Pathogenicity and transmissibility of bovine H5N1 influenza virus.

Highly pathogenic H5N1 avian influenza (HPAI H5N1) viruses occasionally infect, but typically do not transmit, in mammals. In the spring of 2024, an unprecedented outbreak of HPAI H5N1 in bovine herds occurred in the USA, with virus spread within and between herds, infections in poultry and cats, and spillover into humans, collectively indicating an increased public health risk1-4. Here we characterize an HPAI H5N1 virus isolated from infected cow milk in mice and ferrets. Like other HPAI H5N1 viruses, the bovine H5N1 virus spread systemically, including to the mammary glands of both species, however, this tropism was also observed for an older HPAI H5N1 virus isolate. Bovine HPAI H5N1 virus bound to sialic acids expressed in human upper airways and inefficiently transmitted to exposed ferrets (one of four exposed ferrets seroconverted without virus detection). Bovine HPAI H5N1 virus thus possesses features that may facilitate infection and transmission in mammals.

Pre-existing polymerase-specific T cells expand in abortive seronegative SARS-CoV-2.

Individuals with potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) do not necessarily develop PCR or antibody positivity, suggesting that some individuals may clear subclinical infection before seroconversion. T cells can contribute to the rapid clearance of SARS-CoV-2 and other coronavirus infections1-3. Here we hypothesize that pre-existing memory T cell responses, with cross-protective potential against SARS-CoV-2 (refs. 4-11), would expand in vivo to support rapid viral control, aborting infection. We measured SARS-CoV-2-reactive T cells, including those against the early transcribed replication-transcription complex (RTC)12,13, in intensively monitored healthcare workers (HCWs) who tested repeatedly negative according to PCR, antibody binding and neutralization assays (seronegative HCWs (SN-HCWs)). SN-HCWs had stronger, more multispecific memory T cells compared with a cohort of unexposed individuals from before the pandemic (prepandemic cohort), and these cells were more frequently directed against the RTC than the structural-protein-dominated responses observed after detectable infection (matched concurrent cohort). SN-HCWs with the strongest RTC-specific T cells had an increase in IFI27, a robust early innate signature of SARS-CoV-2 (ref. 14), suggesting abortive infection. RNA polymerase within RTC was the largest region of high sequence conservation across human seasonal coronaviruses (HCoV) and SARS-CoV-2 clades. RNA polymerase was preferentially targeted (among the regions tested) by T cells from prepandemic cohorts and SN-HCWs. RTC-epitope-specific T cells that cross-recognized HCoV variants were identified in SN-HCWs. Enriched pre-existing RNA-polymerase-specific T cells expanded in vivo to preferentially accumulate in the memory response after putative abortive compared to overt SARS-CoV-2 infection. Our data highlight RTC-specific T cells as targets for vaccines against endemic and emerging Coronaviridae.

Hybrid immunity improves B cells and antibodies against SARS-CoV-2 variants.

The emergence of SARS-CoV-2 variants is jeopardizing the effectiveness of current vaccines and limiting the application of monoclonal antibody-based therapy for COVID-19 (refs. 1,2). Here we analysed the memory B cells of five naive and five convalescent people vaccinated with the BNT162b2 mRNA vaccine to investigate the nature of the B cell and antibody response at the single-cell level. Almost 6,000 cells were sorted, over 3,000 cells produced monoclonal antibodies against the spike protein and more than 400 cells neutralized the original SARS-CoV-2 virus first identified in Wuhan, China. The B.1.351 (Beta) and B.1.1.248 (Gamma) variants escaped almost 70% of these antibodies, while a much smaller portion was impacted by the B.1.1.7 (Alpha) and B.1.617.2 (Delta) variants. The overall loss of neutralization was always significantly higher in the antibodies from naive people. In part, this was due to the IGHV2-5;IGHJ4-1 germline, which was found only in people who were convalescent and generated potent and broadly neutralizing antibodies. Our data suggest that people who are seropositive following infection or primary vaccination will produce antibodies with increased potency and breadth and will be able to better control emerging SARS-CoV-2 variants.

A nonhuman primate model for genital herpes simplex virus 2 infection that results in vaginal vesicular lesions, virus shedding, and seroconversion.

The most commonly used animal models for evaluating the efficacy of HSV-2 candidate vaccines are mice and guinea pigs. While numerous HSV-2 vaccine candidates have been tested in these animals and were effective in reducing disease and mortality, these results did not predict the effectiveness of the vaccines in human trials. Infection of rhesus macaques rarely results in lesions or HSV-2 specific antibody responses. In seeking an animal model that better recapitulates human disease and that might be more predictive of the efficacy of prophylactic vaccines than mice and guinea pigs, we evaluated Cebus apella (C. apella), a New World primate, in an HSV-2 genital infection model. Infectious HSV-2 was cultured from vaginal swabs from all 4 animals for 9-14 days after intravaginal inoculation of HSV-2 seronegative monkeys. Two of 4 monkeys had vesicular lesions in the vagina or vulva. No neurological symptoms were noted. Recurrent lesions and HSV-2 DNA shedding after acute disease resolved was infrequent. UV irradiation of the genital area did not induce recurrent genital lesions or virus shedding. All 4 monkeys developed HSV-2 neutralizing antibodies as well as virus-specific CD4 and CD8 T cell responses. Reinfection of animals 15 to 19 months after primary infection did not result in lesions; animals had reduced virus shedding and a shorter duration of shedding compared with that during primary infection, suggesting that primary infection induced protective immunity. Primary fibroblasts from C. apella monkeys supported the growth of HSV-2 in vitro; in contrast, HSV-2 did not replicate above the titer of the input inoculum in fibroblasts from rhesus macaques. These observations suggest that the C. apella monkey has potential to serve as a model for evaluating the efficacy of prophylactic vaccines, antivirals, or monoclonal antibodies to HSV-2.

Virological assessment of hospitalized patients with COVID-2019.

Coronavirus disease 2019 (COVID-19) is an acute infection of the respiratory tract that emerged in late 20191,2. Initial outbreaks in China involved 13.8% of cases with severe courses, and 6.1% of cases with critical courses3. This severe presentation may result from the virus using a virus receptor that is expressed predominantly in the lung2,4; the same receptor tropism is thought to have determined the pathogenicity-but also aided in the control-of severe acute respiratory syndrome (SARS) in 20035. However, there are reports of cases of COVID-19 in which the patient shows mild upper respiratory tract symptoms, which suggests the potential for pre- or oligosymptomatic transmission6-8. There is an urgent need for information on virus replication, immunity and infectivity in specific sites of the body. Here we report a detailed virological analysis of nine cases of COVID-19 that provides proof of active virus replication in tissues of the upper respiratory tract. Pharyngeal virus shedding was very high during the first week of symptoms, with a peak at 7.11 × 108 RNA copies per throat swab on day 4. Infectious virus was readily isolated from samples derived from the throat or lung, but not from stool samples-in spite of high concentrations of virus RNA. Blood and urine samples never yielded virus. Active replication in the throat was confirmed by the presence of viral replicative RNA intermediates in the throat samples. We consistently detected sequence-distinct virus populations in throat and lung samples from one patient, proving independent replication. The shedding of viral RNA from sputum outlasted the end of symptoms. Seroconversion occurred after 7 days in 50% of patients (and by day 14 in all patients), but was not followed by a rapid decline in viral load. COVID-19 can present as a mild illness of the upper respiratory tract. The confirmation of active virus replication in the upper respiratory tract has implications for the containment of COVID-19.

A joint Bayesian hierarchical model for estimating SARS-CoV-2 genomic and subgenomic RNA viral dynamics and seroconversion.

Understanding the viral dynamics of and natural immunity to the severe acute respiratory syndrome coronavirus 2 is crucial for devising better therapeutic and prevention strategies for coronavirus disease 2019 (COVID-19). Here, we present a Bayesian hierarchical model that jointly estimates the genomic RNA viral load, the subgenomic RNA (sgRNA) viral load (correlated to active viral replication), and the rate and timing of seroconversion (correlated to presence of antibodies). Our proposed method accounts for the dynamical relationship and correlation structure between the two types of viral load, allows for borrowing of information between viral load and antibody data, and identifies potential correlates of viral load characteristics and propensity for seroconversion. We demonstrate the features of the joint model through application to the COVID-19 post-exposure prophylaxis study and conduct a cross-validation exercise to illustrate the model's ability to impute the sgRNA viral trajectories for people who only had genomic RNA viral load data.

Estimating the key outcomes and hepatocellular carcinoma risk in patients in immune-tolerant phase of chronic hepatitis B virus infection: A systematic review and meta-analysis.

The question of whether patients in the immune-tolerant (IT) phase of chronic hepatitis B virus (HBV) infection should undergo antiviral therapy and determine the optimal regimen remains unclear. A comprehensive search of PubMed, Embase, MEDLINE, Cochrane Library, and Wanfang Data from inception to 5 December 2023, was conducted. Studies reporting on key outcomes such as HBV DNA undetectability, HBeAg loss or seroconversion, HBsAg loss or seroconversion, and hepatocellular carcinoma (HCC) incidence in patients in the IT phase of chronic HBV infection were included. In total, 23 studies were incorporated. Approximately 4% of patients in the IT phase achieved spontaneous HBeAg loss over 48 weeks of follow-up. Antiviral therapy demonstrated a favourable impact on HBV DNA negative conversion (Children: risk ratios [RR] = 6.83, 95% CI: 2.90-16.05; Adults: RR = 25.84, 95% CI: 6.47-103.31) and HBsAg loss rates (Children: RR = 9.49, 95% CI: 1.74-51.76; Adults: RR = 7.35, 95% CI: 1.41-38.27) for patients in the IT phase. Subgroup analysis revealed that in adult patients in the IT phase, interferon plus nucleos(t)ide analogues (NA)-treated patients exhibited a higher pooled rate of HBsAg loss or seroconversion than those treated with NA monotherapy (9% vs. 0%). Additionally, the pooled annual HCC incidence for patients in the IT phase was 3.03 cases per 1000 person-years (95% CI: 0.99-5.88). Adult patients in the IT phase had a significantly lower HCC incidence risk than HBeAg-positive indeterminate phase patients (RR = 0.46, 95% CI: 0.32-0.66), with no significant differences observed between IT and immune-active phases. Presently, there is insufficient evidence solely based on reducing the risk of HCC incidence, to recommend treating patients in the IT phase of chronic HBV infection. However, both adult and paediatric patients in the IT phase responded well to antiviral therapy, showing favourable rates of HBsAg loss or seroconversion.

The Assessment of Anti-SARS-CoV-2 Antibodies in Different Vaccine Platforms: A Systematic Review and Meta-Analysis of COVID-19 Vaccine Clinical Trial Studies.

BACKGROUND AND OBJECTIVE: The COVID-19 pandemic spread rapidly throughout the world and caused millions of deaths globally. Several vaccines have been developed to control the COVID-19 pandemic and reduce the burden it placed on public health. This study aimed to assess the efficacy of different vaccine platforms in inducing potent antibody responses. Moreover, the seroconversion rate and common side effects of vaccine platforms were evaluated. METHODS: This meta-analysis included clinical trials of COVID-19 vaccines that met the eligibility criteria. Electronic databases (including PubMed, Scopus, and Web of Science) and Google Scholar search engine were searched for eligible studies. Regarding the methodological heterogeneity between the included studies, we selected a random-effects model. The geometric mean ratio (GMR) was chosen as the effect size for this meta-analysis. RESULTS: Of the 1838 records identified through screening and after removing duplicate records, the full texts of 1076 records were assessed for eligibility. After the full-text assessment, 56 records were eligible and included in the study. Overall, vaccinated participants had a 150.8-fold increased rate of anti-spike IgG titres compared with the placebo group (GMR = 150.8; 95% CI, 95.9-237.1; I2 = 100%). Moreover, vaccinated participants had a 37.3-fold increased rate of neutralising antibody titres compared with the placebo group (GMR = 37.3; 95% CI, 28.5-48.7; I2 = 99%). The mRNA platform showed a higher rate of anti-spike IgG (GMR = 1263.5; 95% CI, 431.1-3702.8; I2 = 99%), while neutralising antibody titres were higher in the subunit platform (GMR = 53.4; 95% CI, 32.8-87.1; I2 = 99%) than in other platforms. Different vaccine platforms showed different rates of both anti-spike IgG and neutralising antibody titres with interesting results. The seroconversion rate of anti-spike IgG and neutralising antibody titres was more than 98% in the vaccinated participants. CONCLUSION: Inactivated and subunit vaccines produced a high percentage of neutralising antibodies and had a low common adverse reaction rate compared to other platforms. In this regard, subunit and inactivated vaccines can still be used as the main vaccine platforms for effectively controlling infections with high transmission rates.

Global patterns of antigen receptor repertoire disruption across adaptive immune compartments in COVID-19.

Whereas pathogen-specific T and B cells are a primary focus of interest during infectious disease, we have used COVID-19 to ask whether their emergence comes at a cost of broader B cell and T cell repertoire disruption. We applied a genomic DNA-based approach to concurrently study the immunoglobulin-heavy (IGH) and T cell receptor (TCR) ß and δ chain loci of 95 individuals. Our approach detected anticipated repertoire focusing for the IGH repertoire, including expansions of clusters of related sequences temporally aligned with SARS-CoV-2-specific seroconversion, and enrichment of some shared SARS-CoV-2-associated sequences. No significant age-related or disease severity-related deficiencies were noted for the IGH repertoire. By contrast, whereas focusing occurred at the TCRß and TCRδ loci, including some TCRß sequence-sharing, disruptive repertoire narrowing was almost entirely limited to many patients aged older than 50 y. By temporarily reducing T cell diversity and by risking expansions of nonbeneficial T cells, these traits may constitute an age-related risk factor for COVID-19, including a vulnerability to new variants for which T cells may provide key protection.

Correlates of Rotavirus Vaccine Shedding and Seroconversion in a US Cohort of Healthy Infants.

BACKGROUND: Rotavirus is a leading cause of severe pediatric gastroenteritis; 2 highly effective vaccines are used in the United States (US). We aimed to identify correlates of immune response to rotavirus vaccination in a US cohort. METHODS: Pediatric Respiratory and Enteric Virus Acquisition and Immunogenesis Longitudinal (PREVAIL) is a birth cohort of 245 mother-child pairs enrolled in 2017-2018 and followed for 2 years. Infant stool samples and symptom information were collected weekly. Shedding was defined as reverse-transcription polymerase chain reaction detection of rotavirus vaccine virus in stools collected 4-28 days after dose 1. Seroconversion was defined as a 3-fold rise in immunoglobulin A between the 6-week and 6-month blood draws. Correlates were analyzed using generalized estimating equations and logistic regression. RESULTS: Prevaccination immunoglobulin G (IgG) (odds ratio [OR], 0.84 [95% confidence interval {CI}, .75-.94] per 100-unit increase) was negatively associated with shedding. Shedding was also less likely among infants with a single-nucleotide polymorphism inactivating FUT2 antigen secretion ("nonsecretors") with nonsecretor mothers, versus all other combinations (OR, 0.37 [95% CI, .16-.83]). Of 141 infants with data, 105 (74%) seroconverted; 78 (77%) had shed vaccine virus following dose 1. Prevaccination IgG and secretor status were significantly associated with seroconversion. Neither shedding nor seroconversion significantly differed by vaccine product. CONCLUSIONS: In this US cohort, prevaccination IgG and maternal and infant secretor status were associated with rotavirus vaccine response.

Illicit Fentanyl Use and Hepatitis C Virus Seroconversion Among People Who Inject Drugs in Tijuana and San Diego: Results From a Binational Cohort Study.

BACKGROUND: Illicitly manufactured fentanyl (IMF) increases overdose mortality, but its role in infectious disease transmission is unknown. We examined whether IMF use predicts hepatitis C virus (HCV) and human immunodeficiency virus (HIV) incidence among a cohort of people who inject drugs (PWID) in San Diego, California and Tijuana, Mexico. METHODS: PWID were recruited during 2020-2022, undergoing semi-annual interviewer-administered surveys and HIV and HCV serological rapid tests through 2024. Cox regression was conducted to examine predictors of seroconversion considering self-reported IMF use as a 6-month lagged, time-dependent covariate. RESULTS: Of 398 PWID at baseline, 67% resided in San Diego, 70% were male, median age was 43 years, 42% reported receptive needle sharing, and 25% reported using IMF. HCV incidence was 14.26 per 100 person-years (95% confidence interval [CI]: 11.49-17.02), and HIV incidence was 1.29 (95% CI: .49-2.10). IMF was associated with HCV seroconversion, with a univariable hazard ratio (HR) of 1.64 (95% CI: 1.09-2.40), and multivariable HR of 1.57 (95% CI: 1.03-2.40). The direction of the relationship with HIV was similar, albeit not significant (HR 2.39; 95% CI: .66-8.64). CONCLUSIONS: We document a novel association between IMF and HCV seroconversion among PWID in Tijuana-San Diego. Few HIV seroconversions (n = 10) precluded our ability to assess if a similar relationship held for HIV. IMF's short half-life may destabilize PWID-increasing the need for repeat dosing and sharing smoking materials and syringes. New preventive care approaches may reduce HCV transmission in the fentanyl era.

Antibody Status and Incidence of SARS-CoV-2 Infection in Health Care Workers.

BACKGROUND: The relationship between the presence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the risk of subsequent reinfection remains unclear. METHODS: We investigated the incidence of SARS-CoV-2 infection confirmed by polymerase chain reaction (PCR) in seropositive and seronegative health care workers attending testing of asymptomatic and symptomatic staff at Oxford University Hospitals in the United Kingdom. Baseline antibody status was determined by anti-spike (primary analysis) and anti-nucleocapsid IgG assays, and staff members were followed for up to 31 weeks. We estimated the relative incidence of PCR-positive test results and new symptomatic infection according to antibody status, adjusting for age, participant-reported gender, and changes in incidence over time. RESULTS: A total of 12,541 health care workers participated and had anti-spike IgG measured; 11,364 were followed up after negative antibody results and 1265 after positive results, including 88 in whom seroconversion occurred during follow-up. A total of 223 anti-spike-seronegative health care workers had a positive PCR test (1.09 per 10,000 days at risk), 100 during screening while they were asymptomatic and 123 while symptomatic, whereas 2 anti-spike-seropositive health care workers had a positive PCR test (0.13 per 10,000 days at risk), and both workers were asymptomatic when tested (adjusted incidence rate ratio, 0.11; 95% confidence interval, 0.03 to 0.44; P = 0.002). There were no symptomatic infections in workers with anti-spike antibodies. Rate ratios were similar when the anti-nucleocapsid IgG assay was used alone or in combination with the anti-spike IgG assay to determine baseline status. CONCLUSIONS: The presence of anti-spike or anti-nucleocapsid IgG antibodies was associated with a substantially reduced risk of SARS-CoV-2 reinfection in the ensuing 6 months. (Funded by the U.K. Government Department of Health and Social Care and others.).

Metabolic Dysfunction-Associated Steatotic Liver Disease Facilitates Hepatitis B Surface Antigen Seroclearance and Seroconversion.

BACKGROUND & AIMS: Hepatitis B surface antigen (HBsAg) seroclearance is the goal of functional cure for hepatitis B virus (HBV) infection. However, the impact of metabolic dysfunction-associated steatotic liver disease (MASLD) on this favorable outcome remains unclear. METHODS: Patients with chronic hepatitis B (CHB) were consecutively recruited. MASLD was defined by the newly proposed disease criteria. Cumulative incidences and associated factors of HBsAg seroclearance/seroconversion were compared between the MASLD and non-MASLD groups. RESULTS: From 2006 to 2021, 4084 treatment-naive hepatitis B e antigen (HBeAg)-negative CHB patients were included. At baseline, CHB patients with concurrent MASLD (n = 887) had significantly lower levels of HBsAg and HBV DNA than the non-MASLD group (n = 3197). During a median follow-up of 5.0 years, MASLD was associated with a higher likelihood of HBsAg seroclearance (adjusted hazard ratio [aHR], 1.43; 95% confidence interval [CI], 1.10-1.85; P = .007), and the accumulation of individual metabolic dysfunctions additively facilitated HBsAg seroclearance. In addition, a higher rate of HBsAg seroconversion was observed in patients with MASLD versus those without MASLD (aHR, 1.37; 95% CI, 1.00-1.86; P = .049). In sensitivity analysis, patients with intermittent MASLD had an intermediate probability of HBsAg seroclearance. After balancing clinical and virologic profiles by inverse probability of treatment weighting (IPTW), MASLD was still associated with a higher HBsAg seroclearance rate (IPTW-adjusted HR, 1.41; 95% CI, 1.09-1.84; P = .010). CONCLUSIONS: In untreated HBeAg-negative CHB patients, concurrent MASLD is associated with higher rates of HBsAg seroclearance and seroconversion. Metabolic dysfunctions have additive effects on the functional cure of CHB.

Utility of a Third Heplisav-B Dose in Patients With Inflammatory Bowel Disease Without Immunity After 2-Dose Heplisav-B Vaccination.

INTRODUCTION: Hepatitis B virus (HBV) vaccination is recommended in patients with inflammatory bowel disease (IBD). Although the 2-dose Heplisav-B vaccine has proven effective, more than 20% of patients with IBD do not seroconvert. We prospectively evaluated the effectiveness of a third Heplisav-B dose in patients with IBD lacking HBV immunity despite 2-dose vaccination. METHODS: Adults with IBD who had received 2-dose Heplisav-B vaccination between 2018 and 2023 were identified. Seroconversion was defined as hepatitis B surface antibody (HBsAb) ≥ 10 IU/L measured at ≥4 weeks after vaccination. Patients who did not seroconvert were prospectively offered a third Heplisav-B dose, followed by repeat HBsAb measurement. Demographic, clinical, medication, and vaccination data were compared between those who did and did not seroconvert. RESULTS: Of 192 patients identified, 71.9% (138/192) seroconverted after 2-dose Heplisav-B vaccination. The 54 patients (28.1%) who did not seroconvert were more likely to be male, have diabetes, chronic kidney disease, or elevated Charlson Comorbidity Index. Of the 54 patients, 30 (55.6%) elected to receive a third Heplisav-B dose, with 56.7% (17/30) achieving seroconversion (median HBsAb titer 376 IU/L, IQR 47-1,000 IU/L) despite a median intervaccination time of 416 days (IQR 90.8-667.8). No differences were noted between patients who did vs did not seroconvert after third-dose vaccination. DISCUSSION: In patients with IBD lacking HBV immunity despite 2-dose Heplisav-B vaccination, administration of a third dose resulted in a 56.7% seroconversion rate. Our results suggest that administration of an additional Heplisav-B dose may be an effective strategy in patients lacking immunity despite primary 2-dose vaccination.

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.

Association of HBeAg decline rate from mid-pregnancy to delivery with HBeAg seroconversion after delivery in hepatitis B virus-infected mothers.

There is still controversy about whether to continue antiviral therapy (AVT) after delivery, especially for pregnant women in the immune tolerance (IT) phase. In this study, a retrospective cohort study was conducted to explore the relationship between hepatitis B e antigen (HBeAg) decline rate (%) from mid-pregnancy to delivery and HBeAg seroconversion postpartum among patients using nucleos(t)ide analogs (NAs) to prevent mother-to-child transmission (MTCT), with the goal of identifying the ideal candidates for postpartum AVT continuation. This retrospective cohort study included 151 postpartum women. Univariate and multivariable logistic regression analyses were conducted to assess the association between the HBeAg decline rate (%) from mid-pregnancy to delivery and HBeAg seroconversion postpartum. Receiver operating characteristic (ROC) analysis was utilized to evaluate the predictive capacity of the HBeAg decline rate (%) and determine the optimal cut-off point. The univariate analysis revealed a significant association between the HBeAg decline rate (%) and HBeAg seroconversion postpartum (OR 1.068, 95% CI: 1.034-1.103, p < .001). In the multivariate regression analysis, adjusting for age, hepatitis B surface antigen (HBsAg) titre (log10 IU/mL) at mid-pregnancy, HBeAg titre (log10 S/CO) at mid-pregnancy, and hepatitis B virus (HBV) DNA load decline rate (%) from mid-pregnancy to delivery, the HBeAg decline rate(%) remained significantly associated with HBeAg seroconversion postpartum (OR 1.050, 95% CI: 1.015-1.093, p = .009). Then HBeAg decline rate (%) was treated as a categorical variable (tertiles) for sensitivity analysis. In the three distinct models, taking Tertile1 as a reference, women in Tertile3 still had a 4.201-fold (OR 4.201, 95% CI: 1.382-12.773, p = .011) higher risk of developing HBeAg seroconversion (p for trend <.05) after adjusting above covariates. The area under the curve (AUC) was 0.723 (95% CI: 0.627-0.819). The optimal cut-off value was 5.43%, with a sensitivity of 0.561, specificity of 0.791, and Youden's index of 0.352.A higher HBeAg decline rate (%) from mid-pregnancy to delivery independently correlated with an increased risk of HBeAg seroconversion postpartum. This decline rate can serve as a valuable clinical indicator for predicting HBeAg seroconversion.

Network-based strategies to combat HCV: Examining social and spatial drivers of transmission among PWID in New Delhi.

People who inject drugs (PWID) account for some of the fastest-growing HCV epidemics globally. While individual risk factors for infection are understood, less is known about network and spatial factors critical for elimination strategies. Two thousand five hundred twelve PWID in New Delhi, India, were recruited (2017-19) through network referrals. Biometrics identified duplicates and cross-network linkages. Participants completed semi-annual surveys and blood tests for HCV antibodies and RNA. Poisson regression and network analyses identified predictors of incident HCV and compared network-based intervention approaches. Baseline HCV antibody prevalence was 65.1%, of whom 79.6% were HCV RNA-positive. We observed 92 HCV seroconversions over 382.25 person-years (incidence: 24.1 per 100 person-years). Of the 92 seroconverters, 67% (62) were directly connected to an RNA-positive participant, and all were within one degree of separation from an RNA-positive participant. Individual-level factors associated with seroconversion included age, sexual activity, and injection behaviours. After adjusting for individual-level factors, seroconversion was significantly associated with number of RNA-positive partners (adjusted incidence rate ratio [AIRR] = 1.30) and injecting at a particular venue (AIRR = 2.53). This association extended to indirect ties, with 17% reduced odds of seroconversion for each degree of separation from the venue (AIRR = 0.83). Network analyses comparing intervention strategies found that targeting venues identified more cases compared to a treat-a-friend approach. We observed a fast-growing HCV epidemic driven by viremia within individuals' immediate networks and indirect social and spatial ties, demonstrating the importance of achieving broad, sustained virologic response and rethinking network-based interventions to include venues.

CXCL10 and its receptor in patients with chronic hepatitis B and their ability to predict HBeAg seroconversion during antiviral treatment with TDF.

The serum chemokine C-X-C motif ligand-10 (CXCL10) and its unique receptor (CXCR3) may predict the prognosis of patients with chronic hepatitis B (CHB) treated with tenofovir disoproxil fumarate (TDF). Nevertheless, there are few reports on the profile of CXCL10 and CXCR3 and their clinical application in HBeAg (+) CHB patients during TDF antiviral therapy. CXCL10 and CXCR3 were determined in 118 CHB patients naively treated with TDF for at least 96 weeks at baseline and at treatment weeks 12 and 24. In addition, gene set enrichment analysis was used to examine the associated dataset from Gene Expression Omnibus and explore the gene sets associated with HBeAg seroconversion (SC). The change of CXCL10 (ΔCXCL10, baseline to 48-week TDF treatment) and CXCR3 (ΔCXCR3) is closely related to the possibility of HBeAg SC of CHB patients under TDF treatment. Immunohistochemical analysis of CXCL10/CXCR3 protein in liver tissue shows that there is a significant difference between paired liver biopsy samples taken before and after 96 weeks of successful TDF treatment of CHB patients (11 pairs) but no significance for unsuccessful TDF treatment (14 pairs). Multivariate Cox analysis suggests that the ΔCXCL10 is an independent predictive indicator of HBeAg SC, and the area under the receiver operating characteristic curve of the ΔCXCL10 in CHB patients is 0.8867 (p < 0.0001). Our results suggest that a lower descending CXCL10 level is associated with an increased probability of HBeAg SC of CHB patients during TDF therapy. Moreover, liver tissue CXCL10 might be involved in the immunological process of HBeAg SC.

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.

Anti-Spike IgG antibodies as correlates of protection against SARS-CoV-2 infection in the pre-Omicron and Omicron era.

Anti-Spike IgG antibodies against SARS-CoV-2, which are elicited by vaccination and infection, are correlates of protection against infection with pre-Omicron variants. Whether this association can be generalized to infections with Omicron variants is unclear. We conducted a retrospective cohort study with 8457 blood donors in Tyrol, Austria, analyzing 15,340 anti-Spike IgG antibody measurements from March 2021 to December 2022 assessed by Abbott SARS-CoV-2 IgG II chemiluminescent microparticle immunoassay. Using a Bayesian joint model, we estimated antibody trajectories and adjusted hazard ratios for incident SARS-CoV-2 infection ascertained by self-report or seroconversion of anti-Nucleocapsid antibodies. At the time of their earliest available anti-Spike IgG antibody measurement (median November 23, 2021), participants had a median age of 46.0 years (IQR 32.8-55.2), with 45.3% being female, 41.3% having a prior SARS-CoV-2 infection, and 75.5% having received at least one dose of a COVID-19 vaccine. Among 6159 participants with endpoint data, 3700 incident SARS-CoV-2 infections with predominantly Omicron sublineages were recorded over a median of 8.8 months (IQR 5.7-12.4). The age- and sex-adjusted hazard ratio for SARS-CoV-2 associated with having twice the anti-Spike IgG antibody titer was 0.875 (95% credible interval 0.868-0.881) overall, 0.842 (0.827-0.856) during 2021, and 0.884 (0.877-0.891) during 2022 (all p < 0.001). The associations were similar in females and males (Pinteraction = 0.673) and across age (Pinteraction = 0.590). Higher anti-Spike IgG antibody titers were associated with reduced risk of incident SARS-CoV-2 infection across the entire observation period. While the magnitude of association was slightly weakened in the Omicron era, anti-Spike IgG antibody continues to be a suitable correlate of protection against newer SARS-CoV-2 variants.