Development of Graves' Disease After SARS-CoV-2 mRNA Vaccination: A Case Report and Literature Review

Background: Mounting evidence has revealed the interrelationship between thyroid and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to explain the thyroid dysfunction and autoimmune thyroid disorders observed after coronavirus disease 2019 (COVID-19). There are limited reports of thyroid dysfunction after SARS-CoV-2 vaccination.Methods: We report a case of a 40-year-old Chinese woman who developed Graves' disease after BNT162b2 mRNA vaccine. A search of PubMed and Embase databases from 1 September 2019 to 31 August 2021 was performed using the following keywords: “COVID,” “vaccine,” “thyroid,” “thyroiditis,” and “Graves.”Results: A 40-year-old Chinese woman who had 8-year history of hypothyroidism requiring thyroxine replacement. Her anti-thyroid peroxidase and anti-thyroglobulin antibodies were negative at diagnosis. She received her first and second doses of BNT162b2 mRNA vaccine on 6 April and 1 May 2021, respectively. She developed thyrotoxicosis and was diagnosed to have Graves' disease 5 weeks after the second dose of vaccine, with positive thyroid stimulating immunoglobulin level, diffuse goiter with hypervascularity on thyroid ultrasonography and diffusely increased thyroid uptake on technetium thyroid scan. Both anti-thyroid peroxidase and anti-thyroglobulin antibodies became positive. She was treated with carbimazole. Literature search revealed four cases of Graves' disease after SARS-CoV-2 vaccination, all after mRNA vaccines; and nine cases of subacute thyroiditis, after different types of SARS-CoV-2 vaccines.Conclusion: Our case represents the fifth in the literature of Graves' disease after SARS-CoV-2 vaccination, with an unusual presentation on a longstanding history of hypothyroidism. Clinicians should remain vigilant about potential thyroid dysfunction after SARS-CoV-2 vaccination in the current pandemic.

Subcutaneous Tocilizumab for Thyroid Eye Disease

Purpose: To demonstrate the efficacy of subcutaneous tocilizumab (TCZ-SC) treatment for recalcitrant thyroid eye disease (TED) refractory to intravenous methylprednisolone (MP) and oral methotrexate (MTX).Case summary: (Case 1) A 52-year-old man, smoker, with hyperthyroidism presented with a 3-months history of TED. The initial clinical activity score (CAS) was 5 (total score of 7). High-dose intravenous MP and oral MTX failed to improve the symptoms. He was treated with four doses of 162 mg TCZ-SC at an interval of 2 weeks. Pre-treatment laboratory test results were within normal limits. CAS was reduced to 2 weeks after the final injection, and there were no recurrences during the 6-month follow-up. (Case 2) A 37-year-old woman, non-smoker, with a 3-months history of hyperthyroidism presented with conjunctival injection and upper eyelid erythema. The initial CAS was 4, and thyroid-stimulating immunoglobulin level was raised (475% of normal). The symptoms did not improve with 7.5 g intravenous MP and oral MTX. The patient was treated with 162 mg TCZ-SC. Pre-treatment laboratory test results were within normal limits. CAS was reduced to 1 after the final injection, and there were no recurrences during the 6-months follow-up.Conclusions: TCZ-SC improves symptoms of corticosteroid-resistant TED, and may be a reasonable option in recalcitrant TED cases. However, further studies are required to justify the use of TCZ-SC for TED.

A Third Anti-Sars-Cov2 mRNA Dose Does Not Overcome the Pejorative Impact of Anti-CD20 Therapy and/or Low Immunoglobulin Level in CLL/Lymphoma Patients

Introduction: Patients with lymphoma and chronic lymphocytic leukemia (CLL) share immune-deficiencies due to the biological features of these diseases per se and to their treatments. They are at risk to develop severe and/or prolonged forms of Covid-19. The efficacy of vaccination against COVID in lymphoma/CLL patients also raises specific concerns: Antibody response to mRNA COVID-19 vaccine was shown to be negatively affected by CLL stage and its treatments, especially in case of previous administration of anti-CD20 antibodies (Herishanu et al). Therefore, the addition of a third dose of vaccine in immunosuppressed patients is currently recommended in France. Methods: To analyse the determinants of the antibody response after anti-SARS-Cov2 mRNA vaccines (Pfizer or Moderna), we conducted a retrospective monocentric study among adults with a past or current lymphoma/CLL who underwent serology 2 weeks or more after 2 or 3 previous injections. The decision of a third dose was at the discretion of each physician. Data were extracted from the patients' medical charts on their demographics, lymphoma history and detailed treatments, vaccinations and biological parameters (immunoglobulin (Ig) G dosage, lymphocytic, B-cell and T-cell counts) and serology (Elecsys ® Anti-SARS-CoV-2 S). Statistical tests were two-tailed and p-values < 0.05 were considered significant. Multivariable analysis was conducted using independent variables having univariate significance below 0.1. This study was conducted in accordance with the Declaration of Helsinki, and approved by the ethics committee of our institution. Results: Ninety-one patients with non-Hodgkin's lymphomas (NHL) (n=48), CLL (32) or Hodgkin's lymphoma (11) were enrolled. With a median interval since last dose of 47 days (range 15-125), 48 patients (53%) had a negative serology (Table). Gender and age were not associated with antibody response. The proportion of seronegativity was 57% among patients with B-cell NHL, and 41% among those with CLL. Among the biological variables reflecting immune deficiency, lymphocytopenia (<1.5G/L), low B-cell counts (<0.2G/L) and IgG levels (<6g/L) were significantly associated with a higher risk of seronegativity with odds-ratios (OR, [95% confidence interval]) of 5.1 [1.8-15.3], p<7x10 -4 , 15.0 [3.0-147.9], p<7x10 -5, and 15.3 [3.7-93.0], p<9x10 ⁻6 respectively). Patients under watch and wait attitude and those who did not have a lymphoma/CLL treatment since at least 12 months before vaccination had a much lower risk of negative serology (OR: 0.08 [<0.01 ; 0.4], p< 2.10 -4). Among lymphoma/CLL therapies, chemotherapy overall or targeted therapy with BTK inhibitors or Venetoclax were not significantly associated with a lower risk of negative serology. In contrast, the administration of anti-CD20 therapy during the year before first dose of vaccine was associated with a higher risk of negative serology (OR: 4.5 [1.7; 12.1], p<8.10 -4). Of note, this treatment was also significantly associated with both lymphocytopenia and low B-cell counts. There was no association between the number of vaccine doses and the risk of negative serology, 59% of the patients who received 3 doses remained seronegative.A multivariable analysis associating IgG level and treatment history showed that negative serology is significantly associated with a low level of IgG (OR: 25.74 [5.58; 201.14], p < 10 -3) and anti-CD20 treatment (OR: 28.70 [4.14, 382.60], p = 3x10 -3). Conclusion: Overall, previous anti-CD20 therapy and low IgG levels are the main independent factors associated with a lack of serological response after anti-SARS-Cov2 mRNA vaccine. Administration of a third vaccine does not overcome their pejorative impact. This should contribute to the elaboration of guidelines for the management of lymphoma/CLL patients during the Covid-19 era. In particular, in all non-critical clinical situation, SARS-CoV-2 vaccination should be proposed before the onset of lymphoma/CLL therapy. Meanwhile, individuals with CLL/lymphoma should receive the Covid-19 vaccine, be informed that they are unlikely to be protected and continue social distancing and adhere to other proven mitigation strategies. Systematic vaccination of their proxies and hospital workers should also benefit directly to patients. Figure 1 Figure 1. Disclosures Rigaudeau: Takeda: Membership on an entity's Board of Directors or advisory committees.

Correlation between Vitamin A Deficiency and the Severity of Mycoplasma Pneumoniae Pneumonia in Children

Mycoplasma pneumoniae pneumonia is a problem that has attracted the attention of children’s respiratory department in recent years. The relationship between vitamin A deficiency (VA) and the severity of Mycoplasma disease (MPP) in children was studied. In this paper, the hospitalized children with Mycoplasma pneumoniae pneumonia (MPP) in our hospital were selected as the research objects, and they were divided into common type and refractory type (RMPP) for comparative experiment. The VA and immunoglobulin levels of the two groups were compared. Attention should be paid to the normal ratio of VA deficiency (CVAD) and sub deficiency (svad) in the two groups. In this paper, the relationship between infection, immunoglobulin level and VA level was analyzed. The results showed that CVAD was 27.27% in MPP group and 63.75% in RMPP group. Comparison of immunoglobulin levels between the two groups: the levels of IgM, IgA and IgG in the normal MPP group were significantly lower than those in the RMPP group. On the other hand, the detection rate of CVAD was 81.48% in RMPP with infection and 54.72% in RMPP without infection. The detection rate of CVAD in patients with infection was significantly higher than that in patients without infection. There was a correlation between VA Deficiency and MPP classification.

A blend of herbal essential oils enhanced the growth performance, blood bio-immunology traits, and intestinal health of Nile tilapia (Oreochromis niloticus)

Nile tilapia fed four levels (0, 0.25, 0.5, and 1 ml/kg) of a liquid blend of herbal essential oils (EOs) contains carvacrol, oregano, 1,8 cineol, thymol, pinene, pinene β, limonene, and propylene glycol for 60 days. The results showed higher final weight, weight gain, and specific growth rate (P<0.05) in fish delivered 0.25 and 0.5 ml EOs/kg than the control. However, the feed conversion ratio was markedly reduced in fish fed 0.5 and 1 ml EOs/kg (P<0.05). Lipase showed enhanced activity in fish subjected to a blend of EOs, while fish fed 0.5 ml/kg of EOs blend had higher amylase activity (P<0.05) than the other levels. Lysozyme activity and superoxide dismutase showed a higher value in fish received 0.5 ml EOs/kg. Additionally, phagocytic and catalase activities enhanced in fish received 0.5 and 1 ml/kg while phagocytic index enhanced in fish fed 1 ml/kg (P<0.05). Interestingly, the total immunoglobulin level was markedly higher, while malondialdehyde was lower in EOs-subjected fish (P<0.05) than in control. The histomorphology appearance of the intestine, liver, and spleen were enriched in EOs-treated fish comparing the control fish. In conclusion, the growth performance, feed efficiency, and blood bio-immunological indices of fish fed 0.5–1 ml of EOs blend per kg had the best performances.

Evaluation of the effect of lidocaine epidural injection on immunological indices in dogs under total intravenous anesthesia submitted to ovariohysterectomy

This study aimed to evaluate the effects of epidural anaesthesia with lidocaine in combination with general anaesthesia with propofol on some immunologic indices in dogs undergoing ovariohysterectomy. Twelve adult dogs were anesthetized with propofol (induction: 7 mg/kg; maintenance: 0.4 mg/kg/min) and were then allocated into either groups of epidural saline (control) or epidural lidocaine (4 mg/kg; treatment). All the included animals underwent ovariohysterectomy operation. The immune responses, hematologic parameters and cortisol levels were assessed in the predetermined intervals. Evaluation of the innate immunity revealed higher significant levels in the bactericidal, lysozyme and myeloperoxidase activities at 4 hours after surgery in the treatment. In the humoral immunity, the total immunoglobulin level was significantly higher in the treatment. In the assessment of cellular immunity, higher significant values were detected in the delayed skin sensitivity to phytohemagglutinine injection after 48 and 72 hours in the treatment. Moreover, higher significant levels were observed in the number and percentage of lymphocytes as well as an increase in the percentage of monocytes in the treatment at 4 hours after the operation. Notably, the cortisol hormone in the treatment was lower than control at 4 hours of the surgery. In conclusion, epidural anaesthesia with lidocaine when added to general anaesthesia with propofol attenuated the suppression of the innate and cellular immune responses produced by anaesthesia and surgery in the dogs.

Immunoglobulin levels in systemic lupus erythematosus: A narrative review

Immunoglobulins play a fundamental role in the protection of the human body against internal and external threats. They also contribute to the immune system homeostasis and maintenance of self-tolerance. Hypogammaglobulinemia is occasionally encountered in routine clinical practice by rheumatologists. Low levels of immunoglobulins can occur as primary or secondary issues and may predispose patients to various forms of infection. However, the impact of the low immunoglobulin level abnormality varies with the underlying condition. In this narrative review, we shed light on the overall types and functions of immunoglobulins for clinicians. We discuss important principles of immunoglobulin measurements. We then consider the primary and secondary causes of low immunoglobulins with a special focus on hypogammaglobulinemia in patients with systemic lupus erythematosus (SLE).

COVID-19 in Russia: Clinical and Immunological Features of the First-Wave Patients

The coronavirus disease outbreak in 2019 (COVID-19) has now achieved the level of a global pandemic and affected more than 100 million people on all five continents and caused over 2 million deaths. Russia is, needless to say, among the countries affected by SARS-CoV-2, and its health authorities have mobilized significant efforts and resources to fight the disease. The paper presents the result of a functional analysis of 155 patients in the Moscow Region who were examined at the Central Clinical Hospital of the Russian Academy of Sciences during the first wave of the pandemic (FebruaryJuly, 2020). The inclusion criteria were a positive PCR test and typical, computed tomographic findings of viral pneumonia in the form of ground-glass opacities. A clinical correlation analysis was performed in four groups of patients: (1) those who were not on mechanical ventilation, (2) those who were on mechanical ventilation, and (3) those who subsequently recovered or (4) died. The correlation analysis also considered confounding comorbidities (diabetes, metabolic syndrome, hypertension, etc.). The immunological status of the patients was examined (levels of immunoglobulins of the M, A, G classes and their subclasses, as well as the total immunoglobulin level) using an original SARS-CoV-2 antibody ELISA kit. The ELISA kit was developed using linear S-protein RBD-SD1 and NTD fragments, as well as the N-protein, as antigens. These antigens were produced in the prokaryotic E. coli system. Recombinant RBD produced in the eukaryotic CHO system (RBD CHO) was used as an antigen representing conformational RBD epitopes. The immunoglobulin A level was found to be the earliest serological criterion for the development of a SARS-CoV-2 infection and it yielded the best sensitivity and diagnostic significance of ELISA compared to that of class M immunoglobulin. We demonstrated that the seroconversion rate of early N-protein-specific IgM and IgA antibodies is comparable to that of antibodies specific to RBD conformational epitopes. At the same time, seroconversion of SARS-CoV-2 N-protein-specific class G immunoglobulins was significantly faster compared to that of other specific antibodies. Our findings suggest that the strong immunogenicity of the RBD fragment is for the most part associated with its conformational epitopes, while the linear RBD and NTD epitopes have the least immunogenicity. An analysis of the occurrence rate of SARS-CoV-2-specific immunoglobulins of different classes revealed that RBD- and N-specific antibodies should be evaluated in parallel to improve the sensitivity of ELISA. An analysis of the immunoglobulin subclass distribution in sera of seropositive patients revealed uniform induction of N-protein-specific IgG subclasses G1G4 and IgA subclasses A1A2 in groups of patients with varying severity of COVID-19. In the case of the S-protein, G1, G3, and A1 were the main subclasses of antibodies involved in the immune response.

Effect of Fermented Rapeseed Meal on the Gastrointestinal Microbiota and Immune Status of Rabbit (Oryctolagus cuniculus)

The present study was conducted to determine the effect of the use of varying amounts of fermented rapeseed meal in diets for rabbits on the immune status and microbiota of segments of the GIT. Forty 35 day old rabbits used in the experiment were assigned to four groups: the control group (group C) were fed a standard diet and the experimental received 4%, 8% or 12% fermented rapeseed meal (included in place of standard soybean meal). Class A, G and M immunoglobulins were determined in the blood plasma. In the food content collected after slaughter, microbiological parameters were determined for individual sections of the digestive tract. Rabbits from the groups receiving a diet with an increased proportion of fermented rapeseed meal (8% or 12%) had lower concentrations of anaerobic bacteria and Escherichia coli in the intestinal contents. Research has shown that the increase in intake of fermented rapeseed meal was correlated with an increase in the correlations between the immunoglobulin level and the size of the microbial population in the GIT. In light of the presented results fermented rapeseed meal, by supplying valuable bioactive substances, appears to be a good component in the diet of rabbits, enhancing immune system development and helping to prevent disturbances of the gut microbiota.