Seronegative Group Research Articles

Diseases associated antibodies anti-MOG and double seronegative NMOsd during the COVID-19 pandemic. Interim analysis of a cohort study. (P13-5.012)

<h3>Objective:</h3> To describe the clinical and demographic findings of patients from the National Institute of Neurology and Neurosurgery anti-MOG validation cohort tested for anti-MOG and anti-AQP4. <h3>Background:</h3> Anti-MOG associated diseases (MOGAD) include demyelinating disease phenotypes such as optic neuritis, longitudinally extensive transverse myelitis, acute disseminated encephalomyelitis, Neuromyelitis Optica syndrome (NMOsd) among others. In our country, the incidence of this pathology is unknown, mainly due to the lack of diagnostic tools. <h3>Design/Methods:</h3> As part of the cohort of the National Institute of Neurology and Neurosurgery in Mexico, for the validation of a MOG CBA-assay, anti-AQP4 and MOG antibody tests were requested from those patients who met the Jarius 2018 criteria for MOGAD. Measurements of central tendency are made for each group and we analyze the MOG+ and double seronegative groups with Fisher’s exact and Mann Whitney. <h3>Results:</h3> Eighteen patients were analyzed. Seven patients were MOG+, 62% women. The mean age for patients with MOG was 40 years. Presentation was 100% atypical optic neuritis. The anterior segment was more affected in 42% of the patients. Five (71.4%) patients had a deficit &gt;200/100, 3 of them improved to 20/40 regardless of whether or not they received plasmapheresis (X2 0.833 p=0.361). Post-vaccination possibility was documented in 57%. There were no significant differences between patients with different sero-status. Four patients are maintained with Rituximab support treatment. <h3>Conclusions:</h3> MOG+ patients were mostly women, despite a severe initial deficit, an adequate visual recovery was documented regardless of the plasmapheresis time. A larger number of patients are required to perform a pairwise comparison with those with AQP4+. <b>Disclosure:</b> Dr. Rodriguez has nothing to disclose. Dr. Aguilar-Gonzalez has nothing to disclose. Veronica Rivas has nothing to disclose. Dr. Flores-Rivera has nothing to disclose. Teresita Corona Vazquez has nothing to disclose.

Clinical significance of anti-NT5c1A autoantibody in Korean patients with inflammatory myopathies.

To explore the clinical significance of anti-cytosolic 5'-nucleoditase 1A (NT5c1A) antibody seropositivity in inflammatory myopathies, we measured anti-NT5c1A antibodies and analyzed their clinical features. Anti-NT5c1A antibodies were measured in the sera of 103 patients with inflammatory myopathies using an enzyme-linked immunosorbent assay. Positivity for anti-NT5c1A antibody was found in 13 (12.6%) of 103 patients with inflammatory myopathy. Anti-NT5c1A antibody was most frequently identified in patients with inclusion body myositis (IBM) (8/20, 40%), followed by dermatomyositis (2/13, 15.4%), immune-mediated necrotizing myopathy (2/28, 7.1%), and polymyositis (1/42, 2.4%). In eight patients with the anti-NT5c1A antibody-seropositive IBM, the median age at symptom onset was 54 years (interquartile range [IQR]: 48-57 years), and the median disease duration was 34 months (IQR: 24-50 months]. Knee extension weakness was greater than or equal to hip flexion weakness in eight (100%) patients, and finger flexion strength was less than shoulder abduction in three (38%) patients. Dysphagia symptoms were found in three (38%) patients. The median serum CK level was 581 IU/l (IQR: 434-868 IU/L]. Clinically significant differences were not found between anti-NT5c1A antibody-seropositive and seronegative IBM groups with respect to gender, age at symptom onset, age at diagnosis, disease duration, serum CK values, presence of other autoantibodies, dysphagia, and the pattern of muscle impairment. Although anti-NT5c1A antibody is known to be associated with IBM, seropositivity has also been noted in non-IBM inflammatory myopathies, and is insufficient to have clinical significance by itself. These findings have important implications for interpreting anti-NT5c1A antibody test results as the first study in Korea.

The role of regulatory micro-RNAs in inflammatory processes and production of tumor necrosis factor-alpha in patients with rheumatoid arthritis

Background. Micro-RNAs are fundamental agents of post-transcriptional control of gene expression. In recent years many works have appeared on the possible role of micro-RNAs in rheumatoid arthritis (RA). Studies of the role of micro-RNA and the relationship with the synthesis of tumor necrosis factor-α (TNF-α) are very promising for understanding the pathogenesis and treatment of RA and other autoimmune diseases. The purpose of the research was to study the role of regulatory micro-RNAs in inflammatory processes and the possible connection with the production of TNF-α in patients with RA. Materials and methods. 29 patients with active RA and 20 healthy individuals (control) were examined. All subjects were examined for 16 micro-RNAs. The choice of micro-RNA was based on previous studies and theoretical conclusions (according to the miRWalk database). Rheumatoid factor, the level of antibodies to cyclic peptides containing citrulline, C-reactive protein (СRP), levels of TNF-α (serum, spontaneous, and stimulated) were determined in the blood of patients. Results. Statistical analysis demonstrated significant overexpression of miR-221, miR-203, miR-146b, miR-132, miR-21 and miR-17-3p and inhibition of miR-223 synthesis in RA patients. The activation of TNF-α synthesis at rest and the increased production of TNF-α by mononuclear cells after stimulation in RA were shown. Differences in the levels of relative expression of some micro-RNAs between seropositive and seronegative groups of RA patients were found, but only hyperexpression of miR-155 was highly reliable. For the first time, a possible relationship between TNF-α production and miR-29 and miR-155 micro-RNAs, as well as a correlation between miR-16, miR-99b and miR-203 and CRP levels, was revealed. Conclusions. The obtained data on the profile of micro-RNAs in RA makes it possible to distinguish the most “interesting” micro-RNAs for further study of pathogenesis, their role in inflammation, to study the choice of TNF-α inhibitors, and predicting the effectiveness of that treatment.

Diagnostic and prognostic markers of seronegative rheumatoid arthritis

Introduction. Rheumatoid arthritis (RA) is the most common inflammatory disease of the joints, the prevalence of which is increasing in the population, leading to the emergence of new cases of the disease in young and middle-aged people, which has enormous medical and social significance. The study objective was to optimize the diagnosis and prediction of seronegative early rheumatoid arthritis outcomes by identifying the most significant clinical, laboratory and instrumental predictors of joint destruction. Material and methods. The study includes 82 patients (22 men and 60 women), aged 17 to 70 years (average of 45.02±12.4 years), with the presence of articular syndrome (arthritis). All subjects were classified in the following groups: group I – 41 patients - 11 men and 30 women, whose average age was 44.46±13.36 years (average duration of the disease 6.0±2.9 months) with early seronegative rheumatoid arthritis (eRA), and group II consisted of 41 patients aged 45.55±11.12 years - 11 men and 30 women, with a diagnosis of seropositive rheumatoid arthritis (RA) (average duration of the disease of 6.8±3.7 months). Results. In the seronegative eRA group, the average Value of “prognostic index” (PrI) calculated from the data at the time of the initial survey was 5.67±1.72 points. PrI values in patients with transformation in RA within 1 year were significantly higher – 6.68±1.61, than without transformation in RA 4.52±0.96 points, p &lt; 0.0001. At the same time, the values of PrI &lt; 6 points were observed in 17 (20.7%) patients, PrI &gt; 8 – in 25 (30.48%) patients, intermediate values (between 6 and 8 points) – in 40 (48.78%) patients, p &lt; 0.001. Thus, in most patients with transformation in RA, the PrI values were more than 6 points. Conclusions. In 53% of patients with seronegative RA, there is a transformation into seropositive rheumatoid arthritis during the first 18 months of the development of the disease. Features of early rheumatoid arthritis, in comparison with stabile RA are a polyarthritis presentation of the onset with damage to the joints of the hands, prolonged morning stiffness (more than 1 hour), moderate or high level of activity, the presence of productive synovitis and erosion during ultrasonography.

A comparative analysis of demographic, clinical and imaging features of myelin oligodendrocyte glycoprotein antibody positive, aquaporin 4 antibody positive, and double seronegative demyelinating disorders - An Indian tertiary care center prospective study.

The aim of the study was to study the demographical, clinical, radiological features, and outcome of anti-myelin oligodendrocyte glycoprotein (MOG) antibody spectrum disorder and compare these features with patients negative for anti-MOG antibody. MOG antibody-associated disease (MOGAD) and aquaporin-4 (AQP4) antibody-related diseases are immunologically distinct pathologies. Our aim was to compare the clinical and radiological features of MOG antibody-related diseases with AQP4 antibody-related diseases and seronegative demyelinating diseases (Non-multiple sclerosis). This was a prospective and cohort study conducted at an apex tertiary care institute in the northern part of India from Jan 2019 to May 2021. We compared clinical, laboratory, and radiological findings of patients with MOGAD, AQP4 antibody-related diseases, and seronegative demyelinating disease. There were a total of 103 patients - 41 patients of MOGAD, 37 patients of AQP4 antibody-related diseases and 25 seronegative demyelinating disease. Bilateral optic neuritis was the most frequent phenotype in patients with MOGAD (18/41) whereas myelitis was the most common phenotype in the AQP4 (30/37) and seronegative groups (13/25). Cortical, juxtacortical lesions, anterior segment optic neuritis, optic sheath enhancement, and conus involvement in myelitis were radiological findings that separated MOGAD from AQP4 related diseases. Nadir Expanded Disability Status Scale (EDSS) and visual acuity were similar across the groups. Last follow-up EDSS was significantly better in the MOG antibody group as compared to AQP4 antibody group (1 [0-8] vs. 3.5 [0-8]; P = 0.03). Encephalitis, myelitis, and seizures were more common in the younger population (<18 vs. >18 years) in MOGAD (9 vs. 2, P = 0.001; 9 vs. 7, P = 0.03; 6 vs. 0, P = 0.001). We identified several clinical and radiological features that can help physicians to distinguish MOGAD from AQP4-immunoglobulin G+neuromyelitis optica spectrum disorder. Differentiation is vital as treatment response might vary among both groups.

Assessment of Prognostic Factors and Validity of Scoring Models in Childhood Autoimmune Encephalitis.

The aim of this study is to evaluate the prognostic factors in a single-center pediatric cohort with autoimmune encephalitis. The study group consisted of 23 pediatric autoimmune encephalitis patients (seropositive autoimmune encephalitis: 15, seronegative autoimmune encephalitis: 8). Five group prognostic parameters were evaluated: clinical manifestations, elect roenc ephal ograp hy features, magnetic resonance imaging characteristics, biomarkers, and treatment modalities. Three scoring models were applied: the Antibody Prevalence in Epilepsy and Response to Immunotherapy in Epilepsy for predicting autoimmune-related epilepsy in the whole cohort and the anti-N-methyl-d-aspartate receptor Encephalitis 1-Year Functional Status score for overall outcome in patients with anti-N-methyl-d-aspartate receptor encephalitis. The initial clinical spectrum of the disease was similar in the seronegative and seropositive groups. Almost half of the patients (48%) recovered without any complications with first-line immunotherapy. The patients with movement disorders in the acute phase of the disease needed more likely second-line immunotherapy (P = .039). The presence of status epilepticus at admission was significantly associated with adverse outcomes and the development of autoimmune-related epilepsy (P = .019). Autoimmune-related epilepsy was defined in an equal proportion of patients (91.5%) with 2 immune epilepsy scores (Antibody Prevalence in Epilepsy and Response to Immunotherapy in Epilepsy). The N-methyl-d-aspartate receptor Encephalitis 1-Year Functional Status score and the modified Rankin score assessed for the first-year prognosis were strongly correlated among the patients with anti-N-methyl-d-aspartate receptor encephalitis (P = .03, Spearmen's rho = 0.751). The presence of status epilepticus was the most important prognostic factor in the patients with the adverse outcome. The studied scoring models (Anti-N-methyl-d-aspartate receptor Encephalitis 1-Year Functional Status, Antibody Prevalence in Epilepsy, and Response to Immunotherapy in Epilepsy) have also been proven to be applicable to the pediatric age group for predicting overall outcome and autoimmune-related epilepsy.

Characteristics of COVID-19 vaccinated and unvaccinated patients admitted to Careggi University Hospital, Florence, Italy

More than 11.5 billion COVID-19 vaccine doses have been administered around the world. Although vaccine effectiveness for severe infections is reported to be 89.0%, breakthrough infections are common and may lead to severe outcome in fragile population. We conducted a real-world observational study on 420 COVID-19 admitted patients from July 2021 to January 2022 in a tertiary level Italian hospital. We collected patient’s vaccination and SARS-CoV-2 serological status, SARS-CoV-2 treatments, oxygen supports, intensive (ICU) and subintensive (sub-ICU) care unit admissions, length of staying (LoS) and in-hospital mortality. One-hundred-seventy-two vaccinated and 248 unvaccinated patients were admitted during the study period. Vaccinated group (Vg) had a significantly more elevated Charlson Comorbidity Index than Unvaccinated group (UVg), and no statistical differences were found in terms of in-hospital mortality, LoS or ICU and sub-ICU admissions. Among Vg, anti-S antibodies were detected in 86.18% of patients (seropositives). Vaccinated seronegative patients’ in-hospital mortality was significantly higher than vaccinated seropositive patients (33.33% vs 10.69%, p = 0.0055): in particular, mortality rate in 45–69 years old population was higher in vaccinated seronegative group, and comparable in patients ≥ 70 years old. No differences in terms of outcome were registered between Vg and UVg, taking into account that Vg was considerably older and with more comorbidities. In line with other recent observations, higher mortality rate was evidenced for seronegative vaccinated patients. Primary prophylaxis and early treatments result to be necessary, especially for older and immunosuppressed populations.

Tixagevimab and Cilgavimab (Evusheld™) Prophylaxis Prevents Breakthrough COVID-19 Infections in Immunosuppressed Population: 6-Month Prospective Study.

Persons with neuroinflammatory diseases (pwNID) treated with potent immunosuppressives are at risk of severe COVID-19 outcomes and reduced vaccine seroconversion. We aimed at determining the real-world efficacy of tixagevimab and cilgavimab (Evusheld™) in immunosuppressed pwNID in preventing breakthrough COVID-19 infections. 31 immunosuppressed pwNID were followed for 6 months after administration of tixagevimab and cilgavimab as a prophylactic COVID-19 medication (January 2022-July 2022). Only pwNID treated with anti-CD20 monoclonal antibodies and sphingosine-1-phosphate modulators were considered eligible for the study. A control group of 126 immunosuppressed pwNID (38 seropositive and 88 seronegative after SARS-CoV-2 vaccination) were included. Breakthrough COVID-19 infections rate and their severity was determined over the follow-up. The pwNID treated with tixagevimab and cilgavimab had more comorbidities when compared with the total and seronegative pwNID control group (54.8% vs. 30.2% vs. 27.3%, p = 0.02 and p = 0.005, respectively). After a 6-month follow-up, significantly lower numbers of pwNID treated with tixagevimab and cilgavimab had breakthrough COVID-19 when compared with the control pwNID group (6.5% vs. 34.1%, p = 0.002) and seronegative control pwNID group (6.5% vs. 38.6%, p < 0.001). All COVID-19 infections in Evusheld-treated pwNID were mild, whereas 9/43 COVID-19 infections in the control group were moderate/severe. No side effects to tixagevimab and cilgavimab were recorded. In pwNID treated with immunosuppressive therapies, tixagevimab and cilgavimab (Evusheld™) significantly reduced the numbers and severity of breakthrough COVID-19 infections during the Omicron (BA.2-BA.5 variants) wave.

SG-APSIC1049: Immunogenicity of Gam-COVID-Vac and Sinopharm BBIBP-CorV vaccines in seropositive and seronegative adults

Objectives: Data comparing the immunogenicity of Sputnik-V and Sinopharm vaccines in seropositive and seronegative groups are lacking. We compared the immunogenicity of Sputnik-V (Gam-COVID-Vac) and Sinopharm (BBIBP-CorV) vaccines in seronegative and seropositive groups. Methods: In total, 60 adults participated the study. The immune response after vaccination was assessed using enzyme immunoassay. IgG levels were measured in all participants at 3 time points: before vaccination, 42 days after the first vaccine dose, and 6 months after the first vaccine dose. The results of the SARS-CoV-2 antibody test were quantified according to the WHO First International Standard and expressed in international units (BAU per mL). Results: The study participants were divided into 2 groups: 30 people (50%) were vaccinated with Sputnik-V (Gam-COVID-Vac) and 30 people (50%) were vaccinated with Sinopharm (BBIBP-CorV). The groups had no difference in sex composition. The highest antibody levels were observed 42 days after vaccination in both the seronegative group (P = .006) and the seropositive group (P &lt; .001). At 6 months after vaccination, the IgG value declined much farther among the seronegative group (P = .003) compared to those who had recovered from COVID-19 before vaccination. However, the “hybrid immunity” generated by the Sputnik-V vaccine had greater strength and duration (P &lt; .001). Conclusions: This study showed that IgG levels in vaccinated individuals who previously recovered from SARS-CoV-2 infection (“hybrid immunity”) were higher than in SARS-CoV-2–naïve individuals. In a comparative part of the study, the Sputnik-V vaccine had greater strength and duration of immune response across the 6-month observation period (P &lt; .001).

Assessment of intelligence quotient in patients with neuromyelitis optica spectrum disease and multiple sclerosis.

Cognitive impairment is common in people living with neuromyelitis optica spectrum disease (NMOSD) and multiple sclerosis (MS). However, there is little published data on intelligence quotient (IQ) in NMOSD patients. Therefore, we performed the present study to compare IQ scores across NMOSD, MS, and control groups. In this cross-sectional study, 49 NMOSD (30 with positive aquaporin4 antibody), 41 MS, and 20 control individuals were recruited. The IQ score for each person was measured using Wechsler Adult Intelligence Scale-Revised (WAIS-R). Participants were reported on eleven scores of subsets, verbal IQ (VIQ), performance IQ (PIQ), and full score IQ (FSIQ). The scores of FSIQ, VIQ, PIQ, vocabulary, similarities, and digit-symbol in NMOSD and MS individuals were lower than the control group. Relative to control, NMOSD patients reported a lower score of information. We found no difference between NMOSD and MS groups, except in vocabulary and similarities. No significant difference between seropositive and seronegative NMOSD groups was observed except for the information and block design. In NMOSD group, a greater EDSS score was associated with decreased scores of FSIQ, VIQ, and PIQ. Being employed and being married were associated with greater scores of VIQ and PIQ, respectively. In both NMOSD and MS groups, advanced education was associated with increased scores of FSIQ and VIQ. Our study showed decreased IQ scores in NMOSD and MS. Further studies are required to examine intellectual quotient in people with NMOSD and MS.

Alterations in Renin-Angiotensin System (RAS) Peptide Levels in Patients with HIV.

Chronic HIV infection has long been associated with an increased risk for cardiovascular diseases. The metabolites of the renin−angiotensin system (RAS) such as angiotensin II (AngII) play an important role in regulating blood pressure and fluid dynamics. Cross-sectional analysis of HIV-positive individuals (n = 71, age > 40 years, stable ART > 3 months with HIV viral load < 50 copies/mL) were compared to a similar HIV seronegative group (n = 72). High-resolution B-mode ultrasound images of the right carotid bifurcation (RBIF) and right common carotid artery (RCCA) were conducted to measure the extent of carotid atherosclerotic vascular disease. Plasma RAS peptide levels were quantified using a liquid chromatography-mass spectrometry-based metabolomics assay. RAS peptide concentrations were compared between persons with HIV and persons without HIV, correlating their association with clinical and cardiac measures. Median precursor peptides (Ang(1-12) and AngI) were significantly higher in the HIV-positive group compared to the HIV-negative. Analyses of the patient subgroup not on antihypertensive medication revealed circulating levels of AngII to be four-fold higher in the HIV-positive subgroup. AngII and TNF-alpha levels were found to have a positive association with RCCA, and AngI/Ang(1-12) ratio and TNF-alpha levels were found to have a positive association with RBIF. In both predictive models, AngIII had a negative association with either RCCA or RBIF, which may be attributed to its ability to bind onto AT2R and thus oppose pro-inflammatory events. These results reveal systemic alterations in RAS as a result of chronic HIV infection, which may lead to the activation of inflammatory pathways associated with carotid thickening. RAS peptide levels and cytokine markers were associated with RCCA and RBIF measurements.

The Delta Delta: Gaps in screening and patient assessment for hepatitis D virus infection.

Hepatitis D virus (HDV) infection is highly prevalent in patients with chronic hepatitis B (CHB). AASLD guidelines recommend a risk-based screening approach. Our aim was to ascertain if the risk-based approach leads to appropriate HDV screening, identify targets to improve screening rates, and study HDV clinical burden. CHB patients screened for HDV from 01/2016 to 12/2021 were identified. Level of training and specialty of providers ordering HDV screening tests were determined. HDV seropositive (HDV+) patient charts were reviewed for the presence of individual risk factors per the AASLD guidelines to determine if they met screening criteria. The severity of liver disease at the time of HDV screening was compared between the HDV+ group and a matched (based on age, hepatitis B e antigen status, BMI and sex) HDV seronegative (HDV-) group. During the study period, 1444/11,190 CHB patients were screened for HDV. Most screening tests were ordered by gastroenterology (90.2%) specialists and attending physicians (80.5%). HDV+ rate was 88/1444 (6%), and 72 HDV+ patients had complete information for analysis. 18% of HDV+ patients would be missed by a risk-based screening approach due to unreported or negative risk factors (see Table). A significantly higher number of HDV+ patients had developed significant fibrosis (p= 0.001) and cirrhosis (p< 0.01) by the time of screening than HDV- (n= 67) patients. In conclusion, targeted interventions are needed towards trainees and primary care clinics to improve screening rates. Current risk-based criteria do not appropriately screen for HDV. It is time for universal screening of HDV in CHB patients.

Anti-Aspergillus fumigatus IgG in patients with bronchiectasis and its relationship with clinical outcome

Aspergillosis is a mycosis, most commonly affecting the airways. This mycosis can worsen the clinical condition of patients with concurrent lung diseases. We assayed for the presence of serum anti-A. fumigatus IgG in bronchiectasis patients from a tertiary hospital in south Brazil and evaluated the relationship with clinical outcome. Thirty-one patients with bronchiectasis, without cystic fibrosis, were included. Clinical and epidemiological data were collected from all participants. Positive serological tests were detected in 13% (4/31) of the patients. The mortality rate for the year following the assay was, in the seropositive group, 75% (3/4), whereas in the seronegative group, 15% (4/27). An illustrative case is also shown and discussed. Our study highlights the diagnostic challenge and the possible impact of Aspergillus infection on these patients, indicating the necessity of more and larger investigations in the field.

Acute Inflammatory Diseases of the Central Nervous System After SARS-CoV-2 Vaccination.

Acute inflammatory CNS diseases include neuromyelitis optica spectrum disorders (NMOSDs) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Both MOGAD and acute disseminated encephalomyelitis (ADEM) have been reported after vaccination. Consequently, the mass SARS-CoV-2 vaccination program could result in increased rates of these conditions. We described the features of patients presenting with new acute CNS demyelination resembling NMOSDs or MOGAD within 8 weeks of SARS-CoV-2 vaccination. The study included a prospective case series of patients referred to highly specialized NMOSD services in the UK from the introduction of SARS-CoV-2 vaccination program up to May 2022. Twenty-five patients presented with new optic neuritis (ON) and/or transverse myelitis (TM) ± other CNS inflammation within 8 weeks of vaccination with either AstraZeneca (ChAdOx1S) or Pfizer (BNT162b2) vaccines. Their clinical records and paraclinical investigations including MRI scans were reviewed. Serologic testing for antibodies to myelin oligodendrocyte glycoprotein (MOG) and aquaporin 4 (AQP4) was performed using live cell-based assays. Patients' outcomes were graded good, moderate, or poor based on the last clinical assessment. Of 25 patients identified (median age 38 years, 14 female), 12 (48%) had MOG antibodies (MOGIgG+), 2 (8%) had aquaporin 4 antibodies (AQP4IgG+), and 11 (44%) had neither. Twelve of 14 (86%) antibody-positive patients received the ChAdOx1S vaccine. MOGIgG+ patients presented most commonly with TM (10/12, 83%), frequently in combination with ADEM-like brain/brainstem lesions (6/12, 50%). Transverse myelitis was longitudinally extensive in 7 of the 10 patients. A peak in new MOGAD cases in Spring 2021 was attributable to postvaccine cases. Both AQP4IgG+ patients presented with brain lesions and TM. Four of 6 (67%) seronegative ChAdOx1S recipients experienced longitudinally extensive TM (LETM) compared with 1 of 5 (20%) of the BNT162b2 group, and facial nerve inflammation was reported only in ChAdOx1S recipients (2/5, 40%). Guillain-Barre syndrome was confirmed in 1 seronegative ChAdOx1S recipient and suspected in another. ChAdOx1S was associated with 12/14 antibody-positive cases, the majority MOGAD. MOGAD patients presented atypically, only 2 with isolated ON (1 after BNT162b2 vaccine) but with frequent ADEM-like brain lesions and LETM. Within the seronegative group, phenotypic differences were observed between ChAdOx1S and BNT162b2 recipients. These observations might support a causative role of the ChAdOx1S vaccine in inflammatory CNS disease and particularly MOGAD. Further study of this cohort could provide insights into vaccine-associated immunopathology.

Correlation between latent toxoplasmosis and thyroid hormone levels in sera of schizophrenic patients

Latent toxoplasmosis is a prevalent chronic infection caused by a protozoan parasite called Toxoplasma gondii. Recent studies have shown that T. gondii may affect thyroid hormone levels and thus induce behavioral alteration. However, this correlation has been inadequately investigated. Therefore, we aimed to examine the relationship between latent toxoplasmosis and thyroid hormone levels in schizophrenic patients. For this purpose, blood samples and sociodemographic information were collected from 101 schizophrenic patients attending three psychiatric hospitals in Kurdistan region of Iraq. Anti-T. gondii-IgG antibodies and thyroid hormones levels (TSH, T3, T4) were determined in sera of all patients using ELISA technique. Anti-T. gondii-IgG antibodies were detected in sera of 40 (39.6%) out of 101 schizophrenic patients. Logistic regression analysis showed significant association between toxoplasmosis and schizophrenic patients in 50-60 age group (OR=6.177, p=0.05), and un-employed patients (OR=3.562, p=0.05). Data analysis showed non-significant difference in TSH levels between IgG seropositive and IgG seronegative group (p&gt;0.05). On the other hand, T4 levels were significantly higher in the seropositive (10.16 ± 2.61) than seronegative group (7.01 ± 2.01), with highly significant positive correlation between IgG and T4 levels (p= 0.001). Finally, T3 levels were significantly higher in the seropositive (1.91 ± 0.5) than seronegative group (1.12 ± 0.43), with non-significant positive correlation between IgG and T3 levels (p=0.30). Owing to the fact that there was statistically significant increase in thyroid hormone levels in T. gondii seropositive patients, our results suggest that there is a significant association between toxoplasmosis and thyroid hormone levels in schizophrenic patients.

Impact of latent toxoplasmosis on thyroid diseases during gestation

Toxoplasmosis is among the most widely diseases that distributed by the protozoan parasite Toxoplasma gondii. So in the case of pregnancy, latent toxoplasmosis is a risk factor which causes thyroid disease. The aim of the study was to determine the effect of latent toxoplasmosis on thyroid diseases during gestation. 214 blood samples were collected from pregnant women who admitted to different hospitals in Erbil governorate. ELISA technique was used for detecting Toxoplasma IgG antibody, as well as determining serum levels of thyroid hormone levels. Overall, 23.37% of tested samples were Toxoplasma gondii IgG seropositive. Latent toxoplasmosis has a positive correlation with thyroxin (T4) (p=0.026), however, no significant correlation was found with both thyroid stimulating hormone (TSH) and triiodothyronine (T3) (p&gt;0.05). No significant differences were found between Toxoplasma IgG seropositive and seronegative groups as related to trimester, age, city, place, blood group, occupation, food habit, animal contact, disease, and vitamin D level, except the characteristic of abortion, which was significant at a p=0.042. In conclusion, latent toxoplasmosis had significant impact on the occurrence of T4 secretion during gestation. Whereas, TSH and T3 had no significant association with latent toxoplasmosis. Increasing the awareness of toxoplasmosis among pregnant women is required to avoid their deleterious effects, which has a notable impact on lowering the rate of abortion caused by this parasite.

Efficacy and safety of the SARS-CoV-2 mRNA vaccine in lung transplant recipients: a possible trigger of rejection.

ObjectiveSolid organ transplant recipients have an increased risk of developing severe coronavirus disease 2019 (COVID-19). Although SARS-CoV-2 mRNA vaccination has been strongly recommended for solid organ transplant recipients, its efficacy and safety have remained unknown.MethodsWe performed an observational prospective cohort study in 18 lung transplant recipients who received two doses of SARS-CoV-2 mRNA vaccine, including BNT162b2 (n = 17) or mRNA-1273 (n = 1), between June and October 2021. The titers of IgG antibodies against the SARS-CoV-2 spike protein (S-IgG) were measured in serum samples collected before the prime dose, three weeks after the prime dose, and four weeks after the booster dose. Reactogenicity and adverse events were evaluated after vaccination.ResultsThere were no recipients with previous SARS-CoV-2 infection prior to vaccination. S-IgG levels were elevated in 2/18 (11.1%) recipients after the prime dose and in 5/18 recipients (27.8%) after the booster dose (31.7 ± 30.6 U/ml). The time from transplantation to vaccination tended to be longer in the seropositive group than the seronegative group [7.5 (3.9–10.2) vs 2.8 (1.9–4.0) years, p = 0.059]. Maintenance dose of mycophenolate mofetil tended to be lower in the seropositive group than in the seronegative group [500 (250–500) vs 1000 (1000–1000) mg/day, p = 0.088]. Regarding the adverse events after vaccination, the development of chronic lung allograft dysfunction (CLAD) or antibody-mediated rejection (AMR) were observed in two seropositive patients.ConclusionsThe antibody response to the SARS-CoV-2 mRNA vaccine was quite poor in lung transplant recipients. We experienced cases that developed clinical CLAD or AMR that was likely related to SARS-CoV-2 vaccination.

Durability of ChAdOx1 nCoV-19 (AZD1222) vaccine and hybrid humoral immunity against variants including omicron BA.1 and BA.4 6 months after vaccination (COV005): a post-hoc analysis of a randomised, phase 1b–2a trial

BackgroundCOVID-19 vaccine rollout is lagging in Africa, where there has been a high rate of SARS-CoV-2 infection. We aimed to evaluate the effect of SARS-CoV-2 infection before vaccination with the ChAdOx-nCoV19 (AZD1222) vaccine on antibody responses through to 180 days.MethodsWe did an unmasked post-hoc immunogenicity analysis after the first and second doses of AZD1222 in a randomised, placebo-controlled, phase 1b–2a study done in seven locations in South Africa. AZD1222 recipients who were HIV-uninfected, were stratified into baseline seropositive or seronegative groups using the serum anti-nucleocapsid (anti-N) immunoglobulin G (IgG) electroluminescence immunoassay to establish SARS-CoV-2 infection before the first dose of AZD1222. Binding IgG to spike (anti-S) and receptor binding domain (anti-RBD) were measured before the first dose (day 0), second dose (day 28), day 42, and day 180. Neutralising antibody (NAb) against SARS-CoV-2 variants D614G, beta, delta, gamma, and A.VOI.V2, and omicron BA1 and BA.4 variants, were measured by pseudovirus assay (day 28, day 42, and day 180). This trial is registered with ClinicalTrials.gov, NCT04444674, and the Pan African Clinicals Trials Registry, PACTR202006922165132.FindingsOf 185 individuals who were randomly assigned to AZD1222, we included 91 individuals who were baseline seropositive and 58 who were baseline seronegative, in the final analysis. In the seropositive group, there was little change of anti-S IgG (and anti-RBD IgG) or neutralising antibody (NAb) titres at day 42 compared with at day 28. Anti-S (and anti-RBD) IgG geometric mean concentrations (GMCs) were higher throughout in the seropositive compared with the seronegative group, including at day 180 (GMCs 517·8 [95% CI 411·3–651·9] vs 82·1 [55·2–122·3] BAU/mL). Also D614G NAb geometric mean titres (GMTs) were higher in the seropositive group than the seronegative group, as was the percentage with titres of at least 185 (80% putative risk reduction threshold [PRRT] against wild-type–alpha COVID-19), including at day 180 (92·0% [74·0–99·0] vs 18·2% [2·3–51·8). Similar findings were observed for beta, A.VOI.V2, and gamma. For delta, BA.1, and BA.4, NAb GMTs and the proportion with titres above the PRRT were substantially higher in the seropositive compared with seronegative group at day 28 and day 42, but no longer differed between the groups by day 180.InterpretationA single dose of AZD1222 in the general African population, where COVID-19 vaccine coverage is low and SARS-CoV-2 seropositivity is 90%, could enhance the magnitude and quality of antibody responses to SARS-CoV-2.FundingThe Bill & Melinda Gates Foundation, the South African Medical Research Council, the UK Research and Innovation, the UK National Institute for Health Research, and the South African Medical Research Council.TranslationFor the Zulu translation of the abstract see Supplementary Materials section.

Retrospective study on clinical manifestation, thigh MRI and electrophysiology characteristics of immune-mediated necrotizing myopathy

Objective: To summarize the clinical, thigh magnetic resonance (tMRI) and electromyographic (EMG) characteristics in patients with immune-mediated necrotizing myopathy (IMNM). Methods: A total of 32 IMNM patients who were admitted to the Department of Neurology from April 2019 to April 2021 were enrolled at the First Medical Centre of Chinese PLA General Hospital. According to the type of antibody, the patients were divided into anti-SRP antibody positive (SRP+) group, anti-HMGCR antibody positive (HMGCR+) group and seronegative (SN) group. The gender, age, course of disease, myositis antibodies, extramuscular manifestations, EMG were collected and analyzed among three groups. The characteristics of skeletal muscle were assessed by tMRI inflammatory edema and fat infiltration scores. Analysis of variance, Kruskal-Wallis test and Chi-square test were used to compare the differences in different clinical characteristics and tMRI scores among the three groups. When there was a statistical difference among the three groups, the comparison between the two groups was corrected by the Bonferroni method. Result: (1) Of the 32 patients, 20 were females (62.5%).The median age of onset was 47±14 years, 25 (78.1%) patients had an acute or subacute course.There were 17 (53.1%) with SRP+, 8 (25.0%) with HMGCR+, and 7 (21.9%) with MSAs (myositis specific antibodies) negative. Anti-Ro52 antibody was the most common combined antibody (12/32, 37.5%), among which 10 were in SRP+group.(2) The CK of all patients were elevated, median was 5 948 (4 229, 7 664) U/L. There was no statistical difference of MMT scores among three groups. The proximal limb score was lower than distal limb (P<0.01). The axial muscle score was lower than the distal limb score (P<0.05).(3) Extramuscular manifestations of HMGCR+ group were lower than those of the other two groups (12.5% vs. 71.4% and 76.5%, P<0.017). Rash (60.0% vs.14.3%, P<0.05) and interstitial pulmonary diseases (70.0% vs. 14.3%, P<0.05) were more common in patients with anti-SRP coexistence with anti-Ro52 than those with isolated anti-SRP. Connective tissue disease was more common in SN group (57.1% vs. 11.8% and 0, P<0.017).(4) tMRI showed fascial edema of SN group was more obvious than that of the other two groups (P<0.017). There was no statistical difference in the degree of fat infiltration and inflammatory edema among three groups, but SRP+ group had more cases of early fat infiltration.(5) Myotonic potentials (25.0% vs. 0 and 0, P<0.017) and compound repetitive discharges (CRDs) (50.0% vs. 5.9% and 0, P<0.017) were common in HMGCR+ group. Proteomic analysis found significantly different expressed proteins in skeletal muscle of patients with myotonic potentials or CRDs were associated with cytoskeleton, cell junction and extracellular matrix. Conclusion: IMNM with pure anti-SRP antibody positive and anti-HMGCR positive were mainly affected by skeletal muscles. Those who were co-positive for anti-SRP antibody and anti-Ro52 antibody had more extramuscular manifestations, which might be a special subtype of SRP+ group. This study proposed for the first time that myofascial inflammatory edema is an early sign of SN-IMNM injury. EMG of HMGCR+group were more prone to myotonia potential and CRDs.

The association between Toxoplasma infection and mortality: the NHANES epidemiologic follow-up study

BackgroundToxoplasma gondii has been reported to be associated with higher mortality in patients with schizophrenia. This study aimed to explore the relationship between T. gondii infection and 25-year mortality based on data from the Third National Health and Nutrition Examination Survey (NHANES III) database.MethodsCases with serum T. gondii antibody test results were included in this study and the corresponding mortality dataset was obtained from the US National Center for Health Statistics (NCHS). Propensity score matching (PSM) was used to match age and sex between groups. The Cox proportional hazards model was used to evaluate the effect of T. gondii infection on mortality.ResultsA total of 14,181 cases were included in the analysis, of which 3831 (27.0%) were seropositive for T. gondii antibody. The median follow-up time of the whole cohort was 22.5 (interquartile range 16.3, 24.5) years. A total of 5082 deaths were observed in this cohort, a mortality rate of 35.8%. All-cause mortality was significantly higher in the seropositive group than in the seronegative group (50.0% vs 30.6%, P < 0.001). Kaplan–Meier analysis showed a significant difference in the survival time between two groups before and after PSM. Multivariate analysis showed that T. gondii infection was independently associated with higher all-cause mortality after adjusting for potential confounders.ConclusionsToxoplasma gondii infection is associated with higher mortality in general population.Graphical