A longitudinal study on SARS-CoV-2 seroconversion, reinfection and neutralisation spanning several variant waves and vaccination campaigns, Heinsberg, Germany, April 2020 to November 2022.

BackgroundSince its emergence in December 2019, over 700 million people worldwide have been infected with SARS-CoV-2 up to May 2024. While early rollout of mRNA vaccines against COVID-19 has saved many lives, there was increasing immune escape of new virus variants. Longitudinal monitoring of population-wide SARS-CoV-2 antibody responses from regular sample collection irrespective of symptoms provides representative data on infection and seroconversion/seroreversion rates.AimTo examine adaptive and cellular immune responses of a German SARS-CoV-2 outbreak cohort through several waves of infection with different virus variants.MethodsUtilising a 31-month longitudinal seroepidemiological study (n = 1,446; mean age: 50 years, range: 2-103) initiated during the first SARS-CoV-2 superspreading event (February 2020) in Heinsberg, Germany, we analysed acute infection, seroconversion and virus neutralisation at five follow-up visits between October 2020 and November 2022; cellular and cross-protective immunity against SARS-CoV-2 Omicron variants were also examined.ResultsSARS-CoV-2 spike (S)-specific IgAs decreased shortly after infection, while IgGs remained stable. Both increased significantly after vaccination. We predict an 18-month half-life of S IgGs upon infection. Nucleocapsid (N)-specific responses declined over 12 months post-infection but increased (p < 0.0001) during Omicron. Frequencies of SARS-CoV-2-specific TNF-alpha+/IFN-gamma+ CD4+ T-cells declined over 12 months after infection (p < 0.01). SARS-CoV-2 S antibodies and neutralisation titres were highest in triple-vaccinated participants infected between April 2021 and November 2022 compared with infections between April 2020 and January 2021. Cross neutralisation against Omicron BQ.1.18 and XBB.1.5 was very low in all groups.ConclusionInfection and/or vaccination did not provide the population with cross-protection against Omicron variants.

Impact of cytomegalovirus (CMV) seroconversion pre-allogeneic hematopoietic cell transplantation on posttransplant outcomes.

Cytomegalovirus (CMV) reactivation post-allogeneic hematopoietic cell transplantation (post-alloHCT) increases morbidity and mortality. We sought to determine the frequency of CMV seroconversion in patients pre-alloHCT and to investigate the impact on posttransplant outcomes. We retrospectively investigated 752 adult patients who underwent alloHCT at our center from January 2015 to February 2020 before the adoption of letermovir prophylaxis. CMV serology was assessed at consult and pretransplant. The cohort was divided into four groups based on pretransplant CMV seroconversion: negative to positive (Group 1), positive to negative (Group 2), consistently negative (Group 3), and consistently positive (Group 4). Eighty-nine patients (12%) had seroconverted from negative to positive, 17 (2%) from positive to negative, 151 (20%) were consistently seronegative, and 495 (66%) were consistently seropositive pretransplant. For the four CMV serostatus groups, cumulative incidence of CMV reactivation at 6 months posttransplant was 4.5%, 47.1%, 6.6%, and 76.6% for Groups 1, 2, 3, and 4, respectively (p < .0001). No differences between groups were seen regarding Grade III-IV acute graft-versus-host disease (GVHD) (p = .91), moderate/severe chronic GVHD (p = .41), or graft failure (p = .28). On multivariable analysis, there was no impact of CMV serostatus group on overall survival (p = .67), cumulative incidence of relapse (p = .83) or non-relapse mortality. alloHCT patients who demonstrate CMV seroconversion pretransplant from negative to positive have a very low risk of CMV reactivation posttransplant. The observed seroconversion may be due to passive CMV immunity acquired through blood products. Quantitative CMV immunoglobulin G/immunoglobulin M pretransplant may help differentiate between true seroconversion and passively transmitted CMV immunoglobulin.

Rapid tests should be used with caution for HIV-1 primary infection screening.

Rapid tests allow outpatient, low cost, reliable, screening for chronic HIV infection. However, data regarding their sensitivity on primary infection remain scarce. The objective of this study was to assess sensitivity of nine HIV rapid tests for primary HIV-1 infection screening. Seventy-five serum samples from patients during HIV-1 primary infection were included. Primary infection was diagnosed by a positive 4th generation ELISA and HIV-1 RNA positivity confirmed by Western blot patterns associated with HIV-1 primary infection. Early seroconversion was defined as the absence of antibodies on HIV-1 Western blot associated with HIV-1 RNA and p24-antigen positivity. An identical sensitivity (95% CI) of 76.7% (65.2-84.2%) was observed for HIV 1/2 STAT-PAK® Assay (STAT-PAK), INSTI™ HIV-1/HIV-2 antibody Test (INSTI), SURE CHECK® HIV 1/2 (SURE CHECK) and MULTISURE HIV rapid test (MULTISURE) with visual reading. Sensitivity was 74.7% (63.8-83.1%) for MULTISURE (automatic reading), 77.0% (66.3-85.1%) for FIRST RESPONSE® Test VIH 1-2.O CARTE (FIRST RESPONSE), 83.8% (73.8-90.5%) for VIKIA HIV1/2® (VIKIA), 88.0% (78.7-93.6%) for Genie™ Fast HIV 1/2 (Genie Fast), 88.6% (79.0-94.1%) for Hexagon HIV (Hexagon), and 92.8% (83.6-96.3%) for Exacto® TEST HIV Pro (Exacto). However, rapid tests performed poorly for the early seroconversion subgroup (n = 14), with sensitivities ranging from 7% (1.3-31.5%) for STAT-PAK, INSTI, SURE CHECK, MULTISURE (automatic reading), to 29% (12-55%) for FIRST RESPONSE, 31% (13-58%) for VIKIA, 43% (21-67%) for Hexagon and 57.1% (32.6-78.6%) for Exacto and Genie Fast. Overall, despite significant discrepancies in sensitivity, HIV rapid tests should be used with caution in the context of a suspected primary infection.

Factors associated with PrEP-era HIV seroconversion in a 4-year U.S. national cohort of n = 6059 sexual and gender minority individuals who have sex with men, 2017-2022.

INTRODUCTION: Community-based cohort studies of HIV seroconversion can identify important avenues for enhancing HIV prevention efforts in the era of pre-exposure prophylaxis (PrEP). Within individuals, one can assess exposure and outcome variables repeatedly and with increased certainty regarding temporal ordering. This cohort study examined the association of several risk factors with subsequent HIV seroconversion. METHODS: We report data from a 4-year study (2017-2022) of 6059 HIV seronegative sexual and gender minority individuals who have sex with men who had indications for-, but were not using-, PrEP at enrolment. Participants completed repeat exposure assessments and self-collection of biospecimens for HIV testing. We examined the roles of race and ethnicity, socio-economic status, methamphetamine use and PrEP uptake over the course of follow-up in relation to HIV seroconversion. RESULTS: Over 4 years, 303 of the participants seroconverted across 18,421 person-years (incidence rate = 1.64 [95% CI: 1.59-1.70] per 100 person-years). In multivariable discrete-time survival analysis, factors independently associated with elevated HIV seroconversion risk included being Black/African American (adjusted risk ratio [aRR]: 2.44, 1.79-3.28), Hispanic/Latinx (1.53, 1.19-1.96), housing instability (1.58, 1.22-2.05) and past year methamphetamine use (3.82, 2.74-5.33). Conversely, time since study enrolment (24 vs. 12 months, 0.67, 0.51-0.87; 36 months, 0.60, 0.45-0.80; 48 months, 0.48, 0.35-0.66) and higher education (master's degree or higher vs. less than or equal to high school, 0.36, 0.17-0.66) were associated with reduced seroconversion risk. Compared to non-PrEP users in the past 2 years without a current clinical indication, those who started PrEP but then discontinued had higher seroconversion risk, irrespective of clinical indication (3.23, 1.74-6.46) or lack thereof (4.30, 1.85-9.88). However, those who initiated PrEP in the past year (0.14, 0.04-0.39) or persistently used PrEP in the past 2 years (0.33, 0.14-0.74) had a lower risk of seroconversion. Of all HIV seroconversions observed during follow-up assessments (12, 24, 36 and 48 months), methamphetamine was reported in the 12 months prior 128 (42.2%) times (overall). CONCLUSIONS: Interventions that acknowledge race and ethnicity, economic variables such as education and housing instability, and methamphetamine use are critically needed. Not only are interventions to engage individuals in PrEP care needed, but those that retain them, and re-engage those who may fall out of care are essential, given the exceptionally high risk of seroconversion in these groups.

HIV seroconversion among female sex workers: retrospective cohort study from a large-scale HIV prevention and sexual and reproductive health program in Tanzania.

Introduction: In 2016, UNAIDS set ambitious targets to reduce global HIV infections by 75% by 2020 and 90% by 2030, based on the 2.1 million new infections reported in 2010. However, by 2022, new HIV infections had only decreased by 38%, from 2.1 million in 2010 to 1.3 million in 2022, raising concerns about reaching the 2030 goal. Female sex workers (FSWs) in sub-Saharan Africa face a disproportionately high risk of HIV acquisition, contributing 5%-20% of all new infections in several countries in the region. This analysis investigates HIV seroconversion and associated factors among FSWs, offering insights into critical interventions for preventing HIV transmission in this population and advancing the goal of ending the HIV pandemic by 2030. Methods: We conducted a retrospective cohort study involving 17,977 FSWs who initially tested HIV negative upon enrollment in the Sauti project between October 2016 and September 2018. HIV incidence rates were calculated by dividing the number of new HIV cases by observed person-time within the cohort. Cox regression analysis identified factors associated with seroconversion. Results: The study revealed an HIV incidence rate of 8.6 per 100 person-years among FSWs [95% confidence interval (CI): 8.1-9.1]. Factors independently associated with HIV seroconversion included age 35 years or older [adjusted hazard ratio (aHR): 2.53; 95% CI: 2.03-3.14], unprotected sex (aHR: 1.27; 95% CI: 1.13-1.42), STI symptoms (aHR: 1.99; 95% CI: 1.67-2.38), and alcohol consumption before sex (aHR: 1.20; 95% CI: 1.07-1.34). Conclusion: Targeted interventions are vital in curbing HIV transmission among FSWs, with a focus on expanding access to primary HIV prevention services, particularly for older FSWs who face heightened risk. Tailored sexual health education programs are imperative to encourage consistent condom use and enable informed decision-making. Accessible and timely STI screening and treatment services are crucial to mitigate HIV transmission risk. Collaborative partnerships between healthcare providers, community organizations, and government agencies are essential in implementing these interventions among FSWs.

Efficacy of COVID-19 Vaccines in Patients with Hematological Malignancy Compared to Healthy Controls: A Systematic Review and Meta-analysis.

Background: The possibility of developing a severe coronavirus infectious (COVID-19) disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has increased, particularly in patients with hematological malignancies. These patients are more likely to produce less antibody protection due to the immunocompromised nature of the disease and the anticancer treatments. Therefore, the present systematic review intended to evaluate the seroconversion rate of COVID-19 vaccines in patients with hematological malignancies compared with healthy controls. Methods: A comprehensive systematic search was conducted in Medline via PubMed, EMBASE, and the World Health Organization COVID-19 Research Database, as well as other searches (i.e., reference list from article search and manual searches), from December 2020 to May 2022. The outcome of interest included estimating the seroconversion rates following COVID-19 vaccination in patients with hematological malignancies and comparing them with those in healthy controls. After two-step screening, the data were extracted and the summary measures were calculated using a random-effects model. Results: A total of 39 articles regarding patients with hematological malignancies were included in the present review. After the first vaccine dose, these patients had considerably lower antibody response rates (37.0%) compared with healthy controls (74.5%). Following the second vaccine dose, the seroconversion rate in patients reached 66.8%, whereas it peaked at 97.9% in the healthy controls following complete immunization. Notably, the BNT162b2 and ChAdOx1 vaccine combination achieved the highest seropositivity rate of approximately 70%. Multiple myeloma, chronic lymphocytic leukemia, and lymphoma were the cancers of interest in most of the studies. Conclusions: The results of the present study highlighted the comparatively low seropositivity rates in patients with hematological malignancies, with substantial variations in rates across disease groups. The findings emphasize the possibility of additional booster doses for these individuals to enhance their immunity against SARS-CoV-2.

A Randomized Controlled Study of Efficacy and Safety of Accelerated Versus Standard Hepatitis B Vaccination in Patients With Advanced CKD.

Introduction: Hepatitis B virus (HBV) vaccination is crucial for seronegative patients with advanced chronic kidney disease (CKD) for protection during dialysis while preparing for transplantation. A standard regimen for HBV vaccination requires 24 weeks to be completed. An accelerated HBV vaccination regimen completed within 8 weeks has shown early effective seroconversion in healthcare workers. However, data for patients with advanced CKD are limited. Methods: A randomized controlled trial was conducted in patients with advanced CKD (estimated glomerular filtration rate [GFR] <30 ml/min per 1.73 m2) and patients on dialysis. The patients were randomly assigned to either a standard HBV vaccination regimen (Engerix B; 40 µg at 0, 4, 8, and 24 weeks) or an accelerated regimen (40 µg at 0, 1, 4, and 8 weeks). The hepatitis B surface antibodies (anti-HBs) were measured at 12, 28, and 52 weeks. Seroconversion were defined as anti-HBs ≥10 IU/l. Results: At 12 weeks, among the intention-to-treat (ITT) population of 133 participants (65 in the accelerated and 68 in the standard groups), the accelerated group demonstrated significantly higher rates of seroconversion (83.08% vs. 63.24%, P = 0.01). In the per-protocol (PP) analysis of 125 patients (62 in the standard and 63 in the accelerated groups), the accelerated group exhibited higher seroconversion rate compared with the standard group (85.71% vs. 69.35%, P = 0.03). At 28 and 52 weeks, the seroconversion rates were similar between the 2 groups. Conclusion: In patients with advanced CKD, the accelerated HBV vaccination regimen demonstrated a significantly higher seroconversion rate at 12 weeks of vaccination. This finding suggests that the accelerated regimen is an effective option to achieve rapid seroconversion before initiating hemodialysis or before undergoing kidney transplantation.

Predictive role of early treatment dynamics of HBV RNA and HBcrAg for HBeAg seroconversion in children with chronic hepatitis B.

This study aimed to assess the predictive capacity of emerging serological markers, serum HBV RNA and HBcrAg, for HBeAg seroconversion in children with HBeAg-positive chronic hepatitis B (CHB). Treatment-naïve HBeAg-positive CHB children who admitted to the Liver Disease Center of Hunan Children's Hospital between April 2021 and September 2022 and received treatment with the combined entecavir and interferon-alpha treatment were recruited. Serum HBV RNA and HBcrAg were measured at baseline and Weeks 12, 24, and 48 of treatment. Our study showed that serum HBV RNA (HR = 0.71, 95% CI: 0.56-0.91, p = 0.006), HBcrAg (HR = 0.60, 95% CI: 0.43-0.84, p = 0.003), and HBsAg (HR = 0.49, 95%CI: 0.36-0.69, p < 0.001) at Week 12 were independent predictors of HBeAg seroconversion. ROC curve analysis presented that serum HBV RNA decline value (ΔHBV RNA) at Week 36 and HBcrAg decline value (ΔHBcrAg) at Week 12 (AUC = 0.871, p = 0.003 and AUC = 0.810, p = 0.003, respectively) could effectively predict HBeAg seroconversion. Furthermore, the optimal critical values were determined and the children with ΔHBV RNA > 3.759 log10 copies/mL at Week 36 or ΔHBcrAg >0.350 log10 U/mL at Week 12 more likely to achieve HBeAg seroconversion. The serum HBV RNA and HBcrAg provide new insights into the treatment of CHB in children. Early assessment of serum HBV RNA and HBcrAg during treatment can assist clinical decision-making and optimize individualized therapeutic approaches.

Epidemiology Tools to Evaluate the Control of Proliferative Enteropathy in Commercial Pig Herds.

Proliferative enteropathy (PE) is characterized by diarrhea and reduced weight gains in growing pigs and intestinal hemorrhage in finishers. Vaccination, antibiotic medication, and improved hygiene can control PE, but their efficacy depends upon the epidemiology of PE. This study monitored the timing and severity of PE in 84 commercial pens across seven treatments, including disinfection, vaccination, no treatment, medication with olaquindox (50, 25 and 12.5 ppm), and combined disinfection and vaccination. Vaccination with or without lime disinfection suppressed clinical signs of PE and reduced the number of excreted L. intracellularis relative to untreated pigs housed in cleaned or cleaned and disinfected pens between 9 and 17 weeks of age. Continuous olaquindox mediation to 17 weeks of age prevented L. intracellularis infection, leaving finisher pigs naïve. These finisher pigs suffered an outbreak of hemorrhagic enteropathy with significant reductions in weight gain, feed intake, and mortalities of 4.6%. Over the 13 week grow/finish period, vaccinated pigs housed in disinfected pens showed significantly higher weight gain and feed intake relative to all other treatments, equating to a weight gain difference of between 3.6 and 3.9 kg per pig. Monitoring the immune response and fecal excretion of L. intracellularis in pens of pigs enabled effective PE control strategies to be evaluated on the farm.

Serum IgG antibodies to HPV6 L1, E2, E4, E6, and E7 proteins among children prospectively followed-up for three years.

BACKGROUND: Current knowledge implicates that human papillomavirus (HPV) infection can be acquired at early age. However, the role of HPV-specific passive immunization from mother to neonate is nearly unexplored, especially against the HPV early proteins. We analyzed IgG antibodies against HPV6 early (E2, E4, E6, E7) and late (L1) proteins in children prospectively followed-up for three years. METHODS: A total of 272 children and their mothers from the Finnish Family HPV Study were included in these analyses. Serum samples were obtained from pregnant mothers at their third trimester and from newborn/infants at 1-, 2-, 6-, 12-, 24-, and 36-month visits after birth. Antibodies to the early and late proteins were analyzed by multiplex serology based on glutathione S-transferase fusion protein capture to fluorescent beads. RESULTS: Maternal antibodies to all tested HPV6 proteins were transferred to neonates, concordance between maternal and neonates' antibody levels being highly significant (p<0.001). Seropositivity of HPV6 L1 in the neonates declined during the first six months of life, whereas changes in the E-protein antibodies were less obvious. After the maternal antibodies have vanished, seroconversion to HPV6 L1 at 12 months (median) and to the HPV6 E-proteins between 23-35 months was observed. CONCLUSION: IgG antibodies against HPV6 E- and L-proteins are transferred from mothers to their children. Seroconversion against HPV6 L1, E2, E4, E6, and E7 does occur in early childhood, as a sign of acquired HPV6 infection by vertical or horizontal transmission starting at 12 months of age.

Longevity of serologic responses following a single dose of typhoid conjugate vaccine among children living with HIV in Pakistan: A prospective cohort study.

BACKGROUND: This study aimed to assess the longevity of serologic response and seroconversion rates at several time points following TCV vaccination among children living with HIV aged 6 months to 15 years in Pakistan. METHODS: From November 20, 2020, to January 2, 2021; 336 children were enrolled and followed up prospectively for 12 months. Blood samples were collected before the administration of TCV and at 4-6 weeks, 6 months, and 1 year after administration of a single dose (0.5 ml) of intramuscular Typbar TCV®. Samples were analyzed for anti-Vi-IgG antibodies using ELISA. Geometric mean titers (GMTs), seroconversion rates (fourfold rise in anti-Vi-IgG from baseline), and factors associated with sustained seroconversion at 1 year were evaluated using generalized linear mixed models. FINDINGS: The seroconversion rates were significantly lower in children aged 6 months to 5 years compared to children > 5 years; (127/216 (58·8%)) versus (81/111 (73·0%)) at 6 months and (110/217 (50·7%)) versus (78/109 (71·6%)) at 1 year, only two-third; 188/326 (57·7%) remained seroconverted at 1 year. The GMTs (95 % CI) were significantly lower in children aged 6 months to 5 years compared to children > 5 years, 9·6 (7·6, 12·0) versus 28·9 (20·2, 41·4) at 6 months, and 6·6 (5·4, 8·0) versus 23·1 (16·4, 32·5) at 1 year time point. The odds of sustained seroconversion significantly decreased with time (adjusted odds ratio (aOR): 0·232; 95 % CI: 0·136,0·396). The odds of sustained seroconversion following 1 year of TCV vaccination were significantly higher among children with non-severe HIV clinical disease (aOR: 10·6; 95 % CI: 1·5, 73·9) and children in elder age group (aOR: 7·45; 95 % CI: 11·2, 47·0). CONCLUSIONS: There was a decline in seroconversion after one year of TCV in children living with HIV. The decline was significant in children with severe or advanced HIV disease. A significant decrease in seroconversion rates was observed among children living with HIV following one year of TCV administration.

Nine-Month Trend of IgG Antibody Persistence and Associated Symptoms Post-SARS-CoV-2 Infection.

Between 2 and 8.5% of patients who recover from COVID-19 do not develop antibodies, and the durability of IgG antibodies is under scrutiny. Therefore, the presence and persistence of IgM and IgG antibodies were evaluated in a group of patients diagnosed with SARS-CoV-2 from May to August 2020. Out of 2199 suspected COVID-19 cases, 1264 were confirmed for SARS-CoV-2 by rRT-PCR; 328 consented to participate in the study, with 220 participants followed for 9 months, including 124 men (56%) and 96 women (44%). The primary symptoms were headache, dry cough, and fever. IgG antibodies developed in 95% of patients within 4 weeks post-diagnosis, and a second evaluation at 9 months showed that 72.7% still had detectable IgG antibodies. The presence of IgM in one individual (0.45%) suggested the possibility of reinfection.

18-month longitudinal SARS COV-2 neutralizing antibody dynamics in haemodialysis patients receiving heterologous 3-dose vaccination (AZD-1222- AZD-1222- BNT162b2) in a lower middle income setting.

BACKGROUND: Patients with chronic kidney disease on haemodialysis (HD) were given priority COVID-19 vaccination due to increased disease risk. The immune response to COVID-19 vaccination in patients on HD was diminished compared to healthy individuals in 2-dose studies. This study aimed to evaluate seroconversion rate, neutralizing antibody (nAB) levels and longitudinal antibody dynamics to 3-dose heterologous vaccination against COVID-19 in a cohort of HD patients compared to healthy controls and assess patient factors associated with antibody levels. METHODS: This study was a case-control longitudinal evaluation of nAB dynamics in 74 HD patients compared to 37 healthy controls in a low/middle income setting. Corresponding samples were obtained from the two cohorts at time-points (TP) 1-1-month post 2nd dose of AZD1222 vaccine, TP2- 4 months post 2nd dose, TP4- 2 weeks post 3rd dose with BNT162b2 vaccine, TP5-5 months post 3rd dose and TP6-12 months post 3rd dose. Additional data is available at TP0- pre 2nd dose and TP3- 6 months post 2nd dose in HC and HD cohorts respectively. Anti-SARS-CoV-2 nAB were detected using Genscript cPassTM pseudoviral neutralization kit. Demographic and clinical details were obtained using an interviewer administered questionnaire. RESULTS: Cohorts were gender matched while mean age of the HD cohort was 54.1yrs (vs HCs mean age, 42.6yrs, p < 0.05). Percentage seroconverted and mean/median antibody level (MAB) in the HD cohort vs HCs at each sampling point were, TP1-83.7% vs 100% (p < 0.05), MAB-450 IU/ml vs 1940 IU/ml (p < 0.0001); TP2-71.4% vs 100%, (p < 0.001), MAB- 235 IU/ml vs 453 IU/ml, (p < 0.05); TP4-95.2% vs 100% (p > 0.05), MAB-1029 IU/ml vs 1538 IU/ml (p < 0.0001); TP5-100% vs 100%, MAB-1542 IU/ml vs 1741IU/ml (p > 0.05); TP6-100% vs 100%, MAB-1961 IU/ml vs 2911 IU/ml (p > 0.05). At TP2, patients aged < 60 years (p < 0.001) were associated with maintaining seropositivity compared to patients > 60 years. CONCLUSION: Two dose vaccination of haemodialysis patients provided poor nAB levels which improved markedly following 3rd dose vaccination, the effect of which was long- lasting with high nAB levels in both patients and controls detectable at 1 year follow-up.

Immunogenicity of mRNA-1273 and BNT162b2 in Immunocompromised Patients: Systematic Review and Meta-analysis Using GRADE.

INTRODUCTION: Immunocompromised (IC) patients mount poor immune responses to vaccination. Higher-dose coronavirus disease 2019 (COVID-19) vaccines may offer increased immunogenicity. METHODS: A pairwise meta-analysis of 98 studies reporting comparisons of mRNA-1273 (50 or 100 mcg/dose) and BNT162b2 (30 mcg/dose) in IC adults was performed. Outcomes were seroconversion, total and neutralizing antibody titers, and cellular immune responses. RESULTS: mRNA-1273 was associated with a significantly higher seroconversion likelihood [relative risk, 1.11 (95% CI, 1.08, 1.14); P < 0.0001; I2 = 66.8%] and higher total antibody titers [relative increase, 50.45% (95% CI, 34.63%, 66.28%); P < 0.0001; I2 = 89.5%] versus BNT162b2. mRNA-1273 elicited higher but statistically nonsignificant relative increases in neutralizing antibody titers and cellular immune responses versus BNT162b2. CONCLUSION: Higher-dose mRNA-1273 had increased immunogenicity versus BNT162b2 in IC patients.

Improving the sensitivity of myelin oligodendrocyte glycoprotein-antibody testing: exclusive or predominant MOG-IgG3 seropositivity-a potential diagnostic pitfall in patients with MOG-EM/MOGAD.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis (MOG-EM; also termed MOG antibody-associated disease, MOGAD) is the most important differential diagnosis of both multiple sclerosis and neuromyelitis optica spectrum disorders. A recent proposal for new diagnostic criteria for MOG-EM/MOGAD explicitly recommends the use of immunoglobulin G subclass 1 (IgG1)- or IgG crystallizable fragment (Fc) region-specific assays and allows the use of heavy-and-light-chain-(H+L) specific assays for detecting MOG-IgG. By contrast, the utility of MOG-IgG3-specific testing has not been systematically evaluated. OBJECTIVE: To assess whether the use of MOG-IgG3-specific testing can improve the sensitivity of MOG-IgG testing. METHODS: Re-testing of 22 patients with a definite diagnosis of MOG-EM/MOGAD and clearly positive MOG-IgG status initially but negative or equivocal results in H+L- or Fc-specific routine assays later in the disease course (i.e. patients with spontaneous or treatment-driven seroreversion). RESULTS: In accordance with previous studies that had used MOG-IgG1-specific assays, IgG subclass-specific testing yielded a higher sensitivity than testing by non-subclass-specific assays. Using subclass-specific secondary antibodies, 26/27 supposedly seroreverted samples were still clearly positive for MOG-IgG, with MOG-IgG1 being the most frequently detected subclass (25/27 [93%] samples). However, also MOG-IgG3 was detected in 14/27 (52%) samples (from 12/22 [55%] patients). Most strikingly, MOG-IgG3 was the predominant subclass in 8/27 (30%) samples (from 7/22 [32%] patients), with no unequivocal MOG-IgG1 signal in 2 and only a very weak concomitant MOG-IgG1 signal in the other six samples. By contrast, no significant MOG-IgG3 reactivity was seen in 60 control samples (from 42 healthy individuals and 18 patients with MS). Of note, MOG-IgG3 was also detected in the only patient in our cohort previously diagnosed with MOG-IgA+/IgG- MOG-EM/MOGAD, a recently described new disease subvariant. MOG-IgA and MOG-IgM were negative in all other patients tested. CONCLUSIONS: In some patients with MOG-EM/MOGAD, MOG-IgG is either exclusively or predominantly MOG-IgG3. Thus, the use of IgG1-specific assays might only partly overcome the current limitations of MOG-IgG testing and-just like H+L- and Fcγ-specific testing-might overlook some genuinely seropositive patients. This would have potentially significant consequences for the management of patients with MOG-EM/MOGAD. Given that IgG3 chiefly detects proteins and is a strong activator of complement and other effector mechanisms, MOG-IgG3 may be involved in the immunopathogenesis of MOG-EM/MOGAD. Studies on the frequency and dynamics as well as the clinical and therapeutic significance of MOG-IgG3 seropositivity are warranted.

A prospective observational cohort study of covid-19 epidemiology and vaccine seroconversion in South Western Sydney, Australia, during the 2021-2022 pandemic period.

BACKGROUND: It is known that COVID-19 disproportionally adversely affects the immunocompromised, including kidney transplant recipients (KTR), as compared to the general population. Risk factors for adverse outcomes and vaccine seroconversion patterns are not fully understood. Australia was uniquely positioned to reduce initial case numbers during the 2021-2022 pandemic period due to its relative isolation and several significant public health interventions. South-Western Sydney Local Heath District was one of the predominant regions affected. METHODS: A single centre, prospective cohort study of prevalent renal transplant recipients was conducted between 25th July 2021 and 1st May 2022. Baseline characteristics, COVID-19 vaccination status, COVID-19 diagnosis and outcomes were determined from the electronic medical record, Australian vaccination register and Australian and New Zealand Dialysis and Transplant Registry. Assessment of vaccine-induced seroconversion was assessed with ELISA in a subpopulation. Analysis was performed using SPSS v.28. RESULTS: We identified 444 prevalent transplant recipients (60% male, 50% diabetic, median age 58 years (Interquartile range (IQR)21.0) and eGFR 56 ml/min/1.73m2 (IQR 21.9). COVID-19 was identified in 32% (n = 142) of patients, of which 38% (n = 54) required hospitalisation and 7% (n = 10) died. At least one COVID-19 vaccination was received by 95% (n = 423) with 17 (4%) patients remaining unvaccinated throughout the study period. Seroconversion after 2 and 3 doses of vaccine was 22% and 48% respectively. Increased COVID-19 related deaths were associated with older age (aOR 1.1, 95% CI 1.004-1.192, p = 0.040), smoking exposure (aOR 8.2, 05% CI 1.020-65.649, p = 0.048) and respiratory disease (aOR 14.2, 95%CI:1.825-110.930, p = 0.011) on multi-variable regression analysis. Receipt of three doses of vaccination was protective against acquiring COVID-19 (aOR 0.48, 95% CI 0.287-0.796, p = 0.005) and death (aOR 0.6, 95% CI: 0.007-0.523, p = 0.011), but not against hospitalisation (p = 0.32). Seroconversion was protective for acquiring COVID-19 on multi-variable regression independent of vaccination dose (aOR 0.1, 95%CI: 0.0025-0.523, p = 0.011). CONCLUSIONS: COVID-19 was associated with a high mortality rate. Older age, respiratory disease and prior smoking exposure may be risk factors for increased mortality. Vaccination of 3 doses is protective against acquiring COVID-19 and death, however not hospitalisation. Antibody response is protective for acquiring COVID-19, however seroconversion rates are low.

Does native vitamin D, or active vitamin D modulate the neutralising antibody responses to COVID-19 vaccination in haemodialysis patients?

INTRODUCTION: Several studies have reported that patients with low levels of Vitamin D3 have impaired responses to vaccination, including COVID-19 vaccines, so we reviewed the response to COVID-19 vaccination in haemodialysis patients, who typically have reduced Vitamin D3 levels. METHODS: The inhibitory antibody (IC50) responses to several COVID-19 variants following vaccination in a cohort of United Kingdom haemodialysis patients receiving two vaccinations between March 2021 and May 2021 were reviewed. RESULTS: A total of 183 haemodialysis patients, 65.5% male, mean age 65.6 ± 14.1 years, 46.4% diabetic, 42.1% white ethnicity, body mass index 26.9 ± 6.5 kg/m2 dialysis vintage 36.2 (18.3-69.3) months were studied. Following the first vaccination, the median IgG microneutralisation IC50 response was undetectable for all variants (wild-type, alpha, beta and delta). Follow-up after the second vaccination showed that the microneutralisation response to all variants increased and was greater for the wild-type variant compared to alpha, beta and delta, all p < 0.001, There were no differences comparing the IC50 responses according to 25-Vitamin D3 levels, and the prescription of activated Vitamin D. Although patients who had previously tested positive for COVID-19 prescribed higher doses of alfacalcidol had higher seroprotection responses to the alpha (χ2 = 15, p = 0.002) and beta variants. (χ2 = 13, p = 0.005). CONCLUSIONS: The response to COVID-19 vaccination was reduced in our elderly haemodialysis patients compared to younger less frail patients, however there was no overall demonstrable effect of either 25-Vitamin D3 levels or the prescription of activated forms of Vitamin D on the immune response following vaccination against COVID-19, unless patients had previously tested positive for COVID-19.

Factors Positively Correlated with Hepatitis B Surface Antigen Seroconversion in Chronic Hepatitis B.

BACKGROUND AND AIMS: Chronic hepatitis B virus (HBV) infection is a global public health challenge since more than 250 million individuals are affected worldwide. Since different treatment modalities are available and not all patients are candidates for antiviral treatment, biomarkers that potentially predict the possibility of HBsAg clearance and seroconversion may be useful in clinical practice. PATIENTS AND METHODS: In this retrospective study, we aimed to identify factors positively correlated with HBsAg seroconversion in a large cohort of 371 chronic hepatitis B patients treated at a German tertial center between 2005 and 2020. RESULTS: Seroconversion occurred in 25/371 (6.7%) and HBsAg loss in 29/371 patients (7.8%) with chronic HBV infection. Antiviral therapy was associated with a lower chance of seroconversion (seroconversion antiviral therapy 14/260 (5.4%) vs. therapy-naïve patients 11/111 (9.9%), p = 0.027). Seroconversion rates were higher in patients with (very) low titers of HBV DNA (best cut-off value 357 IU/mL) and quantitative HBsAg. The best cut-off value with regard to seroconversion was 357 IU/mL for HBV DNA (AUC 0.693 (95%-CI 0.063-0.422), sensitivity 0.714, specificity 0.729; p < 0.0005) and 33,55 IU/mL for HBsAg (AUC 0.794 (95%-CI 0.651-0.937), sensitivity 0.714, specificity 0.949; p < 0.0005). However, male gender was positively associated with seroconversion (seroconversion: males 7.6% vs. females 2.7%, p = 0.036). CONCLUSIONS: Treatment-naïve male chronic HBV patients with low viral load and inflammatory activity have the best chance to achieve seroconversion. In the absence of cirrhosis, antiviral therapy should therefore not be performed in this patient collective.

Antiviral therapy response in patients with chronic hepatitis B and fatty liver: A systematic review and meta-analysis.

The impact of concurrent fatty liver (FL) on response to antiviral therapy in chronic hepatitis B (CHB) patients has not been well characterized. We aimed to systematically review and analyse antiviral treatment response in CHB patients with and without FL. We searched PubMed, Embase, Web of Science and the Cochrane Library databases from inception to 31 May 2023 for relevant studies. Biochemical response (BR), complete viral suppression (CVS) and hepatitis B e antigen (HBeAg) seroconversion in CHB patients with FL (CHB-FL) and without FL (non-FL CHB) were compared. In an initial pool of 2101 citations, a total of 10 studies involving 2108 patients were included. After 12 weeks of treatment, CHB-FL patients as compared with non-FL CHB patients had lower BR rate (48.37% [108/227] vs. 72.98% [126/174], p = .04) but similar trend for CVS (36.86% [80/227] vs. 68.81% [114/174], p = .05) and similar rates of HBeAg seroconversion (6.59% [7/103] vs. 7.40% [7/110], p = .89). However, at week 48, there were no statistically significant differences between CHB-FL and non-FL CHB patients in any of the outcomes, including BR (60.03% [213/471] vs. 69.37% [314/717], p = .67), CVS (65.63% [459/746] vs. 73.81% [743/1132], p = .27) and HBeAg seroconversion (10.01% [30/275] vs. 14.06% [65/453], p = .58) with similar findings for week 96. BR rate was lower in CHB-FL patients after 12 weeks of antiviral treatment. However, after a longer follow-up of either 48 or 96 weeks, no statistically significant differences were observed in BR, CVS or HBeAg seroconversion rates between CHB patients with and without FL.

Duration of maternally derived antibodies of porcine parvovirus in growing pigs and presence of antibodies in gilts and sows vaccinated with three different parvovirus vaccines.

While gilts and sows are regularly vaccinated against the porcine parvovirus (PPV), little is known on the presence of antibodies in vaccinated sows nor the decline of maternally derived antibodies (MDA) in their offspring. On twelve farms serum samples were taken from 180 gilts and sows vaccinated at least twice with one of three different commercial PPV vaccines. On nine farms, additional 270 serum samples were collected from growing pigs of three different age categories. All 450 samples were examined for PPV antibodies (Abs) by ELISA and haemagglutination inhibition (HI) assay. In total, 65% of all gilts vaccinated twice with either vaccine 1 or vaccine 3 were seronegative by HI assay. In each farm, there were at least three animals with high Ab titres (≥ 1:1280) indicating the presence of PPV in all twelve study farms. However, PPV DNA could not be detected in collected faecal samples. While low to moderately high Ab titres (1:10-1:640) were measured in 98% of twelve-weeks-old pigs, ELISA was only positive in 30% of the same pigs. Though, the statement on the duration of MDA may depend on the applied test, we could confirm an exponential decay of MDA. In addition, we could demonstrate that applied serological tools are insufficient for the confirmation of successful vaccination.