-CoV-2 vaccines, to motivate scientists' and clinicians' interest for an optimal, individualized, and holistic management of this unprecedented pandemic.
Keywords: COVID-19; Hippocrates; Primum non nocere; SARS-COV-2; ofelein i mi vlaptin; vaccination; vaccine.
Conflict of interest statement
Dr Doulberis has received a travel grant by Gilead Sciences Switzerland Sàrl. Rest of the authors declare no conflict of interest.
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35
Clin Transl Immunology. 2021 Mar 7;10(3):e1260.
doi: 10.1002/cti2.1260. eCollection 2021.
Antibodies to neutralising epitopes synergistically block the interaction of the receptor-binding domain of SARS-CoV-2 to ACE 2
Manisha Pandey 1, Victoria Ozberk 1, Sharareh Eskandari 1, Ahmed O Shalash 2, Michael A Joyce 3, Holly A Saffran 3, Christopher J Day 1, Ailin Lepletier 1, Belinda L Spillings 1, Jamie-Lee Mills 1, Ainslie Calcutt 1, Fan Fan 4, James T Williams 5, Danielle I Stanisic 1, Laetitia Hattingh 5, John Gerrard 5, Mariusz Skwarczynski 2, Johnson Mak 1, Michael P Jennings 1, Istvan Toth 2, D Lorne Tyrrell 3, Michael F Good 1
Affiliations expand
PMID: 33732459
PMCID: PMC7937407
DOI: 10.1002/cti2.1260
Free PMC article
Abstract
Objectives: A major COVID-19 vaccine strategy is to induce antibodies that prevent interaction between the Spike protein's receptor-binding domain (RBD) and angiotensin-converting enzyme 2 (ACE2). These vaccines will also induce T-cell responses. However, concerns were raised that aberrant vaccine-induced immune responses may exacerbate disease. We aimed to identify minimal epitopes on the RBD that would induce antibody responses that block the interaction of the RBD and ACE2 as a strategy leading to an effective vaccine with reduced risk of inducing immunopathology.
Methods: We procured a series of overlapping 20-amino acid peptides spanning the RBD and asked which were recognised by plasma from COVID-19 convalescent patients. Identified epitopes were conjugated to diphtheria-toxoid and used to vaccinate mice. Immune sera were tested for binding to the RBD and for their ability to block the interaction of the RBD and ACE2.
Results: Seven putative vaccine epitopes were identified. Memory B-cells (MBCs) specific for one of the epitopes were identified in the blood of convalescent patients. When used to vaccinate mice, six induced antibodies that bound recRBD and three induced antibodies that could partially block the interaction of the RBD and ACE2. However, when the sera were combined in pairs, we observed significantly enhanced inhibition of binding of RBD to ACE2. Two of the peptides were located in the main regions of the RBD known to contact ACE2. Of significant importance to vaccine development, two of the peptides were in regions that are invariant in the UK and South African strains.
Conclusion: COVID-19 convalescent patients have SARS-CoV-2-specific antibodies and MBCs, the specificities of which can be defined with short peptides. Epitope-specific antibodies synergistically block RBD-ACE2 interaction.
Keywords: ACE‐2; SARS‐CoV‐2; memory B cells; peptide epitopes; receptor‐binding domain; tetramer staining; vaccine.
© 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.
Conflict of interest statement
The authors declare no conflict of interest.
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36
Case Reports
Case Rep Neurol Med. 2021 Feb 15;2021:8824512.
doi: 10.1155/2021/8824512. eCollection 2021.
Peculiar Presentation of COVID-19: A Case Report of Concurrent Stroke and Guillain-Barré Syndrome
Behnaz Ansari 1, Helia Hemasian 1
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PMID: 33680523
PMCID: PMC7904341
DOI: 10.1155/2021/8824512
Free PMC article
Abstract
Background: Coronavirus disease 2019 (COVID-19) is a newly recognized infectious disease that has turned into a pandemic. There are few studies reporting Guillain-Barré syndrome (GBS) and stroke separately associated with COVID-19. In this study, we report an unusual case of COVID-19 with stroke and GBS concurrently. Case Report. A 59-year-old woman presented with left-sided weakness of two weeks' duration followed by right-sided weakness and foot paresthesia. She also complained of cough, myalgia, and respiratory distress of three weeks' duration. On examination, the patient had respiratory distress. The limb examination revealed asymmetric weakness. All limb reflexes were absent. Pinprick sensation was impaired. The chest CT scan and PCR of nasopharyngeal swab confirmed the diagnosis of COVID-19. Further evaluation revealed acute cerebral infarction and GBS. Consequently, the patient was treated by plasmapheresis, and her symptoms partially improved.
Conclusion: According to reports, 36.4% of COVID-19 cases display neurological complications. The neurological manifestations of the disease can involve both the central and peripheral nervous systems. Previously, a few cases of GBS and cerebrovascular disease have been reported in association with COVID-19 separately, while in the present case, CNS and PNS involvement occurred concurrently. It is hypothesized that this concurrence is related to the imbalance of the systemic inflammatory responses and blood vessel autonomous dysfunction.
Copyright © 2021 Behnaz Ansari and Helia Hemasian.
Conflict of interest statement
The authors declare that they have no conflicts of interest.
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Neuroepidemiology. 2021;55(2):109-118.
doi: 10.1159/000513647. Epub 2021 Feb 25.
Surveillance Study of Acute Neurological Manifestations among 439 Egyptian Patients with COVID-19 in Assiut and Aswan University Hospitals
Eman M Khedr 1, Noha Abo-Elfetoh 2, Enas Deaf 3, Hebatallah M Hassan 3, Mariam T Amin 4, Radwa K Soliman 5, Alaa A Attia 6, Amro A Zarzour 6, Mohamed Zain 7, Aliae Mohamed-Hussein 8, Maiada K Hashem 8, Sahar M Hassany 9, Ahmed Aly 10, Ahmed Shoyb 11, Mostafa Saber 11
Affiliations expand
PMID: 33631765
PMCID: PMC8018217
DOI: 10.1159/000513647
Free PMC article
Abstract
Background: COVID-19 can be accompanied by acute neurological complications of both central and peripheral nervous systems (CNS and PNS). In this study, we estimate the frequency of such complications among hospital inpatients with COVID-19 in Assiut and Aswan university hospitals.
Materials and methods: We screened all patients with suspected COVID-19 admitted from 1 June to 10 August 2020 to the university hospitals of Assiut and Aswan in Upper Egypt. Clinical and laboratory tests, CT/MRI of the chest and brain, and neurophysiology study were performed for each patient if indicated.
Results: 439 patients had confirmed/probable COVID-19; neurological manifestations occurred in 222. Of these, 117 had acute neurological disease and the remainder had nonspecific neuropsychiatric symptoms such as headache, vertigo, and depression. The CNS was affected in 75 patients: 55 had stroke and the others had convulsions (5), encephalitis (6), hypoxic encephalopathy (4), cord myelopathy (2), relapse of multiple sclerosis (2), and meningoencephalitis (1). The PNS was affected in 42 patients: the majority had anosmia and ageusia (31) and the others had Guillain-Barré syndrome (4), peripheral neuropathy (3), myasthenia gravis (MG, 2), or myositis (2). Fever, respiratory symptoms, and headache were the most common general symptoms. Hypertension, diabetes mellitus, and ischemic heart disease were the most common comorbidities in patients with CNS affection.
Conclusion: In COVID-19, both the CNS and PNS are affected. Stroke was the most common complication for CNS, and anosmia and/or ageusia were common for PNS diseases. However, there were 6 cases of encephalitis, 2 cases of spinal cord myelopathy, 2 cases of MG, and 2 cases of myositis.
Keywords: Ageusia; Anosmia; COVID-19; Central nervous system; Cerebrovascular stroke; Encephalitis; Guillain-Barré syndrome; Myelopathy; Myositis; Peripheral nervous system; Seizure; Spinal cord infarct; Transverse myelitis.
© 2021 S. Karger AG, Basel.
Conflict of interest statement
The authors have no conflicts of interest to declare.
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Autoimmun Rev. 2021 Apr;20(4):102791.
doi: 10.1016/j.autrev.2021.102791. Epub 2021 Feb 18.
Molecular mimicry between SARS-CoV-2 and human proteins
Affiliations expand
PMID: 33610750
PMCID: PMC7890341
Free PMC article
No abstract available
Keywords: Autoimmunity; Molecular mimicry; Severe acute respiratory syndrome coronavirus 2.
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39
Review
Clin Immunol. 2021 May;226:108694.
doi: 10.1016/j.clim.2021.108694. Epub 2021 Feb 19.
Coronavirus-induced autoimmunity
Affiliations expand
PMID: 33610741
PMCID: PMC8005338
Free PMC article
Abstract
The pandemic of Coronavirus disease 2019 (COVID-19), caused by a new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spotlighted the link between viral infection and autoimmunity. In this review, we focus on coronavirus-induced autoimmunity based on evidence from experimental animal models, SARS-CoV infection with in vitro studies of molecular mimicry and COVID-19 with several clinical reports of autoimmune manifestations of this disease. Further studies will be needed to better characterize the role of SARS-CoV-2 in the development of autoimmunity.
Keywords: Autoimmunity; COVID-19; Coronavirus.
Copyright © 2021 Elsevier Inc. All rights reserved.
Conflict of interest statement
The authors have no conflicts to declare.
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40
Front Immunol. 2021 Jan 19;11:617089.
doi: 10.3389/fimmu.2020.617089. eCollection 2020.
Reaction of Human Monoclonal Antibodies to SARS-CoV-2 Proteins With Tissue Antigens: Implications for Autoimmune Diseases
Aristo Vojdani 1 2, Elroy Vojdani 3, Datis Kharrazian 2 4 5
Affiliations expand
PMID: 33584709
PMCID: PMC7873987
Free PMC article
Abstract
We sought to determine whether immune reactivity occurs between anti-SARS-CoV-2 protein antibodies and human tissue antigens, and whether molecular mimicry between COVID-19 viral proteins and human tissues could be the cause. We applied both human monoclonal anti-SARS-Cov-2 antibodies (spike protein, nucleoprotein) and rabbit polyclonal anti-SARS-Cov-2 antibodies (envelope protein, membrane protein) to 55 different tissue antigens. We found that SARS-CoV-2 antibodies had reactions with 28 out of 55 tissue antigens, representing a diversity of tissue groups that included barrier proteins, gastrointestinal, thyroid and neural tissues, and more. We also did selective epitope mapping using BLAST and showed similarities and homology between spike, nucleoprotein, and many other SARS-CoV-2 proteins with the human tissue antigens mitochondria M2, F-actin and TPO. This extensive immune cross-reactivity between SARS-CoV-2 antibodies and different antigen groups may play a role in the multi-system disease process of COVID-19, influence the severity of the disease, precipitate the onset of autoimmunity in susceptible subgroups, and potentially exacerbate autoimmunity in subjects that have pre-existing autoimmune diseases. Very recently, human monoclonal antibodies were approved for use on patients with COVID-19. The human monoclonal antibodies used in this study are almost identical with these approved antibodies. Thus, our results can establish the potential risk for autoimmunity and multi-system disorders with COVID-19 that may come from cross-reactivity between our own human tissues and this dreaded virus, and thus ensure that the badly-needed vaccines and treatments being developed for it are truly safe to use against this disease.
Keywords: COVID-19; SARS-CoV-2; autoimmunity; cross-reactivity; molecular mimicry.
Copyright © 2021 Vojdani, Vojdani and Kharrazian.
Conflict of interest statement
AV is the co-owner, CEO and employee of Immunosciences Lab., Inc. EV is the owner and employee of Regenera Medical, a private medical practice. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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41
Case Reports
J Immunother Cancer. 2021 Feb;9(2):e001870.
doi: 10.1136/jitc-2020-001870.
COVID-19 lung injury as a primer for immune checkpoint inhibitors (ICIs)-related pneumonia in a patient affected by squamous head and neck carcinoma treated with PD-L1 blockade: a case report
Angelo Dipasquale 1 2, Pasquale Persico 1 2, Elena Lorenzi 1 2, Daoud Rahal 3, Armando Santoro 1 2, Matteo Simonelli 1 2
Affiliations expand
PMID: 33574054
PMCID: PMC7880093
Free PMC article
Erratum in
Correction: COVID-19 lung injury as a primer for immune checkpoint inhibitors (ICIs)-related pneumonia in a patient affected by squamous head and neck carcinoma treated with PD-L1 blockade: a case report.[No authors listed]J Immunother Cancer. 2021 Aug;9(8):e001870corr1. doi: 10.1136/jitc-2020-001870corr1.PMID: 34353850 Free PMC article. No abstract available.
Abstract
By the beginning of the global pandemic, SARS-CoV-2 infection has dramatically impacted on oncology daily practice. In the current oncological landscape, where immunotherapy has revolutionized the treatment of several malignancies, distinguishing between COVID-19 and immune-mediated pneumonitis can be hard because of shared clinical, radiological and pathological features. Indeed, their common mechanism of aberrant inflammation could lead to a mutual and amplifying interaction.We describe the case of a 65-year-old patient affected by metastatic squamous head and neck cancer and candidate to an experimental therapy including an anti-PD-L1 agent. COVID-19 ground-glass opacities under resolution were an incidental finding during screening procedures and worsened after starting immunotherapy. The diagnostic work-up was consistent with ICIs-related pneumonia and it is conceivable that lung injury by SARS-CoV-2 has acted as an inflammatory primer for the development of the immune-related adverse event.Patients recovered from COVID-19 starting ICIs could be at greater risk of recall immune-mediated pneumonitis. Nasopharyngeal swab and chest CT scan are recommended before starting immunotherapy. The awareness of the phenomenon could allow an easier interpretation of radiological changes under treatment and a faster diagnostic work-up to resume ICIs. In the presence of clinical benefit, for asymptomatic ICIs-related pneumonia a watchful-waiting approach and immunotherapy prosecution are suggested.
Keywords: clinical trials as topic; head and neck neoplasms; immunotherapy; investigational; programmed cell death 1 receptor; therapies.
© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
Conflict of interest statement
Competing interests: None declared.
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42
Review
Front Immunol. 2020 Dec 22;11:586111.
doi: 10.3389/fimmu.2020.586111. eCollection 2020.
Host Genetics at the Intersection of Autoimmunity and COVID-19: A Potential Key for Heterogeneous COVID-19 Severity
Tugce Karaderi 1 2, Halin Bareke 3 4, Imge Kunter 5, Adil Seytanoglu 3, Ilgin Cagnan 3, Deniz Balci 3, Burc Barin 6, Mevhibe B Hocaoglu 7 8, Nilufer Rahmioglu 9 10, Esra Asilmaz 11, Bahar Taneri 3 12
Affiliations expand
PMID: 33414783
PMCID: PMC7783411
Free PMC article
Abstract
COVID-19 presentation is very heterogeneous across cases, and host factors are at the forefront for the variables affecting the disease manifestation. The immune system has emerged as a key determinant in shaping the outcome of SARS-CoV-2 infection. It is mainly the deleterious unconstrained immune response, rather than the virus itself, which leads to severe cases of COVID-19 and the associated mortality. Genetic susceptibility to dysregulated immune response is highly likely to be among the host factors for adverse disease outcome. Given that such genetic susceptibility has also been observed in autoimmune diseases (ADs), a number of critical questions remain unanswered; whether individuals with ADs have a significantly different risk for COVID-19-related complications compared to the general population, and whether studies on the genetics of ADs can shed some light on the host factors in COVID-19. In this perspective, we discuss the host genetic factors, which have been under investigation in association with COVID-19 severity. We touch upon the intricate link between autoimmunity and COVID-19 pathophysiology. We put forth a number of autoimmune susceptibility genes, which have the potential to be additional host genetic factors for modifying the severity of COVID-19 presentation. In summary, host genetics at the intersection of ADs and COVID-19 may serve as a source for understanding the heterogeneity of COVID-19 severity, and hence, potentially holds a key in achieving effective strategies in risk group identification, as well as effective treatments.
Keywords: COVID-19; SARS-CoV-2; autoimmunity; cytokine; host genetics; immune response; polymorphism; susceptibility.
Copyright © 2020 Karaderi, Bareke, Kunter, Seytanoglu, Cagnan, Balci, Barin, Hocaoglu, Rahmioglu, Asilmaz and Taneri.
Conflict of interest statement
BB was employed by The Emmes Company. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Cancers (Basel). 2020 Nov 16;12(11):3383.
doi: 10.3390/cancers12113383.
Cancer and Immune Checkpoint Inhibitor Treatment in the Era of SARS-CoV-2 Infection
Thilo Gambichler 1, Judith Reuther 1, Christina H Scheel 1 2, Laura Susok 1, Peter Kern 3, Jürgen C Becker 4 5
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PMID: 33207589
PMCID: PMC7698088
Free PMC article
Abstract
Whether cancer patients receiving immune checkpoint inhibitors (ICI) are at an increased risk of severe infection and mortality during the corona pandemic is a hotly debated topic that will continue to evolve. Here, we summarize and discuss current studies regarding COVID-19 and anti-cancer treatment with an emphasis on ICI. Importantly, several lines of evidence suggest that patients currently treated with ICI do not display an increased vulnerability to infection with SARS-CoV-2. Data regarding morbidity and mortality associated with COVID-19 in cancer patients receiving ICI are less clear and often conflicting. Although mostly based on experimental data, it is possible that ICI can promote the exacerbated immune response associated with adverse outcome in COVID-19 patients. On the other hand, mounting evidence suggests that ICI might even be useful in the treatment of viral infections by preventing or ameliorating T cell exhaustion. In this context, the right timing of treatment might be essential. Nevertheless, some cancer patients treated with ICI experience autoimmune-related side effects that require the use of immunosuppressive therapies, which in turn may promote a severe course of infection with SARS-CoV-2. Although there is clear evidence that withholding ICI will have more serious consequences, further studies are urgently needed in to better evaluate the effects of ICI in patients with COVID-19 and the use of ICI during the corona pandemic in general.
Keywords: COVID-19; coronavirus; cytotoxic T lymphocyte antigen-4; immune checkpoint inhibitors; programmed cell death protein.
Conflict of interest statement
T.G. has received speakers and/or advisory board honoraria from BMS, Sanofi-Genzyme, MSD, Novartis Pharma, Roche, Abbvie, Almirall, Janssen, Lilly, Pfizer, Pierre Fabre, Merck-Serono, outside the submitted work. J.C.B. is receiving speaker’s bureau honoraria from Amgen, Pfizer, Merck-Serono, Recordati and Sanofi, is a paid consultant/advisory board member for Boehringer Ingelheim, eTheRNA, In ProTher, MerckSerono, Pfizer, 4SC and Sanofi. His group receives research grants from BMS, Merck Serono, HTG, IQVIA, and Alcedis. L.S. has received speakers and/or advisory board honoraria from BMS, Sun-Pharma, MSD, and Novartis. J.R., C.S., and P.K. have no conflict of interest to declare.
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45
Case Reports
Medicina (Kaunas). 2020 Oct 5;56(10):521.
doi: 10.3390/medicina56100521.
Positive Anti-SSA/Ro Antibody in a Woman with SARS-CoV-2 Infection Using Immunophenotyping: A Case Report
Po-I Huang 1, Ting-Chun Lin 2, Feng-Cheng Liu 3, Yi-Jung Ho 2 4, Jeng-Wei Lu 5, Te-Yu Lin 6
Affiliations expand
PMID: 33028028
PMCID: PMC7600347
Free PMC article
Abstract
The clinical spectrum of novel coronavirus infection appears to be wide, encompassing asymptomatic infection, mild upper respiratory tract illness, and severe viral pneumonia, with respiratory failure and even death. Autoantibodies, especially antiphospholipid antibodies, can occur in severe infections. Other autoantibodies are seldom reported. Here, a 60-year-old female patient without dry-mouth symptoms detected positive for anti-60 kDa SSA/Ro antibodies on day 43 after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To investigate this unique clinical case of SARS-CoV-2 infection, immunological characteristics of this case were detected by using flow cytometry and were compared to the other three groups of patients-health subjects, 2019 novel coronavirus disease (COVID-19) recovery patients, and Sjögren's syndrome (SS) patients. Monitoring the autoantibody level and the development of subsequently related autoimmune diseases are warranted after SARS-CoV-2 infection.
Keywords: COVID-19; SARS-CoV-2; Sjögren’s syndrome; autoimmune; immunophenotyping.
Conflict of interest statement
The authors have no conflict of interest.
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46
Review
SN Compr Clin Med. 2020;2(11):2048-2058.
doi: 10.1007/s42399-020-00521-8. Epub 2020 Sep 19.
Immune Thrombocytopenia Secondary to COVID-19: a Systematic Review
Sukrita Bhattacharjee # 1, Mainak Banerjee # 2
Affiliations expand
PMID: 32984764
PMCID: PMC7501509
Free PMC article
Abstract
Immune thrombocytopenia, often known as immune thrombocytopenic purpura (ITP), has emerged as an important complication of COVID-19. A systematic review was done to analyze the clinical profile and outcomes in a total of 45 cases of new-onset ITP in COVID-19 patients described in literature until date. A comprehensive approach is essential for diagnosing COVID-19-associated ITP after excluding several concomitant factors that can cause thrombocytopenia in COVID-19. Majority of ITP cases (71%) were found to be elderly (> 50 years) and 75% cases had moderate-to-severe COVID-19. Three patients (7%) were in the pediatric age group. Reports of ITP in asymptomatic COVID-19 patients (7%) underscore the need for COVID-19 testing in newly diagnosed patients with ITP irrespective of COVID-19 symptoms amid this pandemic. ITP onset occurred in 20% cases 3 weeks after onset of COVID-19 symptoms, with many reports after clinical recovery. SARS-CoV-2-mediated immune thrombocytopenia can be attributed to the underlying immune dysregulation, susceptibility mutations in SOCS 1, and other mechanisms, including molecular mimicry, cryptic antigen expression, and epitope spreading. No bleeding manifestations were reported in 31% cases at diagnosis. Severe life-threatening bleeding was uncommon. One case of mortality was attributed to intracranial hemorrhage. Secondary Evans syndrome was diagnosed in one case. Good initial response to short course of glucocorticoids and intravenous immunoglobulin has been found with the exception of delayed lag response in one case. Thrombopoietin receptor agonist usage as a second-line agent has been noted in few cases for short duration with no adverse events. In the relatively short follow-up period, four relapses of ITP were found.
Keywords: Bleeding; COVID-19; Hematological complication; ITP; Low platelet; Purpura.
© Springer Nature Switzerland AG 2020.
Conflict of interest statement
Conflict of InterestThe authors declare that they have no conflicts of interest.
Comment in
Frequently Relapsing Post-COVID-19 Immune Thrombocytopenia.Serrano C, Español I, Cascales A, Moraleda JM.SN Compr Clin Med. 2021;3(12):2389-2392. doi: 10.1007/s42399-021-01019-7. Epub 2021 Jul 20.PMID: 34308259 Free PMC article. No abstract available.
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47
J Trace Elem Med Biol. 2020 Dec;62:126649.
doi: 10.1016/j.jtemb.2020.126649. Epub 2020 Sep 21.
Impact of catch-up vaccination on aluminum exposure due to new laws and post social distancing
James Lyons-Weiler 1, Grant McFarland 2, Elaine La Joie 2
Affiliations expand
PMID: 32980768
PMCID: PMC7505097
Free PMC article
Abstract
Background: The COVID-19 pandemic has placed significant stressors on the medical community and on the general public. Part of this includes patients skipping well-child visits to reduce risk of exposure to SARS-CoV-2 virus. Published estimates of the duration of whole-body aluminum (Al) toxicity from vaccines in infants from birth to six months indicate that CDC's recommended vaccination schedule leads to unacceptably long periods of time in which infants are in aluminum toxicity (as measured by %AlumTox).
Methods: We utilize these established clearance and accumulation models to calculate expected per-body-weight whole-body toxicity of aluminum from vaccines considering for children of all ages under CDC's Catch-Up schedule from birth to ten years, assuming social distancing for 6 months. Our updated Pediatric Dose Limit (PDL) model assumes a linear improvement in renal function from birth to two years.
Results: Our results indicate that due diligence in considering alternative spacing and use of non-aluminum containing vaccines when possible will reduce whole body toxicity and may reduce risk of morbidity associated with exposure to aluminum.
Conclusions: While reduction or elimination of aluminum exposure from all sources is always a good idea, our results indicate that careful consideration of expected aluminum exposures during regular and Catch-Up vaccination is found to be especially important for infants and children below 2 years of age. We urge caution in the mass re-starting of vaccination under CDC's Catch-Up schedule for children under 12 months and offer alternative strategies to minimize per-day/week/month exposure to aluminum hydroxide following the COVID-19 period of isolation.
Keywords: Aluminum; COVID-19; Vaccination; Vaccines.
Copyright © 2020 The Author(s). Published by Elsevier GmbH.. All rights reserved.
Conflict of interest statement
Dr. Lyons-Weiler has served as an expert witness in the National Vaccine Injury Compensation Program.
Grant McFarland and Elaine La Joie have not conflicts of interest to report.
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48
Review
Biology (Basel). 2020 Aug 20;9(9):240.
doi: 10.3390/biology9090240.
COVID-19 in Light of Seasonal Respiratory Infections
Irina Kiseleva 1, Elena Grigorieva 1, Natalie Larionova 1, Mohammad Al Farroukh 1, Larisa Rudenko 1
Affiliations expand
PMID: 32825427
PMCID: PMC7564908
Free PMC article
Abstract
A wide diversity of zoonotic viruses that are capable of overcoming host range barriers facilitate the emergence of new potentially pandemic viruses in the human population. When faced with a new virus that is rapidly emerging in the human population, we have a limited knowledge base to work with. The pandemic invasion of the new SARS-CoV-2 virus in 2019 provided a unique possibility to quickly learn more about the pathogenesis of respiratory viruses. In this review, the impact of pandemics on the circulation of seasonal respiratory viruses is considered. The emergence of novel respiratory viruses has often been accompanied by the disappearance of existing circulating strains. Some issues arising from the spread of pandemic viruses and underlying the choices of a strategy to fight the coronavirus infection are discussed.
Keywords: COVID-19; epidemics; influenza; pandemics; viral respiratory infections.
Conflict of interest statement
The author declares no conflict of interest.
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49
Review
Antioxidants (Basel). 2020 Aug 13;9(8):742.
doi: 10.3390/antiox9080742.
Hesperidin and SARS-CoV-2: New Light on the Healthy Function of Citrus Fruits
Paolo Bellavite 1, Alberto Donzelli 2
Affiliations expand
PMID: 32823497
PMCID: PMC7465267
Free PMC article
Abstract
Among the many approaches to Coronavirus disease 2019 (COVID-19) prevention, the possible role of nutrition has so far been rather underestimated. Foods are very rich in substances, with a potential beneficial effect on health, and some of these could have an antiviral action or be important in modulating the immune system and in defending cells from the oxidative stress associated with infection. This short review draws the attention on some components of citrus fruits, and especially of the orange (Citrus sinensis), well known for its vitamin and flavonoid content. Among the flavonoids, hesperidin has recently attracted the attention of researchers, because it binds to the key proteins of the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several computational methods, independently applied by different researchers, showed that hesperidin has a low binding energy, both with the coronavirus "spike" protein, and with the main protease that transforms the early proteins of the virus (pp1a and ppa1b) into the complex responsible for viral replication. The binding energy of hesperidin to these important components is lower than that of lopinavir, ritonavir, and indinavir, suggesting that it could perform an effective antiviral action. Furthermore, both hesperidin and ascorbic acid counteract the cell damaging effects of the oxygen free radicals triggered by virus infection and inflammation. There is discussion about the preventive efficacy of vitamin C, at the dose achievable by the diet, but recent reviews suggest that this substance can be useful in the case of strong immune system burden caused by viral disease. Computational methods and laboratory studies support the need to undertake apposite preclinical, epidemiological, and experimental studies on the potential benefits of citrus fruit components for the prevention of infectious diseases, including COVID-19.
Keywords: COVID-19; Citrus sinensis; SARS-CoV-2; citrus fruits; hesperidin; sweet orange; virus and oxidative stress; vitamin C.
Conflict of interest statement
The authors declare no conflict of interest.
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50
Case Reports
Int J Infect Dis. 2020 Oct;99:269-271.
doi: 10.1016/j.ijid.2020.08.002. Epub 2020 Aug 6.
Severe immune thrombocytopenia in a critically ill COVID-19 patient
Ziga Martincic 1, Barbara Skopec 2, Karla Rener 2, Matej Mavric 3, Tomaz Vovko 3, Matjaz Jereb 4, Milica Lukic 3
Affiliations expand
PMID: 32771636
PMCID: PMC7409801
Free PMC article
Abstract
The novel coronavirus SARS-CoV-2 can cause a severe and even fatal respiratory illness named COVID-19. Apart from respiratory failure, COVID-19 may be associated with various autoimmune complications. We present a case of a critically ill patient with COVID-19 who developed severe immune thrombocytopenia that was successfully treated with a concomitant use of corticosteroids and intravenous immunoglobulins.
Keywords: COVID-19; SARS-CoV-2; corticosteroids; immune thrombocytopenia; intravenous immunoglobulins.
Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.
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51
Review
Rheumatol Int. 2020 Oct;40(10):1539-1554.
doi: 10.1007/s00296-020-04639-9. Epub 2020 Jul 14.
Autoimmune and rheumatic musculoskeletal diseases as a consequence of SARS-CoV-2 infection and its treatment
Sanket Shah 1, Debashish Danda 2, Chengappa Kavadichanda 1, Saibal Das 3, M B Adarsh 1, Vir Singh Negi 4
Affiliations expand
PMID: 32666137
PMCID: PMC7360125
Free PMC article
Abstract
The coronavirus disease-2019 (COVID-19) pandemic is likely to pose new challenges to the rheumatology community in the near and distant future. Some of the challenges, like the severity of COVID-19 among patients on immunosuppressive agents, are predictable and are being evaluated with great care and effort across the globe. A few others, such as atypical manifestations of COVID-19 mimicking rheumatic musculoskeletal diseases (RMDs) are being reported. Like in many other viral infections, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection can potentially lead to an array of rheumatological and autoimmune manifestations by molecular mimicry (cross-reacting epitope between the virus and the host), bystander killing (virus-specific CD8 + T cells migrating to the target tissues and exerting cytotoxicity), epitope spreading, viral persistence (polyclonal activation due to the constant presence of viral antigens driving immune-mediated injury) and formation of neutrophil extracellular traps. In addition, the myriad of antiviral drugs presently being tried in the treatment of COVID-19 can result in several rheumatic musculoskeletal adverse effects. In this review, we have addressed the possible spectrum and mechanisms of various autoimmune and rheumatic musculoskeletal manifestations that can be precipitated by COVID-19 infection, its therapy, and the preventive strategies to contain the infection.
Keywords: Autoimmunity; Coronavirus disease-2019 (COVID-19); Rheumatic musculoskeletal diseases (RMDs); Rheumatology.
Conflict of interest statement
The authors declare that they have no conflict of interest.
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52
Review
J Immunother Cancer. 2020 Jul;8(2):e001145.
doi: 10.1136/jitc-2020-001145.
On the use of immune checkpoint inhibitors in patients with viral infections including COVID-19
Thilo Gambichler 1, Judith Reuther 1, Christina H Scheel 1 2, Jürgen Christian Becker 3 4
Affiliations expand
PMID: 32611687
PMCID: PMC7358098
Free PMC article
Erratum in
Correction: On the use of immune checkpoint inhibitors in patients with viral infections including COVID-19.[No authors listed]J Immunother Cancer. 2021 Apr;9(4):1. doi: 10.1136/jitc-2020-001145corr1.PMID: 33837056 Free PMC article. No abstract available.
Abstract
The present review summarizes up-to-date evidence addressing the frequently discussed clinical controversies regarding the use of immune checkpoint inhibitors (ICIs) in cancer patients with viral infections, including AIDS, hepatitis B and C, progressive multifocal leukoencephalopathy, influenza, and COVID-19. In detail, we provide available information on (1) safety regarding the risk of new infections, (2) effects on the outcome of pre-existing infections, (3) whether immunosuppressive drugs used to treat ICI-related adverse events affect the risk of infection or virulence of pre-existing infections, (4) whether the use of vaccines in ICI-treated patients is considered safe, and (5) whether there are beneficial effects of ICIs that even qualify them as a therapeutic approach for these viral infections.
Keywords: T-lymphocytes; immune evation; review; tumor escape; vaccination.
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.
Conflict of interest statement
Competing interests: TG has received speakers and/or advisory board honoraria from BMS, Sanofi-Genzyme, MSD, Novartis Pharma, Roche, Abbvie, Almirall, Janssen, Lilly, Pfizer, Pierre Fabre, Merck-Serono, outside the submitted work. JR and CHS declare that they have no competing interests. JCB is receiving speaker’s bureau honoraria from Amgen, Pfizer, Merck-Serono, Recordati and Sanofi, is a paid consultant/advisory board member for Boehringer Ingelheim, eTheRNA, In ProTher, MerckSerono, Pfizer, 4SC and Sanofi. His group receives research grants from Bristol-Myers Squibb, Merck Serono, HTG, IQVIA, and Alcedis.
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53
J Clin Med. 2020 Jun 29;9(7):2038.
doi: 10.3390/jcm9072038.
Does SARS-CoV-2 Trigger Stress-InducedAutoimmunity by Molecular Mimicry? A Hypothesis
Francesco Cappello 1 2, Antonella Marino Gammazza 1, Francesco Dieli 1, de Macario 2 3, Alberto Jl Macario 2 3
Affiliations expand
PMID: 32610587
PMCID: PMC7408943
DOI: 10.3390/jcm9072038
Free PMC article
Abstract
Viruses can generate molecular mimicry phenomena within their hosts. Why shouldsevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) not be considered one of these?Information in this short review suggests that it might be so and, thus, encourages research aimingat testing this possibility. We propose, as a working hypothesis, that the virus induces antibodiesand that some of them crossreact with host's antigens, thus eliciting autoimmune phenomena withdevasting consequences in various tissues and organs. If confirmed, by in vitro and in vivo tests,this could drive researchers to find effective treatments against the virus.
Keywords: COVID-19; SARS-CoV-2; antistress proteins; cell stress; crossreactive antibodies; molecular chaperones; molecular mimicry.
Conflict of interest statement
Authors declare no conflict of interest.
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54
J Neurol. 2020 Nov;267(11):3135-3153.
doi: 10.1007/s00415-020-09990-2. Epub 2020 Jun 19.
Neurological involvement of coronavirus disease 2019: a systematic review
Malik Ghannam 1, Qasem Alshaer 2, Mustafa Al-Chalabi 3, Lara Zakarna 4, Jetter Robertson 5, Georgios Manousakis 6
Affiliations expand
PMID: 32561990
PMCID: PMC7304377
Free PMC article
Abstract
Background: In December 2019, unexplained cases of pneumonia emerged in Wuhan, China, which were found to be secondary to the novel coronavirus SARS-CoV-2. On March 11, 2020, the WHO declared the Coronavirus Disease 2019 (COVID-2019) outbreak, a pandemic.
Objective: To clarify the neurological complications of SARS-CoV-2 infection including the potential mechanisms and therapeutic options.
Methods: We conducted a systematic literature search from December 01, 2019 to May 14, 2020 using multiple combinations of keywords from PubMed and Ovid Medline databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included articles with cases of COVID-19 where neurological involvement was evident.
Results: We were able to identify 82 cases of COVID-19 with neurological complications. The mean age was 62.3 years. 37.8% of the patients were women (n = 31). 48.8% of the patients (n = 40) had cerebrovascular insults, 28% (n = 23) had neuromuscular disorders, and 23% of the patients (n = 19) had encephalitis or encephalopathy.
Conclusions: Neurological manifestations of COVID-19 are not rare, especially large vessel stroke, Guillain-Barre syndrome, and meningoencephalitis. Moving forward, further studies are needed to clarify the prevalence of the neurological complications of SARS-CoV-2 infection, investigate their biological backgrounds, and test treatment options. Physicians should be cautious not to overlook other neurological diagnoses that can mimic COVID-19 during the pandemic.
Keywords: Neurological complications; Pandemic; SARS-CoV-2.
Conflict of interest statement
The authors declare that they have no competing interests.
Comment in
Guillain-Barré syndrome in the early post-partum period following COVID-19 infection.Abdelnasser A, Mostafa M, Hasanin A, El-Sakka A, Hassanein H.Int J Obstet Anesth. 2021 Aug;47:103172. doi: 10.1016/j.ijoa.2021.103172. Epub 2021 May 1.PMID: 33994275 Free PMC article. No abstract available.
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55
J Eur Acad Dermatol Venereol. 2020 Nov;34(11):e667-e670.
doi: 10.1111/jdv.16753. Epub 2020 Jul 2.
Cutaneous autoimmune diseases during COVID-19 pandemic
C Günther 1, R Aschoff 1, S Beissert 1
Affiliations expand
PMID: 32534461
PMCID: PMC7322985
DOI: 10.1111/jdv.16753
Free PMC article
No abstract available
Conflict of interest statement
The authors have declared no conflict of interest.
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56
Comment
J Am Acad Dermatol. 2020 Sep;83(3):e249.
doi: 10.1016/j.jaad.2020.06.003. Epub 2020 Jun 4.
Could antiphospholipid antibodies contribute to coagulopathy in COVID-19?
Aurora Parodi 1, Giulia Gasparini 2, Emanuele Cozzani 1
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PMID: 32505779
PMCID: PMC7271853
Free PMC article
No abstract available
Comment on
A dermatologic manifestation of COVID-19: Transient livedo reticularis.Manalo IF, Smith MK, Cheeley J, Jacobs R.J Am Acad Dermatol. 2020 Aug;83(2):700. doi: 10.1016/j.jaad.2020.04.018. Epub 2020 Apr 10.PMID: 32283229 Free PMC article. No abstract available.
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57
Editorial
Endocrine. 2020 Jun;68(3):467-470.
doi: 10.1007/s12020-020-02349-7. Epub 2020 Jun 2.
Possible long-term endocrine-metabolic complications in COVID-19: lesson from the SARS model
Laura M Mongioì 1, Federica Barbagallo 1, Rosita A Condorelli 1, Rossella Cannarella 1, Antonio Aversa 2, Sandro La Vignera 3, Aldo E Calogero 1
Affiliations expand
PMID: 32488837
PMCID: PMC7266418
Free PMC article
Abstract
The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is centralizing the interest of the scientific world. In the next months, long-term consequences on the endocrine system may arise following COVID-19. In this article, we hypothesized the effects of SARS-CoV-2 taking into account what learned from the severe acute respiratory syndrome coronavirus (SARS-CoV) that caused SARS in 2003.
Keywords: Adrenal Glands; COVID-19; Diabetes; Obesity; Pituitary gland; SARS.
Conflict of interest statement
The authors declare that they have no conflict of interest.
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58
Review
Environ Toxicol Pharmacol. 2020 Aug;78:103411.
doi: 10.1016/j.etap.2020.103411. Epub 2020 May 15.
Two important controversial risk factors in SARS-CoV-2 infection: Obesity and smoking
Ayse Basak Engin 1, Evren Doruk Engin 2, Atilla Engin 3
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PMID: 32422280
PMCID: PMC7227557
Free PMC article
Abstract
The effects of obesity and smoking in the coronavirus disease 2019 (COVID-19) pandemic remain controversial. Angiotensin converting enzyme 2 (ACE2), a component of the renin-angiotensin system (RAS), is the human cell receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. ACE2 expression increases on lung alveolar epithelial cells and adipose tissue due to obesity, smoking and air pollution. A significant relationship exists between air pollution and SARS-CoV-2 infection, as more severe COVID-19 symptoms occur in smokers; comorbid conditions due to obesity or excess ectopic fat accumulation as underlying risk factors for severe COVID-19 strongly encourage the virus/ACE2 receptor-ligand interaction concept. Indeed, obesity, air pollution and smoking associated risk factors share underlying pathophysiologies that are related to the Renin-Angiotensin-System in SARS-CoV-2 infection. The aim of this review is to emphasize the mechanism of receptor-ligand interaction and its impact on the enhanced risk of death due to SARS-CoV-2 infection.
Keywords: Air pollution; Angiotensin II; Angiotensin-converting-enzyme inhibitors; COVID-19; Obesity; Smoking.
Copyright © 2020 Elsevier B.V. All rights reserved.
Conflict of interest statement
Declaration of Competing Interest The authors have no conflict of interest.
Whoa! Huge data drop. Thanks. Saved. Forwarded.
Amazing. What a list! Great work.