A potential antiviral role for CCR5+CD8+ T cells in children with hepatitis B.

While dysfunctional exhausted CD8+ T cells hamper viral control when children acquire hepatitis B virus (HBV) infection, it's crucial to recognize that CD8+ T cells have diverse phenotypes and functions. This study explored a subset of CD8+ T cells expressing C-C chemokine receptor type 5 (CCR5) in children with HBV infection. Thirty-six patients in the immune tolerant group, 33 patients in the immune active group, 55 patients in the combined response group, and 22 healthy control children were enrolled. The frequency, functional molecules, and effector functions of the CCR5+CD8+ T cell population in different groups were evaluated. The frequency of CCR5+CD8+ T cells correlated positively with the frequency of CCR5+CD4+ T cells and patient age, and it correlated negatively with alanine aminotransferase, aspartate transaminase, HBV DNA, hepatitis B surface antigen, and lactic dehydrogenase levels. CCR5+CD8+ T cells had higher levels of inhibitory and activated receptors and produced higher levels of IFN-γ, IL-2, and TNF-α than CCR5-CD8+ T cells. CCR5+CD8+ T cells were partially exhausted but possessed a stronger antiviral activity than CCR5-CD8+ T cells. The identification of this subset increases our understanding of CD8+ T cell functions and serves as a potential immunotherapeutic target for children with HBV infection.

Clinical characteristics and immunogenicity after Omicron breakthrough infection in patients with chronic hepatitis B infection: A longitudinal observational study.

The clinical and immunological features after breakthrough infection (BTI) during Omicron wave in patients with chronic hepatitis B virus infection (CHB) are still unclear. A total of 101 patients with CHB from our previous coronavirus disease 2019 (COVID-19) vaccination cohort (NCT05007665), were continued to be followed up at the Second Affiliated Hospital of Chongqing Medical University after BTI, while an additional 39 healthcare workers after BTI were recruited as healthy controls (HCs). Clinical data were collected using questionnaire survey and electronic medical record. Blood samples were used to determine the antibody responses, as well as B and T cell responses. After BTI, the clinical symptoms of COVID-19 were mild to moderate in patients with CHB, with a median duration of 5 days. Compared with HCs, patients with CHB were more susceptible to develop moderate COVID-19. The liver function was not significantly damaged, and HBV-DNA was not activated in patients with CHB after BTI. Patients with CHB could elicit robust antibody responses after BTI (NAbs 13.0-fold, BA.5 IgG: 24.2-fold, respectively), which was also significantly higher than that in every period after vaccination (all p < 0.001), and compared to that in HCs after BTI. The CD4+, cTfh, and CD8+ T cell responses were also augmented in patients with CHB after BTI, while exhibiting comparability to those observed in HCs. In patients with CHB after BTI, the immune imprint was observed in B cell responses, rather than in T cell responses. In conclusion, Omicron breakthrough infection induced mild to moderate COVID-19 symptoms in patients with CHB, without exacerbating the progress of liver diseases. Meanwhile, BTI demonstrated the ability to induce robust antibody and T cell responses in patients with CHB, which was comparable to those observed in HCs.

Clinical and immunological features of COVID-19 in patients with anti-MDA5 dermatomyositis during the omicron wave in Chongqing, China.

Patients with anti-melanoma differentiation-associated gene 5 (anti-MDA5) dermatomyositis (DM) have a higher risk of coronavirus disease 2019 (COVID-19) infection. In this longitudinal observational study, we aimed to investigate the clinical and immunological features of these patients after COVID-19 infection. A total of 73 patients with anti-MDA5 DM were recruited from the Second Affiliated Hospital of Chongqing Medical University during the Omicron wave epidemic. Clinical data were collected by questionnaire survey and electronic medical records. Blood samples were used to determine the immunity responses. From December 9, 2022 to March 31, 2023, 67 patients were eligible for final analysis; 68.7% of them were infected with COVID-19. The most common symptoms observed in COVID-19 were upper respiratory symptoms, most cases were mild or moderate (97.8%). The clinical laboratory indexes were relativity stable in patients after infection (all p > 0.05). Vaccination is not a protective factor against the Omicron infection (odds ratio: 2.69, 95% confidence interval: 0.81-8.93, p = 0.105). Both wildtype (WT) neutralizing antibodies titer and BA.5-specific immunoglobulin G titer were significantly enhanced after infection (all p < 0.01), which was as high as healthy controls (HCs). The memory B-cell responses were similar between the patients with anti-MDA5 DM and HCs (p > 0.05). However, both the WT-specific CD8+ T cells and CD4+ T cells were reduced in patients with anti-MDA5 DM (all p < 0.05). In conclusion, patients with anti-MDA5 DM did not deteriorate the COVID-19, in turn, COVID-19 infection did not increase the risk of anti-MDA5 DM exacerbation. The humoral responses were robust but the cellular responses were weakened after COVID-19 infection.

Study of the Cold Curing Characteristics of Isocyanate-Modified Asphalt.

Isocyanate esters are widely recognized for their superior curing capabilities. Leveraging this attribute, the current research formulated a modified cold-mixed asphalt blend using 4,4'-methylene diphenyl diisocyanate (MDI). Tests and analyses of the MDI-modified asphalt with varying inclusion percentages of MDI revealed that a mixture containing 15% rock asphalt and 15% MDI-modified asphalt exhibited a more balanced, comprehensive performance. We also conducted an examination of the role and properties of MDI in asphalt modification using molecular dynamics simulations. The cold-curing properties of MDI-modified asphalt as compared to petroleum asphalt were evaluated based on its density, free volume analysis, cohesive energy density, and glass transition temperature. Implementing the LB-13 gradation-a cold-mixed asphalt gradation with a nominal particle size of 13.2 mm recommended by Chinese specifications-we prepared MDI-modified cold-mixed asphalt and carried out analyses of its mechanical characteristics, high-temperature performance, and water damage resistance. The results demonstrated that MDI-modified asphalt showcases excellent ductility, flexibility, and aging resistance, surpassing the performance of petroleum asphalt. The stability, high-temperature rutting, and water damage resistance of the MDI-modified cold-mixed asphalt exceeded the requirements for hot-mixed asphalt. This research provides theoretical and experimental support for isocyanate ester applications in asphalt engineering, presenting significant value for practical engineering applications.

Safety and Immunogenicity After Primary and Booster Inactivated SARS-Cov-2 Vaccination in Patients with Autoimmune Liver Diseases.

Background and Aims: SARS-CoV-2 vaccines-associated autoimmune liver diseases have been reported in several case reports. However, the safety and immunogenicity after primary and booster inactivated SARS-CoV-2 vaccination in patients with autoimmune liver diseases (AILD) is still unknown. Methods: Eighty-four patients with AILD were prospectively followed up after the second dose (primary) of inactivated SARS-CoV-2 vaccine. Some of them received the third dose (booster) of inactivated vaccine. Adverse events (AEs), autoimmune activation, and liver inflammation exacerbation after primary and booster vaccination were recorded. Meanwhile, dynamics of antireceptor-binding-domain IgG (anti-RBD-IgG), neutralizing antibodies (NAbs) and RBD-specific B cells responses were evaluated. Results: The overall AEs in AILD patients after primary and booster vaccination were 26.2% and 13.3%, respectively. The decrease of C3 level and increase of immunoglobulin light chain κ and λ levels were observed in AILD patients after primary vaccination, however, liver inflammation was not exacerbated, even after booster vaccination. Both the seroprevalence and titers of anti-RBD-IgG and NAbs were decreased over time in AILD patients after primary vaccination. Notably, the antibody titers were significantly elevated after booster vaccination (10-fold in anti-RBD-IgG and 7.4-fold in NAbs, respectively), which was as high as in healthy controls. Unfortunately, the inferior antibody response was not enhanced after booster vaccination in patients with immunosuppressants. Changes of atypical memory B cells were inversely related to antibody levels, which indicate that the impaired immune memory was partially restored partly by the booster vaccination. Conclusions: The well tolerability and enhanced humoral immune response of inactivated vaccine supports an additional booster vaccination in AILD patients without immunosuppressants.

GW9662 ameliorates nonalcoholic steatohepatitis by inhibiting the PPARγ/CD36 pathway and altering the gut microbiota.

BACKGROUND & AIMS: Peroxisome proliferator-activated receptors (PPARs) are currently among the most focused-on therapeutic targets for non-alcoholic steatohepatitis (NASH), although no clinical transformation has been achieved to date. In this study, we aimed to evaluate the effects of GW9662 on choline-deficient, L-amino acid-defined high-fat diet (CDAA-HFD)-induced NASH mice and reveal the mechanism underlying this effect. METHODS: GW9662 (1 mg/kg) was administered in CDAA-HFD mouse model of NASH. The effect of GW9662 on hepatic lipid metabolism was investigated using liver RNA-seq and HepG2 cells induced by oleic acid and palmitic acid. In addition, 16S rRNA gene sequencing was performed to analyze the effects of GW9662 on the composition and function of the fecal microbiota. RESULTS: GW9662 improved the CDAA-HFD caused elevation in the levels of ALT, AST, hepatic free fatty acids and triglycerides. The liver pathological analysis indicated that GW9662 alleviated the hepatic steatosis and fibrosis. The NAFLD activity score and RNA-Seq revealed that GW9662 mainly regulated the fatty acids transport and lipid synthesis by inhibiting PPARγ, CD36, FABP1, FASN, and SCD1, and through the up-regulation of PPARα. Moreover, GW9662 reduced the epididymal fat weight. GW9662 reversed the gut microbiota disorder by increasing the abundance of the beneficial bacteria Dubosiella and Lactobacillus and decreasing the abundance of harmful bacteria Lachnospiraceae_NK4A136_group, Helicobacteraceae, Desulfovibriaceae, and Rickenaceae. CONCLUSIONS: GW9662 ameliorated lipid metabolism by inhibiting the PPARγ/CD36 pathway and altering the composition of the gut microbiota in NASH mice. Therefore, the PPARγ antagonist GW9662 deserves more attention as a potential therapeutic agent for NASH.

Molecular epidemiology of hepatitis C virus genotypes in different geographical regions of Chinese mainland and a phylogenetic analysis.

BACKGROUND: Hepatitis C virus (HCV) infection remains a major public health problem in Chinese mainland. Investigation of the distribution of genotypes contributed to the prevention, diagnosis and treatment of HCV infection. Therefore, we conducted a study on the distribution of HCV genotypes and phylogenetic analysis to provide an up-to-date understanding of the molecular epidemiology of genotypes in Chinese mainland. METHODS: Our retrospective multicenter study enrolled 11,008 samples collected between August 2018 and July 2019 from 29 provinces/municipalities (Beijing, Hebei, Inner Mongolia, Shanxi, Tianjin, Gansu, Ningxia, Shaanxi, Xinjiang, Heilongjiang, Jilin Liaoning, Henan, Hubei Hunan, Anhui, Fujian, Jiangsu, Jiangxi, Shandong, Shanghai Zhejiang, Guangdong, Guangxi, Hainan, Chongqing, Guizhou, Sichuan and Yunnan). Phylogenetic analysis of each subtype was performed to infer the evolutionary relationship of sequences from diverse regions. Two independent samples t tests were used for the comparison of continuous variables, and chi-square tests were used for the comparison of categorical variables. RESULTS: Four genotypes (1, 2, 3 and 6) were found, including 14 subtypes. HCV genotype 1 was dominant, accounting for 49.2%, followed by genotypes 2, 3 and 6, accounting for 22.4%, 16.4%, and 11.9%, respectively. Additionally, the top five subtypes were 1b, 2a, 3b, 6a and 3a. Proportions of genotypes 1 and 2 decreased while genotypes 3 and 6 increased over past years (P < 0.001). Genotypes 3 and 6 were concentrated in the population aged 30 to 50 years, and male carriers had lower proportions of subtypes 1b and 2a than female carriers (P < 0.01). Genotypes 3 and 6 were more prevalent in southern parts of Chinese mainland. Nationwide spreads of subtypes 1b and 2a were associated with sequences from northern parts of Chinese mainland, while subtypes 3a, 3b and 6a were associated with sequences from southern parts of Chinese mainland. CONCLUSIONS: HCV subtypes 1b and 2a remained the most common subtypes in Chinese mainland, and their proportions decreased over the past years, while the proportions of genotypes 3 and 6 increased. Our investigation provided an accurate epidemiological picture of the circulating viral strains in Chinese mainland, contributing to the prevention, diagnosis and treatment of HCV infection. TRIAL REGISTRATION: Not applicable.

Humoral immune responses to inactivated COVID-19 vaccine up to 1 year in children with chronic hepatitis B infection.

Background: Inactivated SARS-CoV-2 vaccination has recently been approved for children aged 3-17 years in China. However, data on long-term humoral responses to inactivated vaccines in children with chronic hepatitis B (CHB) are still limited. Methods: In this prospective observational study, CHB children after primary inactivated SARS-CoV-2 vaccines were recruited consecutively and followed up for 1 year. CHB adults from another cohort study (NCT05007665) were used as a control. The receptor-binding domain IgG antibody (anti-RBD-IgG), neutralizing antibody (NAb), neutralization against Omicron (BA2.12.1, BA.4 and BA.5), and memory B -cell (MBC) responses were evaluated. Results: Overall, 115 CHB children and 351 CHB adults were included in this analysis. The antibody titers decreased over the first ~180 days and then plateaued up to 1 year in CHB children. However, lower and faster declines in antibody responses were observed in CHB adults. Interestingly, the seroprevalence of antibodies was still high after over 8 months in CHB children (anti-RBD-IgG [90%] and NAbs [83%]). However, neutralization against Omicron subvariants was significantly reduced in CHB children (-3.68-fold to -8.60-fold). Notably, neutralization against the BA.5 subvariant was obviously diminished in CHB children compared with adults. Moreover, CHB children had similar RBD-specific MBCs but higher RBD-specific atypical MBCs compared with adults. Conclusion: Inactivated vaccination could elicit more robust and durable antibody responses to the wild-type SARS-CoV-2 strain in CHB children than in CHB adults but showed inferior responses to Omicron subvariants (especially to the BA.5 strain). Hence, new Omicron-related or all-in-one vaccines are needed immediately for CHB children.

The anti-fibrotic efficacy of adelmidrol depends on hepatic PPARγ levels.

Adelmidrol, an anti-inflammatory small-molecule compound, can treat inflammatory diseases like arthritis and colitis in a PPARγ-dependent manner. Effective anti-inflammatory therapy is beneficial in delaying the progression of liver fibrosis. This study aimed to investigate the effect and underlying mechanisms of adelmidrol on hepatic fibrosis induced by CCl4 and CDAA-HFD. In the CCl4 model, adelmidrol (10 mg/kg) significantly reduced the incidence of liver cirrhosis from 76.5% to 38.9%, with a reduction of ALT, AST, and extracellular matrix deposition. RNA-seq revealed adelmidrol markedly inhibited the activation of hepatic scar-associated Trem2+ macrophages and PDGFRα+ stellate cells. Adelmidrol exhibited a limited anti-fibrotic effect in CDAA-HFD-induced fibrosis. Further, inconsistencies were observed in the expression trends in liver PPARγ in both models. CCl4 injury led to the continuous decrease in hepatic PPARγ levels, adelmidrol treatment up-regulated hepatic PPARγ expression and down-regulated the expression of pro-inflammatory factor NF-κB and pro-fibrotic factor TGF-ß1. Adelmidrol also inhibited the activation of macrophages and HSCs in a PPARγ-dependent manner in vitro. GW9662, a specific PPARγ antagonist, counteracted the anti-fibrotic effect of adelmidrol. In CDAA-HFD-induced model, hepatic PPARγ expression gradually increased with the progress of modeling. Adelmidrol enhanced steatosis in hepatocytes by the activation of the PPARγ/CD36 pathway in the CDAA-HFD model and FFA-treated HepG2, showing a limited anti-fibrotic effect. GW9662 reversed the pro-steatotic effect of adelmidrol and improved fibrosis. The anti-fibrotic outcomes of adelmidrol were related to hepatic PPARγ levels, which depends on the synergistic effect of PPARγ agonism caused by adelmidrol on hepatocytes, macrophages, and HSCs in different pathological states.

Dynamic immunogenicity after primary and booster inactivated SARS-CoV-2 vaccination in people living with HIV: A longitudinal observational study.

People living with HIV (PLWH) have poor outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); vaccination reduces the associated mortality. The humoral immune response dynamics after booster inactivated vaccinations in PLWH remain unclear. In this longitudinal observational study, 100 PLWH after primary inactivated SARS-CoV-2 vaccination were consecutively recruited and followed up. After booster vaccination (BV), neutralizing antibodies (NAbs) were detected at 1 month from all the PLWH, and the titer increased sixfold compared to that associated with the primary vaccination (PV), similar to that in healthy controls after BV. The NAbs titer declined over time after BV, but remained higher at 6 months than after PV. The NAbs response was elevated after BV with CD4 count <200 cells/µL, it was the poorest among the different CD4 cell count subgroups. Similar results were observed for anti-RBD-IgG responses. Moreover, RBD-specific MBCs were significantly elevated after BV in PLWH. No serious AEs were observed after BV in PLWH. In conclusion, booster inactivated SARS-CoV-2 vaccination is well tolerated and can elicit robust and durable humoral responses in PLWH. PLWH may benefit from a third dose of the inactivated vaccine.

Humoral responses after primary and booster SARS-CoV-2 inactivated vaccination in patients with chronic hepatitis B virus infection: A longitudinal observational study.

Given the pandemic of severe acute respiratory syndrome coronavirus 2 Omicron variants, booster vaccination (BV) using inactivated virus vaccines (the third dose) has been implemented in China. However, the immune responses after BV, especially those against Omicron, in patients with chronic hepatitis B virus (HBV) infection (CHB) are unclear. In this prospective longitudinal study, 114 patients with CHB and 68 healthy controls (HCs) were recruited after receiving inactivated vaccination. The anti-receptor-binding domain (RBD) immunoglobulin G (IgG), neutralizing antibodies (NAbs), neutralization against Omicron (BA2.12.1, BA.4/5), and specific B/T cells were evaluated. In patients, anti-RBD IgG was elevated significantly after BV; the titers were as high as those in HCs. Similar results were obtained for the NAbs. However, compared with that against wild type (WT), the neutralization against Omicron was compromised after BV. The frequency of RBD+ atypical memory B cells increased, but spike-specific cluster of differentiation 4+ /8+ T cells remained unchanged after BV. Moreover, no serious adverse events or HBV reactivation were observed after BV. These results suggest that BV significantly enhanced antibody responses against WT; however, it resulted in compromised antibody responses against Omicron in patients with CHB. Hence, new all-in-one vaccines and optimal vaccination strategies should be studied promptly.

Impaired antibody responses were observed in patients with type 2 diabetes mellitus after receiving the inactivated COVID-19 vaccines.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) have been reported to be more susceptible to 2019 novel coronavirus (2019-nCoV) and more likely to develop severe pneumonia. However, the safety and immunological responses of T2DM patients after receiving the inactivated vaccines are not quite definite. Therefore, we aimed to explore the safety, antibody responses, and B-cell immunity of T2DM patients who were vaccinated with inactivated coronavirus disease 2019 (COVID-19) vaccines. METHODS: Eighty-nine patients with T2DM and 100 healthy controls (HCs) were enrolled, all of whom had received two doses of full-course inactivated vaccines. At 21-105 days after full-course vaccines: first, the safety of the vaccines was assessed by questionnaires; second, the titers of anti-receptor binding domain IgG (anti-RBD-IgG) and neutralizing antibodies (NAbs) were measured; third, we detected the frequency of RBD-specific memory B cells (RBD-specific MBCs) to explore the cellular immunity of T2DM patients. RESULTS: The overall incidence of adverse events was similar between T2DM patients and HCs, and no serious adverse events were recorded in either group. Compared with HCs, significantly lower titers of anti-RBD-IgG (p = 0.004) and NAbs (p = 0.013) were observed in T2DM patients. Moreover, the frequency of RBD-specific MBCs was lower in T2DM patients than in HCs (p = 0.027). Among the 89 T2DM patients, individuals with lower body mass index (BMI) had higher antibody titers (anti-RBD-IgG: p = 0.009; NAbs: p = 0.084). Furthermore, we found that sex, BMI, and days after vaccination were correlated with antibody titers. CONCLUSIONS: Inactivated COVID-19 vaccines were safe in patients with T2DM, but the antibody responses and memory B-cell responses were significantly decreased compared to HCs. TRIAL REGISTRATION NUMBER AND DATE: NCT05043246. September 14, 2021. (Clinical Trials.gov).

Safety and immunogenicity of the third (booster) dose of inactivated and recombinant protein SARS-CoV-2 vaccine for patients with endocrine-related cancer.

Background: Our study aimed to evaluate the safety and immunogenicity of the third (booster) dose of the COVID-19 vaccine for patients with endocrine-related cancers. Methods: This observational study involved 94 breast cancer patients, 92 thyroid cancer patients, and 123 healthy individuals who had received the third (booster) dose of the COVID-19 vaccine. Data on the adverse effects, serum anti-receptor binding domain (RBD)-immunoglobulin (Ig) G, and neutralizing antibodies (NAbs) were collected prospectively. Results: The serum anti-RBD-IgG and NAb titers were significantly lower for the patients with endocrine-related malignancies than for the healthy controls (3.01 [IQR: 1.11-6.70] vs. 4.19 [1.95-9.11], p = 0.001; 0.23 [0.11-0.52] vs. 0.41 [0.22-0.78], p = 0.001), and the seroconversion rates of anti-RBD-IgG and NAbs showed similar results. The serum antibody titers and seroconversion rates were significantly lower for patients aged ≥65 years with endocrine-related cancers, but there were no significant differences related to gender, vaccine type, or cancer type. Subgroup analysis showed that the antibody titers and seroconversion rates were significantly lower for patients with intermediate to advanced breast cancer, HR-/Her2+ breast cancer, and breast cancer undergoing treatment than for healthy controls. In contrast, breast cancer patients who completed their treatment and those who received endocrine therapy after completing their treatment were not significantly different from healthy controls. The NAbs titers and seroconversion rates were significantly lower for patients with primary thyroid cancer (0.19 [IQR: 0.10-0.46] vs. 0.41 [0.22-0.78], p = 0.003; 55.9 vs. 84.9%, p < 0.001); the seroconversion rates were significantly higher for the patients with combined Hashimoto's thyroiditis than for those without it. Multiple linear regression showed that patients aged ≥65 years who were receiving treatment were at risk of having lower antibody levels. Conclusion: The third (booster) dose of the COVID-19 vaccine is safe and well-tolerated. Our data support a third (booster) dose of the SARS-CoV-2 vaccine for breast and thyroid cancer patients. Breast cancer patients aged ≥65 years who are receiving treatment should be more protected, while thyroid cancer and breast cancer patients who have completed their treatment can be vaccinated like the general population.

Decreased antibody response to influenza vaccine with an enhanced antibody response to subsequent SARS-CoV-2 vaccination in patients with chronic hepatitis B virus infection.

INTRODUCTION: Influenza or SARS-CoV-2 vaccination is especially recommended for people with underlying diseases. For the large number of patients with chronic hepatitis B virus infection (CHB), studies on their immune responses to these vaccines are still lacking. METHODS: A total of 57 CHB patients and 19 healthy controls (HCs) receiving inactivated influenza vaccination were prospectively followed up. Influenza-specific immunoglobulin G (IgG) antibodies (anti-H1N1, anti-H3N2, and anti-B IgG), antibody-secreting cells (ASCs), and circulating T follicular helper cells were assessed simultaneously. Eight CHB patients subsequently got inactivated SARS-CoV-2 vaccination during 1-year follow-up, and levels of serum antibodies against SARS-CoV-2 were further analyzed. RESULTS: On day 28 after influenza vaccination, three influenza antibodies levels appeared to be lower in CHB patients than in HCs. And anti-H1N1 IgG level was significantly decreased in cirrhotic patients (p < .05). Anti-H1N1 IgG levels (day 28) were positively correlated with ASC frequencies (day 7) (p < .05), and negatively correlated with cirrhosis and hepatitis B surface antigen levels (p < .05). Anti-SARS-CoV-2 antibodies were higher in patients with influenza vaccination history than in patients without the history (p < .05). Moreover, positive correlations existed between influenza vaccination history and anti-SARS-CoV-2 antibody levels (p < .01). CONCLUSIONS: CHB patients, especially those with cirrhosis, appeared to have a decreased antibody response to inactivated influenza vaccine. A history of inactivated influenza vaccination within 1 year before inactivated SARS-CoV-2 vaccination might induce stronger anti-SARS-CoV-2 antibody response.

Risk of waning humoral responses after inactivated or subunit recombinant SARS-CoV-2 vaccination in patients with chronic diseases: Findings from a prospective observational study in China.

Heterogeneity of antibody responses has been reported in SARS-CoV-2 vaccination recipients with underlying diseases. We investigated the impact of the presence of comorbidities on the humoral response to SARS-CoV-2 vaccination in patients with chronic disease (PWCD) and assessed the effect of the number of comorbidities on the humoral response to vaccination. In this study, neutralizing antibodies (NAbs) and IgG antibodies against the receptor-binding domain (RBD-IgG) were monitored following a full-course vaccination. In total, 1400 PWCD (82.7%, inactivated vaccines; 17.3%, subunit recombinant vaccine) and 245 healthy controls (65.7% inactivated vaccines, 34.3% subunit recombinant vaccine) vaccinated with inactivated or subunit recombinant SARS-CoV-2 vaccines, were included. The seroconversion and antibody levels of the NAbs and RBD-IgG were different in the PWCD group compared with those in the control group. Chronic hepatitis B (odds ratio [OR]: 0.65; 95% confidence interval [CI]: 0.46-0.93), cancer (OR: 0.65; 95% CI: 0.42-0.99), and diabetes (OR: 0.50; 95% CI: 0.28-0.89) were associated with lower seroconversion of NAbs. Chronic kidney disease (OR: 0.29; 95% CI: 0.11-0.76), cancer (OR: 0.38; 95% CI: 0.23-0.62), and diabetes (OR: 0.37; 95% CI: 0.20-0.69) were associated with lower seroconversion of RBD-IgG. Only the presence of autoimmune disease showed significantly lower NAbs and RBD-IgG titers. Patients with most types of chronic diseases showed similar responses to the controls, but humoral responses were still significantly associated with the presence of ≥2 coexisting diseases. Our study suggested that humoral responses following SARS-CoV-2 vaccination are impaired in patients with certain chronic diseases.

KMCP: accurate metagenomic profiling of both prokaryotic and viral populations by pseudo-mapping.

MOTIVATION: The growing number of microbial reference genomes enables the improvement of metagenomic profiling accuracy but also imposes greater requirements on the indexing efficiency, database size and runtime of taxonomic profilers. Additionally, most profilers focus mainly on bacterial, archaeal and fungal populations, while less attention is paid to viral communities. RESULTS: We present KMCP (K-mer-based Metagenomic Classification and Profiling), a novel k-mer-based metagenomic profiling tool that utilizes genome coverage information by splitting the reference genomes into chunks and stores k-mers in a modified and optimized Compact Bit-Sliced Signature Index for fast alignment-free sequence searching. KMCP combines k-mer similarity and genome coverage information to reduce the false positive rate of k-mer-based taxonomic classification and profiling methods. Benchmarking results based on simulated and real data demonstrate that KMCP, despite a longer running time than all other methods, not only allows the accurate taxonomic profiling of prokaryotic and viral populations but also provides more confident pathogen detection in clinical samples of low depth. AVAILABILITY AND IMPLEMENTATION: The software is open-source under the MIT license and available at https://github.com/shenwei356/kmcp. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Weakened humoral and cellular immune response to the inactivated COVID-19 vaccines in Chinese individuals with obesity/overweight.

Inactivated COVID-19 vaccines have been widely used to vaccinate the Chinese population. However, limited literature exists to explore the effect of obesity on the humoral and cellular immune response to these vaccines. In this study, 132 high BMI (Body mass index) (obesity and overweight, BMI ≥ 24 kg/m2) and 82 normal BMI (BMI < 24 kg/m2) participants were enrolled. Adverse events (AEs), Spike receptor-binding domain IgG antibody (anti-RBD-IgG), neutralizing antibodies (NAbs), and specific B-cell and T-cell responses were evaluated 21-105 days after full-course inactivated COVID-19 vaccination. The overall incidence of AEs was similar in individuals with and without obesity/overweight. No serious vaccine-related AEs occurred. Individuals with obesity/overweight had a reduced seropositivity rate of NAbs compared to those with normal BMI. Anti-RBD-IgG and NAbs titers in the high BMI group were significantly lower than those in the normal BMI group. The frequencies of RBD-specific memory B cells (MBCs) and the numbers of spike-specific TNF-α+ spot-forming cells (SFCs) in individuals with obesity/overweight were reduced compared with those noted in individuals without obesity/overweight. A similar trend of weakened humoral responses was also observed in individuals with central obesity. Our study results suggested that inactivated COVID-19 vaccines were safe and well tolerated but induced poor humoral and cellular immune responses in Chinese individuals with obesity/overweight.

A hepatocyte-targeting nanoparticle for enhanced hepatobiliary magnetic resonance imaging.

Hepatobiliary magnetic resonance imaging (MRI) can inform the diagnosis of liver tumours in patients with liver cirrhosis and hepatitis. However, its clinical utility has been hampered by the lack of sensitive and specific contrast agents, partly because hepatocyte-specific nanoparticles, regardless of their surface ligands, are readily sequestered by Kupffer cells. Here we show, in rabbits, pigs and macaques, that the performance of hepatobiliary MRI can be enhanced by an ultrasmall nanoparticle composed of a manganese ferrite core (3 nm in diameter) and poly(ethylene glycol)-ethoxy-benzyl surface ligands binding to hepatocyte-specific transmembrane metal and anion transporters. The nanoparticle facilitated faster, more sensitive and higher-resolution hepatobiliary MRI than the clinically used contrast agent gadoxetate disodium, a substantial enhancement in the detection rate (92% versus 48%) of early-stage liver tumours in rabbits, and a more accurate assessment of biliary obstruction in macaques. The nanoparticle's performance and biocompatibility support the further translational development of liver-specific MRI contrast agents.