Reimagining the serocatalytic model for infectious diseases: A case study of common coronaviruses.

Similar to the model for Sydenham's chorea, antineuronal antibodies, which develop in response to a preceding streptococcal infection, have been speculated to have a role in the development of Tourette syndrome (TS). Serum antibodies against human caudate, putamen, and globus pallidus (interna and externa) were assayed by enzyme-linked immunosorbent assay (ELISA) and Western blot techniques and results were correlated with clinical characteristics and markers of streptococcal infection. A total of 41 children with TS (mean age, 11.3 years) and 39 controls (mean age, 12.1 years) were included. Compared with controls, TS subjects had a significant increase in the mean (p=0.006) and median (p=0.002) ELISA optical density (OD) levels of serum antibodies against putamen, but not caudate or globus pallidus. Western blots on 20 control and 20 TS serum samples showed that specific antibodies to caudate/putamen occurred more frequently in TS subjects at 83, 67, and 60 kDa; antigens were present in a synaptosomal fraction. TS subjects with a positive family history of tics had higher OD values (p < or = 0.04), but no association was shown with age of tic onset, tic severity, sudden onset of tics, or presence of attention-deficit hyperactivity disorder or obsessive-compulsive disorder. Risk ratio calculations in TS and control groups and in study subjects dichotomized for high and low putamen OD values were similar for titers of antistreptolysin O > or = 166 or antideoxyribonuclease B > or = 170. A subgroup analysis limited to subjects with elevated streptococcal titers, however, showed a significantly (p < or = 0.004) larger number of TS subjects with elevated OD levels. Children and adolescents with TS had significantly higher serum levels of antineuronal antibodies against putamen than did controls, but their relation to clinical characteristics and markers for streptococcal infection remains equivocal.

Heparin-Induced Thrombocytopenia with Very High Antibody Titer Is Associated with Slower Platelet Recovery

Microwave irradiation, as opposed to formalin exposure, has not routinely been used in the preparation of killed vaccines despite the advantages of decreased chemical toxicity, ability to kill cells quickly, ease of completion requiring only a standard microwave, and potential increased protein conservation during irradiation. We evaluated the potential of microwave irradiation versus formalin fixation of bacteria to improve Streptococcus agalactiae vaccine efficacy in 5 gr fish by intraperitoneal (IP) injection and bath immersion (BI). There was no significant difference in the cumulative percent mortality (CPM) post-challenge between fish administered microwave-killed cells (MKC) or formalin killed cells (FKC) within the BI (p S. agalactiae antibody activity. Thirty days after vaccination and just prior to challenge, the optical density (OD) levels of the FKC and MKC groups in the IP trials were significantly higher (p < 0.0001) than that of the TSB group. None of the groups in the BI trial exhibited significantly different OD levels post vaccination. Fourteen days after the challenge, the OD levels of all groups in both trials increased significantly above their pre-challenge levels. Both the FKC and MKC IP groups (p < 0.0001) and only the FKC BI group (p < 0.0351) had significantly increased OD level above that of the corresponding post-challenge TSB group. These results indicate that the FKC vaccine provides marginally greater protection and increased antibody concentrations than the MKC vaccine by BI and the MKC vaccine may become a non-chemical alternative to FKC in vaccination.

Cross-sectional prevalence studies based on immunoassays that discriminate between recent and long-term infections, such as the BED assay, have been widely used to estimate HIV incidence. However, individuals receiving highly active antiretroviral therapy tend to have lower BED levels and are associated with a higher risk for being mistakenly classified as recent infections. To assess the effect of short-term antenatal zidovudine (ZDV) and single-dose nevirapine (sdNVP) on the BED levels in HIV-1C infection, we measured longitudinal BED normalized optical density (OD-n) levels using stored plasma samples collected prenatally and postnatally from 159 pregnant HIV-infected women in Botswana who participated in the randomized clinical Mother-to-Child-Prevention study, the Mashi study. All women received ZDV from 34 weeks gestation through delivery and were randomized to receive either sdNVP or placebo during labor. Among 159 subjects, the OD-n levels decreased from baseline to delivery in 93 subjects (p=0.039), suggesting that short-course ZDV may decrease OD-n levels. sdNVP at delivery did not affect longitudinal BED OD-n levels postdelivery. However, sdNVP appeared to modify the association between CD4 count at delivery and OD-n levels postdelivery. When estimating HIV incidence with the BED assay, special care may be required regarding women who received short-term ZDV for prevention of mother-to-child transmission.

During the COVID-19 pandemic, nonpharmaceutical interventions (NPIs) were introduced to reduce the spread of SARS-CoV-2. This also resulted in a reduction of notifications of other acute respiratory infections and an altered seasonality when NPIs were lifted. Without circulation of pathogens, waning of antibodies is expected, which is a first indicator of decreased immunity. Here, by performing a systematic literature review, we investigated whether reduced antibody levels due to waning immunity contributed to the altered seasonality after NPIs were lifted. Thirteen articles met the inclusion criteria and reported antibody levels or seroprevalence of human respiratory syncytial virus, seasonal human coronavirus, Bordetella pertussis, and influenza virus. We show that the COVID-19 pandemic most likely led to waning of pathogen-specific antibodies, with the strongest evidence for human respiratory syncytial virus and seasonal human coronavirus and with a larger decrease in children vs adults. Waning antibodies might have resulted in out-of-season activity for these pathogens.

Evaluation of epidemiological and serological predictors of human immunodeficiency virus type-1 (HIV-1) infection among high risk professional blood donors with western blot indeterminate results.

Response to COVID-19 Vaccines in Patients Receiving Intensified Post-ASCT Therapy with Daratumumab, Lenalidomide, Bortezomib (Dara-VR) Due to Ultra-High Risk (UHiR) Newly Diagnosed Myeloma (NDMM) or Primary Plasma Cell Leukemia (pPCL): Exploratory Analysis of the UK Optimum/Muknine Trial

Utility of Optical Density Values from Heparin-Platelet Factor 4 Antibody Testing and Probability Scoring Models To Diagnose Patients with Heparin Induced Thrombocytopenia.

Background Immune-mediated inflammatory diseases (IMID) including inflammatory bowel diseases (IBD) and inflammatory arthritides are commonly treated with biological therapies, in particular anti-TNF. Patients on anti-TNF have impaired protective immunity following pneumococcal, influenza and viral hepatitis. However, the serological response to COVID-19 vaccination is still under-studied. Recent studies demonstrated that serologic response is attenuated in IMID patients on immunosuppressive therapy. In this study, the primary outcome is to describe the antibody response in IMID patients according to baseline patient characteristics, type of inflammatory disease, treatment and disease activity. Secondary outcome is to compare antibody response in patients treated with anti-TNF, versus other biologic therapies. Methods This study is a monocentric retrospective study, including 265 IMID patients followed at CHU Saint Pierre, Belgium, between 2021 and 2022. Respective baseline patient characteristics, vaccination status, treatment type, disease activity and SARS-CoV-2 antibody titers (IgG) after first, second and third vaccination were collected and analyzed. Results A total of 265 patients were enrolled (mean age 47 years old, 35% males, 67% IBD patients). Of these, 217 patients (82%) completed the 2 doses of vaccination and 130 patients (49%) the 3 doses, while 40 patients (15%) remained unvaccinated. Antibody titers after 2 doses of vaccination were available for 50 patients. In this group, the median antibody titer was 93 AU/mL [26-421] after first vaccination, raised up to 640 AU/mL [271-800] after the second vaccination (Δ85%, p&amp;lt;0.0001). Similarly, a statistically significant increase was noted in the subgroup of patients with available serologic data after 3 vaccination doses (N=18). The median antibody titer after the first vaccination in anti-TNF subgroup (N=15) was lower than that in other biotherapies subgroup (N=23); 34 AU/mL [6-145] versus 131 AU/mL [34-704] respectively. However, after the second vaccination, higher antibody titers were found in the anti-TNF subgroup, 686 AU/mL [321-800] versus 400 AU/mL [250-800] (p&amp;lt;0.388). Conclusion In our cohort of IMID patients, followed at CHU Saint Pierre, Belgium, there was a statistically significant raise in antibody titers after the second and third dose of COVID-19 vaccination, regardless of the type of inflammatory disease, disease activity, type of treatment and vaccine type. The antibody titers in this particular immunocompromised population were comparable to that found in the literature for the general population. More prospective observational studies are needed with a larger sample size to determine the characteristics of patients with sub-optimal serological response.

Definitions for coronavirus disease 2019 reinfection, relapse and PCR re-positivity

BackgroundHeparin-induced thrombocytopenia (HIT) is an adverse drug reaction caused by antibodies to the heparin/platelet factor 4 (PF4) complex, resulting in thrombocytopenia and prothrombotic state. HIT diagnosis is challenging and depends on clinical presentation and laboratory tests. We investigated the usefulness of clinical scores and heparin/PF4 ELISA optical density (OD) as a diagnostic marker and thrombosis predictor in HIT.MethodsWe analyzed 92 patients with suspected HIT. The heparin/PF4 antibody was measured using a commercial ELISA kit (GTI, USA). For each patient, the 4 T's score and Chong's score were calculated.ResultsOf the 92 patients, 28 were anti-heparin/PF4-seropositive. The 4 T's score and Chong's score showed good correlation (r=0.874). The 4 T's score and OD values showed good performance for diagnosis of the definite and unlikely HIT groups; however, OD levels showed better sensitivity (93.8%) than the 4 T's score used alone (62.5%). Of the 92 patients, 26 developed thrombosis. The OD values were significantly higher in patients with thrombosis than in those without thrombosis (0.52 vs. 0.22, P<0.001). Patients with high OD values (OD>0.4) had an increased risk of thrombosis (adjusted odds ratio 9.44 [3.35-26.6], P<0.001) and a shorter 250-day thrombosis-free survival (32.1% vs. 54.7%, P=0.012).ConclusionsELISA OD values in combination with clinical scoring can improve the diagnosis of and thrombosis prediction in HIT. More attention should be paid to the use of clinical scores and OD values as thrombosis predictors in HIT.

Serological diagnosis of equine influenza using the hemagglutinin protein produced in a baculovirus expression system

Value of ELISA Using Antigen 60 for the Diagnosis of Tuberculosis in Children

Effect of Bruton Tyrosine Kinase Inhibitor on Serologic and Cellular Immune Responses to Recombinant Zoster Vaccine

The emergence of successive SARS-CoV-2 variants of concern (VOC) during 2020-22, each exhibiting increased epidemic growth relative to earlier circulating variants, has created a need to understand the drivers of such growth. However, both pathogen biology and changing host characteristics – such as varying levels of immunity – can combine to influence replication and transmission of SARS-CoV-2 within and between hosts. Disentangling the role of variant and host in individual-level viral shedding of VOCs is essential to inform COVID-19 planning and response, and interpret past epidemic trends. Using data from a prospective observational cohort study of healthy adult volunteers undergoing weekly occupational health PCR screening, we developed a Bayesian hierarchical model to reconstruct individual-level viral kinetics and estimate how different factors shaped viral dynamics, measured by PCR cycle threshold (Ct) values over time. Jointly accounting for both inter-individual variation in Ct values and complex host characteristics – such as vaccination status, exposure history and age – we found that age and number of prior exposures had a strong influence on peak viral replication. Older individuals and those who had at least five prior antigen exposures to vaccination and/or infection typically had much lower levels of shedding. Moreover, we found evidence of a correlation between the speed of early shedding and duration of incubation period when comparing different VOCs and age groups. Our findings illustrate the value of linking information on participant characteristics, symptom profile and infecting variant with prospective PCR sampling, and the importance of accounting for increasingly complex population exposure landscapes when analysing the viral kinetics of VOCs.