Autoimmunity, COVID-19, Post-COVID19 Syndrome and COVID-19 Vaccination

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AUTOIMMUNITY, COVID-19, POST-COVID19 SYNDROME AND COVID-19 VACCINATION
FUTURE OF AUTOIMMUNITY RESEARCH : AUTOIMMUNITY, COVID-19, POST-COVID19 SYNDROME AND COVID-19 VACCINATION
Copyright
Contents
List of contributors
About the editors
Foreword
Preface
1 - Setting a context for autoantibodies, autoimmunity, and autoimmune diseases associated with SARS-CoV2
Introduction
“Causes” of autoimmune diseases: a “mosaic” of genetic, environmental, and hormonal factors
Historical context
Controls and comparators
Phenomenology is not pathology
Time and timing is of the essence
Temporarily does not equal causality
Nobel 2021 PIEZO touch and temperature: COVID-19 myopathy
Summary
References
2 - The mosaic of autoimmunity and autoinflammation and SARS-CoV-2 as an environmental factor
The mosaic of autoimmunity and autoinflammation
SARS-CoV-2 and COVID-19
SARS-CoV-2 and biological mechanisms of virulence
SARS-CoV-2 and COVID-19 as a further cobble of the mosaic of autoimmunity
SARS-CoV-2/COVID-19 and its impact on autoimmune/autoinflammatory disorders
Alopecia areata and telogen effluvium
Amyloidosis
Ankylosing spondylitis
Antiphospholipid syndrome, catastrophic antiphospholipid syndrome, and HELLP syndrome
Atopic dermatitis
Autoimmune myopathies (myositis, dermatomyositis, and polymyositis)
Autoimmune ocular diseases
Autoimmune reproductive diseases
Autoimmune thyroiditis, including Hashimoto's thyroiditis and Graves' disease
Behçet's disease
Celiac disease
Demyelinating syndromes
Autoimmune hemolytic anemia
Immune thrombocytopenia
Inflammatory arthritis/reactive arthritis
Inflammatory bowel diseases
Lichen planus, lichen planopilaris, and lichen sclerosus
Miller–Fisher syndrome
Multiple sclerosis
Myasthenia gravis and other autoimmune neuromuscular junction disorders
Autoimmune myocarditis
Pemphigus vulgaris and other autoimmune blistering diseases
Polymyalgia rheumatica
Postural orthostatic tachycardia syndrome
Primary biliary cholangitis, primary sclerosing cholangitis, and other autoimmune cholangiopathies
Psoriasis
Psoriatic arthritis
Rheumatoid arthritis
Sarcoidosis
Sjögren's syndrome
Systemic lupus erythematosus
Systemic sclerosis and scleroderma
Type 1 diabetes
Vasculitis
Vitiligo
Conclusions and future prospects
References
3 - Innate immune responses in COVID-19
Introduction
Innate immune responses to COVID-19: cells of the innate immune system
Innate immune responses to COVID-19: NETosis and neutrophils
Innate immune responses to COVID-19: inflammasome
Canonical inflammasomes in COVID-19
Noncanonical inflammasomes and COVID-19
Innate immune responses to COVID-19: TLRs
Innate immune responses to COVID-19: cytokines
Innate immune responses to COVID-19: the human leukocyte antigen genotype
Innate immune responses to COVID-19: autophagy
Innate immune responses to COVID-19: the complement system
Mechanisms of complement activation during the SARS-CoV-2 infection
Mechanisms of complement pathogenicity in severe forms of COVID-19
Targeting complement for the treatment of COVID-19
Innate immune responses to COVID-19: protecting or aggravating factors, biomarkers of severity
C-reactive protein (CRP)
Procalcitonin (PCT)
Liver transaminases and albumin
Cardiac biomarkers
Coagulation markers
Innate immune responses to COVID-19: role of microbiota
Innate immune responses to COVID-19: therapeutic developments
IL-6
GM-CSF
IL-1 and IL-1R
Interferons (IFNs)
JAKs
Inflammasomes (sensors)
Gasdermins
Inflammatory caspases and pan-caspase inhibition
General comments and outlook
Acknowledgments
References
4 - The role of T cell immunity in COVID-19
Introduction
Human corona virus
Preformed memory
T cells in the early infection
The cytokine environment
Lymphopenia
Disease severity and T cells
Dynamics of T cells in COVID-19
T cell functionality
TCR signature in COVID-19
Conclusion
References
5 - Laboratory characteristics of cytokine storm syndrome in COVID-19 infection
Cytokine storm or cytokine release syndrome: definition and features
Clinical examples of cytokine storm syndrome
Prognostic value of cytokine measurement in COVID-19
Immunological patterns of secondary hemophagocytic lymphohistiocytosis, bacterial sepsis, and COVID-19
Cytokine storm syndrome score for disease prognosis
Validation of cytokine storm syndrome score and its clinical relationship
Conclusion remarks
References
6 - COVID-19: the impact of the cytokine storm on the immune-neuroendocrine system
Introduction
COVID-19 infection, the cytokine storm and the immuno-neuroendocrine system
The hypothalamic–pituitary–adrenal axis (HPA), COVID-19 infection, and cytokine storm
The hypothalamic–pituitary–thyroid axis (HPT), COVID-19 infection, and cytokine storm
The hypothalamic–pituitary–gonadal axis (HPG), COVID-19 infection, and cytokine storm
The autonomic nervous system: sympathetic and parasympathetic, COVID-19 infection, and cytokine storm
Central nervous system, cytokine storm, and COVID-19
Conclusions
References
7 - Genetic predisposition to COVID-19 and post-COVID syndrome
Introduction
Genetic predisposing factors in COVID-19
The X chromosome—gender
Expression of ACE2 and related proteins
Expression of pro-inflammatory proteins and its receptors
HLA-genotypes
ABO
Predisposition to PCS
Conclusions
References
8 - Molecular mimicry and SARS-CoV-2
The concept of molecular mimicry and its relevance to autoimmunity
Tools to study molecular mimicry
Bioinformatic approaches investigating the role of SARS-CoV-2-related autoimmunity by molecular mimicry
SARS-CoV-2, molecular mimicry, and Guillain–Barré syndrome
SARS-CoV-2, molecular mimicry, and anti-phospholipid syndrome (APS)
SARS-CoV-2 vaccination and autoimmunity
SARS-CoV-2 and evidence of immunological cross-reactivity
Conclusions
References
9 - In silico study of molecular mimicry between SARS-CoV-2 and neutrophil extracellular traps composition in granu ...
Introduction
Materials and methods
Blastp searches
HLA binding predictions
Proteins' features and network images
Results and discussion
Proteins associated with the highest number of different alleles
This study versus HLA association studies of disease severity
General features of the identified proteins
SARS-CoV-2 and COVID-19-related features of the identified proteins
Things-to-improve
Conclusion
Data availability
Appendix
References
10 - COVID-19 and the hyperferritinemic syndromes
References
11 - SARS-CoV-2 and microbiome: pathology, implications and therapeutic options
The microbiome, intestinal ecosystem, and immunoresistance: uniquely balanced
Intestinal immune cells
Signal pattern recognizing receptors
Microbiome functions
Gut microbiome dysbiosis and SARS-CoV-2
Dysbiosis and immune modulation of microbiota
SARS-CoV-2 and microbiota
Microbiome and therapeutic options in SARS-CoV-2 pandemic
Probiotic foods: microbiome restoration and supplementation
The role of probiotics in pathology correction
Modulation of the immune response through microbiota correction
Postvaccination immunity modulation through microbiota correction
Metabolic syndrome correction with probiotics
Impact of COVID-19 on mental health and the role of microbiota
Hyperreactive reactions and microbiota
SARS-CoV-2 associated respiratory syndrome and microbiome
Gastrointestinal pathology and COVID-19
The role of the microbiome in SARS-CoV-2 associated cytokine storm
Metabiotics: novel treatment strategies
Conclusion
References
12 - Molecular and immunological evidence for SARS-CoV-2 being the autoimmune virus
Introduction
Criteria no. 1: identification of cross-reactive epitopes between SARS-CoV-2 and human tissue
Criteria no. 2: reaction of animal and human monoclonal antibodies made against SARS-CoV-2 with human tissue antigens
Criteria no. 3: reaction of antibody to human autoantigens with SARS-CoV-2 proteins
Criteria no. 4: detection of autoantibodies against human tissue antigens in COVID-19 patients with different degrees of se ...
Conclusions
Acknowledgments
References
13 - Autoantibodies neutralizing antiinflammatory mediators in the context of SARS-CoV-2 infection and COVID-19
Hyperinflammation initiated by SARS-CoV-2
Autoantibodies in COVID-19
The break of peripheral immune tolerance in the context of SARS-CoV-2
Posttranslational modifications as triggers of neo-epitope formation and autoimmunity
Proinflammatory autoantibodies in the context of SARS-CoV-2
PGRN-antibodies and immunogenic isoform pSer81PGRN in the context of SARS-CoV-2
IL-1-Ra-antibodies and the immunogenic pThr111 isoform of IL-1-Ra in the context of SARS-CoV-2
Remaining questions around proinflammatory autoantibodies related to SARS-CoV-2
Acknowledgment
References
14 - What is common to MDA5 and COVID-19?
MDA5 receptor and anti-MDA5 autoantibody
What are the similarities between COVID-19 disease and anti-MDA5 dermatomyositis?
The pathophysiology of anti-MDA5 dermatomyositis and COVID-19
Immunomodulatory therapies for COVID-19 disease and anti-MDA5-positive CADM
Conclusion
References
15 - Humoral immunity and thrombosis in COVID-19
Introduction
Autoantibodies and thrombosis
Antiphospholipid antibodies
Antiplatelet factor 4 antibodies
Pro-inflammatory cytokines and thrombosis
The cytokine release syndrome
Cytokines and the endothelium
Cytokines and their effect on platelets and neutrophils
Cytokines and the coagulation cascade
Cytokines and altered fibrinolysis
Targeting the cytokine pathway
Complement activation: endothelial perturbation and interaction with the coagulation cascade
The role of complement
Complement and coagulation cascade
Complement in COVID-19
References
16 - Peripheral nervous system manifestations associated with COVID-19
Introduction
Invasion of SARS-CoV-2 to the nervous system
Neuropathology of SARS-CoV-2
Peripheral nervous system manifestations of SARS-CoV-2
Guillain–Barré syndrome
Cranial abnormalities
Myasthenia gravis
Myopathy and myositis
Conclusion
References
17 - Central nervous system impairments in COVID-19
SARS-CoV-2 infection and olfactory/gustatory disturbances
Acknowledgment
References
18 - Neuropsychiatric side of the COVID-19
Introduction
Pathogenesis
Proof of the COVID-19 invasion into the CNS
Mechanisms of SARS-CoV-2 impact on CNS
COVID-19-associated neuropsychiatric manifestations
Neuropsychiatric manifestations of COVID-19 infection
Delirium
Possible mechanisms of delirium
Delayed and long-term COVID-19-induced neuropsychiatric complications
Mood and anxiety disorders
Posttraumatic stress disorder (PTSD)
COVID-induced psychosis and catatonia
Post-COVID syndrome
Post-COVID syndrome and suicidality
Conclusion
References
19 - Myocarditis following vaccination with Pfizer-BioNTech BNT162b2 against coronavirus infection (COVID-19)
Background
Myocarditis following adult vaccination with two doses of Pfizer-BioNTech BNT162b2
Myocarditis in adolescents following vaccination with two doses of Pfizer-BioNTech BNT162b2
Myocarditis following adult vaccination with a third (booster) dose of Pfizer-BioNTech BNT162b2
mRNA-1273 (Moderna)
Mechanism of action of post-mRNA myocarditis
Myocarditis associated with additional vaccines
Summary
References
20 - Rheumatic manifestations and autoimmunity associated with COVID-19
Introduction
Pathophysiology of COVID-19 as a trigger of autoimmune disease
Rheumatic diseases
Axial SPA
Reactive arthritis and psoriatic arthritis
Rheumatoid arthritis and Still's disease
Viral arthralgia
Sjogren's disease
Lofgren's syndrome
Myositis
Systemic sclerosis
Chilblains
SLE—systemic lupus erythematosus
Hematological diseases
Evan's syndrome
Antiphospholipid antibodies
ITP
Aortic thrombosis
Endocrine diseases
Thyroid
Diabetes mellitus
Neurological diseases
Encephalitis and anti-NMDA receptor encephalitis
Guillain Barre syndrome
Movement disorders
Myasthenia gravis
Other nonrheumatic autoimmune diseases
Autoimmune hepatitis
Pemphigus vulgaris
References
Further reading
21 - SARS-CoV-2 induction and COVID-19 manifestations related to autoimmune gastrointestinal diseases
The COVID -19 pandemic: a short update
The human intestine is a target organ for SARS-CoV-2
Gastrointestinal manifestations of COVID-19
Pathophysiological aspects for SARS-CoV-2-Associated Gastrointestinal Illness
Compromising the beneficial functions of the ACE2 receptors
The saliva adds to the virus intestinal inoculation
The gut microbiome/dysbiome ratio is decreased
Intestinal self-defense and protective barriers are compromised
Tissue-specific patterns of SARS-CoV-2 variants and toll-like receptors (TLR)
The host ACE2, TMPRSS4, and NRP-1 receptors facilitate SARS-CoV-2 infectivity in the GI tract
The nucleotide-binding oligomerization domain 2 (NOD2)
Induction of a leaky gut
Inadequacy of butyrate, tryptophan, and vitamin D3 levels in COVID-19
Coronaviruses egress the host cells by lysosomal exocytosis and disrupt lysosomal and phagocytic functions
Post-COVID-19 gut manifestations
SARS-CoV-2 impact on gastrointestinal diseases
Inflammatory bowel disease (IBD)
Celiac disease (CD)
Conclusions
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References
22 - Multisystem inflammatory syndrome in children
Introduction
Epidemiology
Pathophysiology
Diagnostic approach
Clinical picture
Laboratory results
Microbiology
Radiologic examinations
Diagnosis
Differential diagnosis
Treatment
Immunomodulatory treatment
Immune globulin (IVIG)
Systemic glucocorticoids (GC)
Biologics—anakinra
Anticoagulant and antiplatelet therapy
Treatment targeting the affected organ system
Disease outcome
Reinfection and Mis-C
Vaccinations and Mis-C
Conclusion
References
23 - Anosmia in COVID-19 and post-COVID syndrome
Introduction
Epidemiology of anosmia in COVID-19 and PCS
Pathogenesis
The structure of the olfactory organ
Olfactory receptors (OR)
Pathogenesis of anosmia
Conclusion
References
24 - The effect of COVID-19 on patients with preexisting autoimmune diseases
Introduction
Preexisting autoimmune rheumatic diseases
General aspects
Autoimmune rheumatic diseases and factors that influence COVID 19
Age and gender
Races
Comorbidities
Drugs
Conventional synthetic disease-modifying antirheumatic drugs
Biologic or targeted synthetic disease-modifying antirheumatic drugs
COVID-19 in inflammatory arthritis
COVID 19 in rheumatoid arthritis
COVID-19 in spondyloarthropathies
COVID-19 in antiphospholipid syndrome
COVID-19 in systemic lupus erythematosus
COVID-19 in systemic sclerosis
COVID 19 in primary Sjogren syndrome
COVID 19 in vasculitis
Preexisting endocrine disorders and COVID-19
General aspects
COVID-19 in pituitary disorders
Hypothalamic–pituitary–adrenal axis
Hypothalamic–pituitary-gonadal axis
Hypothalamic–pituitary–thyroid axis
Preexisting pituitary condition, glands disorders, and COVID-19
COVID-19 in hypopituitarism and adrenal insufficiency
COVID-19 in autoimmune thyroids diseases
Autoimmune neurological disease and COVID-19
COVID-19 in multiple sclerosis
COVID-19 in autoimmune encephalitis
Experience in autoimmune diseases and COVID-19 in a single Mexican center
Conclusions
References
Further reading
25 - COVID-19 in patients with Systemic Lupus Erythematosus and the antiphospholipid syndrome
Introduction
COVID-19: the disease in SLE patients with or without APS/aPL
COVID-19 & SLE
COVID-19 & APS
COVID-19 & SLE/APS treatment
Pregnancy
COVID-19: vaccination SLE patients with or without APS/aPL
Immunogenicity and effectiveness of Covid-19 vaccines in SLE patients
Safety of Covid-19 vaccines in patients with SLE
Covid-19 vaccines & aPL
Covid-19 vaccines and pregnancy
Current recommendations by the American College of Rheumatology
Post-COVID and SLE/APS: similar manifestations
References
26 - Psoriatic arthritis and psoriasis in the era of COVID-19
Introduction
Psoriatic arthritis and psoriasis
Pathophysiology
Comorbidities
Metabolic syndrome
Diabetes mellitus type 2
Obesity
Treatment of psoriatic arthritis
Treatment of psoriasis
The SARS-CoV-2 virus
The SARS-CoV-2 pandemic
Risk factors for severe SARS-CoV-2 infection
Obesity and SARS-CoV-2 infection
Psoriatic disease and SARS-CoV-2
Psoriatic arthritis, psoriasis, and SARS-CoV-2 infection
Psoriatic arthritis, psoriasis treatment, and SARS-CoV-2
Psoriatic arthritis, psoriasis management in the COVID-19 pandemic
Protection from COVID-19 infection in psoriatic patients
Treatment of SARS-CoV-2 infection in psoriatic patients
Conclusion
References
27 - Thyroid autoimmunity and COVID-19
Introduction
Autoimmune thyroid diseases
Subacute thyroiditis
The SARS-CoV-2 virus
Mechanism of tissue invasion by the SARS-CoV-2 virus
Mechanism of autoimmunity induction
Autoimmune and inflammatory thyroid diseases and SARS-CoV-2
Subacute thyroiditis
Autoimmune thyroiditis
Graves' disease
Vaccination against SARS-CoV-2 and thyroid disease
Vaccines against SARS-CoV-2
Subacute thyroiditis in the context of the SARS-CoV-2 vaccine
Silent thyroiditis in the context of the SARS-CoV-2 vaccine
Graves' disease in the context of the SARS-CoV-2 vaccine
Mechanisms of thyroid disease in SARS-CoV-2
Conclusion
References
28 - Variation of the COVID-19 characteristics between genders
Introduction
Sex differences in severity and outcome of COVID-19
Comorbidities vary between sexes with consequences for the severity of COVID-19 infections
Sexual dimorphism in SARS-CoV-2 entry pathways
Sex hormone-dependent regulation of ACE2
Sex-dependent differences in the expression of transmembrane protease serine subtype 2 (TMPRSS2)
Sex-dependent dipeptidyl peptidase-4 (DPP4) activity
Hypothalamic–pituitary–adrenal (HPA) axis, sex hormones, and COVID-19
Sex discrepancies in the immune response to COVID-19
Sex-related differences in autoimmunity and COVID-19 vaccines
Sexual dimorphism and long COVID syndrome
Conclusions
References
29 - SARS-CoV-2, fertility-related autoantibodies and reproductive injury
Introduction
SARS-CoV-2 and male fertility
SARS-CoV-2 and female fertility
Mechanisms in which SARS-COV-2 may lead to infertility
ACE2 as a port of entry of SARS-CoV-2 into cells
Sex steroid hormonal abnormalities of SARS-CoV-2 infected patients
Oxidative stress induced by SARS-CoV-2
Molecular mimicry between SARS-CoV-2 and humans
Autoantibodies associated with infertility
References
Further reading
30 - Maternal and fetal issues in COVID-19-mediated thromboinflammation
Introduction
Possible etiopathogenetic mechanisms of thromboinflammation in COVID-19
Maternal–fetal–neonatal issues in COVID-19
Placenta
Fetus
Conclusion
References
31 - Animal models of COVID-19 and complications
Introduction
Animal species used for SARS-CoV-2 infection
Modeling of COVID-19 infection, rodents
Rodents
Mice
Syrian hamsters
Carnivora
Ferrets
Modeling of COVID-19 infection, nonhuman primates
Rhesus macaques
Modeling postacute COVID-19 infection (long covid), rodents
Acknowledgments
References
32 - Risk assessment for aerosol infection by SARS-CoV-2 and protection by respirators and surgical masks
Background
What are the conditions for aerosol infection?
How are these conditions pertain to SARS-CoV-2
Airborne transmission as the dominant route for the spread of COVID-19
Masks and respirators for protection against airborne infection
SARS-CoV-2 transmission and infection with or without masks in closed places and the home
The risk of SARS-CoV-2 transmission from patients to hospital roommates
Universal masking in a health care system and SARS-CoV-2 infection among healthcare workers (HCW)
Effectivity of face masks in limiting particle dissemination and the probability of SARS-CoV-2 transmission
Masks for prevention of respiratory viral infections
The added value of face shields in preventing infections in the community and hospital
Concluding remarks
References
Further reading
33 - Therapeutic options in COVID-19
Overview
Antiviral medications
Passive immunization
Anticoagulation
Immunomodulation
Respiratory support
References
34 - Intravenous immunoglobulin and convalescent plasma treatment in the COVID-19 patient
Introduction
Immunological effect of IVIg in COVID-19
IVIg as possible therapeutical approach for COVID-19
Convalescent plasm: lights and shadows
IVIg in autoimmune disorders induced by SARS-CoV-2
Neurological disorders after SARS-CoV-2 infection
Guillain-Barré Syndrome (GBS)
Acute disseminated encephalomyelitis (ADEM)
Myasthenia gravis
Hematological autoimmune disorders after COVID-19 infection
Immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA)
Fisher Evans syndrome
Pemphigus
Autoimmune diseases related to COVID-19 vaccine
Neurological disorders
Hematological disorders
References
35 - Interaction between vitamin D deficiency and COVID-19
Introduction to vitamin D
Vitamin D and the immune system
Brief overview of the immune system
The immunological effects of vitamin D
Causes of vitamin D deficiency
Factors that compromise the cutaneous synthesis of vitamin D
Factors that decrease the intake and absorption of vitamin D
Factors that alter the metabolism of vitamin D
COVID-19 and vitamin D deficiency
Susceptibility for SARS-CoV-2 infection and vitamin D status
COVID-19 disease severity and vitamin D status
Long COVID and vitamin D status
Vitamin D supplementation in COVID/long COVID patients
COVID vaccine and vitamin D—is there a relationship?
Recommendations
References
36 - Side effects of the COVID-19 vaccines
Introduction
Vaccines
Vaccines: mechanism of the immune response
Vaccines: molecular structure
Types of vaccines anti-COVID-19
Adjuvants
Autoimmune/inflammatory syndrome (ASIA) induced by vaccines
Covid-19 vaccination
Rheumatologic adverse effects
Cardiovascular adverse effects
Endocrine adverse effects
Dermatologic adverse effects
Hematological adverse effects
Nephrological adverse effects
Neurological adverse effects
Other adverse effects
Discussion
Conclusion
References
37 - The post-COVID syndrome
Long COVID or post-COVID-19 syndrome: background and current case definition
Epidemiology
Clinical symptoms of the post-COVID patients
Pathophysiological hypotheses of the post-COVID syndrome
Novel coronavirus infection and autoimmunity
The role of small fiber neuropathy in the development of post-COVID syndrome
The role of macro- and microcirculation disorders in the pathogenesis of post-COVID syndrome
Differential diagnosis
Conclusion
References
38 - Disease course and pathogenesis of post-COVID-19 condition
Post-COVID-19 condition: disease course
Post-COVID-19 condition: disease course probable links of pathogenesis
Neuroinvasion of SARS-CoV-2
Immune-related mechanisms
Vascular mechanisms
Autonomic dysfunction
Endocrine mechanisms
References
39 - Long-term assessment of autoantibodies in post-COVID syndrome
Antibodies to the autonomic nervous system in patients with post-COVID-19 syndrome
Post-COVID-19 syndrome, rheumatological diseases, and antibodies to the components of the immune system
Possible causes of autoantibodies production in the post-COVID-19 condition
Conclusion
References
40 - Post-COVID-19 syndrome and fibromyalgia
References
41 - Treatment and prevention of the post-COVID syndrome
Principles of treatment of the post-COVID syndrome
Immunological manifestations of post-COVID-19 syndrome
Neurological complications of the COVID-19
Internal organ dysfunction in patients with post-COVID-19 condition
Conclusion
References
Index
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