High Prevalence Of Antibodies Research Articles

High Prevalence of Myositis-Specific and Associated Antibodies in Patients with Pulmonary Hypertension

Pulmonary hypertension (PH) is a serious condition linked to immune-system dysfunction. Myositis-specific/associated antibodies (MSAs/MAAs) play a role in idiopathic inflammatory myopathy (IIM) and interstitial lung disease (ILD), but their significance in PH remains unclear. We believe the presence of these antibodies may be underestimated. This study analyzed adult PH patients without pre-existing IIM for MSA/MAA prevalence using a line-blot assay. We compared PH patients with and without ILD signs to a cohort clinically suspected of IIM/ILD (n = 558). Our PH cohort (n = 121) showed a significantly higher prevalence of overall weak positive MSAs/MAAs and positive overlap syndrome-associated MAAs than the suspected IIM/ILD group (p < 0.001). Notably, MSAs/MAAs were found in PH patients both with and without ILD, though more prevalent in those with ILD. Anti-synthetase and anti-overlap syndrome antibodies were the most common. Our study is the first to systematically show a high MSA/MAA prevalence in PH without IIM presentation. This highlights the need to consider PH when diagnosing MSA/MAA-associated conditions. We recommend MSA/MAA screening for newly diagnosed PH, especially in those with ILD, for early detection and potential immunomodulatory treatment. Further research should explore the link between MSAs/MAAs and PH, and the value of monitoring patients with weak MSA/MAA positivity over time.

Microelimination of Hepatitis C in patients with substance use and dual disorders - a Portuguese study.

Chronic hepatitis C is a serious condition with relevant public health implications. In Portugal, the prevalence of detectable HCV antibodies is about 0,54%, with higher values in risk groups. Compared to the general population, the prevalence of HCV infection is higher in individuals with psychiatric disorders. There are no studies reporting the prevalence of HCV antibodies in Portuguese psychiatric patients, or in patients with substance use disorders.We carried an observational, prospective study during a period of one year, for patients followed at the Dual Pathology Outpatient and Inpatient Unity of the Coimbra Hospital and University Center, and patients were tested for HCV antibodies. Of 149 patients, 17.4% had positive HCV antibodies and 7.38% had detectable HCV RNA. Patients with confirmed CHC were mostly male inpatients, aged 50 to 59 years, and reported unprotected sex with more than one concurrent partner in the previous six months; their main psychiatric diagnosis was "Disorders due to use of multiple specified psychoactive substances, including medications".This study reports a very high prevalence of positive HCV antibodies and confirmed CHC in patients followed in the Dual Pathology Outpatient and Inpatient Unity. This prevalence is higher than in general Portuguese population.

High prevalence of anti-Strongyloides antibody in SARS-CoV-2-infected human sera in a Thai hospital: Rapid serological screening

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can stimulate a systemic inflammatory response with severe lung involvement, multisystem dysfunction, and death in some cases. Immunosuppressive treatments have been proposed for management of COVID-19 patients, but these bring the risk of flare-up of pre-existing infections. Strongyloidiasis can become severe or fatal in immunocompromised individuals. This cross-sectional study determined the prevalence of anti-Strongyloides IgG antibody in sera collected from SARS-CoV-2 infected persons in a tertiary-care Thai hospital from January 2021 to January 2022. The survey was conducted using a rapid immunochromatographic test (ICT) kit based on a recombinant antigen of Strongyloides stercoralis known to be IgG-immunoreactive. High prevalence of anti-Strongyloides IgG antibody was found. Out of 297 SARS-CoV-2-infected patients 117 (39.4 %, 95 % CI 33.8–45.2 %) were positive for S. stercoralis according to the ICT kit. In areas where strongyloidiasis is endemic, we suggest using this point-of-care ICT kit for routine rapid screening in seriously ill COVID-19 patients who will be subjected to immunosuppressive treatment. Prompt anthelminthic treatment should be administered to prevent serious systemic strongyloidiasis in at-risk patients.

Domestic dogs in indigenous Amazonian communities: Key players in Leptospira cycling and transmission?

Leptospirosis is the world's most common zoonotic disease. Mitigation and control rely on pathogen identification and understanding the roles of potential reservoirs in cycling and transmission. Underreporting and misdiagnosis obscure the magnitude of the problem and confound efforts to understand key epidemiological components. Difficulties in culturing hamper the use of serological diagnostics and delay the development of DNA detection methods. As a result, especially in complex ecosystems, we know very little about the importance of different mammalian host species in cycling and transmission to humans. We sampled dogs from five indigenous Kichwa communities living in the Yasuní National Park in the Ecuadorian Amazon basin. Blood and urine samples from domestic dogs were collected to assess the exposure of these animals to Leptospira and to identify the circulating species. Microscopic Agglutination Tests with a panel of 22 different serovars showed anti-leptospira antibodies in 36 sampled dogs (75%), and 7 serogroups were detected. Two DNA-based detection assays revealed pathogenic Leptospira DNA in 18 of 19 dog urine samples (94.7%). Amplicon sequencing and phylogenetic analysis of 16S rRNA and SecY genes from 15 urine samples revealed genetic diversity within two of three different Leptospira species: noguchii (n = 7), santarosai (n = 7), and interrogans (n = 1). The high prevalence of antibodies and Leptospira DNA provides strong evidence for high rates of past and current infections. Such high prevalence has not been previously reported for dogs. These dogs live in the peridomestic environment in close contact with humans, yet they are free-ranging animals that interact with wildlife. This complex web of interactions may explain the diverse types of pathogenic Leptospira observed in this study. Our results suggest that domestic dogs are likely to play an important role in the cycling and transmission of Leptospira. Future studies in areas with complex ecoepidemiology will enable better parsing of the significance of genotypic, environmental, and host characteristics.

Prevalence of anti-HLA antibodies in COVID-19 convalescent plasma donors: An Indian experience

BackgroundCOVID-19 convalescent plasma is one of the experimental therapies used widely in moderately sick COVID-19 patients. However, there are a few risks involved in plasma transfusion; notably, transfusion-related acute lung injury (TRALI) caused by antibodies against human leukocyte antigens (HLA). This study was designed to assess the prevalence of anti-HLA antibodies in convalescent plasma donors using the single antigen bead method. Study Design and MethodsThis was a hospital-based observational study of consecutive plasma donors. A total of 252 samples were screened for anti-HLA Class I and Class II antibodies using the microbead assay with the identification of anti-HLA Ab in positive samples being performed using a single antigen bead assay. Luminex-based normalized background cutoff ratios of 10.8 for Class I and 6.9 for Class II and mean fluorescence intensity cutoffs of 2500 for Class I and 1500 for Class II were used for screening and the single bead assay, respectively. ResultsOf 252 screened samples, 28 (11.1%) were positive for Class I, Class II or both Class I and Class II anti-HLA antibodies in donors with no history of a previous immunizing event. Moreover, 20/252 (7.9 %) donors without any history of prior immunization had specific anti-HLA antibodies of Class I or Class II or both by the single bead assay. ConclusionsThe high prevalence of anti-HLA antibodies in our cohort of donors raises an urgent and immediate need for anti-HLA antibody screening in all convalescent plasma donors for safe therapy of COVID-19 patients.

First use of tissue exudate serology to identify Toxocara spp. infection in food animals

Toxocara canis and Toxocara cati are globally distributed, zoonotic roundworm parasites. Human infection can have serious clinical consequences including blindness and brain disorders. In addition to ingesting environmental eggs, humans can become infected by eating infective larvae in raw or undercooked meat products. To date, no studies have assessed the prevalence of Toxocara spp. larvae in meat from animals consumed as food in the UK or assessed tissue exudates for the presence of anti-Toxocara antibodies. This study aimed to assess the potential risk to consumers eating meat products from animals infected with Toxocara spp. Tissue samples were obtained from 155 different food producing animals in the south, southwest and east of England, UK. Tissue samples (n = 226), either muscle or liver, were processed by artificial digestion followed by microscopic sediment evaluation for Toxocara spp. larvae, and tissue exudate samples (n = 141) were tested for the presence of anti-Toxocara antibodies using a commercial ELISA kit. A logistic regression model was used to compare anti-Toxocara antibody prevalence by host species, tissue type and source. While no larvae were found by microscopic examination after tissue digestion, the overall prevalence of anti-Toxocara antibodies in tissue exudates was 27.7%. By species, 35.3% of cattle (n = 34), 15.0% of sheep (n = 60), 54.6% of goats (n = 11) and 61.1% of pigs (n = 18) had anti-Toxocara antibodies. Logistic regression analysis found pigs were more likely to be positive for anti-Toxocara antibodies (odds ration (OR) = 2.89, P = 0.0786) compared with the other species sampled but only at a 10% significance level. The high prevalence of anti-Toxocara antibodies in tissue exudates suggests that exposure of food animals to this parasite is common in England. Tissue exudate serology on meat products within the human food chain could be applied in support of food safety and to identify practices that increase risks of foodborne transmission of zoonotic toxocariasis.

Comparison of the SLE Risk Probability Index (SLERPI) scale against the European League Against Rheumatism/American College of Rheumatology (ACR/EULAR) and Systemic Lupus International Collaborating Clinics (SLICC) criteria.

Timely diagnosis and proper recognition of Systemic Lupus Erythematosus (SLE) is essential to establish early management in inpatients and outpatients. There are different classification scales to identify SLE, which include various clinical and serological aspects. In 2021, the SLE Risk Probability Index (SLERPI) was published, which focuses predominantly on the clinical characteristics of patients with suspected SLE and uses a simple algorithm for early recognition of the disease. The aim of this study is to compare the European League Against Rheumatism/American College of Rheumatology (ACR/EULAR) classification criteria, the Systemic Lupus International Collaborating Clinics (SLICC) criteria, and the SLERPI criteria in a cohort of Colombian patients with SLE and to analyze the correlations observed between their absolute scores. A registry of SLE patients from two referral hospitals in Bogotá, Colombia, was used. 2021 SLERPI, 2019 ACR/EULAR, and 2012 SLICC scores were calculated for each patient and the correlations found between the scales were analyzed. The sensitivities of each were compared, and frequency analyses were conducted among different clinical and laboratory variables. Between 2016 and 2019, 146 patients diagnosed with SLE were registered, including inpatients and outpatients. The median age was 36years (interquartile range 26-51), and 82.2% were women. According to the SLERPI criteria, a high prevalence of antinuclear antibodies (92%), immunological disorders (71%), and arthritis (64%) were observed. The most used treatments were corticosteroids (87.6%) and chloroquine (67.8%). A Spearman evaluation analysis was performed, with a moderately strong correlation of 0.76 (p = .000) between the SLERPI and ACR/EULAR scales and very strong correlation of 0.80 (p = .000) between the SLERPI and SLICC. Patients classified with SLE according to the SLERPI scale exhibited a higher incidence of hematological compromise, along with elevated levels of serological markers such as anti-DNA antibodies. Additionally, this group more commonly received treatments involving corticosteroids and azathioprine, and displayed a higher prevalence of hypertension. The SLERPI scale could be useful in the diagnosis of SLE, especially in early stages, given its good correlation with other classification scales and its good sensitivity.

Seroprevalence of reproductive and infectious diseases in cattle: the case of Madre de Dios in the Peruvian southeastern tropics.

The objective of this study was to determine the seroprevalence of reproductive and infectious diseases in tropical cattle in the Tambopata and Tahuamanu Provinces in the department of Madre de Dios, Peru. 156 bovines from 7 cattle farms were sampled. These farms used exclusive grazing for food and natural mating for reproduction and did not have sanitary or vaccination programs. The serum of blood samples was subjected to ELISA with commercial kits for the detection of antibodies against Neospora caninum, Mycobacterium avium subsp paratuberculosis (MAP), Leptospira interrogans, pestivirus bovine viral diarrhea virus-1, retrovirus bovine leukemia virus (BLV), orbivirus bluetongue virus (BTV), and herpesvirus bovine herpes virus-1 (BHV). The data were analyzed by means of association tests with χ2 (P < .05) and Spearman rank correlation (P < .05) in the SPSS v.15.0 software (IBM Corp). A low prevalence of antibodies to L interrogans, N caninum, M avium subsp paratuberculosis, bovine viral diarrhea virus-1 was found, but it was high to BTV, BLV, and BHV (100%, 53.85%, and 72.44%, respectively). The presence of BLV and BHV was higher in the Las Piedras District, bovines less than 5 years old, and cattle with breed characteristics of zebu and crossbred (P < .01). In addition, there was a significant correlation between both infections, showing 83.3% of BLV positivity that were also BHV positive (P < .01). The high prevalence of antibodies to BTV, BHV, and BLV could be due to livestock management practices, direct contact with infected animals, and variation of the presence of vectors and natural reservoirs in the context of climate change in the tropics.

Prevalence of syphilis among people living with HIV who attend a large urban antiretroviral therapy clinic in Panama: a cross-sectional epidemiological study.

Syphilis is a serious global public health challenge. Despite prior progress in syphilis control, incidence has been increasing in recent years. Syphilis is a common coinfection among people living with HIV (PLHIV). In Panama, few data describe syphilis prevalence among PLHIV. We describe syphilis antibody and high-titer (⩾1:8) active syphilis prevalence and associated factors among individuals who attended an antiretroviral clinic. A cross-sectional study was undertaken during February-March 2022 and September-October 2022 for adults (⩾18 year) assigned male and female at birth, respectively. Participants provided peripheral blood samples and self-administered a questionnaire. Samples were screened using immunochromatography; antibody-positive samples were tested using rapid plasma regain to 1:512 dilutions. Logistic regression was used to identify factors associated with syphilis antibody and high-titer active syphilis. In all, 378 participants gave blood samples; 377 individuals participated in the questionnaire (216 self-reported male sex [males], 158 female [females], and three intersex individuals). Median age was 36 years (interquartile range: 28-45 years). Overall, syphilis antibody prevalence was 32.3% (122/378) (males, 50.7% [108/2013]; females, 5.7% [9/158]; intersex individuals, 100.0% (3/3)], p < 0.01. High-titer active syphilis was found among 24.6% (n = 30) of samples with positive antibody test (males 27.8% [n = 30], females 0.0% [0/9], intersex individuals 0.0% [0/3]). Antibody positivity was associated in the multivariable model with males (50.7%, AOR = 24.6, 95%CI: 1.57-384.53). High-titer active syphilis was associated with younger participant age (18-30 years, 13.2%, OR = 4.82, 95%CI: 1.17-19.83); 31-40 years, 7.8%, OR = 4.24, 95%CI: 1.04-17.21 versus 3.2% >40 years), homosexual identity (16.0% OR = 34.2, 95%CI: 4.50-259.27 versus 0.6% among heterosexual identity); in the multivariable model, associated with sexual identity (bisexual 19.1%, AOR = 10.89, 95%CI: 1.00-119.06) compared to heterosexual identity (0.6%) and weakly associated with concurrency (⩾1 ongoing sexual relationships, 15.9%, AOR = 3.09, 95%CI: 0.94-10.14). This study found very high prevalence of syphilis antibodies and high-titer syphilis among PLHIV in Panama. Those most affected are males, younger in age, those who practice concurrent sexual relationships, and those who reported homosexual and bisexual identity. Targeted interventions should include repetitive testing and treatment, especially among individuals who may be at increased infection risk.

The post-COVID-19 population has a high prevalence of cross-reactive antibodies to spikes from all Orthocoronavirinae genera.

As demonstrated by severe acute respiratory syndrome coronavirus 2, coronaviruses pose a significant pandemic threat. Here, we show that coronavirus disease 2019 mRNA vaccination can induce significant levels of cross-reactive antibodies against diverse coronavirus spike proteins. While these antibodies are binding antibodies that likely have little neutralization capacity and while their contribution to cross-protection is unclear, it is possible that they may play a role in protection from progression to severe disease with novel coronaviruses.

A Retrospective Analysis of Porcine Circovirus Type 3 in Samples Collected from 2008 to 2021 in Mexico.

Porcine circovirus type 3 (PCV3) is a nonenveloped virus of the Circoviridae family. This virus has been identified in pigs of different ages and pigs with several clinical manifestations of the disease or even in apparently healthy pigs. While PCV3 was first reported in 2015, several retrospective studies have reported the virus before that year. The earliest report indicates that PCV3 has been circulated in swine farms since 1996. In this study, we evaluated the presence of PCV3 in samples collected in Mexico in 2008, 2015, 2020, and 2021. This study assessed PCV3 DNA by qPCR and antibodies against CAP protein by indirect ELISA. The results showed that PCV3 (DNA and anti-CAP antibodies) was detected in the samples collected from 2008 to 2021. The highest prevalence was in 2008 (100%), and the lowest was in 2015 (negative). Genetic analysis of ORF2 showed that the virus identified belonged to genotype a, as most of the viruses identified thus far. PCV3 was detected in samples from piglets with respiratory signs and growth retardation, sows with reproductive failure, or asymptomatic piglets and sows. Pigs with respiratory signs, growth retardation, or reproductive failure had a higher prevalence of antibodies and qPCR-positive samples. In conclusion, this study showed that PCV3 has been circulating in Mexico since 2008 and that PCV3 DNA and antibodies were more prevalent in samples from pigs with clinical manifestations of diseases.

B-187 Evaluation of Clinical Utility of LC-MS/MS Method for Thyroglobulin Measurement in Comparison with Immunoradiometric Assay and Chemiluminescence Microparticle Immunoassay

Abstract Background Thyroglobulin (Tg) is the follow-up index of choice for patients with differentiated thyroid cancer (DTC), especially who were undergone total thyroidectomy. However, due to the commonly used immunoassay’s inherent susceptibility to interference combined with the high prevalence of thyroglobulin antibody (TgAb) in DTC patients, the need for more reliable measurement for Tg independent from TgAb has been brought up. In this study, we developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for Tg measurement and compared its clinical usefulness and analytical performance with immunoradiometric assay (IRMA) and chemiluminescence microparticle immunoassay (CMIA). Methods We developed trypsin digestion-peptide immunoaffinity LC-MS/MS methods for Tg measurement. Analysis was performed using an LC-MS/MS system consisting of Agilent 1290 LC (Agilent Technologies, Santa Clara, CA) and Qtrap 5500+ MS/MS system(ABSciex, Framingham, MA). Tryptic Tg specific peptide (FSPDDSAGASALLR) and cleavable internal standard peptide (LSFYWTTTGDPFFDSHSDSLL*RSGPYMPQ, L*: 13C6, 15N) were quantitated against 5-point linear calibration curve with Access Thyroglobulin Calibrators (Beckman Coulter, Pasadena, CA). Three levels of serum control were prepared (3.95, 12.5, and 39.4 ng/mL). Lower limit of quantitation (LLoQ), linearity, precision, and carryover were validated for the assay. For method comparison, serum from patients with DTC or Hashimoto thyroiditis was collected. Tg was also measured with IRMA using BRAHMS TG Plus (Thermo Fisher Scientific, Waltham, MA), and CMIA using Architect Thyroglobulin (Abbott laboratories, Illinois, CA). TgAb was measured with IRMA using BRAMS Anti-Tg (Thermo Fisher Scientific) and the cut-off for TgAb was 60 IU/mL. Also, interference of TgAb was evaluated by comparing the Tg recovery of five sets of TgAb negative samples spiked with diluents and high TgAb samples. Results Within-run and between-run imprecisions were CV 7.8%–13.0% and CV 8.9%–12.7%, respectively. LLoQ was 0.5 ng/mL. The assay was linear through 0.5–650 ng/mL. No significant carryover was observed within the analytical measurement range. Out of the total 193 samples, the number of samples above LLoQ in both LC-MS/MS, and IRMA or CMIA were 73 samples (45 TgAb-positive and 28 TgAb-negative samples) and 69 samples (42 TgAb-positive and 27 TgAb-negative samples), respectively. The result well correlated between LC-MS/MS and IRMA (R2 = 0.99), and LC-MS/MS and CMIA (R2 = 0.98) in overall samples. When analyzed according to TgAb status, LC-MS/MS and IRMA (R2 = 0.84), and LC-MS/MS and CMIA (R2 = 0.93) correlated rather poorly in TgAb-positive samples, while TgAb-negative samples were consistent (R2 = 0.99 for IRMA, R2 = 0.97 for CMIA). We found one case with systemic metastatic thyroid cancer that showed significantly high Tg levels in IRMA and LC-MS/MS (above the upper limit of quantitation), whereas below LLoQ in CMIA. The interference of TgAb was negligible in LC-MS/MS, while significant interference was observed in CMIA, with a mean recovery rate of 57.6% (4.3%–82.5%). In one sample, when measured with CMIA, thyroglobulin level was 3.29 ng/mL when mixed with diluent, but below LLoQ (0.14 ng/mL) when spiked with TgAb-positive samples (TgAb 1700 IU/mL). Conclusion The LC-MS/MS method for Tg measurement was less prone to antibody interference than immunoassays. Measurement of Tg using LC-MS/MS would be useful for reliable diagnosis and proper management in TgAb-positive patients.

Pediyatrik popülasyonda alışılmamış klinik bulgularla bulunan Hashimoto ensefalopatisi: tanı kriterlerinin gözden geçirilmesi

Aim: Hashimoto's encephalopathy is a rare progressive and relapsing disease of presumed &#x0D; autoimmune origin associated with high titers of thyroid antibodies. Also named steroid-responsive &#x0D; encephalopathy, the disease can be cured with early treatment. Hashimoto's encephalopathy may &#x0D; occur with various clinical manifestations, but it often presents with symptoms such as seizures, &#x0D; confusion, hallucination, sleep abnormalities, and behavioural problems. Patients are mostly euthyroid &#x0D; or mildly hypothyroid. Hashimoto encephalopathy is a controversial diagnosis for misdiagnosis and &#x0D; overdiagnosis because of the high prevalence of thyroid antibodies in the population. Therefore, this &#x0D; diagnosis requires strict criteria that can highly indicate the diagnosis. We aimed to present the &#x0D; diagnosis and treatment processes from unusual symptoms of patients who are considered to have &#x0D; Hashimoto's encephalopathy with very strict criteria.&#x0D; Materials and Methods: Here we present five pediatric patients diagnosed with Hashimoto's &#x0D; encephalopathy between 2013 and 2023. The clinical signs and symptoms, laboratory findings, &#x0D; treatment options and response to treatment were obtained from patient records retrospectively.&#x0D; Results: On admission, patients had striking behavioural changes such as hallucinations, insomnia, &#x0D; purposeless laughing as well as signs of encephalopathy such as status epilepticus and confusion; &#x0D; neurological sequelae; history of surgery, and fever. All patients had high levels of thyroid antibodies &#x0D; and they responded perfectly to steroid treatment in a short period of time.&#x0D; Conclusion: Hashimoto’s encephalopathy should be considered in all patients presenting with &#x0D; encephalopathy in the pediatric age group. These patients may have unusual and clinical &#x0D; manifestations.

Effect of seasonal coronavirus immune imprinting on the immunogenicity of inactivated COVID-19 vaccination.

Pre-existing cross-reactive immunity among different coronaviruses, also termed immune imprinting, may have a comprehensive impact on subsequent SARS-CoV-2 infection and COVID-19 vaccination effectiveness. Here, we aim to explore the interplay between pre-existing seasonal coronaviruses (sCoVs) antibodies and the humoral immunity induced by COVID-19 vaccination. We first collected serum samples from healthy donors prior to COVID-19 pandemic and individuals who had received COVID-19 vaccination post-pandemic in China, and the levels of IgG antibodies against sCoVs and SARS-CoV-2 were detected by ELISA. Wilcoxon rank sum test and chi-square test were used to compare the difference in magnitude and seropositivity rate between two groups. Then, we recruited a longitudinal cohort to collect serum samples before and after COVID-19 vaccination. The levels of IgG antibodies against SARS-CoV-2 S, S1, S2 and N antigen were monitored. Association between pre-existing sCoVs antibody and COVID-19 vaccination-induced antibodies were analyzed by Spearman rank correlation. 96.0% samples (339/353) showed the presence of IgG antibodies against at least one subtype of sCoVs. 229E and OC43 exhibited the highest seroprevalence rates at 78.5% and 72.0%, respectively, followed by NL63 (60.9%) and HKU1 (52.4%). The levels of IgG antibodies against two β coronaviruses (OC43 and HKU1) were significantly higher in these donors who had inoculated with COVID-19 vaccines compared to pre-pandemic healthy donors. However, we found that COVID-19 vaccine-induced antibody levels were not significant different between two groups with high levelor low level of pre-existing sCoVs antibody among the longitudinal cohort. We found a high prevalence of antibodies against sCoVs in Chinese population. The immune imprinting by sCoVs could be reactivated by COVID-19 vaccination, but it did not appear to be a major factor affecting the immunogenicity of COVID-19 vaccine. These findings will provide insights into understanding the impact of immune imprinting on subsequent multiple shots of COVID-19 vaccines.

Patients with psychosis spectrum disorders hospitalized during the COVID-19 pandemic unravel overlooked SARS-CoV-2 past infection clustering with HERV-W ENV expression and chronic inflammation

Epidemiology has repeatedly associated certain infections with a risk of further developing psychiatric diseases. Such infections can activate retro-transposable genetic elements (HERV) known to trigger immune receptors and impair synaptic plasticity of neuroreceptors. Since the HERV-W ENV protein was recently shown to co-cluster with pro-inflammatory cytokines in a subgroup of patients with schizophrenia or bipolar disorder, we questioned the influence of the COVID-19 pandemic on patients with psychosis spectrum disorders (PSD). Present results revealed that (i) SARS-CoV-2 serology shows high prevalence and titers of antibodies in PSD, (ii) HERV-W ENV is detected in seropositive individuals only and (iii) SARS-CoV-2 and HERV-W ENV positivity co-clustered with high serum levels of pro-inflammatory cytokines in psychotic patients. These results thus suggest that SARS-CoV-2 infection in many patients with psychotic disorders now admitted in the psychiatry department did not cause severe COVID-19. They also confirm the previously reported association of elevated serum pro-inflammatory cytokines and HERV-W ENV in a subgroup of psychotic patients. In the context of the COVID-19 pandemic, this cluster is only found in SARS-CoV-2 seropositive PSD cases, suggesting a dominant influence of this virus on HERV-W ENV and cytokine expression, and/or patients’ greater susceptibility to SARS-CoV-2 infection. Further investigation on an interplay between this viral infection and the clinical evolution of such PSD patients is needed. However, this repeatedly defined subgroup of psychotic patients with a pro-inflammatory phenotype and HERV expression calls for a differential therapeutic approach in psychoses, therefore for further precision medicine development.

Infection Dynamics and Genomic Mutations of Hepatitis E Virus in Naturally Infected Pigs on a Farrow-to-Finish Farm in Japan: A Survey from 2012 to 2021.

Hepatitis E virus (HEV) causes acute or chronic hepatitis in humans. Pigs are the primary reservoir for zoonotic HEV genotypes 3 and 4 worldwide. This study investigated the infection dynamics and genomic mutations of HEV in domestic pigs on a farrow-to-finish pig farm in Japan between 2012 and 2021. A high prevalence of anti-HEV IgG antibodies was noted among pigs on this farm in 2012, when the survey started, and persisted for at least nine years. During 2012-2021, HEV RNA was detected in both serum and fecal samples, indicating active viral replication. Environmental samples, including slurry samples in manure pits, feces on the floor, floor and wall swabs in pens, and dust samples, also tested positive for HEV RNA, suggesting potential sources of infection within the farm environment. Indeed, pigs raised in HEV-contaminated houses had a higher rate of HEV infection than those in an HEV-free house. All 104 HEV strains belonged to subgenotype 3b, showing a gradual decrease in nucleotide identities over time. The 2012 (swEJM1201802S) and 2021 (swEJM2100729F) HEV strains shared 97.9% sequence identity over the entire genome. Importantly, the swEJM2100729F strain efficiently propagated in human hepatoma cells, demonstrating its infectivity. These findings contribute to our understanding of the prevalence, transmission dynamics, and genetic characteristics of HEV in domestic pigs, emphasizing the potential risks associated with HEV infections and are crucial for developing effective strategies to mitigate the risk of HEV infection in both animals and humans.

Antiphospholipid antibodies in convalescent plasma of donors recovered from mild COVID-19 infection.

Passive immunization by the infusion of convalescent plasma (CP) obtained from patients who have recently recovered from COVID-19, thus having antibodies to severe acute respiratory syndrome coronavirus 2, is a potential strategy to reduce the severity of illness. A high prevalence of antiphospholipid antibodies (APLA) in patients with COVID-19 has been reported during the pandemic, raising a concern whether the use of CP could increase the risk of thrombosis in transfused patients. We aimed to evaluate the prevalence of APLA in COVID-19 CP (CCP) in order to assess the potential prothrombotic influence of transfused CCP to COVID-19 patients. We studied the prevalence of APLA in 122 CCP samples collected from healthy donors who recovered from mild-COVID-19 at two time periods: September 2020-January 2021 (defined as 'early period' samples) and April-May 2021 (defined as 'late period' samples). Thirty-four healthy subjects unexposed to COVID-19 were used as controls. APLA were present in 7 of 122 (6%) CCP samples. One donor had anti-β2-glycoprotein 1(anti-β2GP1) IgG, one had anti-β2GP1 IgM and five had lupus anticoagulant (LAC) using silica clotting time (SCT), all in 'late period' donors. In the control group, one subject had anti-β2GP1 IgG, two had LAC using dilute Russell viper venom time (dRVVT) and four had LAC SCT (both LAC SCT and LAC dRVVT in one subject). The low prevalence of APLA in CCP donors reassures the safety of CCP administration to patients with severe COVID-19.

In vitro assay development to assess successful removal of T and B cell epitopes through Seismic’s IMPACT platform

Abstract Proteases derived from human pathogens can specifically cleave IgG into F(ab’)2 and Fc fragments. IdeS, an IgG cleaving enzyme derived from Streptococcus pyogenes, has shown clinical proof of concept, and is approved for use before kidney transplantation. Due to the immunogenic nature of these proteases, dosing is limited by high prevalence of pre-existing antibodies and the induction of anti-drug antibodies after dosing. Therefore, to mitigate the impact of the immune system on our enzyme, we identify and remove putative T and B cell epitopes using Seismic’s IMPACT platform leveraging machine learning. To experimentally validate in silicopredictions, we developed two complementary in vitroassays using intravenous immunoglobulin (IVIg) to assess removal of B cell epitopes. First, we assess how mutating the wild type (WT) protease sequence impacts pre-existing antibodies in a competitive binding assay followed by evaluating global binding of pre-existing antibodies to our protease. Additionally, we developed an in vitroPBMC proliferation assay to determine the success of T cell epitope removal. Using flow cytometry, we quantitively assess CD4 proliferation via bromodeoxyuridine (BrdU) incorporation. We demonstrate examples of molecules designed through our IMPACT platform to reduce both T and B cell epitopes. The B cell epitope assays show a decrease in competition as compared to the WT protease while achieving a reduction in IVIg binding. These data suggest that these in vitroassays can be used to screen for successful invisibilization of molecules of interest.

Epidemiological characteristics of bovine besnoitiosis (Besnoitia besnoiti) in a beef cattle farm: a cross-sectional serological assessment.

Bovine besnoitiosis is an emerging disease caused by the protozoa Besnoitia besnoiti that can have a serious economic impact on affected farms. The fact that there is no effective vaccine nor treatment, along with the lack of consistent epidemiologic data, renders the implementation of preventive medicine and control strategies much harder. A cross-sectional serological assessment was performed to better understand the distribution and prevalence of this parasite in a large beef cattle farm in Portugal and to establish some epidemiological characteristics of besnoitiosis. A random blood sampling of 450 animals from a farm that keeps around 2,000 cattle head was performed and sera were submitted to an indirect immunofluorescent antibody test (IFAT). Data on breed, age, sex, and birthplace of the tested animals and their mothers were recorded. The overall prevalence of positive animals was 16.89%, with significant differences between under 1-year-old calves (4.8%) and adults (19.67%). A higher antibody prevalence was shown in animals 1-2 years and >7 years old, in Salers breed and in cows imported from France or whose mothers had come from this country. Calves under 1 year old and crossbreed animals with ancestry born in the current farm presented the lowest antibody prevalence. The most significant risk factors revealed were age (>7 years old) and breed (Salers). Genetic studies should be carried out in order to confirm whether indeed there is a breed susceptibility to bovine besnoitiosis. We suggest that similar studies should be performed across southern Europe to establish strong epidemiologic data that would allow a rigorous transnational control program to be launched.

Effects of habitat management on rodent diversity, abundance, and virus infection dynamics.

As anthropogenic factors continue to degrade natural areas, habitat management is needed to restore and maintain biodiversity. However, the impacts of different habitat management regimes on ecosystems have largely focused on vegetation analyses, with limited evaluation of downstream effects on wildlife. We compared the effects of grassland management regimes (prescribed burning, cutting/haying, or no active management) on rodent communities and the viruses they hosted. Rodents were trapped in 13 existing grassland sites in Northwest Arkansas, USA during 2020 and 2021. Rodent blood samples were screened for antibodies against three common rodent-borne virus groups: orthohantaviruses, arenaviruses, and orthopoxviruses. We captured 616 rodents across 5953 trap nights. Burned and unmanaged sites had similarly high abundance and diversity, but burned sites had a higher proportion of grassland species than unmanaged sites; cut sites had the highest proportion of grassland species but the lowest rodent abundance and diversity. A total of 38 rodents were seropositive for one of the three virus groups (34 orthohantavirus, three arenavirus, and one orthopoxvirus). Thirty-six seropositive individuals were found in burned sites, and two orthohantavirus-seropositive individuals were found in cut sites. Cotton rats and prairie voles, two grassland species, accounted for 97% of the rodents seropositive for orthohantavirus. Our study indicates that prescribed burns lead to a diverse and abundant community of grassland rodent species compared with other management regimes; as keystone taxa, these results also have important implications for many other species in food webs. Higher prevalence of antibodies against rodent-borne viruses in burned prairies shows an unexpected consequence likely resulting from robust host population densities supported by the increased habitat quality of these sites. Ultimately, these results provide empirical evidence that can inform grassland restoration and ongoing management strategies.