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Could Sars-coronavirus-2 trigger autoimmune and/or autoinflammatory mechanisms in genetically predisposed subjects?
... In addition, it has been noted that some patients who have COVID-19 infection go on to acquire autoimmune disorders including systemic lupus erythematosus. [9][10][11][12] We present a case of onset of Type I Diabetes followed by plaque morphea in a child after the COVID-19. ...
... Morphea is an uncommon inflammatory connective tissue disease that affects 4 to 27 new cases per million individuals each year. Morphea is shown to have 2 incidence peaks: one occurs in the fifth decade of life, and the other occurs between the ages of 2 and 14. 9,10 Autoimmunity manifestation and COVID-19 have a complicated and nuanced interaction. [9][10][11] Problems may arise when morphea is diagnosed via COVID-19. ...
... Morphea is shown to have 2 incidence peaks: one occurs in the fifth decade of life, and the other occurs between the ages of 2 and 14. 9,10 Autoimmunity manifestation and COVID-19 have a complicated and nuanced interaction. [9][10][11] Problems may arise when morphea is diagnosed via COVID-19. Infection and autoinflammatory response have pathogenesis-based connections. ...
Morphea, is a chronic inflammatory disease of the dermis and subcutaneous tissue. Research has indicated a connection between morphea and Type I Diabetes (T1D). COVID-19 can cause autoimmune diseases like scleroderma, T1D, systemic lupus erythematosus, and others. A 12-year-old girl with type 1 diabetes who was on insulin therapy was brought into the clinic for a metabolic evaluation. The patient had induration, skin hardness, and cutaneous erythema upon inspection. The onset of T1D was following a mild COVID-19 infection. Signs of morphea merged 3 months after the onset of T1D. Known as “long-term COVID,” this sickness phase that follows the acute stage of COVID-19 is most likely the result of autoimmune activation. As this patient under evaluation reveals, COVID-19 has been demonstrated in the literature to cause the production of autoantibodies and to either cause or worsen autoimmune disorders in people who have a genetic susceptibility.
... Based on different studies, the incidence of COVID-19 vaccine related myocarditis has had a range from 0.08 to 3.72 cases per 100,000 individuals [61][62][63][64][65][66][67][68][69][70]. This is due to different diagnostic methods based on ICD codes [62][63][64], clinician reports [65], and reports to the Vaccine Adverse Events Reporting System [66]. ...
... Based on different studies, the incidence of COVID-19 vaccine related myocarditis has had a range from 0.08 to 3.72 cases per 100,000 individuals [61][62][63][64][65][66][67][68][69][70]. This is due to different diagnostic methods based on ICD codes [62][63][64], clinician reports [65], and reports to the Vaccine Adverse Events Reporting System [66]. Another etiology for this range can be due to various patient populations from each study [64,66]. ...
... One proposed mechanism for vaccine-induced myocarditis involves the immune system's response to the mRNA in the vaccine, leading to the activation of inflammatory pathways [61,62]. This immune response may be influenced by genetic factors, such as higher androgen levels in males [63], which may explain the observation of higher incidence in higher males. ...
Purpose of Review
This review examines the pathophysiological interactions between COVID-19 and heart failure, highlighting the exacerbation of heart failure in COVID-19 patients. It focuses on the complex mechanisms driving worse outcomes in these patients.
Recent Findings
Patients with pre-existing heart failure experience more severe symptoms and higher mortality rates due to mechanisms such as cytokine storms, myocardial infarction, myocarditis, microvascular dysfunction, thrombosis, and stress cardiomyopathy. Elevated biomarkers like troponin and natriuretic peptides correlate with severe disease. Long-term cardiovascular risks for COVID-19 survivors include increased incidence of heart failure, non-ischemic cardiomyopathy, cardiac arrest, and cardiogenic shock.
Summary
COVID-19 significantly impacts patients with pre-existing heart failure, leading to severe symptoms and higher mortality. Elevated cardiac biomarkers are indicators of severe disease. Acute and long-term cardiovascular complications are common, calling for ongoing research into targeted therapies and improved management strategies to better prevent, diagnose, and treat heart failure in the context of COVID-19.
... Te pathways implicated in the pathogenesis of vaccineassociated myocarditis closely resemble those observed in viral myocarditis discussed above, suggesting a shared pathophysiology. In this case, however, tumour necrosis factor-alpha (TNF-α), interferon gamma (IFN-c), IL-6, and IL-1 are the infammatory cytokines involved, with genetic predispositions to IL-6-induced infammation thought to exacerbate vaccine reactions [18]. Furthermore, in contrast to classic myocarditis, the spike protein utilized in the vaccine could induce molecular mimicry with α-myosin, akin to phenomena observed in certain COVID-19 infections [19]. ...
... Furthermore, in contrast to classic myocarditis, the spike protein utilized in the vaccine could induce molecular mimicry with α-myosin, akin to phenomena observed in certain COVID-19 infections [19]. Additionally, there is a plausible autoimmune aspect through molecular mimicry [18]. ...
... Notably, cardiac histopathology studies have reported a lack of difuse lymphocytic myocarditis, which is characteristic of the classic presentation [39,40]. Research on infammatory infltrates suggests that an exaggerated innate immune system response, increased pro-infammatory cytokines, and endothelial dysfunction may contribute to the pathophysiology of COVID-19 vaccine-related myocarditis [18]. Certain individuals with genetic predispositions may experience Advances in Medicine hyperimmune responses to mRNA, leading to both aberrant innate and adaptive immune responses [18]. ...
Background
In December 2019, the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) led to the COVID-19 pandemic, with millions of deaths worldwide. Vaccine breakthroughs in late 2020 resulted in the authorization of COVID-19 vaccines. While these vaccines have demonstrated efficacy, evidence from vaccine safety monitoring systems around the globe supported a causal association between COVID-19 vaccines, in particular those using mRNA technology, i.e., Moderna's mRNA-1273 and Pfizer-BioNTech's BNT162b2, and myocarditis.
Objective
This paper aims to investigate the epidemiology of mRNA COVID-19 vaccine-induced myocarditis, including age, ethnicity, and gender associations with these vaccines. It also discusses the immunopathophysiological mechanisms of mRNA COVID-19 vaccine-associated myocarditis and outlines principles of diagnosis, clinical presentation, and management.
Methods
A literature review was conducted using PubMed, Embase, and Queen Mary University of London Library Services databases. Search terms included “myocarditis,” “coronavirus disease 2019,” “SARS-CoV-2,” “mRNA Covid-19 vaccines,” “Covid vaccine-associated myocarditis,” “epidemiology,” “potential mechanisms,” “myocarditis diagnosis,” and “myocarditis management.”
Results
While the definite mechanism of mRNA COVID-19 vaccine-associated myocarditis remains ambiguous, potential mechanisms include molecular mimicry of spike proteins and activation of the adaptive immune response with dysregulated cytokine expression. Male predominance in COVID-19 vaccine-induced myocarditis may be attributed to sex hormones, variations in inflammatory reactions, coagulation states based on gender, and female-specific protective factors. Moreover, an analysis of diagnostic and management strategies reveals a lack of consensus on acute patient presentation management.
Conclusion
In contrast to viral infections that stand as the predominant etiological factor for myocarditis with more severe consequences, the mRNA COVID-19 vaccination elicits a mild and self-limiting manifestation of the condition. There is currently insufficient evidence to confirm the definite underlying mechanism of COVID-19 vaccine-associated myocarditis. Further research is needed to develop preventive and therapeutic solutions in this context.
... At the same time, the negative relationship found between the level of IgG to SARS-CoV-2 in the follicular fluid and the number of total and mature oocytes confirms that COVID-19 can adversely affect reproductive outcomes. Oocytes, embryos, and particularly late blastocysts seem to have the receptor/protease machinery to be susceptible to SARS-CoV-2 infection, although no viral RNA in oocytes has yet been found and data on embryos are conflicting [31]. ...
... It has been shown that COVID-19 can trigger autoimmune processes in genetically susceptible individuals [31]. The emergence of immune thrombocytopenic purpura, Guillain-Barré syndrome, and Miller-Fischer syndrome has been described in COVID-19 convalescents [33]. ...
It is assumed that SARS-CoV-2- and COVID-19-associated autoimmune processes may affect the outcomes in assisted reproductive technology (ART) cycles. This observational prospective study included 240 infertile patients: 105 patients had no history of COVID-19 (group 1) and 135 patients had experienced COVID-19 (group 2) in a mild (n = 85) or moderate (n = 50) form less than 12 months prior to oocyte retrieval. Using ELISAs, the profiles of their serum autoantibodies were determined, including antiphospholipid antibodies and antibodies to nuclear and thyroid antigens. The parameters of oogenesis and embryogenesis, as well as the pregnancy and childbirth rates, did not differ between groups 1 and 2, and also between the subgroups with different severities of COVID-19. However, when oocyte retrieval was performed less than 180 days after COVID-19, a higher proportion of poor-quality blastocysts was obtained (p = 0.006). A high risk of early miscarriage was found in the patients with moderate COVID-19. In group 2, IgG antibodies to annexin V, phosphatidylethanolamine (PE), and TSHr were detected more often than in group 1 (p = 0.035; p = 0.028; and p = 0.033, respectively), and a weak inverse correlation was revealed between anti-PE IgG and the number of oocytes and zygotes obtained. The results of the study suggest a possible adverse effect of COVID-19 and its associated autoantibodies on the outcomes of fresh oocyte ART cycles and early pregnancy, which depends on the severity of COVID-19 and the time interval after the disease.
... Previous studies have also indicated that patients with im-RD are at a higher risk for various COVID-19-related complications, such as pneumonia and secondary infections, compared to the general population im-RD. [36][37][38][39] While less frequently documented, certain case reports and systematic reviews support our findings of increased immune thrombocytopenia 40,41 and cardiovascular complications 42 in patients with im-RD. The lack of differences between patients with im-RD and matched control-II indicates that the established risk factors of age, sex, comorbidities, smoking, and BMI play a more significant role in cardiovascular risk than im-RD alone. ...
Purpose
To assess the impact of severe COVID-19 in patients with immune-mediated rheumatic diseases (im-RD) and compare their morbidity, mortality, hospitalization issues, post-COVID-19 sequelae, and the financial burden of COVID-19 with those of patients without im-RD.
Patients and Methods
We conducted a retrospective case–control study that included 132 consecutive patients with im-RD who visited the Rheumatology Department of a public hospital in the Emirate of Dubai and were hospitalized for COVID-19 infection between March 1st, 2020, and December 31st, 2021, (cases). We included 264 and 132 age- and sex-matched patients without im-RD in matched-I and matched-II control groups, respectively. The median age of patients and controls was 48.5 years, and 74.2% were female. Patients with im-RD were paired with an unforced nearest neighbor match using a caliper width of 0.2 standard deviations of the matched-II control group’s propensity score. We compared the relative risk of death, disease progress, use of medical resources, and financial impact of COVID-19 between patients and controls.
Results
Patients with im-RD had higher mortality rates than the matched-I (odds ratio, OR: 11.2, p < 0.000) and matched-II (OR: 16.8, p < 0.006) control groups. The overall complication rate was also significantly higher in patients with im-RD than in matched-I (OR = 2.9, p < 0.000) and matched-II (OR = 2.8, P < 0.0001) control groups. Lastly, patients with im-RD required more frequent visits to the clinic, a longer recovery time following hospital discharge, and increased healthcare costs compared to the control groups.
Conclusion
COVID-19 infection in patients with im-RD is associated with increased morbidity and mortality, exerting a significant burden on the healthcare system.
... Despite being mostly a respiratory disease, SARS-CoV-2 infection has been involved in various pathogenetic mechanisms, including a cytokine storm that has been associated with a hyperinflammatory environment in multiple organs. New onset of several autoimmune and autoinflammatory conditions has been reported following SARS-CoV-2 infection, while also exacerbation of preexisting autoinflammatory diseases was also evident in various studies [2][3][4][5]. ...
Background: COVID-19 disease has been associated with flares or new onsets of various autoinflammatory diseases such as psoriasis and atopic dermatitis. Our aim is to investigate the occurrence and risk factors of flares or new onsets of Hidradenitis Suppurativa (HS) following COVID-19 disease. Methods: A retrospective cohort study was performed including 310 patients with HS following COVID-19 disease. Data on the rate of HS flares, new lesions, time of flare onset, and flare duration were recorded. Demographics, clinical characteristics, and treatment parameters were compared between patients with and without HS flares. Results: HS flares developed in 69 (22.2%) patients, with 14 experiencing their first episode. The median period between COVID-19 and flare onset was 17 days, with a median flare duration of 14 days. For new HS onset, the median period was 9.5 days, and the median duration was 13 days. Biologic treatment was less common in patients with flares (7.2% vs. 23.2%, p = 0.003), and fewer patients with flares were vaccinated (81.1% vs. 99.1%, p < 0.001). Multivariable analysis showed lower risk for flares in those receiving biologics (aOR = 0.14, p = 0.002) and those who were vaccinated (aOR = 0.02, p < 0.001). Conclusions: COVID-19 may trigger HS flares and new onset, with biologic treatment and vaccination offering protection.
... SARS-CoV-2 infection may trigger autoimmune disease in some patients as a result of cross-reactivity of viral structures. 8,9 Autoantibodies usually target nuclear antigens, and antinuclear antibodies are searched in the differential diagnosis of many autoimmune diseases, including systemic lupus erythematosus. 10 Small-scale studies in Germany and China demonstrated high incidence of antibodies to nuclear antigens in severe COVID-19. ...
Objectives: The study aimed to investigate the possible effects of coronavirus disease 2019 (COVID-19) on autoantibodies.
Patients and methods: Samples of 89,108 individuals (29,033 males, 60,075 females; median: 36 years; range, 0 to 96 years) who underwent autoimmune testing between January 2017 and May 2022 were retrospectively analyzed. The prepandemic period was defined as May 1, 2017, to March 20, 2020, while the pandemic period was defined as March 20, 2020, to May 31, 2022.
Results: Of the participants, 0.55% were of foreign nationality. The positivity rate was 18.12%. Autoantibody positivity rates, when analyzed by sex, were higher in females for antinuclear antibody (ANA), antimitochondrial antibody (AMA), anti-liver kidney microsomal (LKM) antibody, immunoglobulin A (IgA) anti-gliadin antibody, anti-endomysial antibody A, anti-ribosomal P protein antibody, anti-Sjögren’s syndrome A (anti-SSA), anti-Sjögren’s syndrome B (anti-SSB), anti-Smith/ribonucleoprotein (anti-SM/RNP), anti-SM, and c-ANCA (cytoplasmic antineutrophil cytoplasmic antibody). When the prepandemic period was compared with the pandemic period, AMA, anti-LKM antibody, IgA anti-gliadin antibody, anti-endomysial antibody A, and anti-SM/RNP levels were higher in the prepandemic period, while ANA was higher during the pandemic. Additionally, statistically significant differences were found in the distributions of ANA, AMA, anti-LKM antibody, IgA anti-gliadin antibody, anti-endomysial antibody A, anti-ribosomal P protein antibody, anti-SM, anti-SSA, and c-ANCA across the years.
Conclusion: This study could not establish a cause-effect relationship between the changing autoantibody levels during the COVID-19 pandemic and severe acute respiratory syndrome coronavirus 2 infection due to the lack of results from the same patients across different periods. Nonetheless, we believe the quantitative seroprevalence changes in such a large sample of autoantibody screening results over a five-year period, including the pandemic, are valuable.
... Yet, majority of COVID-19 cases are asymptomatic of mild to moderate respiratory illness with full recovery while several independent risk factors that are highly related with severe disease include: advancing age, diabetes mellitus, cardiovascular disease (CVD), obesity and Chronic Obstructive Pulmonary Diseases (COPD) and even cancer [3]. Preventions were limited due to therapeutics, making vaccination the most crucial for the management of COVID-19. ...
Background: COVID-19, and mRNA vaccines can raise the CVDs risk through receptor binding proteins and inflammation, specifically the ACE 2 receptor. Objective: To evaluate the significance of D-dimer and other inflammatory biomarkers in predicting CVD complications among vaccinated patients with COVID-19, along with mild, moderate and severe illness severity. Materials and Methods: Serum samples were collected at baseline, on average 7 days after onset of symptoms from 60 hospitalized COVID-19 patients (71% men, 29% female). We quantified the levels of interleukin 6(IL-6), C-reactive protein (CRP), ferritin, procalcitonin, lactate dehydrogenase (LDH) and D-dimer. Cross-sectional comparisons with COVID-19 severity, diabetes status, vaccination and SARS-CoV-2 variant were made. Results: 50% of patients were diabetic and more patients with severe illness had diabetes. Levels of D-dimer were significantly higher among the diabetic patients with moderate illness than in non-diabetics (p = 0.041). In severe illness, D-dimer levels between diabetic and non-diabetic individuals were comparable (p = 0.066). High D-dimer, prothrombin time and cardiac biomarkers were positively correlated with CVD risks in COVID-19 patients, an apparent inflammatory response was highly observed by daytime temperature during COVID-19 among diabetes patients. Conclusions: This study suggests that COVID-19 and mRNA vaccinations can increase the overall risk of CVDs in patients, especially patients with diabetes by increasing inflammatory markers such as D-dimer. The various D-dimer and other biomarkers can be monitored to determine the risks associated with CVD in this population.
... However, available data on the risk of AM during the follow-up period are debated. Some authors have supposed that the risk of AM is higher in patients admitted to the ICU, where they may have received higher doses of immunomodulatory drugs, affecting their immunosuppression and the cytocidal effect of the virus on the cardiac muscle [36,37]. ...
Background
COVID-19 vaccines reduced mortality, hospitalizations and ICUs admissions. Conversely, the impact of vaccination on Long COVID-19 syndrome is still unclear. This study compared the prevalence of post-acute sequelae at short and long-term follow-up among hospitalized unvaccinated and vaccinated COVID-19 survivors through a multidisciplinary approach.
Methods
After 2 months from discharge, unvaccinated and vaccinated COVID-19 survivors underwent a follow-up visit at a dedicated “post-COVID-19 Outpatient Clinic”. The follow-up visit included a cardiovascular evaluation, blood tests, chest computed tomography, 6-min walking test (6MWT), spirometry. A one-year telephone follow-up was performed to assess re-hospitalizations, death and long-lasting symptoms. An additional 1:1 case-control matching analysis adjusted for baseline characteristics was performed.
Results
Between June 2020 and June 2022, a total of 458 unvaccinated and vaccinated patients (229 per group) underwent the follow-up visit. Vaccinated patients had lower rates of ICU admissions (1.7 % vs 9.6 %, p= <0.001) and severe respiratory complications requiring intubation (1.3 % vs 7 %, p = 0.002) or non-invasive ventilation such as high-flow nasal oxygen therapy (1.7 % vs 7.9 %, p = 0.02), CPAP (1.3 % vs 20.1 %, p= < 0.001), and low-flow oxygen therapy (3.5 % vs 63.3 %, p= <0.001) compared to unvaccinated ones. At 2-month follow-up, vaccinated patients had fewer persistent ground-glass opacities (2.6 % vs 52.8 %, p= <0.001) or consolidations (0.9 % vs 8.3 %, p= <0.001). Additionally, unvaccinated patients experienced more frequent myocarditis (4.8 % vs 0.9 %, p = 0.013) and pulmonary embolism (1.8 % vs 0 %, p = 0.042) and exhibited more significant respiratory impairment as evidenced by desaturation during the 6MWT(10.2 % vs 3.5 %, p = 0.005) and altered spirometry (14 % vs 8.7 %, p = 0.043) compared to vaccinated ones. At one-year, unvaccinated patients reported more symptoms such as dyspnea (20.5 % vs 10 %, p = 0.002), psychological symptoms (10 % vs 3.5 %, p = 0.005) and chronic rhinosinusitis/cough (6,6 % vs 2,6 %, p = 0.04) as compared to vaccinated ones. The 1:1 case-control matching analysis also confirmed these results.
Conclusions
COVID-19 vaccines improve short-term outcomes and may reduce Long COVID-19 prevalence.
... The condition may lead to renal failure through mononuclear cell infiltration, which destroys small-and medium-sized blood vessels. Severe acute respiratory syndrome (SARS) may exacerbate autoimmune diseases [5,6]. Glomerulonephritis (GN), although rare, can occur as a result of moderate to severe COVID-19 and may develop gradually or suddenly. ...
Vasculitis is one of the complications of COVID. Coronavirus may trigger or exacerbate autoimmune diseases, such as systemic vasculitis. We present the case of an elderly individual with a medical history that includes recurrent urinary tract infections, hyperlipidemia, essential hypertension, and peripheral vascular disease. Doctors suspected vasculitis due to declining renal function, clinical condition, and serological findings of the patient. His serum tested positive for antinuclear antibodies. A kidney biopsy was deemed necessary due to the unclear cause of his renal insufficiency. The biopsy revealed focal necrotizing and crescentic glomerulonephritis (GN), a pauci-immune type. It is essential to learn more about COVID-19 and its related complications. This case highlights the difficulties of COVID-19, leading to focal necrotizing and crescentic GN. Maintaining a broad differential is essential while treating a patient who has recovered from the initial infection. This research is important because it will help clinicians to identify this perspective while treating patients. We also review some related articles on the association of COVID-19 with vasculitis.
... Los mecanismos patogénicos y los aspectos clínico -radiológicos compartidos entre las enfermedades hiperinflamatorias y el COVID-19 sugieren que el SARS-CoV-2 podría actuar como un factor desencadenante para el desarrollo de una rápida desregulación autoinmune y / o autoinflamatoria, que conduce a la neumonía intersticial grave en individuos con predisposición genética. 7 El síndrome de distrés respiratorio agudo (SDRA) asociado a COVID-19 es similar a la exacerbación aguda en la enfermedad intersticial pulmonar en la enfermedad del tejido conectivo. 8 La respuesta inmune exuberante observada en el COVID-19 plantea una pregunta sobre la fisiopatología de la enfermedad: ¿es el virus SARS-CoV-2 patogénico por sí mismo o su letalidad está relacionada con una respuesta autoinmune incontrolada? ...
Se puede considerar la autoinmunidad como la condición en la cual el organismo monta una respuesta inmune contra lo propio. Sin embargo, esta definición puede llevar a confusión, si se toma como sinónimo de enfermedad autoinmune.Si incluimos dentro de la definición de autoinmunidad cualquier respuesta inmune contra lo propio, tendríamos que hacer lo mismo con la antiidiotípica normal, que se monta con el objeto de modular la respuesta mediada por anticuerpos, por ejemplo, luego de una infección viral como así también, la de anticuerpos naturales, cuya función es la de eliminar detritus del organismo. Podríamos agregar la respuesta autoinmune contra células transformadas, también de beneficio para el huésped.
... In most cases, the immune response diminishes in the third stage, allowing cytotoxic CD8+ T-lymphocytes to eliminate the virus. However, in some instances, the virus may persist, leading to ongoing damage to cardiac myocytes [18]. In the context of vaccine-associated myocarditis, the inflammatory cytokines involved include TNF-α, IFN-γ, IL-6, and IL-1. ...
Myocarditis is a rare but key adverse event linked to mRNA COVID-19 vaccines, predominantly in young males. Epidemiological data indicate an incidence of approximately 12.6 cases per million doses administered to patients aged 12-39 years, mostly following the second dose of the vaccine. Most patients present with elevated levels of cardiac biomarkers, chest pain, and abnormal ECG findings within a few days of vaccination. Proposed mechanisms for the exact pathophysiology of this include molecular mimicry between the SARS-CoV-2 spike protein and cardiac antigens, activation of immune pathways, and dysregulated cytokine expression. Despite these findings, the overall benefit-risk balance for COVID-19 vaccination remains positive, as the majority of patients recover fully. In contrast, COVID-19-associated myocarditis is more common and more severe, with an estimated incidence of 1,000-1,400 cases per 100,000 infections. Clinical presentation of vaccine-associated myocarditis is usually mild and self-limiting, and most patients do recover without significant long-term effects. Treatment is usually supportive in nature and has an emphasis on ruling out acute coronary syndrome and symptomatic management for heart failure or arrhythmias if present. Given its low incidence and the generally good outcome, vaccination against COVID-19 is recommended from 12 years of age and above, with provision for ongoing surveillance for monitoring and management of rare adverse events like myocarditis.
... Another study showed presence of a pathogenic effect of virus on female Reproductive system, Follicular microvasculature, and ovarian antral folliculogenesis, by altering the follicular fluid content and oocyte quality [27]. Also, correlation with the level of Immunoglobulin G to virus in the albuminous fluid in the follicular antrum and the number optimal numbers of mature oocytes leads to COVID-19 can negatively affect health outcomes cryopreservation it looks like to have the protease system to be sensitive to virus [28,29]. ...
The challenges that happened during the COVID-19 pandemic are preventing infection and synthesizing vaccines against these viral infections. Thyroid peroxidase is antithyroid microsomal antibodies. The presence of antibodies to thyroid peroxidase pointing to an autoimmune disorder. Anti-sperm antibodies are identified in sera of women sub-fertility for unknown reasons. Materials and methods : Biochemical measurements of thyroids hormones levels by AFIAS-10 instrument. Anti-TPO by Maglumi 800 instrument and Anti-sperm antibodies measured by ELISA kit from My Biosource. Results & Discussion : There were no significant changes in T3 and T4 levels. A highly increase in TSH and anti-TPO levels in women previous infected and vaccinated group against COVID-19 group compared with women don't infected and without vaccination group and infected women without vaccination group, and a significant increase in infected women without vaccination group compared with women don't infected and without vaccination group. There was a highly significant increase in anti-sperm ng/mL concentration in women previously infected and vaccinated against COVID-19 group compared with women not infected and without vaccination and infected women without vaccination group.
... It has been hypothesized that the modmRNA injections may trigger pre-existing, dysregulated immunologic pathways, perhaps manifesting as a polyclonal B-cell expansion and resulting in immune complex formation and vasculitis phenomena (Akinosoglou et al., 2021). Notably, in modmRNA-injected individuals with genetic susceptibility, this dysregulation may be exacerbated by epitope spreading and bystander activation, potentially leading to chronic autoimmunity following post-injection SARS-CoV-2 or Omicron infection (Caso et al., 2020). ...
The COVID-19 modified mRNA (modmRNA) lipid nanoparticle-based “vaccines” are not classical antigen-based vaccines but instead prodrugs informed by gene therapy technology. Of considerable note, these products have been linked to atypical adverse and serious adverse event profiles. As discussed in Part 1, health-related risks and drawbacks were drastically misreported and underreported in the Pfizer and Moderna trial evaluations of these genetic products. Now in Part 2, we examine the main structural and functional aspects of these injectables. The COVID-19 modmRNA injectable products introduce a unique set of biological challenges to the human body with the potential to induce an extensive range of adverse, crippling, and life-threatening effects. Based on the fact that there is no current method to quantify host (cell-based) spike protein production in vivo following injection with these prodrugs, there is no standard “dose”. This is in part due to differences in spike protein production output, which depends on cell metabolism and transfection efficiency. It is therefore difficult to predict adverse event profiles on an individual basis, but considering that millions of adults across the world have reported severe and serious adverse events in the context of these modmRNA COVID-19 products, valid concerns are raised regarding injection of infants and younger age groups for whom COVID-19 poses only minimal risks. We address the process-related genetic impurities inherent in mass production of these products, and the potential risks posed by these contaminants. We then categorize the principal adverse events associated with the modmRNA products with a brief systems-based synopsis of each of the six domains of potential harms: (1) cardiovascular, (2) neurological, (3) hematologic; (4) immunological, (5) oncological, and (6) reproductive. We conclude with a discussion of the primary public health and regulatory issues arising from this evidence-informed synthesis of the literature and reiterate the urgency of imposing a global moratorium on the modmRNA-LNP-based platform.
... Chen et al. pinpointed the role of ACE-2 receptor and its polymorphisms in MIS-C development [16,17]. SARS-CoV-2 binds to the ACE-2 receptor and enters the endothelial cells, activating an inflammatory cascade with cytokines production and coagulation abnormalities [18,19]. Thrombotic microangiopathy, endothelial cell damage, fibrinoid necrosis, abnormalities in the coagulation/fibrinolytic system, and monocyte-derived macrophages and neutrophils are all outcomes of post-infectious inflammatory response that follows infection [20]. ...
... Chen et al. pinpointed the role of ACE-2 receptor and its polymorphisms in MIS-C development [16,17]. SARS-CoV-2 binds to the ACE-2 receptor and enters the endothelial cells, activating an inflammatory cascade with cytokines production and coagulation abnormalities [18,19]. Thrombotic microangiopathy, endothelial cell damage, fibrinoid necrosis, abnormalities in the coagulation/fibrinolytic system, and monocyte-derived macrophages and neutrophils are all outcomes of post-infectious inflammatory response that follows infection [20]. ...
Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) microscopic polyangiitis is a rare but life-threatening small vessel vasculitis in childhood that affects multiple systems. Emerging clinical evidence suggests a possible association between SARS-CoV-2 infection or multisystem inflammatory syndrome in children (MIS-C) as well as the futuredevelopment of autoimmune diseases. A 14-year-old boy with a diagnosis of MIS-C two years prior to presentation was admitted to our hospital due to edema and left lower limb joint pain along with concomitant upper surface petechia. The patient had a positive higher SARS-CoV-2 IgG than MIS-C diagnosis titers and MPO-ANCA-positive antibody titers. Kidney biopsy favored a pauci-immune crescentic glomerulonephritis. Restrictive lung disease with concomitant diffusion abnormalities was also observed. Pancreatitis and gastrointestinal wall edema were additional clinical manifestations. SARS-CoV-2 breakthrough infection and MIS-C could contribute to the onset of autoimmune vasculitis through various immunological mechanisms. Further research is still needed to elucidate the role of SARS-CoV-2 in the pathophysiology of newly diagnosed autoimmune vasculitis.
... Moreover, new research suggests a causal link between SARS-CoV-2 infection and the development of certain autoimmune diseases in genetically predisposed individuals. COVID-19 pathophysiology can lead to the presentation or exacerbation of autoimmune diseases [11] such as alopecia areata, vitiligo, systemic lupus erythematosus, vasculitis and paediatric multisystem inflammatory syndrome. Type I, II and III interferons are thought to occupy an important role in the development of autoimmune diseases post-COVID-19 by being involved in producing an appropriate response to pathogens and damaged cells in the body with impaired release of proinflammatory cytokines [12]. ...
Viral infections caused by exposure to viruses such as Epstein–Barr, cytomegalovirus, or Parvovirus B19 have always been considered predisposing environmental factors for the onset of autoimmune diseases. More recently, autoimmune mechanisms such as molecular mimicry, T-cell activation, transient immunosuppression and inflammation have also been observed in cases of SARS-CoV-2 infection. Several newly diagnosed autoimmune disorders have been reported post-COVID-19, such as COVID-19-associated multisystemic inflammatory syndrome in children (MIS-C), type 1 diabetes mellitus, systemic lupus erythematosus, or rheumatoid arthritis. In this article, we present a new case of paediatric systemic lupus erythematosus (SLE) with haematological (macrophage activation syndrome), renal (stage 2), cutaneous (urticarial vasculitis) and digestive involvement, onset three and a half months post-COVID-19. In the dynamics, de novo infection generated by Epstein–Barr exposure was associated. The diagnosis was confirmed based on EULAR/ACR 2019 criteria. The aim of the article is to present a possible correlation between SARS-CoV-2 and Epstein–Barr as extrinsic factors in triggering or activating paediatric systemic lupus erythematosus. Keywords: paediatric systemic lupus erythematosus; post-COVID-19; Epstein–Barr; SARS- CoV-2; case report; paediatric patient.
... 38 The immune response to mRNA may not be suppressed in genetically predisposed individuals, which may activate abnormal innate and acquired immune responses. 38,39 COVID-19 vaccines contain nucleoside-modified mRNA. Vaccine genes may be recognized as antigens by the immune system, thereby generating inflammatory cascades and immunological pathways that may aid in the development of myocarditis. ...
Background
Evidence supporting the possible causal association of myopericarditis with the coronavirus disease (COVID-19) vaccine has mainly come from case reports. Epidemiological evidence indicating an increased relative risk for myopericarditis after COVID-19 vaccination is lacking. Therefore, this study aimed to identify and assess all confirmed COVID-19 vaccine- related cases of myopericarditis presenting to major cardiac centers in the Eastern Region of Saudi Arabia, before and after the introduction of the COVID-19 vaccine.
Methods
According to case definition, the hospital’s information system database detected all confirmed cases at two main cardiac centers.
Results
Of the 18 confirmed myocarditis and myopericarditis cases detected after the administration of COVID-19 vaccines, three were possibly related to COVID-19 immunization. The first case was of myopericarditis following a third dose of mRNA-1273. The second case was myocarditis, which occurred seven days after the first dose of AstraZeneca. The third case was myocarditis, which occurred 12 days after the third dose of BNT162b2. A cardiologist carefully evaluated the cases using recognized protocols and case definitions to demonstrate a direct relationship with vaccination consequences rather than coincidence.
Conclusion
We found no difference in the occurrence of myocarditis and myopericarditis after the COVID-19 vaccine compared with the background rate during a similar period (P = 0.9783). The incidences of myocarditis and myopericarditis following immunization were low. The advantages of the COVID-19 vaccination outweigh the risk of myopericarditis.
... This might explain SARS-CoV-2 acting as a trigger for developing a rapid autoimmune and/or autoinflammatory dysregulation. 12 A part of the COVID-19 virus antigen is presented on the surface of antigen presentation cells (APC), which plays a crucial role in the body's immune response and ultimately leads to the production of IgM and IgG antibodies. 13 In ...
The Coronavirus Disease 2019 (COVID-19) pandemic has unveiled diverse immunological complications extending beyond the acute phase of infection. We present a case series of four patients who developed autoimmune vasculitis and sarcoidosis post-recovery from COVID-19. Case presentations include recurrent fever and respiratory symptoms in a 36-year-old female, granulomatous liver lesions in a 63-year-old male, progressive dyspnea in a 44-year-old female, and diffuse alveolar hemorrhage in a 74-year-old female following severe pneumonia. These cases underscore the importance of vigilance for immunological sequelae in post-COVID-19 patients, particularly those with predisposing comorbidities. We tried to elucidate pathophysiological mechanisms and optimize management strategies for these rare but clinically significant manifestations.
... This might explain SARS-CoV-2 acting as a trigger for developing a rapid autoimmune and/or autoinflammatory dysregulation. 12 A part of the COVID-19 virus antigen is presented on the surface of antigen presentation cells (APC), which plays a crucial role in the body's immune response and ultimately leads to the production of IgM and IgG antibodies. 13 In ...
The Coronavirus Disease 2019 (COVID-19)pandemic has unveiled diverse immunological complications extending beyond the acute phase of infection. We present a case series of four patients who developed autoimmune vasculitis and sarcoidosis post-recovery from COVID-19. Case presentations include recurrent fever and respiratory symptoms in a 36-year-old female, granulomatous liver lesions in a 63-year-old male, progressive dyspnea in a 44-year-old female, and diffuse alveolar hemorrhage in a 74-year-old female following severe pneumonia. These cases underscore the importance of vigilance for immunological sequelae in post-COVID-19 patients, particularly those with predisposing comorbidities. We tried to elucidate pathophysiological mechanisms and optimize management strategies for these rare but clinically significant manifestations.
... This proposed mechanism has been both supported [12] and refuted [13] by research findings. An alternative theory is that the host response directed against the mRNA component of vaccines causes the activation and dysregulation of immunological responses, leading to the development of myocarditis as part of a systemic reaction [392,393]. In both cases, these aberrant responses are more likely to involve individuals with underlying genetic predispositions. ...
Following mass vaccinations for the control of the COVID-19 epidemic, a spectrum of cardiac and neurological disorders was reported among vaccinated individuals. This study examined the range of complications documented and factors related to their occurrence. Three electronic databases were searched for case reports and case series with descriptions of cardiac and/or neurological complications in COVID-19 vaccine recipients. A total of 698 vaccinees were included in this review, of which 259 (37.1%) had cardiac and 439 (62.9%) had neurological complications. Inflammatory conditions were the commonest among the cardiac complications; while polyneuropathy, demyelinating diseases and cerebrovascular disorders were the more common neurological complications. The mean age of those with cardiac complications (33.8 years) was much younger than those with neurological complications (49.7 years). There was no notable difference in the gender distribution between these two groups of vaccine recipients. mRNA vaccines (all brands) were associated with almost 90.0% of the cardiac complications, whereas viral vector vaccines were associated with slightly over half (52.6%) of the neurological complications. With regard to the dose, cardiac complications were more common after the second (69.1%), whereas neurological complications were more common after the first dose (63.6%). The majority of the cases had an uncomplicated clinical course. Nevertheless, 5.9% of cases with neurological complications and 2.5% of those with cardiac complications were fatal, underscoring the significance of the consistent surveillance and vigilant monitoring of vaccinated individuals to mitigate these occurrences.
... Furthermore, autoimmune diseases can be triggered by COVID-19 in genetically predisposed patients, following the activation of an aberrant immune response by the cytokine cascade (TNF-α, IL-6, IL-1β, IL-17, and IL-18) induced by SARS-CoV-2 [9] ( Table 3). Toxidermia can also be potentiated by SARS-CoV-2 infection via complex immune reactivations, even if prior sensitization is lacking, in genetically predisposed subjects. ...
Introduction: Since the beginning of the pandemic, many skin manifestations associated with COVID-19 have been reported. New reports show that COVID-19 can lead to autoimmune diseases (AIDs) and autoinflammatory diseases, especially dermatological.
Methods: A prospective study was conducted by the dermatology department of the Centre Hospitalier Universitaire Ibn Rochd (CHU Ibn Rochd) of Casablanca in Morocco since the beginning of the pandemic including 18 patients with COVID-19-related skin manifestations.
Results: Eighteen cases were collected with confirmed SARS-CoV-2 infection. The mean COVID score was 0.7. A percentage (94.44%) of the cases had general symptoms. Skin involvement was variable, mainly maculopapular rash (44.44%), purpura (27.77%), urticaria, varicelliform rash, necrotic lesions of the face, and pityriasis rosea Gibert (PRG)-like lesions. Mucosal involvement was found in 50%. Viral reactivation was found in 5.55%. Telogen effluvium was found in 22.22%. Moreover, AID was triggered by COVID-19: lupus (11.11%), associated with antiphospholipid syndrome (APL Sd) (5.55%), psoriasis (11.11%), alopecia, and pemphigus. Severe toxidermia was potentiated by SARS-CoV-2 infection (22.22%): Stevens-Johnson syndrome (Sd), acute generalized exanthematous pustulosis (APEG), and drug reaction with eosinophilia and systemic symptoms (DRESS).
Conclusion: The interest of this work is to report our experience during the COVID-19 pandemic to understand some pathophysiological mechanisms of its dermatological manifestations and to draw the attention of clinicians to the link of this infection with autoimmune and autoinflammatory diseases and toxidermia.
... Although it is primarily a respiratory disease, there are various extrapulmonary manifestation of COVID-19 now reported (2). It is well recognised that SARS-Cov-2 infection is linked to hyperinflammation and there is a potential mechanistic link to autoimmunity (3)(4)(5). ...
Background and aim
SARS-CoV-2 infection has been linked to hyperinflammation in multiple organs with a potential mechanistic link with resulting autoimmunity. There have been reports of many inflammatory complications following COVID-19, including sarcoidosis. A literature review on new-onset sarcoidosis following COVID-19 is lacking. We evaluated potential associations between COVID-19 and development of new-onset sarcoidosis.
Methods
Articles discussing biopsy-proven sarcoidosis after confirmed COVID-19 infection, published 1956 until April 2023, were included. All article types were deemed eligible except opinion and review articles.
Results
A pooled total of 15 patients with new-onset diagnosis of sarcoidosis after COVID-19 infection were included, 45.5% female, mean age 46.1 years (standard deviation 14.7) at onset of sarcoidosis. Patients were from: Europe (n=11); North America (n=2); South America (n=1); Asia (n=1). The mean time between COVID-19 infection and diagnosis of sarcoidosis was 56.3 days, although this ranged from 10 to 140 days. Organ systems predominantly affected by sarcoidosis were: pulmonary (n=11); cutaneous (n=3); cardiac (n=2); ocular (n=1); systemic (n=1) (with overlapping features in certain patients). Sarcoidosis was treated as follows: glucocorticoids (n=8); azathioprine (n=1); cardiac re-synchronisation therapy (n=1); heart transplant (n=1). All patients were reported to have survived, with one requiring intensive care admission.
Conclusions
Our result suggests there is a potential link between COVID-19 and new-onset sarcoidosis. The potential mechanism for this is through cytokine mediated immune modulation in COVID-19 infection. Obtaining a tissue sample remains key in confirming the diagnosis of sarcoidosis and this may be delayed during active COVID-19 infection.
... Autoinflammatory dysregulation appears to have contributed to tissue damage in several cases of SARS-CoV-2 infection [22]. It is thought that SARS-CoV-2 could act as a triggering factor for autoinflammatory dysregulation in genetically predisposed individuals [25]. AIH has been reported in patients following SARS-CoV-2 infection, including in unvaccinated patients, but has rarely occurred after COVID-19 vaccination [3,[26][27][28][29]. ...
... 28 Molecular autoimmune mimicry between the Spike glycoprotein and troponin C1 may account for the cardiac insult after vaccine introduction and this may be due to an autoimmune crossreaction between IgM antibodies to the SARS-CoV-2 Spike glycoprotein and cardiac autoantigens, 20 and potentially induce myocardial inflammation. 29 The role of sex hormones is thus incriminated in myocardial inflammation, given the frequency of the latter especially in young people. This pathophysiological hypothesis is based on the fact that testosterone activates specific helper T-cell responses, whereas estrogen inhibits proinflammatory T-cell responses. ...
Introduction
A few months after the beginning of the coronavirus disease of 2019 (COVID-19) vaccination, several reports of myocarditis secondary to the vaccines were published, sometimes with fulminant cases, but until today there is no proven causal link between these 2 events, but with many hypotheses proposed.
Methods
A systematic review of current evidence regarding myocarditis after COVID-19 vaccination was performed by searching several databases including PubMed/Medline and Web of Science. The quality of Meta-analysis was assessed using the AMSTAR-2 tool as well as other qualitative criteria.
Results
Our umbrella review appraised 4 Meta-analysis of retrospective studies (range: 5-12), The number of vaccine doses included ranged from 12 to 179 million, with the number of myocarditis cases observed ranging from 343 to 1489. All types of vaccines were evaluated, with no exclusions. The overall incidence ranged from 0.89 to 2.36 cases of myocarditis per 100 000 doses of vaccine received. Heterogeny was assessed in 3 of the Meta-analysis, and was highly significant (>75%) in all included studies, and with a significant P-value (P < .05). Regarding publication bias, 3 of the Meta-analysis conducted the egger and begg regression, with a significant result in only 1. Regarding the assessment of the methodology by the AMSTAR-2 scale indicating that the quality was very critical in 1, low in 2, and moderate in 1 Meta-analysis.
Conclusion
The quality of current non-randomized evidence on real causality and incidence of myocarditis after COVID-19 vaccine is still low.
... Autoantibodies as a hallmark of autoimmune diseases can also be detected in COVID-19 patients [16,17]. Thus, after a systematic review analysis, we found an association between COVID-19 and the tendency of patients to develop multiple types of autoantibodies [18][19][20] and autoimmune diseases [21,22], such as Guillain-Barré syndrome [23], systemic lupus erythematosus [24] and autoimmune hepatitis [25]. Indeed, an increase in new-onset autoimmune phenomena after COVID-19 vaccination have been reported recently (e.g. ...
Nowadays, data concerning the risk of autoimmune disease after SARS-CoV-2 (COVID-19) vaccination is controversial. The aim of this single centre prospective follow-up study was to evaluate whether healthcare workers (HCWs) vaccinated with BNT162b2 mRNA and mRNA-1273 will show a development and/or a persistence of autoantibodies, focussing on the detection of antibodies against nuclear antigens (antinuclear antibodies, ANA). We enrolled 155 HCWs, however only 108 of them received the third dose and were considered for further analysis. Blood samples were collected before vaccine inoculation (T0), at 3 (T1) and 12 months (T2) after the first dose. All samples were analysed for the presence of a) ANA using indirect Immunofluorescence [IIF] (dilutions of 1:80, 1:160. 1:320 and 1:640), and anti-smooth muscle antibodies (ASMA); b) anti-myeloperoxidase (anti-MPO), anti-proteinase 3 (anti-PR3) and anti-citrullinated peptide antibodies (aCCP) [FEIA]; c) anti-phospholipid antibodies (anticardiolipin [aCL], anti-beta-2- glycoprotein I [anti-ß-2GPI] (Chemiluminescence). Line-blot technology was performed using the following kit: EUROLINE ANA profile 3 plus DFS70 (IgG). Our research suggests that mRNA based anti-SARSCoV-2 vaccines can induce the production of de novo ANA in 22/77(28,57%) of subjects and that the percentage of positivity seems to be directly correlated to the number of vaccine expositions: 6/77 (7,79%) after 2 doses; 16/77 (20,78%) after 3 doses. Since it is known that hyperstimulation of the immune system could lead to autoimmunity, these preliminary results seem to further sustain the idea that the hyperstimulation of the immune system might lead to an autoinflammatory mechanism and eventually to autoimmune disorders. However, the link between SARS-CoV-2 vaccination and the development of autoimmune diseases needs to be further investigated.
... Creating opportunities and support systems to ensure equal access to education and training in healthcare fields can foster a truly inclusive and equitable healthcare system. 46 ...
This review examines the immunological and autoimmune adverse events associated with COVID-19 vaccines, highlighting their frequencies, reported cases, and associations with specific vaccine classes. The concept of vaccine-induced immune thrombotic thrombocytopenia is crucial in addressing vaccine skepticism. Understanding this concept helps healthcare professionals identify and manage potential adverse events after vaccination. Despite their rarity, immunological and autoimmune adverse events cause concern and anxiety among the public. To maintain public trust in vaccination programs, healthcare professionals and public health agencies must actively monitor and address these adverse events, promptly disclose suspicious incidents, take measures to mitigate dangers, and inform the public with transparency and accurate information. Continuing research and surveillance are essential for understanding the underlying mechanisms of these adverse events and developing strategies to minimize their occurrence.
... Emerging evidence has highlighted the possible contributions of triggering and persistence of autoimmune activation in SARS-CoV-2-infected COVID-19 patients Lerma et al., 2020;Sacchi et al., 2021). Several studies demonstrated clinical and immunological similarities between SARS-CoV-2 infection and hyperinflammatory diseases, leading to the hypothesis that COVID-19 might trigger autoimmune responses in genetically predisposed subjects (Caso et al., 2020). A recent study revealed that SARS-CoV-2 causes the development of new-onset IgG autoantibodies that positively correlated with immune responses to SARS-CoV-2 proteins in a significant proportion of hospitalized COVID-19 patients . ...
Coronavirus disease 2019 (COVID-19) is an infectious disease affecting multiple systems and organs, including the reproductive system. SARS-CoV-2, the virus that causes COVID-19, can damage reproductive organs through direct (angiotensin converting enzyme-2, ACE-2) and indirect mechanisms. The immune system plays an essential role in the homeostasis and function of the male and female reproductive systems. Therefore, an altered immune response related to infectious and inflammatory diseases can affect reproductive function and fertility in both males and females. This narrative review discussed the dysregulation of innate and adaptive systems induced by SARS-CoV-2 infection. We reviewed the evidence showing that this altered immune response in COVID-19 patients is the major indirect mechanism leading to adverse reproduction outcomes in these patients. We summarized studies reporting the long-term effect of SARS-CoV-2 infection on women's reproductive function and proposed the chronic inflammation and chronic autoimmunity characterizing long COVID as potential underlying mechanisms. Further studies are needed to clarify the role of autoimmunity and chronic inflammation (long COVID) in altered female reproduction function in COVID-19.
... Possible pathological mechanisms responsible for autoimmune responses in SARS-CoV-2 infected patients include molecular mimicry, bystander activation, epitope spreading, cryptic antigen presentation, B-cell polyclonal activation and the existence of the superantigens have been suggested as possible pathological mechanisms behind autoimmune responses in SARS-CoV-2 infected patients [6,7]. Either of these mechanisms might have resulted in recurrence of inflammation in our cases. ...
Background
Immunologic and inflammatory adverse effects following vaccination against COVID-19 are being reported. While some reactions may develop denovo others concern its immunogenic effect in patients with pre-existing inflammatory conditions.
Methods
Retrospective consecutive patients diagnosed with ocular inflammatory manifestations within 8 weeks of receiving COVID-19 vaccination who presented to a tertiary eye care centre in South India.
Results
Ninety-eight eyes of 67 patients presenting with ocular inflammatory manifestations within 8 weeks following COVID-19 vaccination were studied. The mean age was 43 years (+/- 14.82; range 19–80 years). The most common presentations were anterior uveitis (n = 31, 31.7%), followed by panuveitis (n = 24, 24.5%). The mean time to onset of symptoms was 25 days (+/- 15.48; range 2–55 days) following a dose of vaccine.
Among all patients, 39 (58.2%) had a previous history of ocular inflammation. Mean presenting visual acuity was 0.4 (0-4) logMAR units and mean final visual acuity was 0.2 (0-4) logMAR units. The causes for reduced vision included of cystoid macular edema (n=2, 2%), chorioretinal atrophy (n=2.2%), optic atrophy (n=1.1%), retinal vascular occlusion (n=1.1%) and acute retinal necrosis (n=1.1%).
Conclusion
Infective and immunogenic adverse events should be watched out for after COVID-19 vaccination. It is difficult to establish causality for such manifestations, nevertheless, most of them were mild and had good final visual outcomes.
... Moreover, lung tissues collected from COVID-19 patients were enriched in CCR6 and IL-17A co-expressing cells [85]. Thus, patients with acute COVID-19 infection are characterized by decreased Tfr, along with elevated Tfh levels, that were able to contribute to mounting humoral autoimmune responses and the emergence of autoimmune pathologies in post-COVID-19 syndrome [86][87][88]. ...
Unlabelled:
COVID-19 infection not only profoundly impacts the detection of tuberculosis infection (Tbc) but also affects modality in tuberculosis patient immune response. It is important to determine immune response alterations in latent tuberculosis infection as well as in SARS-CoV-2-infected tuberculosis patients. Such changes may have underlying effects on the development and course of further tuberculosis. Here, we aimed to review the characteristics of immune response in TB patients or convalescent COVID-19 patients with latent TB infection (LTBI).
Materials and methods:
We analyzed the features of immune response in tuberculosis and COVID-19 patients. For this, we analyzed publications released from December 2019 to March 2023; those which were published in accessible international databases ("Medline", "PubMed", "Scopus") and with keywords such as "COVID-19", "SARS-CoV-2", "tuberculosis", "pulmonary tuberculosis", "latent tuberculosis infection", "Treg", "follicular Treg", and "Treg subsets", we considered.
Results:
Through our analysis, we found that tuberculosis patients who had been infected with COVID-19 previously and elevated Th1 and Th2 cell levels. High levels of Th1 and Th2 cells may serve as a positive marker, characterizing activated immune response during TB infection. COVID-19 or post-COVID-19 subjects showed decreased Th17 levels, indicating a lack of tuberculosis development. Moreover, the typical course of tuberculosis is associated with an increase in Treg level, but COVID-19 contributes to a hyperinflammatory response.
Conclusion:
According to the data obtained, the course of tuberculosis proceeds in a dissimilar way due to the distinct immune response, elicited by SARS-CoV-2. Importantly, the development of active tuberculosis with a severe course is associated with a decline in Treg levels. Both pathogens lead to disturbed immune responses, increasing the risk of developing severe TB. The insights and findings of this paper may be used to improve the future management of individuals with latent and active tuberculosis.
... PIMS-TS is a serious disease that affects pediatric patients who manifest, among other symptoms, hyperinflammatory shock that can involve several organs. 12 Specifically, children present with high fever, rash, conjunctivitis, peripheral edema, and gastrointestinal symptoms. The latest bulletin from the Brazilian Ministry of Health 13 reported 319 cases of PIMS-TS (aged 0-19 years), with 23 deaths recorded. ...
... Специалистами выявлены повышенная аутореактивность Т-хелперов, цитотоксических Т-клеток, продукция аутоантител и дифференцировка В-клеток при СКВ. Это приводит к нарушению продукции интерферона-γ, BAFF/BLyS, интерлейкина (ИЛ)-1, 2, 6, 10, 1β, 15, 17 и 18 и фактора некроза опухоли α, что ставит под угрозу Th1-тип ответа на вирусные инфекции, который, как правило, более эффективен, чем Th2-тип ответа [7][8][9][10][11]. ...
The article addresses the impact of the new coronavirus infection on the occurrence of cutaneous forms of lupus erythematosus (LE). Since the beginning of the COVID-19 pandemic, there has been an increase in the incidence of cutaneous LE worldwide, the emergence of new cases, and exacerbation and aggravation of the severity of existing ones. The pathogenesis of cutaneous LE, and the role of viral infections in its occurrence, mainly COVID-19, is reviewed. The need for the SARS-CoV-2 vaccination and its potential as a possible trigger is described. It is necessary to note the importance of clinicians in diagnosing LE since it is essential for the dermatologist to know the features of its course and be able to suspect and diagnose even the rarest forms of this disease. Proper awareness and correct diagnosis determine the optimal drug therapy and patient health in the future.
... of an unspecific inflammatory response secondary to vaccination and cross-reactivity of antibodies due to the molecular mimicry have been hypothesized [20].Another proposed mechanism is that through research is required to clarify these possibilities [24]. In addition, IL-18 has been proven to play a role in the pathogenesis of cardiovascular diseases. ...
... Molecular mimicry would be one of the fundamental mechanisms by which peptide structures in the infectious agent SARS-CoV-2 similar to those of the host can activate T or B lymphocytes and trigger the phenomenon of autoimmunity, but molecular mimicry is not the only mechanism in the development of autoimmune responses. Many other factors can participate in this phenomenon, among which we mention the genetic structure of the host, the interaction with the microbiota, chemical adjuvants, disruption of immune tolerance, nonspecific activation with the persistence of some cryptic external antigens, the response of autoreactive T lymphocytes, the activation of autoimmune B cells, etc. [135][136][137]. ...
For over three years, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents has generated repercussions, especially a few weeks after infection, for symptomatic patients who tested positive, for asymptomatic ones, or even just the contacts of an infected person, and evolved from severe forms such as multisystem inflammatory syndrome in children (MIS-C) to multifarious clinical manifestations in long COVID (LC). Referred to under the umbrella term LC, the onset of persistent and highly heterogeneous symptoms such as fatigue, post-exertion malaise, cognitive dysfunction, and others have a major impact on the child’s daily quality of life for months. The first aim of this review was to highlight the circumstances of the pathophysiological changes produced by COVID-19 in children and to better understand the hyperinflammation in COVID-19 and how MIS-C, as a life-threatening condition, could have been avoided in some patients. Another goal was to better identify the interplay between infection, dysbiosis, and inflammation at a molecular and cellular level, to better guide scientists, physicians, and pediatricians to advance new lines of medical action to avoid the post-acute sequelae of SARS-CoV-2 infection. The third objective was to identify symptoms and their connection to molecular pathways to recognize LC more easily. The fourth purpose was to connect the triggering factors of LC with related sequelae following acute SARS-CoV-2 injuries to systems and organs, the persistence of the virus, and some of its components in hidden reservoirs, including the gut and the central nervous system. The reactivation of other latent infectious agents in the host’s immune environments, the interaction of this virus with the microbiome, immune hyperactivation, and autoimmunity generated by molecular mimicry between viral agents and host proteins, could initiate a targeted and individualized management. New high-tech solutions, molecules, probiotics, and others should be discovered to innovatively solve the interplay between RNA persistent viruses, microbiota, and our immune system.
Background
The COVID-19 pandemic has raised concerns about potential links between SARS-CoV-2 infection and autoimmune diseases. This study investigated changes in the incidence rate (IR) of autoimmune diseases among children following the pandemic's onset.
Methods
A retrospective cross-sectional study analyzed data from Clalit Health Services, Israel's largest healthcare provider, examining the IR of different autoimmune diseases in children aged 0–18. The study compared pre-pandemic (2019) with pandemic/post-pandemic periods (2020–2023), encompassing a cohort of over 1.5 million children.
Results
Significant IR increases were observed across multiple autoimmune diseases. Rheumatic diseases (Juvenile Idiopathic Arthritis, Systemic Lupus Erythematosus, Henoch Schoenlein Purpura (HSP)) showed consistent increases, with HSP demonstrating the most pronounced trend. Endocrine disorders exhibited diverse patterns, with autoimmune thyroid diseases and Type 1 diabetes showing overall increases, while diabetic ketoacidosis exhibited an initial spike followed by a decline. Gastrointestinal diseases displayed heterogeneous patterns; Celiac disease and Ulcerative colitis showed general increases, Crohn's disease showed a downward trend, and autoimmune hepatitis exhibited an initial significant decrease followed by a significant increase. Dermatological conditions, including Psoriasis and Vitiligo, demonstrated consistent elevations throughout 2020–2023. Immune Thrombocytopenia Purpura showed initial decreases followed by significant increases in 2022–2023.
Conclusions
This comprehensive analysis reveals significant changes in pediatric autoimmune disease incidence following the COVID-19 pandemic, suggesting potential associations between SARS-CoV-2 infection and autoimmune dysregulation. The diverse patterns observed across different conditions highlight the complex interplay between viral infection and autoimmunity, emphasizing the need for continued surveillance and investigation of long-term immunological consequences of COVID-19 in pediatric populations.
Systemic sclerosis (SSc) has been reported in rare cases following COVID-19 vaccination, raising concerns about potential autoimmune triggers. Herein, we describe the third documented case of diffuse SSc post-vaccination in a 22-year-old woman with no prior autoimmune history. Symptoms, including Raynaud's phenomenon, polyarthritis, and sclerodactyly, emerged within a month after the first dose of the Pfizer-BioNTech vaccine. Laboratory and clinical evaluations confirmed the diagnosis, with no evidence of interstitial lung disease or internal organ involvement. Previous reports and the temporal association suggest a potential role of vaccination in SSc onset, emphasizing the need for further research into autoimmune risks linked to immunization.
Objective
By extracting early chest CT radiomic features of COVID-19 patients, we explored their correlation with laboratory indicators and oxygenation index (PaO2/FiO2), thereby developed an Artificial Intelligence (AI) model based on radiomic features to predict the deterioration of oxygenation function in COVID-19 patients.
Methods
This retrospective study included 384 patients with COVID-19, whose baseline information, laboratory indicators, oxygenation-related parameters, and non-enhanced chest CT images were collected. Utilizing the PaO2/FiO2 stratification proposed by the Berlin criteria, patients were divided into 4 groups, and differences in laboratory indicators among these groups were compared. Radiomic features were extracted, and their correlations with laboratory indicators and the PaO2/FiO2 were analyzed, respectively. Finally, an AI model was developed using the PaO2/FiO2 threshold of less than 200 mmHg as the label, and the model’s performance was assessed using the area under the receiver operating characteristic curve (AUC), sensitivity and specificity. Group datas comparison was analyzed using SPSS software, and radiomic features were extracted using Python-based Pyradiomics.
Results
There were no statistically significant differences in baseline characteristics among the groups. Radiomic features showed differences in all 4 groups, while the differences in laboratory indicators were inconsistent, with some PaO2/FiO2 groups showed differences and others not. Regardless of whether laboratory indicators demonstrated differences across different PaO2/FiO2 groups, they could all be captured by radiomic features. Consequently, we chose radiomic features as variables to establish an AI model based on chest CT radiomic features. On the training set, the model achieved an AUC of 0.8137 (95% CI [0.7631–0.8612]), accuracy of 0.7249, sensitivity of 0.6626 and specificity of 0.8208. On the validation set, the model achieved an AUC of 0.8273 (95% CI [0.7475–0.9005]), accuracy of 0.7739, sensitivity of 0.7429 and specificity of 0.8222.
Conclusion
This study found that the early chest CT radiomic features of COVID-19 patients are strongly associated not only with early laboratory indicators but also with the lowest PaO2/FiO2. Consequently, we developed an AI model based on CT radiomic features to predict deterioration in oxygenation function, which can provide a reliable basis for further clinical management and treatment.
Background:
This investigation aims to identify and evaluate the most common and critical drugs associated with the risk of noninfectious myocarditis utilizing the US Food and Drug Administration Adverse Event Reporting System (FAERS) database.
Methods:
Data pertaining to noninfectious myocarditis from 2004 Q1 to 2024 Q2 were extracted. Following data standardization, multiple signal quantification techniques, including Reporting Odds Ratio (ROR) and Proportional Reporting Ratio, were employed for analysis.
Results:
The study identified a total of 10,763 adverse event reports associated with noninfectious myocarditis. Disproportionality analysis revealed that the top 5 drugs by ROR were phendimetrazine tartrate (ROR 104.64), trimethoprim + sulfamethoxazole (ROR 67.65), aldesleukin (ROR 52.67), mesalazine (ROR 49.73), and balsalazide disodium (ROR 45.26). Notably, among the 30 drugs with the strongest ROR signals, 8 drugs lacked myocarditis risk information in their package inserts.
Conclusion:
Through comprehensive analysis of the FAERS database, our study identified drugs with a strong signal for myocarditis that are not currently indicated on their labels. The findings suggest that the potential risk of myocarditis associated with these medications is significant and warrants close monitoring in clinical practice.
Sarcoidosis and tuberculosis are both granulomatous diseases that have many similarities, making the differential diagnosis of sarcoidosis and tuberculosis difficult, as well as leading to inappropriate treatment selection of both diseases. Autoimmune inflammation (AI) is one of the processes identified tuberculosis and sarcoidosis. Current evidences about the risk and clinical outcomes of COVID-19 infection in patient with sarcoidosis and M. tuberculosis co-infection are still not well understood. SARS-CoV-2 has direct damage to the epithelial cells of the respiratory system, and in-directly due to circulatory disorders. Materials and methods. In the study we analyzed characteristics of autoimmune response in patients with granulomatosis diseases (tuberculosis and sarcoidosis) after COVID-19. We have analyzed articles for the period of December 2019 to March 2023, published in international database (“Medline”, “PubMed”, “Scopus”). The keywords we used “COVID-19”, “SARS-CoV-2”, “tuberculosis”, “sarcoidosis”, “granulomatosis diseases”, “T cells”, “B cells”, “Treg”, “follicular Treg” and “Treg subsets”. The narrative review was carried out in accordance with the PRISMA protocol (http://www.prisma-statement.org) used for this type of study (ID-423604). Results. The influence of COVID-19 infection can also make a significant contribution to the violation of the T- and B-cell immune response, the violation of the nature of cellular metabolism, which will affect the course of granulomatous inflammation in various ways. According to the different researches, autoimmune inflammation can be an important protective mechanism in sarcoidosis and, at the same time, exacerbates the course of tuberculosis infection with the disease progression and pathogen drug resistance formation subsequently. The study of immune response features in patients with COVID-19 showed the presence of several similar characteristics in cellular components of the immune response. Conclusion. Evidence of the presence of autoimmune inflammation in patients with these granulomatous lung diseases, the development of patient immunotypes, including the transferred COVID-19, will be a significant contribution to the development of personalized patient management tactics, taking into account the identified violations of the immune response mechanisms.
Coronaviruses belong to the family Coronaviridae andare zoonotic in origin causing severe respiratory syndrome that may be fatal. Pathogenicity of COVID-19 results from genetic immune reactions that stimulate or activate by environmental factors. The current study aims to evaluate the effect of some molecular, immunological, and hematological indicators on the clinical conditions and severity of hospitalized COVID19 patients by investigating VKORC1(rs9923231 and rs9934438) gene polymorphisms, Hb, WBC, ABO blood groups, platelets and lymphocyte and determination of serum levels of IL-17 and IL-2RA(CD25). This casecontrol study included 100 patients diagnosed with COVID-19 and 100 healthy individuals as the control group. Allele Specific-PCR master mix was performed for genotyping of VKORC1 (rs9923231 and rs9934438) gene polymorphism and quantitative determination of Human IL-17 and Interleukin IL-2RA (CD25 marker) performed by ELISA assay. ARCHITECT auto analyzer is a fully automated device used to determine D-Dimer. In additional, a complete blood count is performed for each blood sample by an automatic RUBY system. Furthermore, the blood grouping reagents were used to detect the presence or absence of ABO and Rhesus Antigens on the surface of human red blood cells based on hemagglutination using the slide technique. In the present results, the mean of patients age was 59.07 years and most of them are males (53%) so most of the infections were within the age group of 70-79 years, especially in patients who have a positive Rh (83%) and were carriers of the A blood group. Age, smoking, and obesity appeared as factors for susceptibility to viral infections. Blood tests showed, the level of D-dimer,WBC, platelets were higher in cases (1497ng/ml, 18.48 X109/L, 388.69 X109/L respectively) compared to control group (220 ng/ml, 7.93 X109/L, 328.21 X109/L respectively) while the mean of lymphocytes and hemoglobin were lower in the patient group (11.67% and 11.97 g/dl respectively) in comparison to the control group (15.12 % and 12.55 g/dl respectively). Immunologically, the concentration of IL-17 and CD25 levels was higher in the cases with severe disease (213.28 and 3689.9 pg/ml respectively) compared to the control group disease (100.69 and 2572.8 pg/ml respectively). The results showed that an increase in the concentration of IL-17 and CD25 coincided with a positive linear increase in WBC and platelets, and to a lesser extent with hemoglobin. Heterozygote and mutant genotypes of VKORC1 (rs9934438/TT) and VKORC1 (rs9923231 AA) appeared as effector factors for the distribution of COVID-19 infection while Wild genotypes (CC and GG respectively) were observed as protective factors. Moreover, The highest frequency of mutant and heterozygote genotypes of VKORC1 (rs9934438 C/T) and (rs9923231 G/A) appeared in severe cases in contrast to wild genotypes that appeared mainly in moderate cases. Patients carrying the mutant genotype TT of VKORC1 (rs9934438) SNP have high levels of IL-17, CD25, D-Dimer, platelets and hemoglobin (219.94 pg/ml, 5861pg/ml, 8372.5 ng/ml, 447.5 X109/L, 13.35 g/dl respectively) so patients who carrier to mutant genotype (AA) of VKORC1 (rs9923231) SNP have high levels of IL-17 (231.18 pg/ml), CD25 (4458.4 pg/ml), WBC (14.63X 10 9 /L) and platelets (388.33X 10 9 /L). In conclusion, a clear association of the studied genetic of (VKORC1), immune, and blood factors with the incidence and severity of COVID-19 infection has been found. It’s also found other factors such as advanced age, smoking, and obesity that have a clear relationship with the deterioration of the health condition of the infected people
COVID-19 is similar to immunoinflammatory rheumatic diseases in clinical manifestations, immune responses and pathogenetic mechanisms. Specific autoantibodies as markers of autoimmune diseases can be detected in patients with coronavirus infection. Most often, after COVID-19, antinuclear antibodies, antibodies to phospholipids, to cardiolipin, to β2-glycoprotein, to cytoplasmic antigens SS-A and SS/B, and cyclic citrulline-containing peptide are detected. In moderate and severe cases of COVID-19 infection with pulmonary-renal syndrome, cytokine storm, antineutrophil cytoplasmic antibodies, antibodies to myeloperoxidase and to proteinase 3 have become more frequent, which can trigger neutrophil NETosis with the formation of extracellular neutrophil traps — networks and induce the development of autoimmune processes and the appearance of de novo immunoinflammatory rheumatic diseases: arthritis , systemic lupus erythematosus, vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA vasculitis). Our study presents 4 clinical cases of patients with ANCA vasculitis with a history of recent coronavirus infection, chronologically verified. The average time after COVID-19 and the onset of ANCA vasculitis was about 3 months; damage to the upper respiratory tract, lower respiratory tract, skin and renal syndromes were observed. The severity of ANCA vasculitis did not depend on the severity of coronavirus infection: a mild course of COVID-19 infection did not exclude a severe course of ANCA vasculitis. It is recommended that all patients during and after coronavirus infection with post-COVID syndrome in the presence of damage to the ENT organs, kidneys, and skin are screened the presence of antineutrophil cytoplasmic antibodies to exclude the onset of ANCA vasculitis.
Aims
This study reports the prevalence and characteristics related to the development of thyroid autoimmunity among children newly diagnosed with type I diabetes (T1D) during the COVID‐19 pandemic in Kuwait.
Materials and Methods
This is a prospective observational study of all children under age 14 years newly diagnosed with T1D in Kuwait. We define the duration of the COVID‐19 pandemic from the official declaration of the first identified positive COVID‐19 case on 24 February 2020 until 31 December 2022. For comparison, we use the time period directly before the COVID‐19 pandemic, 1 January 2017 to 23 February 2020.
Results
One thousand twenty‐four (1024) children newly diagnosed with T1D in Kuwait during the study period were included. Among newly diagnosed children, 20.3% tested positive for thyroid antibodies during the COVID‐19 pandemic, compared with 14.5% during the pre‐pandemic period ( p = 0.015). Children with positive COVID‐19 status were more likely to present with thyroid antibodies ( p = 0.035). After adjusting for other characteristics, patients diagnosed with T1D during the COVID‐19 pandemic had double the odds of testing positive for thyroid antibodies (Adjusted odds ratio = 2.173, 95%CI: 1.108, 4.261, p = 0.024).
Conclusions
Incident cases of T1D during the COVID‐19 pandemic may be different in aetiology or contextual factors leading to a higher risk of thyroid autoimmunity. Longitudinal studies are needed to understand the role of COVID‐19 in the onset and progression of T1D and on thyroid autoimmunity and disease.
Cronkhite-Canada syndrome is a rare gastrointestinal polyposis syndrome with distinctive clinical features and endoscopic findings. Diagnosis can be challenging without suspicion, and the disease carries high mortality due to complications such as infection, gastrointestinal bleeding, and malignancies. This paper presents two cases of Cronkhite-Canada syndrome occurring after coronavirus disease 2019 (COVID-19) mRNA vaccination. Both cases exhibited typical clinical findings, including hypogeusia, onychodystrophy, alopecia, and weight loss. Typical polyposis in the gastrointestinal tract was confirmed through endoscopies. As symptomatic treatment did not improve the symptoms, corticosteroids were administered, and symptoms and laboratory test results improved immediately. The patients improved upon corticosteroids tapering. These cases illustrate typical presentations of Cronkhite-Canada syndrome and the course of the disease following corticosteroid treatment. Additionally, they suggest the possibility that Cronkhite-Canada syndrome may be triggered by COVID-19 mRNA vaccination.
Guillain–Barré syndrome associated with Coronavirus-2-related severe acute respiratory syndrome (COV-GBS) occurs as para- or post-infectious forms, depending on the timing of disease onset. In these two forms, we aimed to compare the cerebrospinal fluid (CSF) and serum proinflammatory cytokine profiles to evaluate differences that could possibly have co-pathogenic relevance.
We studied a retrospective cohort of 26 patients with either post-COV-GBS (n = 15), with disease onset occurring > 7 days after SARS-CoV-2 infection, or para-COV-GBS (n = 11), with disease onset 7 days or less. TNF-α, IL-6, and IL-8 were measured in the serum with SimplePlex™ Ella™ immunoassay. In addition to the para-/post-COV-GBS patients, serum levels of these cytokines were determined in those with non-COVID-associated-GBS (NC-GBS; n = 43), paucisymptomatic SARS-CoV-2 infection without GBS (COVID, n = 20), and in healthy volunteers (HV; n = 12). CSF cytokine levels were measured in patients with para-/post-COV-GBS, in those with NC-GBS (n = 29), or with Alzheimer’s disease (AD; n = 24).
Serum/CSF cytokine levels did not differ in para- vs post-COV-GBS. We found that SARS-CoV-2 infection raises the serum levels of TNF-α, IL-6, and IL-8, as well as an increase of IL-6 (in serum and CSF) and IL-8 (in CSF) in either NC-GBS or COV-GBS than controls. CSF and serum cytokine levels resulted independent one with another.
The change of cytokines linked to SARS-CoV-2 in COV-GBS appears to be driven by viral infection, although it has unique characteristics in GBS as such and does not account for cases with para- or post-infectious onset.
Background Coronavirus disease 2019 (COVID-19) is associated with coagulation abnormalities and increased risk for venous and arterial thrombi. This study aimed to evaluate D-dimer levels and lupus anticoagulant (LAC) positivity in pregnant individuals with and without Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
Study Design This was a prospective cohort study of pregnant individuals delivering at a single academic institution from April 2020 to March 2022. Individuals with a positive SARS-CoV-2 result during pregnancy were compared with a convenience sample of those without a positive SARS-CoV-2 result. For individuals with SARS-CoV-2 infection, severity was assessed based on the National Institutes of Health classification system. The primary outcome was D-dimer level measured during delivery admission. The secondary outcomes were LAC positivity and thromboembolic events. Outcomes were compared between individuals with and without a positive SARS-CoV-2 result, and further by disease severity.
Results Of 98 participants, 77 (78.6%) were SARS-CoV-2 positive during pregnancy. Among individuals with SARS-CoV-2 infection, severity was asymptomatic in 20 (26.0%), mild in 13 (16.9%), moderate in 4 (5.2%), severe in 38 (49.4%), and critical in 2 (2.6%). The D-dimer concentration at delivery did not significantly differ between those with a SARS-CoV-2 positive result compared with those without (mean 2.03 µg/mL [95% confidence interval {CI} 1.72–2.40] vs. 2.37 µg/mL [95% CI 1.65–3.40]; p = 0.43). Three individuals (4%) with SARS-CoV-2 infection and none (0%) without infection were LAC positive (p = 0.59). There were no clinically apparent thromboses in either group. D-dimer concentrations and LAC positive results did not differ by COVID-19 severity.
Conclusion Thrombotic markers did not differ in pregnant individuals by SARS-CoV-2 infection; however, high rates of LAC positivity were detected.
Key Points
Aims:
Data regarding the risk of incident pericarditis in coronavirus disease 2019 (COVID-19) recovered patients are lacking. We determined the risk of incident pericarditis after COVID-19 infection by performing a systematic review and meta-analysis of available data.
Methods:
Following the PRISMA guidelines, we searched MEDLINE and Scopus to locate all articles published up to 11 February 2023 reporting the risk of incident pericarditis in patients who had recovered from COVID-19 infection compared to noninfected patients (controls) defined as those who did not experience the disease over the same follow-up period. Pericarditis risk was evaluated using the Mantel-Haenszel random effects models with hazard ratio (HR) as the effect measure with 95% confidence interval (CI) while heterogeneity was assessed using Higgins I2 statistic.
Results:
Overall, 16 412 495 patients (mean age 55.1 years, 76.8% males), of whom 1 225 715 had COVID-19 infection, were included. Over a mean follow-up of 9.6 months, pericarditis occurred in 3.40 (95% CI: 3.39-3.41) out of 1000 patients who survived COVID-19 infection compared with 0.82 (95% CI: 0.80-0.83) out of 1000 control patients. Recovered COVID-19 patients presented a higher risk of incident pericarditis (HR: 1.95, 95% CI: 1.56-2.43, I2: 71.1%) compared with controls. Meta-regression analysis showed a significant direct relationship for the risk of incident pericarditis using HT (P = 0.02) and male sex (P = 0.02) as moderators, while an indirect association was observed when age (P = 0.01) and the follow-up length (P = 0.02) were adopted as moderating variables.
Conclusions:
Recovered COVID-19 patients have a higher risk of pericarditis compared with patients from the general population.
Currently there are a large number of people diagnosed with SARS-CoV-2, drawing attention to the appearance of some diseases of autoimmune origin after exposure to this infection. It is believed that their association is given by mechanisms that include molecular mimicry, autoantibodies and stimulation of inflammatory signaling. Objective. To identify the relationship between COVID-19 and the development of autoimmune diseases. Methodology. A systematic review of the literature was carried out, using scientific search engines in the following database: Pubmed, Cocharne, Scielo and Science Direct. The information search was carried out from 2020 to 2022, using keywords and search algorithm with the combination of terms: "COVID-19", "autoimmune diseases", "autoimmunity", in addition to this, Boolean operators "And", "Or" and "Not" were used in order to obtain better results in the abruptness. Conclusion. The main mechanisms involved in the development of autoimmunity following SARS-CoV-2 infection include molecular mimicry, the presence of autoantibodies and the cytokine storm characteristic of COVID-19 infection. The autoimmune diseases with which a direct relationship was established are: Guillan-Barre syndrome, autoimmune encephalitis, Graves' disease, Hashimoto's thyroiditis, autoimmune thrombocytopenic purpura and vasculitis, in addition to Kawasaki-like disease, systemic lupus erythematosus, which still need further studies to establish their exact mechanism of action in relation to SARS-CoV-2 infection.
Background:
In December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan and rapidly spread throughout China.
Methods:
Demographic and clinical data of all confirmed cases with COVID-19 on admission at Tongji Hospital from January 10 to February 12, 2020, were collected and analyzed. The data of laboratory examinations, including peripheral lymphocyte subsets, were analyzed and compared between severe and non-severe patients.
Results:
Of the 452 patients with COVID-19 recruited, 286 were diagnosed as severe infection. The median age was 58 years and 235 were male. The most common symptoms were fever, shortness of breath, expectoration, fatigue, dry cough and myalgia. Severe cases tend to have lower lymphocytes counts, higher leukocytes counts and neutrophil-lymphocyte-ratio (NLR), as well as lower percentages of monocytes, eosinophils, and basophils. Most of severe cases demonstrated elevated levels of infection-related biomarkers and inflammatory cytokines. The number of T cells significantly decreased, and more hampered in severe cases. Both helper T cells and suppressor T cells in patients with COVID-19 were below normal levels, and lower level of helper T cells in severe group. The percentage of naïve helper T cells increased and memory helper T cells decreased in severe cases. Patients with COVID-19 also have lower level of regulatory T cells, and more obviously damaged in severe cases.
Conclusions:
The novel coronavirus might mainly act on lymphocytes, especially T lymphocytes. Surveillance of NLR and lymphocyte subsets is helpful in the early screening of critical illness, diagnosis and treatment of COVID-19.
Background:
A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients.
Methods:
All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not.
Findings:
By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0-58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0-13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα.
Interpretation:
The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies.
Funding:
Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
Objective
Systemic juvenile idiopathic arthritis (JIA) is associated with a recently recognized, albeit poorly defined and characterized, lung disease (LD). The objective of this study was to describe the clinical characteristics, risk factors, and histopathologic and immunologic features of this novel inflammatory LD associated with systemic JIA (designated SJIA‐LD).
Methods
Clinical data collected since 2010 were abstracted from the medical records of patients with systemic JIA from the Cincinnati Children's Hospital Medical Center. Epidemiologic, cellular, biochemical, genomic, and transcriptional profiling analyses were performed.
Results
Eighteen patients with SJIA‐LD were identified. Radiographic findings included diffuse ground‐glass opacities, subpleural reticulation, interlobular septal thickening, and lymphadenopathy. Pathologic findings included patchy, but extensive, lymphoplasmacytic infiltrates and mixed features of pulmonary alveolar proteinosis (PAP) and endogenous lipoid pneumonia. Compared to systemic JIA patients without LD, those with SJIA‐LD were younger at the diagnosis of systemic JIA (odds ratio [OR] 6.5, P = 0.007), more often had prior episodes of macrophage activation syndrome (MAS) (OR 14.5, P < 0.001), had a greater frequency of adverse reactions to biologic therapy (OR 13.6, P < 0.001), and had higher serum levels of interleukin‐18 (IL‐18) (median 27,612 pg/ml versus 5,413 pg/ml; P = 0.047). Patients with SJIA‐LD lacked genetic, serologic, or functional evidence of granulocyte–macrophage colony‐stimulating factor pathway dysfunction, a feature that is typical of familial or autoimmune PAP. Moreover, bronchoalveolar lavage (BAL) fluid from patients with SJIA‐LD rarely demonstrated proteinaceous material and had less lipid‐laden macrophages than that seen in patients with primary PAP (mean 10.5% in patients with SJIA‐LD versus 66.1% in patients with primary PAP; P < 0.001). BAL fluid from patients with SJIA‐LD contained elevated levels of IL‐18 and the interferon‐γ–induced chemokines CXCL9 and CXCL10. Transcriptional profiling of the lung tissue from patients with SJIA‐LD identified up‐regulated type II interferon and T cell activation networks. This signature was also present in SJIA‐LD human lung tissue sections that lacked substantial histopathologic findings, suggesting that this activation signature may precede and drive the lung pathology in SJIA‐LD.
Conclusion
Pulmonary disease is increasingly detected in children with systemic JIA, particularly in association with MAS. This entity has distinct clinical and immunologic features and represents an uncharacterized inflammatory LD.
Aim:
To investigate the association between IL-6 polymorphisms (-174G/C, -572G/C and -597G/A) and susceptibility to chronic hepatitis B virus (CHB) infection.
Method:
Total 108 subjects with CHB infection and 102 healthy controls were enrolled in this study. IL-6 (-174G/C) was genotyped using Mutagenically separated Polymerase Chain Reaction (MS-PCR) while sequence specific primers-PCR (SSP-PCR) was used for studying -572G/C and -597G/A. IL-6 plasma level was measured using Enzyme-linked immunosorbent assay (ELISA).
Results:
A significant increase (P < 0.01, P < 0.01, P < 0.001) in -174GG, -572GC and -597GA; respectively in the CHB group compared to control group, while -572GG genotype was significantly decreased (P < 0.01) in CHB patients. A significant increase (p < 0.01, p < 0.01) in -174 G and -597A alleles was observed in the CHB patient group; respectively. GGA haplotype is significantly increased (P < 0.05) while GCA haplotype is significantly decreased (P < 0.001) in the patient group. A moderate linkage disequilibrium (LD) (D' = 0.719, r2 = 0.474; P < 0.001) between IL-6 (-572G/C and -597G/A) was observed. A significant reduction (P < 0.01) in IL-6 plasma level in CHB patients compared to healthy controls (22.28 ± 1.93 versus 32.08 ± 2.41), which was negatively correlated (r = -0.216; P < 0.01) with HBV infection.
Conclusions:
This study pointed to the potential role of IL-6 (-174G/C, -572 G/C and -597G/A) gene polymorphisms in the susceptibility to HBV infection. Our results allow for only preliminary conclusions due to relatively small sample size. There is a need for further larger scale studies to fully examine the possible relationship between these cytokine gene polymorphisms and the development of CHB.
Interleukin 6 (IL-6), promptly and transiently produced in response to infections and tissue injuries, contributes to host defense through the stimulation of acute phase responses, hematopoiesis, and immune reactions. Although its expression is strictly controlled by transcriptional and posttranscriptional mechanisms, dysregulated continual synthesis of IL-6 plays a pathological effect on chronic inflammation and autoimmunity. For this reason, tocilizumab, a humanized anti-IL-6 receptor antibody was developed. Various clinical trials have since shown the exceptional efficacy of tocilizumab, which resulted in its approval for the treatment of rheumatoid arthritis and juvenile idiopathic arthritis. Moreover, tocilizumab is expected to be effective for other intractable immune-mediated diseases. In this context, the mechanism for the continual synthesis of IL-6 needs to be elucidated to facilitate the development of more specific therapeutic approaches and analysis of the pathogenesis of specific diseases.
The autoinflammatory diseases are characterized by seemingly unprovoked episodes of inflammation, without high-titer autoantibodies or antigen-specific T cells. The concept was proposed ten years ago with the identification of the genes underlying hereditary periodic fever syndromes. This nosology has taken root because of the dramatic advances in our knowledge of the genetic basis of both mendelian and complex autoinflammatory diseases, and with the recognition that these illnesses derive from genetic variants of the innate immune system. Herein we propose an updated classification scheme based on the molecular insights garnered over the past decade, supplanting a clinical classification that has served well but is opaque to the genetic, immunologic, and therapeutic interrelationships now before us. We define six categories of autoinflammatory disease: IL-1beta activation disorders (inflammasomopathies), NF-kappaB activation syndromes, protein misfolding disorders, complement regulatory diseases, disturbances in cytokine signaling, and macrophage activation syndromes. A system based on molecular pathophysiology will bring greater clarity to our discourse while catalyzing new hypotheses both at the bench and at the bedside.
The outbreak of the new coronavirus infections COVID-19 in December 2019 in China has quickly become a global health emergency. Given the lack of specific anti-viral therapies, the current management of severe acute respiratory syndrome coronaviruses (SARS-CoV-2) is mainly supportive, even though several compounds are now under investigation for the treatment of this life-threatening disease. COVID-19 pandemic is certainly conditioning the treatment strategy of a complex disorder as rheumatoid arthritis (RA), whose infectious risk is increased compared to the general population because of an overall impairment of immune system typical of autoimmune diseases combined with the iatrogenic effect generated by corticosteroids and immunosuppressive drugs. However, the increasing knowledge about the pathophysiology of SARS-CoV-2 infection is leading to consider some anti-rheumatic drugs as potential treatment options for the management of COVID-19. In this review we will critically analyse the evidences on either positive or negative effect of drugs commonly used to treat RA in this particular scenario, in order to optimize the current approach to RA patients.
OBJECTIVE. The increasing number of cases of confirmed coronavirus disease (COVID-19) in China is striking. The purpose of this study was to investigate the relation between chest CT findings and the clinical conditions of COVID-19 pneumonia. MATERIALS AND METHODS. Data on 101 cases of COVID-19 pneumonia were retrospectively collected from four institutions in Hunan, China. Basic clinical characteristics and detailed imaging features were evaluated and compared between two groups on the basis of clinical status: nonemergency (mild or common disease) and emergency (severe or fatal disease). RESULTS. Patients 21-50 years old accounted for most (70.2%) of the cohort, and five (5.0%) patients had disease associated with a family outbreak. Most patients (78.2%) had fever as the onset symptom. Most patients with COVID-19 pneumonia had typical imaging features, such as ground-glass opacities (GGO) (87 [86.1%]) or mixed GGO and consolidation (65 [64.4%]), vascular enlargement in the lesion (72 [71.3%]), and traction bronchiectasis (53 [52.5%]). Lesions present on CT images were more likely to have a peripheral distribution (88 [87.1%]) and bilateral involvement (83 [82.2%]) and be lower lung predominant (55 [54.5%]) and multifocal (55 [54.5%]). Patients in the emergency group were older than those in the non-emergency group. Architectural distortion, traction bronchiectasis, and CT involvement score aided in evaluation of the severity and extent of the disease. CONCLUSION. Patients with confirmed COVID-19 pneumonia have typical imaging features that can be helpful in early screening of highly suspected cases and in evaluation of the severity and extent of disease. Most patients with COVID-19 pneumonia have GGO or mixed GGO and consolidation and vascular enlargement in the lesion. Lesions are more likely to have peripheral distribution and bilateral involvement and be lower lung predominant and multifocal. CT involvement score can help in evaluation of the severity and extent of the disease.
Objective
To investigate the characteristics and risk factors of a novel parenchymal lung disease (LD), increasingly detected in systemic juvenile idiopathic arthritis (sJIA).
Methods
In a multicentre retrospective study, 61 cases were investigated using physician-reported clinical information and centralised analyses of radiological, pathological and genetic data.
Results
LD was associated with distinctive features, including acute erythematous clubbing and a high frequency of anaphylactic reactions to the interleukin (IL)-6 inhibitor, tocilizumab. Serum ferritin elevation and/or significant lymphopaenia preceded LD detection. The most prevalent chest CT pattern was septal thickening, involving the periphery of multiple lobes ± ground-glass opacities. The predominant pathology (23 of 36) was pulmonary alveolar proteinosis and/or endogenous lipoid pneumonia (PAP/ELP), with atypical features including regional involvement and concomitant vascular changes. Apparent severe delayed drug hypersensitivity occurred in some cases. The 5-year survival was 42%. Whole exome sequencing (20 of 61) did not identify a novel monogenic defect or likely causal PAP-related or macrophage activation syndrome (MAS)-related mutations. Trisomy 21 and young sJIA onset increased LD risk. Exposure to IL-1 and IL-6 inhibitors (46 of 61) was associated with multiple LD features. By several indicators, severity of sJIA was comparable in drug-exposed subjects and published sJIA cohorts. MAS at sJIA onset was increased in the drug-exposed, but was not associated with LD features.
Conclusions
A rare, life-threatening lung disease in sJIA is defined by a constellation of unusual clinical characteristics. The pathology, a PAP/ELP variant, suggests macrophage dysfunction. Inhibitor exposure may promote LD, independent of sJIA severity, in a small subset of treated patients. Treatment/prevention strategies are needed.
Haemophagocytic syndromes (haemophagocytic lymphohistiocytosis) have a wide range of causes, symptoms, and outcomes, but all lead to a hyperinflammatory response and organ damage-mainly reported in paediatric patients, but reports of adult presentation are increasing. Analysis of the genetic and molecular pathophysiology of these syndromes have improved the understanding of the crosstalk between lymphocytes and histiocytes and their regulatoty mechanisms. Clinical presentations with a broad differential diagnosis, and often life-threatening outcome, complicate the management, which might include supportive intensive care, immunosuppressive and biological treatments, or haemopoietic stem cell transplantation. Insufficient knowledge of these syndromes could contribute to poor prognosis. Early diagnosis is essential to initiate appropriate treatment and improve the quality of life and survival of patients with this challenging disorder.
COVID-19 infection and rheumatoid arthritis: Faraway, so close! Autoimm Rev
- E G Favalli
- F Ingegnoli
- De Lucia
- O Cincinelli
- G Cimaz
- R Caporali
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- D Milojevic
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- K Phillippi
- S Prahalad
- S Radhakrishna
- A Reinhardt
- M Riskalla
- N Rosenwasser
- J Roth
- R Schneider
- D Schonenberg-Meinema
Milojevic D, Mombourquette J, Onel K, Ozen S, Perez M, Phillippi K, Prahalad S, Radhakrishna S,
Reinhardt A, Riskalla M, Rosenwasser N, Roth J, Schneider R, Schonenberg-Meinema D, Shenoi
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on behalf of the HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression Lancet
- P Mehta
- D F Mcauley
- M Brown
- E Sanchez
- R S Tattersall
- J J Manson
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, on behalf of the HLH
Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and
immunosuppression Lancet 2020. doi. 10.1016/S0140-6736(20)30628-0