An outbreak of hepatitis E virus genotype 4d caused by consuming undercooked pig liver in a nursing home in Zhejiang Province, China.

Hepatitis E infection is typically caused by contaminated water or food. In July and August 2022, an outbreak of hepatitis E was reported in a nursing home in Zhejiang Province, China. Local authorities and workers took immediate actions to confirm the outbreak, investigated the sources of infection and routes of transmission, took measures to terminate the outbreak, and summarized the lessons learned. An epidemiological investigation was conducted on all individuals in the nursing home, including demographic information, clinical symptoms, history of dietary, water intake and contact. Stool and blood samples were collected from these populations for laboratory examinations. The hygiene environment of the nursing home was also investigated. A case-control study was conducted to identify the risk factors for this outbreak. Of the 722 subjects in the nursing home, 77 were diagnosed with hepatitis E, for an attack rate of 10.66 %. Among them, 18 (23.38 %, 18/77) individuals had symptoms such as jaundice, fever, and loss of appetite and were defined as the population with hepatitis E. The average age of people infected with hepatitis E virus (HEV) was 59.96 years and the attack rate of hepatitis E among women (12.02 %, 59/491) was greater than that among men (7.79 %, 18/231). The rate was the highest among caregivers (22.22 %, 32/144) and lowest among logistics personnel (6.25 %, 2/32); however, these differences were not statistically significant (P > 0.05). Laboratory sequencing results indicated that the genotype of this hepatitis E outbreak was 4d. A case-control study showed that consuming pig liver (odds ratio (OR) = 7.50; 95 % confidence interval [CI]: 3.84-16.14, P < 0.001) and consuming raw fruits and vegetables (OR = 5.92; 95 % CI: 1.74-37.13, P = 0.017) were risk factors for this outbreak of Hepatitis E. Moreover, a monitoring video showed that the canteen personnel did not separate raw and cooked foods, and pig livers were cooked for only 2 min and 10 s. Approximately 1 month after the outbreak, an emergency vaccination for HEV was administered. No new cases were reported after two long incubation periods (approximately 4 months). The outbreak of HEV genotype 4d was likely caused by consuming undercooked pig liver, resulting in an attack rate of 10.66 %. This was related to the rapid stir-frying cooking method and the hygiene habit of not separating raw and cooked foods.

Intensity and drivers of subtypes interference between seasonal influenza viruses in mainland China: A modeling study.

Subtype interference has a significant impact on the epidemiological patterns of seasonal influenza viruses (SIVs). We used attributable risk percent [the absolute value of the ratio of the effective reproduction number (Rₑ) of different subtypes minus one] to quantify interference intensity between A/H1N1 and A/H3N2, as well as B/Victoria and B/Yamagata. The interference intensity between A/H1N1 and A/H3N2 was higher in southern China 0.26 (IQR: 0.11-0.46) than in northern China 0.17 (IQR: 0.07-0.24). Similarly, interference intensity between B/Victoria and B/Yamagata was also higher in southern China 0.14 (IQR: 0.07-0.24) than in norther China 0.10 (IQR: 0.04-0.18). High relative humidity significantly increased subtype interference, with the highest relative risk reaching 20.59 (95% CI: 6.12-69.33) in southern China. Southern China exhibited higher levels of subtype interference, particularly between A/H1N1 and A/H3N2. Higher relative humidity has a more pronounced promoting effect on subtype interference.

Characteristics of circulating immune cells in HBV-related acute-on-chronic liver failure following artificial liver treatment.

BACKGROUND AND AIM: Liver failure, which is predominantly caused by hepatitis B (HBV) can be improved by an artificial liver support system (ALSS). This study investigated the phenotypic heterogeneity of immunocytes in patients with HBV-related acute-on-chronic liver failure (HBV-ACLF) before and after ALSS therapy. METHODS: A total of 22 patients with HBV-ACLF who received ALSS therapy were included in the study. Patients with Grade I according to the ACLF Research Consortium score were considered to have improved. Demographic and laboratory data were collected and analyzed during hospitalization. Immunological features of peripheral blood in the patients before and after ALSS were detected by mass cytometry analyses. RESULTS: In total, 12 patients improved and 10 patients did not. According to the immunological features data after ALSS, the proportion of circulating monocytes was significantly higher in non-improved patients, but there were fewer γδT cells compared with those in improved patients. Characterization of 37 cell clusters revealed that the frequency of effector CD8+ T (P = 0.003), CD4+ TCM (P = 0.033), CD4+ TEM (P = 0.039), and inhibitory natural killer (NK) cells (P = 0.029) decreased in HBV-ACLF patients after ALSS therapy. Sub group analyses after treatment showed that the improved patients had higher proportions of CD4+ TCM (P = 0.010), CD4+ TEM (P = 0.021), and γδT cells (P = 0.003) and a lower proportion of monocytes (P = 0.012) compared with the non-improved patients. CONCLUSIONS: Changes in effector CD8+ T cells, effector and memory CD4+ T cells, and inhibitory NK cells are associated with ALSS treatment of HBV-ACLF. Moreover, monocytes and γδT cells exhibited the main differences when patients obtained different prognoses. The phenotypic heterogeneity of lymphocytes and monocytes may contribute to the prognosis of ALSS and future immunotherapy strategies.

Prevalence of hepatitis E virus in China from 1997 to 2022: a systematic review and meta-analysis.

Introduction: Several studies have reported on hepatitis E virus (HEV) prevalence in various regions of China, but the results vary widely. Herein, we conducted a systematic review and meta-analysis to assess the seroprevalence, RNA-positive rate, genotype distribution of HEV in China, and its risk factors. Methods: We included 208 related studies involving 1,785,569 participants published between 1997 and 2022. Random-effects models were used to pool prevalence, and subgroup analyses were conducted by population, gender, age, study period, regions, and rural-urban distribution. The meta regression models and pooled odds ratios (OR) were performed to identify risk factors for HEV infections. Results: The pooled anti-HEV IgG, IgM, and Ag seroprevalence, and RNA detection rates in China from 1997 to 2022 were 23.17% [95% confidence interval (CI): 20.23-26.25], 0.73% (95% CI: 0.55-0.93), 0.12% (95% CI: 0.01-0.32), and 6.55% (95% CI: 3.46-12.05), respectively. The anti-HEV IgG seropositivity was higher in the occupational population (48.41%; 95% CI: 40.02-56.85) and older adult aged 50-59 years (40.87%; 95% CI: 31.95-50.11). The dominant genotype (GT) of hepatitis E in China was GT4. Notably, drinking non-tap water (OR = 1.82; 95% CI: 1.50-2.20), consumption of raw or undercooked meat (OR = 1.47; 95% CI: 1.17-1.84), and ethnic minorities (OR = 1.50; 95% CI: 1.29-1.73) were risk factors of anti-HEV IgG seroprevalence. Discussions: Overall, the prevalence of hepatitis E was relatively high in China, especially among older adults, ethnic minorities, and humans with occupational exposure to pigs. Thus, there is a need for preventive measures, including HEV infection screening and surveillance, health education, and hepatitis E vaccine intervention in high-risk areas and populations. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023397036.

Global burden and trends of respiratory syncytial virus infection across different age groups from 1990 to 2019: A systematic analysis of the Global Burden of Disease 2019 Study.

OBJECTIVE: Understanding the global patterns of respiratory syncytial virus (RSV) is crucial for developing effective prevention and control strategies. METHODS: Data on RSV-related burden were extracted from the Global Burden of Disease 2019. Joinpoint regression models were used to assess the global temporal trends of RSV and further stratified analyses were conducted according to the Socio-demographic Index (SDI), which is a composite measure of income, education, and total fertility. Age-period-cohort model was used to evaluate age, period, and cohort effects. RESULTS: In 2019, the global age-standardized rate of mortality (ASMR) and disability-adjusted life years (ASR-DALYs) of RSV were 4.79/100,000 (95% uncertainty interval [95% UI]: 1.82/100,000-9.32/100,000) and 218.34/100,000 (95% UI: 92.06/100,000-376.80/100,000), respectively. The burden of RSV was higher in men than women. The highest ASMR (10.26/100,000, 3.80/100,000-20.16/100,000) and ASR-DALYs (478.71/100,000, 202.40/100,000-840.85/100,000) were reported in low-SDI region. Although mortality and DALYs rates in all age groups declined globally, the pace of decline was not uniform across age groups. Mortality rate in the elderly over 70 years surpassed that in children under 5 years in 2019. CONCLUSION: This study highlights the need for targeted interventions to reduce the burden of RSV, particularly in low-SDI region, and among the elderly over 70 years.

Prolyl endopeptidase remodels macrophage function as a novel transcriptional coregulator and inhibits fibrosis.

Macrophages are immune cells crucial for host defense and homeostasis maintenance, and their dysregulation is involved in multiple pathological conditions, such as liver fibrosis. The transcriptional regulation in macrophage is indispensable for fine-tuning of macrophage functions, but the details have not been fully elucidated. Prolyl endopeptidase (PREP) is a dipeptidyl peptidase with both proteolytic and non-proteolytic functions. In this study, we found that Prep knockout significantly contributed to transcriptomic alterations in quiescent and M1/M2-polarized bone marrow-derived macrophages (BMDMs), as well as aggravated fibrosis in an experimental nonalcoholic steatohepatitis (NASH) model. Mechanistically, PREP predominantly localized to the macrophage nuclei and functioned as a transcriptional coregulator. Using CUT&Tag and co-immunoprecipitation, we found that PREP was mainly distributed in active cis-regulatory genomic regions and physically interacted with the transcription factor PU.1. Among PREP-regulated downstream genes, genes encoding profibrotic cathepsin B and D were overexpressed in BMDMs and fibrotic liver tissue. Our results indicate that PREP in macrophages functions as a transcriptional coregulator that finely tunes macrophage functions, and plays a protective role against liver fibrosis pathogenesis.

The global region-specific epidemiologic characteristics of influenza: World Health Organization FluNet data from 1996 to 2021.

OBJECTIVES: This study aimed to investigate region-specific epidemiologic characteristics of influenza and influenza transmission zones (ITZs). METHODS: Weekly influenza surveillance data of 156 countries from 1996 to 2021 were obtained using FluNet. Joinpoint regression was used to describe global influenza virus trends, and clustering analyses were used to classify the ITZs. RESULTS: The global median average positive rate for total influenza virus was 16.19% (interquartile range: 11.62-25.70%). Overall, three major subtypes (influenza H1, H3, and B viruses) showed alternating epidemics. Notably, the proportion of influenza B viruses increased significantly from July 2020 to June 2021, reaching 62.66%. The primary peaks of influenza virus circulation in the north were earlier than those in the south. Global influenza virus circulation was significantly characterized by seven ITZs, including "Northern America" (primary peak: week 10), "Eastern & Southern-Asia" (primary peak: week 10), "Europe" (primary peak: week 11), "Asia-Europe" (primary peak: week 12), "Southern-America" (primary peak: week 30), "Oceania-Melanesia-Polynesia" (primary peak: week 39), and "Africa" (primary peak: week 46). CONCLUSION: Global influenza virus circulation was significantly characterized by seven ITZs that could be applied to influenza surveillance and warning.

Global influenza vaccination rates and factors associated with influenza vaccination.

OBJECTIVES: Influenza vaccination is an effective method for preventing influenza virus infection. Herein, we performed a meta-analysis to quantify global influenza vaccination rates (IVRs) and the factors influencing its uptake in the general population, individuals with chronic diseases, pregnant women, and healthcare workers. METHODS: Related articles were obtained from online databases and screened according to the inclusion criteria. The pooled IVRs were calculated using the random effects model. Subgroup analyses and multivariate meta-regression were performed to determine the factors associated with influenza vaccine uptake. RESULTS: We included 522 studies from 68 countries/regions. Most studies were conducted in the European region (247 studies), followed by the Western Pacific (135 studies) and American regions (100 studies). The IVRs with 95% confidence intervals (CIs) in the general population were lower (24.96%, 23.45%-26.50%) than in individuals with chronic diseases (41.65%, 40.08%-43.23%), healthcare workers (36.57%, 33.74%-39.44%), and pregnant women (25.92%, 23.18%-28.75%). The IVRs in high-income countries/regions were significantly higher than that in middle-income countries/regions. A free national or regional vaccination policy, perception of influenza vaccine efficacy and disease severity, a recommendation from healthcare workers, and having a history of influenza vaccination were positive factors for vaccine uptake (P <0.01). CONCLUSION: Overall, global IVRs were low, especially in the general population. The studies on the IVRs, especially for priority populations, should be strengthened in Eastern Mediterranean, South-East Asian, and African regions. Free vaccination policies and the dissemination of continuous awareness campaigns are effective measures to enhance vaccination uptake.

Global burden and trends of rotavirus infection-associated deaths from 1990 to 2019: an observational trend study.

BACKGROUND: Rotavirus is the leading global pathogen of diarrhea-associated mortality and poses a great threat to public health in all age groups. This study aimed to explore the global burden and 30-year change patterns of rotavirus infection-associated deaths. METHODS: Based on the Global Burden of Disease 2019 Study (GBD 2019), we analyzed the age-standardized death rate (ASDR) of rotavirus infection by sex, geographical region, and sociodemographic index (SDI) from 1990 to 2019. A Joinpoint regression model was used to analyze the global trends in rotavirus infection over the 30 years, SaTScan software was used to detect the spatial and temporal aggregations, and a generalized linear model to explore the relationship between sociodemographic factors and death rates of rotavirus infection. RESULTS: Globally, rotavirus infection was the leading cause of diarrheal deaths, accounting for 19.11% of deaths from diarrhea in 2019. Rotavirus caused a higher death burden in African, Oceanian, and South Asian countries in the past three decades. The ASDR of rotavirus declined from 11.39 (95% uncertainty interval [95% UI] 5.46-19.48) per 100,000 people in 1990 to 3.41 (95% UI 1.60-6.01) per 100,000 people in 2019, with an average annual percentage change (AAPC) (- 4.07%, P < 0.05). However, a significant uptrend was found in high-income North America (AAPC = 1.79%, P < 0.05). The death rate was the highest among children under 5 years worldwide. However, the death rates of elderly individuals over 70 years were higher than those of children under 5 years in 2019 among high, high-middle, middle, and low-middle SDI regions. Current health expenditure, gross domestic product per capita, and the number of physicians per 1000 people were significantly negatively correlated with death rates of rotavirus. CONCLUSIONS: Although the global trends in the rotavirus burden have decreased substantially over the past three decades, the burden of rotavirus remained high in Africa, Oceania, and South Asia. Children under 5 years and elderly individuals over 70 years were the populations most at risk for rotavirus infection-associated deaths, especially elderly individuals over 70 years in relatively high SDI regions. More attention should be paid to these areas and populations, and effective public health policies should be implemented in the future.

Meteorological Factors Affecting Infectious Diarrhea in Different Climate Zones of China.

Meteorological factors and the increase in extreme weather events are closely related to the incidence rate of infectious diarrhea. However, few studies have explored whether the impact of the same meteorological factors on the incidence rate of infectious diarrhea in different climate regions has changed and quantified these changes. In this study, the time series fixed-effect Poisson regression model guided by climate was used to quantify the relationships between the incidence rate of various types of infectious diarrhea and meteorological factors in different climate regions of China from 2004 to 2018, with a lag of 0-2 months. In addition, six social factors, including per capita Gross Domestic Product (GDP), population density, number of doctors per 1000 people, proportion of urbanized population, proportion of children aged 0-14 years old, and proportion of elderly over 65 years old, were included in the model for confounding control. Additionally, the intercept of each province in each model was analyzed by a meta-analysis. Four climate regions were considered in this study: tropical monsoon areas, subtropical monsoon areas, temperate areas and alpine plateau areas. The results indicate that the influence of meteorological factors and extreme weather in different climate regions on diverse infectious diarrhea types is distinct. In general, temperature was positively correlated with all infectious diarrhea cases (0.2 ≤ r ≤ 0.6, p < 0.05). After extreme rainfall, the incidence rate of dysentery in alpine plateau area in one month would be reduced by 18.7% (95% confidence interval (CI): -27.8--9.6%). Two months after the period of extreme sunshine duration happened, the incidence of dysentery in the alpine plateau area would increase by 21.9% (95% CI: 15.4-28.4%) in that month, and the incidence rate of typhoid and paratyphoid in the temperate region would increase by 17.2% (95% CI: 15.5-18.9%) in that month. The meta-analysis showed that there is no consistency between different provinces in the same climate region. Our study indicated that meteorological factors and extreme weather in different climate areas had different effects on various types of infectious diarrhea, particularly extreme rainfall and extreme sunshine duration, which will help the government develop disease-specific and location-specific interventions, especially after the occurrence of extreme weather.

Global Burden and Trends of Norovirus-Associated Diseases From 1990 to 2019: An Observational Trend Study.

Introduction: As an important pathogen causing diarrheal diseases, the burden and change in the death rate of norovirus-associated diseases (NADs) globally are still unknown. Methods: Based on global disease burden data from 1990 to 2019, we analyzed the age-standardized death rate (ASDR) of NADs by age, region, country, and Socio-Demographic Index (SDI) level. The discrete Poisson model was applied in the analysis of NADs' spatiotemporal aggregation, the Joinpoint regression model to analyze the trend of death burden of NADs over 30 years, and a generalized linear model to identify the risk factors for the death rate from NADs. Results: The ASDR of NADs significantly decreased by a factor of approximately 2.7 times, from 5.02 (95% CI: 1.1, 11.34) in 1990 to 1.86 (95% CI: 0.36, 4.16) in 2019 [average annual percent change (AAPC) = -3.43, 95% CI: -3.56, -3.29]. The death burden of NADs in 2019 was still highest in African regions despite a great decline in recent decades. However, the ASDR in high SDI countries presented an uptrend [0.12 (95% CI: 0.03, 0.26) in 1990 and 0.24 (95% CI: 0.03, 0.53) in 2019, AAPC = 2.52, 95% CI: 2.02-3.03], mainly observed in the elderly over 70 years old. Compared to children under 5 years old, the 2019 death rate of elderly individuals over 80 years old was much higher in high SDI countries. The generalized linear model showed that factors of the number of physicians (RR = 0.67), the proportions of children under 14 years old (RR = 1.21), elderly individuals over 65 years old (RR = 1.13), educational level (RR = 1.03) and urbanization proportion (RR = 1.01) influenced the ASDR of NADs. Conclusions: The death burden of NADs has remained high in developing regions over the last three decades and has increased among the elderly in countries with high SDI levels, even though the global trend in NAD-associated deaths has decreased significantly in the past three decades. More effective public health policies against NADs need to be implemented in high SDI regions and for the elderly.

Immune Checkpoint Molecules Expressed on CD4+ T Cell Subsets in Chronic Asymptomatic Hepatitis B Virus Carriers With Hepatitis B e Antigen-Negative.

Background: Chronic hepatitis B virus (HBV) infection remains a major public health problem worldwide. Immune checkpoint molecules expressed on CD4+ T cells play critical roles in chronic HBV infection. However, their roles in chronic asymptomatic HBV carriers (ASCs) with hepatitis B e antigen (HBeAg)-negative remain unclear. In this study, we explored the role of immune checkpoint molecules expressed on CD4+ T cell subsets in chronic ASCs with HBeAg-negative. Methods: Human peripheral blood mononuclear cells (PBMCs) from the ASCs with HBeAg-negative and healthy controls (HC) were isolated, and immune checkpoint molecules expressed on CD4+ T cell subsets and serum cytokines were detected by flow cytometry. Moreover, the mRNA expressions of immune checkpoint molecules were analyzed by a real-time quantitative PCR assay. Results: In comparison with HC, CD4+ T cells highly expressed LAG-3, TIM-3, and PD-1 in PBMCs from chronic ASCs with HBeAg-negative. Interestingly, the expressions of TIM-3 and PD-1 on circulating follicular helper T (Tfh) cells in ASCs were significantly high. Moreover, high expressions of LAG-3, TIM-3, and PD-1 were different among Treg, Th1, Th2, and Th17 cells. In addition, the expressions of TIM-3 and CTLA-4 mRNA in PBMCs from ASCs were significantly elevated. However, the frequency of CTLA-4+CD4+ T cell subsets in PBMCs from ASCs was not different from HC. The levels of six cytokines in serum from ASCs were not clearly different from HC. Conclusion: Immune checkpoint molecules highly expressed on CD4+ T cell subsets indicated an important role in chronic ASCs with HBeAg-negative, which provided potential therapeutic targets in the pathogenesis of chronic HBV infection.

Exhausted phenotype of circulating CD8+ T cell subsets in hepatitis B virus carriers.

BACKGROUND: Chronic hepatitis B virus (HBV) infection is characterized by the presence of dysfunctional exhausted CD8+ T cells that hamper viral control. We investigated the phenotypic heterogeneity of exhausted CD8+ T cells in HBV carriers. METHODS: We enrolled 31 HBV carriers and 23 healthy controls (HCs) in our study. Peripheral blood mononuclear cells (PBMCs) were isolated, and flow cytometry was used to determine the phenotypic distribution of CD8+ T cell subsets. Expression of cytokines such as TNF-α and IFN-γ was detected by quantitative reverse transcription-PCR, a fluorescence flow cytometry-based immunomicrobead assay and flow cytometry. RESULTS: There were no significant differences in the baseline characteristics between the 31 HBV carriers and the 23 sex- and age-matched HCs. CD8+ T cells exhibited higher levels of inhibitory receptors (TIM3 and PD1) in the HBV carriers than in the HCs (P < 0.05); in particular, Tfc cells (CXCR5+CD25-) expressed higher levels of TIM3 and PD1 than non-Tfc cells in the HBV carriers. In addition, among the subsets of Tc cells, the Tc17 (CXCR5-CD25-CCR6+) subset displayed increased expression of TIM3 and LAG3 in the HBV carriers. Our findings further showed that CD8+ T cells produced lower levels of IFN-γ, TNF-α, and Granzyme B. Paired analysis of the Tfc subset and the Tc subset indicated that higher levels of cytokines (IFN-γ and TNF-α) were produced by the Tfc subset in the HBV carriers. Among the Tc subsets, the Tc17 subset produced lower levels of cytokines. CONCLUSION: The Tfc subset exhibited an enhanced exhausted phenotype but possessed some functional properties during chronic HBV infection, while the Tc subset showed a lower functional level. The identification of these unique subsets may provide a potential immunotherapeutic target in chronic HBV infection.

Psychological stress; knowledge, attitude and practice and acceptance of antiviral therapy in pregnant women with hepatitis B in Zhejiang, China: a case comparison study.

OBJECTIVES: To determine knowledge, attitude and practice (KAP) and antiviral therapy's acceptance during pregnancy of pregnant women with hepatitis B and influencing factors. DESIGN: Case-comparison study. SETTING: The study was conducted in Zhejiang province, China, from September 2019 to December 2020. PARTICIPANTS: Pregnant and postpartum women with chronic hepatitis B. PRIMARY AND SECONDARY OUTCOME MEASURES: The stress scores, self-assessed health score, KAP, antiviral therapy's acceptance rate during pregnancy and influencing factors were analysed. The Perceived Stress Scale-10 was used to assess stress. Logistic regression was used to analyse influencing factors on antiviral therapy. RESULTS: The self-assessed health score of pregnant women without liver diseases (82.4±9.3) was significantly higher than that of pregnant women with chronic hepatitis B (75.5±9.5) and postpartum (75.1±14.1). Psychological stress of pregnant women with chronic hepatitis B was significantly high with a 14.9±3.6 score, but there was no significant difference between hepatitis B postpartum and non-liver disease women (12.7±3.5 vs 12.9±3.5, p=0.75). The acceptance rate of pregnant women with hepatitis B for antiviral therapy was 84.2%, while that of postpartum women was even higher. Logistic regression analysis showed that patients with positive hepatitis B e antigen (HBeAg) (OR, 3.35; 95% CI, 1.21 to 9.26) and higher scores on hepatitis B-related knowledge (OR, 3.52, 95% CI, 2.18 to 5.69) were more likely to accept antiviral therapy during pregnancy. CONCLUSIONS: Pregnant women with hepatitis B in Zhejiang have heavy psychological stress and a high antiviral therapy acceptance rate during pregnancy. Acceptance is related to HBeAg status and level of understanding of hepatitis B during pregnancy. It is necessary to provide education on hepatitis B to reduce psychological stress and increase acceptance of antiviral therapy during pregnancy.

Impact of Coinfection With SARS-CoV-2 and Influenza on Disease Severity: A Systematic Review and Meta-Analysis.

Background: Although coinfection with influenza in COVID-19 patients has drawn considerable attention, it is still not completely understood whether simultaneously infected with these two viruses influences disease severity. We therefore aimed to estimate the impact of coinfected with SARS-CoV-2 and influenza on the disease outcomes compared with the single infection of SARS-CoV-2. Materials and Methods: We searched the PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure Database (CNKI) to identify relevant articles up to July 9, 2021. Studies that assessed the effect of SARS-CoV-2 and influenza coinfection on disease outcomes or those with sufficient data to calculate risk factors were included. Risk effects were pooled using fixed or random effects model. Results: We ultimately identified 12 studies with 9,498 patients to evaluate the risk effects of SARS-CoV-2 and influenza coinfection on disease severity. Results indicated that coinfection was not significantly associated with mortality (OR = 0.85, 95%CI: 0.51, 1.43; p = 0.55, I2 = 76.00%). However, mortality was found significantly decreased in the studies from China (OR = 0.51, 95%CI: 0.39, 0.68; I2 = 26.50%), while significantly increased outside China (OR = 1.56, 95%CI: 1.12, 2.19; I2 = 1.00%). Moreover, a lower risk for critical outcomes was detected among coinfection patients (OR = 0.64, 95%CI: 0.43, 0.97; p = 0.04, I2 = 0.00%). Additionally, coinfection patients presented different laboratory indexes compared with the single SARS-CoV-2 infection, including lymphocyte counts and APTT. Conclusion: Our study revealed that coinfection with SARS-CoV-2 and influenza had no effect on overall mortality. However, risk for critical outcomes was lower in coinfection patients and different associations were detected in the studies from different regions and specific laboratory indexes. Further studies on influenza strains and the order of infection were warranted. Systematic testing for influenza coinfection in COVID-19 patients and influenza vaccination should be recommended.

Follicular Helper T Cells in the Immunopathogenesis of SARS-CoV-2 Infection.

Coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a serious infectious disease that has led to a global pandemic with high morbidity and mortality. High-affinity neutralizing antibody is important for controlling infection, which is closely regulated by follicular helper T (Tfh) cells. Tfh cells play a central role in promoting germinal center reactions and driving cognate B cell differentiation for antibody secretion. Available studies indicate a close relationship between virus-specific Tfh cell-mediated immunity and SARS-CoV-2 infection progression. Although several lines of evidence have suggested that Tfh cells contribute to the control of SARS-CoV-2 infection by eliciting neutralizing antibody productions, further studies are needed to elucidate Tfh-mediated effector mechanisms in anti-SARS-CoV-2 immunity. Here, we summarize the functional features and roles of virus-specific Tfh cells in the immunopathogenesis of SARS-CoV-2 infection and in COVID-19 vaccines, and highlight the potential of targeting Tfh cells as therapeutic strategy against SARS-CoV-2 infection.

Advances in Multi-Omics Applications in HBV-Associated Hepatocellular Carcinoma.

Hepatitis B virus (HBV) specifically infects liver cells, leading to progressive liver cirrhosis and significantly increasing the risk of hepatocellular carcinoma (HCC). The maturity of sequencing technology, improvement in bioinformatics data analysis and progress of omics technologies had improved research efficiency. The occurrence and progression of HCC are affected by multisystem and multilevel pathological changes. With the application of single-omics technologies, including genomics, transcriptomics, metabolomics and proteomics in tissue and body fluid samples, and even the novel development of multi-omics analysis on a single-cell platform, HBV-associated HCC changes can be better analyzed. The review summarizes the application of single omics and combined analysis of multi-omics data in HBV-associated HCC and proposes the importance of multi-omics analysis in the type of HCC, which provide the possibility for the precise diagnosis and therapy of HBV-associated HCC.

Associations between Temperature and Influenza Activity: A National Time Series Study in China.

Previous studies have reported that temperature is the main meteorological factor associated with influenza activity. This study used generalized additive models (GAMs) to explore the relationship between temperature and influenza activity in China. From the national perspective, the average temperature (AT) had an approximately negative linear correlation with the incidence of influenza, as well as a positive rate of influenza H1N1 virus (A/H1N1). Every degree that the monthly AT rose, the influenza cases decreased by 2.49% (95%CI: 1.24%-3.72%). The risk of influenza cases reached a peak at -5.35 °C with RRs of 2.14 (95%CI: 1.38-3.33) and the monthly AT in the range of -5.35 °C to 18.31 °C had significant effects on the incidence of influenza. Every degree that the weekly AT rose, the positive rate of A/H1N1 decreased by 5.28% (95%CI: 0.35%-9.96%). The risk of A/H1N1 reached a peak at -3.14 °C with RRs of 4.88 (95%CI: 1.01-23.75) and the weekly AT in the range of -3.14 °C to 17.25 °C had significant effects on the incidence of influenza. Our study found that AT is negatively associated with influenza activity, especially for A/H1N1. These findings indicate that temperature could be integrated into the current influenza surveillance system to develop early warning systems to better predict and prepare for the risks of influenza.

Epidemiological Trends and Hotspots of Other Infectious Diarrhea (OID) in Mainland China: A Population-Based Surveillance Study From 2004 to 2017.

Background: The incidence of other infectious diarrhea (OID) ranked second in class C notifiable disease in China. It has posed a great threat to public health of all age groups. The aim of this study was to investigate the epidemiological trends and hotspots of OID in mainland China. Materials and Methods: Incidence and mortality data for OID stratified by date, age and region from 2004 to 2017 was extracted from the data-center of China public health science. Joinpoint regression and space-time analyses were performed to explore the epidemiological trends and hotspots of OID. Results: The average annual incidence of OID was 60.64/100,000 and it showed an increased trend in the mainland China especially after 2006 (APC = 4.12, 95 CI%: 2.06-6.21). Children of 0-4 year age group accounts for 60.00% (5,820,897/11,414,247) of all cases and its incidence continuously increased though 2004-2017 (APC = 6.65, 95 CI%: 4.39-8.96). The first-level spatial and temporal aggregation areas were located in Beijing and Tianjin, with the gathering time from 2005/1/1 to 2011/12/31 (RR = 5.52, LLR = 572893.59, P < 0.001). The secondary spatial and temporal aggregation areas covered Guangdong, Guangxi, Hainan and Guizhou from 2011/1/1 to 2017/12/31 (RR = 1.98, LLR = 242292.72, P < 0.001). OID of Tianjin and Beijing presented a decreased trend since 2006. However, the incidence of OID in Guangdong, Guangxi, Hainan and Guizhou showed increased trends through 2004-2017. Conclusion: Our study showed that OID showed a constantly increasing trend and brought considerable burden in China especially in the 0-4 age group. The high-risk periods and clusters of regions for OID were identified, which will help government develop disease-specific and location-specific interventive measures.

Comparison of HBV-DNA and HBeAg as antiviral therapeutic indicators among HBV-infected pregnant women: a systematic review and meta-analysis.

BACKGROUND: Hepatitis B virus deoxyribonucleic acid level (HBV-DNA) ≥5.3 log10IU/mL among pregnant women was recommended as an antiviral therapeutic indicator. However, implementation of HBV-DNA testing has varying difficulties in places. In this study, we explored the implementation rate of HBV-DNA testing worldwide, and possibility of hepatitis B e antigen (HBeAg) testing replacing HBV-DNA as an antiviral treatment indicator during pregnancy. METHODS: We searched five electronic databases including PubMed, Embase, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNKI) for studies published between Jan 1, 2000, and Nov 16, 2020. Studies were eligible for inclusion if HBV DNA testing implementation rate is available, or if maternal HBV DNA level could be analyzed by HBeAg status. The rates were pooled after data was made a Freeman-Tukey double arcsine transformation. This study is registered with PROSPERO, CRD42021235711. RESULTS: A total of 9,575 studies were identified, 79 were finally included in this study. The HBV-DNA testing implementation rate was 36.6% (95% CI, 28.3-45.3%) globally. The rate of HBV-DNA ≥5.3 log10IU/mL was 81.51% (95% CI, 71.68-89.74%) among HBeAg positive pregnant women, and was 4.08% (95% CI, 2.14-6.54%) in HBeAg negative pregnant women. Even if infants were immunized with hepatitis B vaccine and hepatitis B immunoglobulin, the rate of mother-to-child transmission was still 4.87% (95% CI, 4.10-5.68%) among HBeAg positive mothers, and was 0 (95% CI, 0-0.07%) among HBeAg negative mothers, with a RR of 30.40 (95% CI, 11.31-81.72). CONCLUSIONS: The implementation rate of HBV DNA testing varies from region to region. Limited studies show that HBV DNA testing does not cover all pregnant women with hepatitis B. When HBV-DNA testing is not available, it is worth considering to use HBeAg positivity as an antiviral therapeutic indicator among HBV-infected pregnant women for preventing MTCT.