[POST-COVID SYNDROME, SICK BUILDING SYNDROME, SILICONE BREAST SYNDROME, CHRONIC FATIGUE SYNDROME, FIBROMYALGIA; AUTOIMMUNITY TO THE AUTONOMIC NERVOUS SYSTEM].

INTRODUCTION: POST-COVID SYNDROME, SICK BUILDING SYNDROME, SILICONE BREAST SYNDROME, CHRONIC FATIGUE SYNDROME, FIBROMYALGIA; AUTOIMMUNITY TO THE AUTONOMIC NERVOUS SYSTEM.

[Post-Covid Syndrome, Sick Building Syndrome, Silicone Breast Syndrome, Choric Fatigue Syndrome, Fibromyalgia -Autoimmunity to the Autonomic Nervous System].

INTRODUCTION: Post-Covid Syndrome, Sick Building Syndrome, Silicone Breast Syndrome, Choric Fatigue Syndrome, Fibromyalgia -Autoimmunity to the Autonomic Nervous System.

Anti-TPO-mediated specific features of the placenta immunohistochemical profile and possible mechanisms for fetal loss.

Passive transfer of antithyroid antibodies in mice leads to reproductive disorders. The purpose was to assess the placental tissue of experimental animals under the influence of the circulating thyroperoxidase antibodies. We performed an immunohistochemical examination of murine placentae after a passive transfer of thyroperoxidase antibodies. Placentae of mice that passively transferred IgG from healthy donors were used as control samples. For histological examination, 30 placental samples were selected from mice from the anti-TPO group and 40 placental samples were taken from mice from the IgG group. Immunostaining for VEGFR1, THBS 1, Laminin, CD31, CD34, FGF-ß, CD56, CD14, TNF-α, kisspeptin, MCL 1, and Annexin V was performed. There is a significant decrease in the relative area of the expression of VEGFR1 (23.42 ± 0.85 vs. 33.44 ± 0.35, P < 0.01), thrombospondin 1 (31.29 ± 0.83 vs. 34.51 ± 0.75, P < 0.01), CD14 (25.80 ± 0.57 vs. 32.07 ± 0.36, P < .01), CD56 (30.08 ± 0.90 vs. 34.92 ± 0.15, P < 0.01), kisspeptin (25.94 ± 0.47 vs. 31.27 ± 0.57, P < 0.01), MCL 1 (29.24 ± 1.06 vs. 38.57 ± 0.79, P < 0.01) in the labyrinth zone of the placentae of mice from the anti-TPO group compared with control group. A significant increase in the relative expression of laminin and FGF-ß was noted in the group of mice to which antibodies to thyroperoxidase were transferred, compared with the control group (36.73 ± 1.38 vs. 29.83 ± 0.94, P < 0.01 and 23.26 ± 0.61 vs. 16.38 ± 1.01, P < 0.01respectively). Our study exposed an imbalance of pro- and anti-angiogenic factors, decreased representation of placental macrophages and NK cells, abnormal trophoblast invasion processes, and insufficient expression of antiapoptotic factors in the placentae of mice in which anti-TPO antibodies were passively transferred.

The persistent viral infections in the development and severity of myalgic encephalomyelitis/chronic fatigue syndrome.

BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a multifactorial disease with an unexplained aetiology in which viral infections are possible trigger factors. The aim of this study was to determine the involvement of human herpesvirus (HHV)-6A/B, HHV-7, and parvovirus B19 (B19V) in the etiopathogenesis of ME/CFS. METHODS: 200 patients with clinically diagnosed ME/CFS and 150 apparently healthy individuals were enrolled in this study. Single-round, nested, and quantitative real-time polymerase chain reactions (PCR) were used to detect the presence and load of HHV-6A/B, HHV-7, and B19V. HHV-6A and HHV-6B were distinguished by PCR and restriction analysis. Immunoenzymatic assays were applied to estimate the presence of virus-specific antibodies and the level of cytokines. RESULTS: HHV-6A/B, HHV-7, and B19V specific antibodies were detected among patients and healthy individuals in 92.1% and 76.7%, 84.6% and 93.8%, and 78% and 67.4% of cases. HHV-6B had 99% of HHV-6 positive patients. Latent HHV-6A/B, HHV-7, and B19V infection/co-infection was observed in 51.5% of the patients and 76.7% of the healthy individuals, whereas active-45% of the ME/CFS patients and 8.7% of healthy individuals. HHV-6A/B load in patients with a persistent infection/co-infection in a latent and active phase was 262 and 653.2 copies/106 cells, whereas HHV-7 load was 166.5 and 248.5 copies/106 cells, and B19V-96.8 and 250.8 copies/106 cells, respectively. ME/CFS patients with persistent infection in an active phase had a higher level of pro-inflammatory cytokines (interleukin(IL)-6, tumor necrosis factor-alpha(TNF-α) and IL-12) and anti-inflammatory (IL-10) than with a persistent infection in a latent phase. A significant difference was revealed in the levels of TNF-α, IL-12, and IL-10 among the patient groups without infection, with latent infection/co-infection, active single, double and triple co-infection. The levels of TNF-α, IL-12, and IL-10 are significantly higher in patients with severe compared with a moderate course of ME/CFS. CONCLUSIONS: Significantly more persistent HHV-6A/B, HHV-7, and B19V infection/co-infection in an active phase with a higher viral load and elevated levels of pro- and anti-inflammatory cytokines among patients with ME/CFS than healthy individuals indicate the importance of these infections/co-infections in ME/CFS development. The presence of these infections/co-infections influences the ME/CFS clinical course severity.

Cross-sectional analysis reveals autoantibody signatures associated with COVID-19 severity.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with increased levels of autoantibodies targeting immunological proteins such as cytokines and chemokines. Reports further indicate that COVID-19 patients may develop a broad spectrum of autoimmune diseases due to reasons not fully understood. Even so, the landscape of autoantibodies induced by SARS-CoV-2 infection remains uncharted territory. To gain more insight, we carried out a comprehensive assessment of autoantibodies known to be linked to diverse autoimmune diseases observed in COVID-19 patients in a cohort of 231 individuals, of which 161 were COVID-19 patients (72 with mild, 61 moderate, and 28 with severe disease) and 70 were healthy controls. Dysregulated IgG and IgA autoantibody signatures, characterized mainly by elevated concentrations, occurred predominantly in patients with moderate or severe COVID-19 infection. Autoantibody levels often accompanied anti-SARS-CoV-2 antibody concentrations while stratifying COVID-19 severity as indicated by random forest and principal component analyses. Furthermore, while young versus elderly COVID-19 patients showed only slight differences in autoantibody levels, elderly patients with severe disease presented higher IgG autoantibody concentrations than young individuals with severe COVID-19. This work maps the intersection of COVID-19 and autoimmunity by demonstrating the dysregulation of multiple autoantibodies triggered during SARS-CoV-2 infection. Thus, this cross-sectional study suggests that SARS-CoV-2 infection induces autoantibody signatures associated with COVID-19 severity and several autoantibodies that can be used as biomarkers of COVID-19 severity, indicating autoantibodies as potential therapeutical targets for these patients.

COVID-19 and SLE: Infection and autoimmunity at its best.

If one had any doubts before the pandemic regarding the correlation between infections and autoimmunity, COVID-19 left us fascinated on the strong bond between the two entities. The immune and autoimmune reactions seen in patients infected with SARS-CoV-2 have served as a base for this assumption. Later on, the use of immunosuppressants such as systemic glucocorticoids, among other biological agents, turned this assumption to a fact. This was no different when it comes to the vaccines against COVID-19. Through several postulated mechanisms these vaccines, although generally considered safe, are thought to have the potential to result in autoimmune reactions making them not more innocent than the infection itself. When systemic lupus erythematous (SLE) is viewed as a classical autoimmune multisystemic disorder, the connection with SARS-CoV-2 infection and COVID-19 vaccination is of extreme importance. This is because early reports during the pandemic have shown increased rates of SARS-CoV-2 infection among patients known previously to have SLE and much more interestingly, cases of new-onset SLE after COVID-19 have been documented in the literature. Subsequently vaccines against COVID-19, those mRNA-based and adenovirus-vector based, were reported to induce new SLE cases, trigger immune thrombocytopenia or lupus nephritis, two common presentations of SLE, or exacerbate flares. In our paper, we concluded various aspects of available and recent data regarding SLE and COVID-19 as both an infection and vaccination.

Primary antiphospholipid syndrome with and without limb ischemia: A retrospective observational study.

OBJECTIVE: To compare clinical and laboratory data obtained from patients with primary Antiphospholipid Syndrome (PAPS) with and without limb ischemia (LI). METHODS: A transverse study with 66 (83.3% female) PAPS patients was performed. All data were evaluated. Patients were subdivided into one of two groups: PAPS with LI and PAPS without LI and compared. RESULTS: Sixty-six primary APS were selected. PAPS with LI group exhibited a longer disease duration (p = .012) and more arterial events (p = .002). A lower frequency of venous events was observed in PAPS with LI (p = .007), and deep venous thrombosis (p = .016). Furthermore, PAPS with LI patients had more deficiency of protein C of coagulation (p = .015) than the others. CONCLUSION: PAPS and LI have a distinct clinical and laboratory spectra from those without LI and it is characterized by an increased frequency of protein C deficiency, and a lower frequency of venous events, deep venous thrombosis and IgM anticardiolipin.

Primary antiphospholipid syndrome as a cause of impaired left ventricular diastolic function: experience from a Serbian cohort.

OBJECTIVES: Cardiovascular manifestations, encountered in antiphospholipid syndrome, may develop as a consequence of acquired thrombophilia mediated by antiphospholipid antibodies and accelerated atherosclerosis as well. Our study aims to assess the impairment of the left ventricular diastolic performance, as early evidence of myocardial involvement in primary antiphospholipid syndrome (PAPS). METHODS: We analysed 101 PAPS patients, with the average age of 47.70±13.14y. Anticardiolipin antibodies (aCL IgG/IgM), anti-ß2 glycoprotein-I (anti-ß2GPI IgG/IgM), and lupus anticoagulant (LAC) were determined. Abnormal cut-off values used for left ventricular diastolic dysfunction (LVDD) were septal E ́<7 cm/sec, lateral E ́ <10 cm/sec, average E/E ́ ratio >14, LA volume index (LAVI) >34 mL/m2, and peak tricuspid regurgitation velocity >2.8 m/sec. LVDD was present if more than half parameters were with abnormal values. The results were compared to 90 healthy, age and sex-matched controls. RESULTS: LVDD was significantly more prevalent in PAPS patients compared to healthy controls (24.8% vs. 2.2%, p=0.001). In PAPS patients, it was signi cantly related to age, body mass index, hyperlipidaemia, thromboses and LAC positivity (p=0.0001, p=0.008, p=0.039, p=0.001, p=0.047 respectively). Patients with PAPS had higher LAVI (29.76±6.40 ml/m2 vs. 26.62±7.8 ml/m2, p=0.012), higher isovolumic relaxation time, lower lateral É velocity and lower E/É ratio compared to controls (p=0.0001, p=0.020, p=0.038, respectively). In multivariate analysis, thromboses in PAPS were significant, and independent predictors of LVDD. CONCLUSIONS: Thrombotic PAPS patients are at higher risk of LVDD development. Strong action against standard atherosclerotic risk factors and adequate therapy regimes seems to be crucial to preserve good diastolic performance of the left ventricle in PAPS.

Humoral Response of Different Types of SARS-CoV-2 Vaccines in Patients with Autoimmune Rheumatic Diseases: Experiences from a Serbian Cohort.

BACKGROUND: Data are scarce on the immunogenicity of coronavirus disease 2019 vaccines in patients with autoimmune rheumatic diseases (ARD). OBJECTIVES: To measure the immunoglobulin G (IgG) response after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization and to evaluate clinical characteristics associated with seropositivity. METHODS: Samples were collected after the second and third doses of the three different types of vaccines in ARD patients. Seroconversion rates and IgG antibody S1/S2 titers were measured. RESULTS: The type of ARD diagnosis and previous treatment had no significant impact on the serum IgG antibody levels measured after the second (P = 0.489 and P = 0.330, respectively) and boost dose (P = 0.441 and P = 0.446, respectively). What made a significant difference regarding serum IgG antibody levels after the second dose was the type of SARS-CoV-2 vaccine. The difference was highly statistically significant for all vaccine types (P = 0.001 with the highest odds ratio for the mRNA vaccine). After the boost with the mRNA vaccine, all patients achieved a high level of serum IgG antibody levels (t = 10.31, P = 0.001). No ARD patients experienced serious post-vaccinal reactions. Eight patients developed COVID-19 before the boost dose. CONCLUSIONS: In ARDs patients, the highest level of serum IgG antibody against S1/S2 proteins was achieved with the mRNA vaccine, irrespective of the therapy applied or the type of the disease. We recommend a booster dose with mRNA vaccine in all ARDs for the highest SARS-CoV-2 protection without serious post-vaccinal reactions observed.

Possible Association Between Anti-Trisulfated-Heparin-Disaccharide (TS-HDS) Immunoglobulin M Autoantibody and Fibromyalgia Syndrome.

BACKGROUND: Fibromyalgia syndrome (FMS) is estimated to affect 2-4% of the general population. While FMS has some known environmental and genetic risk factors, the disorder has no clear etiology. A common coexisting disorder with FMS is small fiber neuropathy (SFN). High levels of serum immunoglobulin M (IgM) binding to trisulfated-heparin-disaccharide (TS-HDS) were recently found to be associated with SFN. OBJECTIVES: To evaluate potential differences in anti-TS-HDS antibody titers in women with FMS compared to healthy controls. METHODS: In this cross-sectional study, we evaluated 51 female participants: 30 with a diagnosis of FMS and 21 healthy controls who had been recruited at the Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Israel. All of the participants were older than 18 years of age. Anti-TS-HDS IgM levels were measured in their sera using the enzyme immunoassay technique. RESULTS: The mean anti-TS-HDS IgM levels were significantly lower in the FMS group, compared with the control group (7.7 ± 5 vs. 13.2 ± 8.6 U/ml, respectively; P = 0.013). CONCLUSIONS: There is a possible association between FMS and anti-TS-HDS IgM. This association might be the missing link for the coexistence of SFN and FMS, but further study should be performed to assess this association and this auto-antibody characteristic.

The Prognostic Value of Anti-PLA2R Antibodies Levels in Primary Membranous Nephropathy.

Anti-PLA2R antibodies (Ab) are a diagnostic and prognostic biomarker in primary membranous nephropathy (PMN). We assessed the relationship between the levels of anti-PLA2R Ab at diagnosis and different variables related to disease activity and prognosis in a western population of PMN patients. Forty-one patients with positive anti-PLA2R Ab from three nephrology departments in Israel were enrolled. Clinical and laboratory data were collected at diagnosis and after one year of follow-up, including serum anti-PLA2R Ab levels (ELISA) and glomerular PLA2R deposits on biopsy. Univariable statistical analysis and permutation-based ANOVA and ANCOVA tests were performed. The median [(interquartile range (IQR)) age of the patients was 63 [50-71], with 28 (68%) males. At the time of diagnosis, 38 (93%) of the patients had nephrotic range proteinuria, and 19 (46%) had heavy proteinuria (≥8 gr/24 h). The median [IQR] level of anti-PLA2R at diagnosis was 78 [35-183] RU/mL. Anti-PLA2R levels at diagnosis were correlated with 24 h proteinuria, hypoalbuminemia and remission after one year (p = 0.017, p = 0.003 and p = 0.034, respectively). The correlations for 24 h proteinuria and hypoalbuminemia remained significant after adjustment for immunosuppressive treatment (p = 0.003 and p = 0.034, respectively). Higher levels of anti-PLA2R Ab at diagnosis in patients with active PMN from a western population are associated with higher proteinuria, lower serum albumin and remission one year after the diagnosis. This finding supports the prognostic value of anti-PLA2R Ab levels and their possible use in stratifying PMN patients.

Impact of Antithyroperoxidase Antibodies (Anti-TPO) on Ovarian Reserve and Early Embryo Development in Assisted Reproductive Technology Cycles.

Autoimmune thyroid disease (AITD) is one of the most common endocrinopathies and is more prevalent in women. It becomes evident that the circulating antithyroid antibodies that often follow AITD have effects on many tissues, including ovaries, and therefore that this common morbidity might have an impact on female fertility, the investigation of which is the aim of the present research. Ovarian reserve, ovarian response to stimulation and early embryo development in infertile patients with thyroid autoimmunity were assessed in 45 women with thyroid autoimmunity and 45 age-matched control patients undergoing infertility treatment. It was demonstrated that the presence of anti-thyroid peroxidase antibodies is associated with lower serum anti-Müllerian hormone levels and antral follicle count. Further investigation revealed the higher prevalence of sub-optimal response to ovarian stimulation in TAI-positive women, lower fertilization rate and lower number of high-quality embryos in this group of patients. The cut-off value for follicular fluid anti-thyroid peroxidase antibody affecting the above-mentioned parameters was determined to be 105.0 IU/mL, highlighting the necessity of closer monitoring in couples seeking infertility treatment with ART.

Ferritin - from iron, through inflammation and autoimmunity, to COVID-19.

While it took decades to arrive to a conclusion that ferritin is more than an indicator of iron storage level, it took a short period of time through the COVID-19 pandemic to wonder what the reason behind high levels of ferritin in patients with severe COVID-19 might be. Unsurprisingly, acute phase reactant was not a satisfactory explanation. Moreover, the behavior of ferritin in patients with severe COVID-19 and the subsequent high mortality rates in patients with high ferritin levels necessitated further investigations to understand the role of ferritin in the diseases. Ferritin was initially described to accompany various acute infections, both viral and bacterial, indicating an acute response to inflammation. However, with the introduction of the hyperferritinemic syndrome connecting four severe pathological conditions such as adult-onset Still's disease, macrophage activation syndrome, catastrophic antiphospholipid syndrome, and septic shock added another aspect of ferritin where it could have a pathogenetic role rather than an extremely elevated protein only. In fact, suggesting that COVID-19 is a new member in the spectrum of hyperferritinemic syndrome besides the four mentioned conditions could hopefully direct further search on the pathogenetic role of ferritin. Doubtlessly, improving our understanding of those aspects of ferritin would enormously contribute to better coping with severe diseases in terms of treatment and prevention of complications. The origin, history, importance, and the advances of searching the role of ferritin in various pathological and clinical processes are presented hereby in our article. In addition, the implications of ferritin in COVID-19 are addressed.

Comparative safety of mRNA COVID-19 vaccines to influenza vaccines: A pharmacovigilance analysis using WHO international database.

Two messenger RNA (mRNA) vaccines developed by Pfizer-BioNTech and Moderna are being rolled out. Despite the high volume of emerging evidence regarding adverse events (AEs) associated with the COVID-19 mRNA vaccines, previous studies have thus far been largely based on the comparison between vaccinated and unvaccinated control, possibly highlighting the AE risks with COVID-19 mRNA vaccination. Comparing the safety profile of mRNA vaccinated individuals with otherwise vaccinated individuals would enable a more relevant assessment for the safety of mRNA vaccination. We designed a comparative safety study between 18 755 and 27 895 individuals who reported to VigiBase for adverse events following immunization (AEFI) with mRNA COVID-19 and influenza vaccines, respectively, from January 1, 2020, to January 17, 2021. We employed disproportionality analysis to rapidly detect relevant safety signals and compared comparative risks of a diverse span of AEFIs for the vaccines. The safety profile of novel mRNA vaccines was divergent from that of influenza vaccines. The overall pattern suggested that systematic reactions like chill, myalgia, fatigue were more noticeable with the mRNA COVID-19 vaccine, while injection site reactogenicity events were more prevalent with the influenza vaccine. Compared to the influenza vaccine, mRNA COVID-19 vaccines demonstrated a significantly higher risk for a few manageable cardiovascular complications, such as hypertensive crisis (adjusted reporting odds ratio [ROR], 12.72; 95% confidence interval [CI], 2.47-65.54), and supraventricular tachycardia (adjusted ROR, 7.94; 95% CI, 2.62-24.00), but lower risk of neurological complications such as syncope, neuralgia, loss of consciousness, Guillain-Barre syndrome, gait disturbance, visual impairment, and dyskinesia. This study has not identified significant safety concerns regarding mRNA vaccination in real-world settings. The overall safety profile patterned a lower risk of serious AEFI following mRNA vaccines compared to influenza vaccines.

The clinical significance of low complement levels in patients with catastrophic antiphospholipid syndrome: A descriptive analysis of 73 patients from the "Catastrophic antiphospholipid syndrome registry".

OBJECTIVES: To explore the prevalence and clinical significance of low complement levels in patients with catastrophic antiphospholipid syndrome (CAPS). METHODS: We reviewed data from the "CAPS Registry" on C3 and/or C4 complement plasma protein levels during acute CAPS episodes. Patients were classified into those with low and normal complement levels. Data on clinical presentation, with special focus on thrombotic microangiopathy (TMA) features, diagnosis of systemic lupus erythematosus (SLE), and antiphospholipid antibody (aPL) profile were reviewed. The chi-square exact test was performed to evaluate differences between categorical data. RESULTS: The "CAPS Registry" includes 566 patients with a total of 578 episodes of CAPS. Data on complement plasma protein levels was available in 73 episodes from the same number of patients. Low levels of C3 and/or C4 complement plasma proteins were detected in 42 (58%) CAPS episodes. Low complement levels were more common in SLE patients (55% SLE vs. 19% No SLE; p<0.001). The frequencies of clinical TMA (72% vs. 80%; p=0.4) or TMA syndrome (86% vs. 84%, p=0.9), frequency of triple aPL triple positivity (67% vs 33%; p=0.3), or the mortality (35% vs. 31%; p=0.7) were similar between low and normal complement groups. CONCLUSION: In our study, low levels of C3 and C4 plasma proteins are detected in 58% episodes of CAPS, which were not associated with clinical presentation including TMA features, aPL triple positivity, or mortality.

The Effect of Exercise on Neurogenesis in the Brain.

BACKGROUND: The connection between physical exercise and the brain has long been studied. The evidence showing that physical exercise plays a significant role on neurogenesis and cognitive function has primarily been based on research examining aerobic exercise. In this review, we described three exercise modalities: aerobic, anaerobic, and resistance exercise and their impact on brain plasticity and cognitive function. While each of these exercise modalities have been demonstrated to positively influence brain plasticity and cognitive function, the specific mechanism that stimulates these changes appear to differ to some degree between these training modalities. The effect of aerobic and anaerobic exercise appears to be primarily mediated by changes in expression of brain-derived neurotrophic factor (BDNF), lactate, vascular endothelial growth factor (VEGF), and several additional proteins within the brain. However, resistance exercise appears to influence brain plasticity by myokines such as irisin, insulin-growth factor-1 (IGF1), and BDNF that are secreted from skeletal tissue and stimulate neurogenesis within the brain. In addition to the various training modes, manipulation of various acute program variables such as intensity, volume, and rest intervals leads to numerous possible training paradigms that can provide a different stimulus for neurogenesis. This review focuses on the three primary training modes and their connection to neurogenesis and cognitive function.

[ERYTHROCYTE SEDIMENTATION RATE - PURPOSEFUL REVIEW FOR CLINICAL APPLICATION].

INTRODUCTION: This is a review article which examines the use of erythrocyte sedimentation rate (ESR) compared to C-reactive protein in current medicine. The objective is to review and present a purposeful description of the medical literature in the question of the specificity and sensitivity of each of the markers in many common diseases. Described are normal ESR, the methods' limitations, and the etiologies of high and low ESR. Additionally, explained are the implementation and measurement of bedside ESR and factors which distort the results.

Influenza infection, SARS, MERS and COVID-19: Cytokine storm - The common denominator and the lessons to be learned.

The outbreak of COVID-19 reminds us that the emerging and reemerging respiratory virus infections pose a continuing threat to human life. Cytokine storm syndromes of viral origin seem to have a common pathogenesis of the imbalanced immune response with the exaggerated inflammatory reaction combined with the reduction and functional exhaustion of T cells. Immunomodulatory therapy is gaining interest in COVID-19, but this strategy has received less attention in other respiratory viral infections than it deserved. In this review we suggest that based on the similarities of the immune dysfunction in the severe cases of different respiratory viral infections, some lessons from the immunomodulatory therapy of COVID-19 (particularly regarding the choice of an immunomodulatory drug, the selection of patients and optimal time window for this kind of therapy) could be applied for some cases of severe influenza infection and probably for some future outbreaks of novel severe respiratory viral infections.

Perspectives on vaccine induced thrombotic thrombocytopenia.

As the novel SARS-CoV-2 continues to infect numerous individuals worldwide, one of the leading approaches in dealing with the global health crisis is vaccination against the COVID-19. Due to recent reports, vaccination with ChAdOx1 nCov-19 (developed by Oxford and AstraZeneca) may result in a vaccine-induced catastrophic thrombotic thrombocytopenia disorder. Thus, as of March 16 of 2021, vaccination programs in 18 countries had been suspended until further examination, including Sweden, Germany and France. This disorder presents as extensive thrombosis in atypical sites, primarily in the cerebral venous, alongside thrombocytopenia and the production of autoantibody against platelet-factor 4 (PF4). PF4 autoantibody has the ability to binds the human FcRγIIA receptor of platelets and contribute to their aggregation. This rare adverse effect extremely resembles the clinical presentation of the classical immune-mediated HIT disorder, which occurs following exposure to heparin. Surprisingly, none of these patients had been pre-exposed to heparin before disease onset, leading to the hypothesis that a viral antigen from the vaccine had triggered the response. Importantly, COVID-19 had been associated with numerous autoimmune manifestations, including the production of pathogenic autoantibodies, new onset of autoimmune diseases and disorders. As the ChAdOx1 nCov-19 vaccination leads to the synthesis of specific SARS-CoV-2-proteins, they may trigger a production of PF4 autoantibody though molecular mimicry phenomena, while vaccination compounds lead to a rigorous bystander activation of immune cells. If existing, removing such homological sequences from the vaccine may eliminate this phenomenon. In contrast, it needs to be emphasized that the ChAdOx1 nCoV-19 vaccine was found to be safe and efficacious against symptomatic COVID-19 in randomized controlled trials, which included 23,848 participants from the UK, Brazil and South Africa.

Autoimmune dysautonomia in women with silicone breast implants.

IMPORTANCE AND OBJECTIVES: There is unmet medical need to understand the pathogenic mechanism of the panoply of clinical manifestations associated with silicone breast implants (SBIs) such as severe fatigue, widespread pain, palpitations, dry mouth and eyes, depression, hearing loss etc. We aimed to determine whether autoantibodies against the autonomic nervous system receptors can explain the enigmatic and subjective clinical manifestation reported by women with SBIs. RESULTS: Circulating level of autoantibodies against G protein-coupled receptors (GPCRs) of the autonomic nervous system (adrenergic, muscarinic, endothelin and angiotensin receptors) have been evaluated in symptomatic women with SBIs using an ELISA method. These women with SBIs addressed our clinic due to various subjective and autonomic-related manifestations such as chronic severe fatigue, cognitive impairment, widespread pain, memory loss, sleep disorders, palpitations, depression, hearing abnormalities etc. We report for the first time, a significant reduction in the sera level of anti-ß1 adrenergic receptor (p < 0.001), anti-angiotensin II type 1 receptor (p < 0.001) and anti-endothelin receptor type A (p = 0.001) autoantibodies in women with SBIs (n = 93) as compared with aged matched healthy women (n = 36). Importantly, anti-ß1 adrenergic receptor autoantibody was found to significantly correlate with autonomic-related manifestations such as: sleep disorders and depression in women with SBIs. CONCLUSIONS: Chronic immune stimulation by silicone material may lead to an autoimmune dysautonomia in a subgroup of potentially genetically susceptible women with SBIs. The appearance of autoantibodies against GPCRs of the autonomic nervous system serve as an explanation for the subjective autonomic-related manifestations reported in women with SBIs.