2022 IDSOG Annual Meeting, Boston, MA, 4-6 August 2022

This journal issue includes s of papers presented at the conference. Topics discusses are: stillbirth during a pandemic;analysis of the female genital tract (FGT) metabolome;effectiveness of REGEN-COV antibody combination to reduce risk of hospitalization;patterns of nucleic acid amplification testing;delta variant neutralizing antibody response following maternal COVID19 vaccination;integrated prenatal and hepatitis c virus care increases linkage;extended interval gentamicin dosing in obstetrics;maternal and infant cytomegalovirus detection among women living with HIV.

A people-centered decentralized outreach model toward HCV micro-elimination in hyperendemic areas: COMPACT study in SARS Co-V2 pandemic.

OBJECTIVES: Gaps in linkage-to-care remain the barriers toward hepatitis C virus (HCV) elimination in the directly-acting-antivirals (DAA) era, especially during SARS Co-V2 pandemics. We established an outreach project to target HCV micro-elimination in HCV-hyperendemic villages. METHODS: The COMPACT provided "door-by-door" screening by an "outreach HCV-checkpoint team" and an "outreach HCV-care team" for HCV diagnosis, assessment and DAA therapy in Chidong/Chikan villages between 2019 and 2021. Participants from neighboring villages served as Control group. RESULTS: A total of 5731 adult residents participated in the project. Anti-HCV prevalence rate was 24.0% (886/3684) in Target Group and 9.5% (194/2047) in Control group (P < 0.001). The HCV-viremic rates among anti-HCV-positive subjects were 42.7% and 41.2%, respectively, in Target and Control groups. After COMPACT engagement, 80.4% (304/378) HCV-viremic subjects in the Target group were successfully linked-to-care, and Control group (70% (56/80), P = 0.039). The rates of link-to-treatment and SVR12 were comparable between Target (100% and 97.4%, respectively) and Control (100% and 96.4%) groups. The community effectiveness was 76.4% in the COMPACT campaign, significantly higher in Target group than in Control group (78.3% versus 67.5%, P = 0.039). The community effectiveness decreased significantly during SARS Co-V2 pandemic in Control group (from 81% to 31.8%, P < 0.001), but not in Target group (80.3% vs. 71.6%, P = 0.104). CONCLUSIONS: The outreach door-by-door screen strategy with decentralized onsite treatment programs greatly improved HCV care cascade in HCV-hyperendemic areas, a model for HCV elimination in high-risk marginalized communities in SARS Co-V2 pandemic.

Impact of an automated reminder for HIV testing in general practice patient monitoring software during the COVID-19 pandemic

In 2017, the French National Health Authority (HAS) reassessed its human immunodeficiency virus (HIV) screening strategy and in 2018, the Joint United Nations Programme on HIV/AIDS (UNAIDS) set the goal of screening 95% of people living with HIV by 2030. The HAS recommends an approach based on target population and gives the general practitioner (GP) a key role in its implementation. It is therefore important to facilitate HIV testing by GPs and to reduce missed opportunities. To this end, a pilot study was conducted on a panel of 2,000 GPs over a 10-month period in 2020 in order to evaluate the impact of a pop-up displayed within prescription assistance software reminding about the frequency of targeted screening recommended by the HAS. The pop-up was displayed for patients with a history of sexually transmitted infection and/or hepatitis C and/or tuberculosis in the previous 12 months and without a known HIV serology or diagnosis. The impact was measured by comparing the prospective follow-up of consultations made during the "pilot" in 2020 with the retrospective follow-up of consultations made during the "pre-pilot" period in 2019. The results showed a significant increase in HIV serology prescriptions during the pilot study, despite the COVID-19 pandemic. Difficulties in objectively identifying target patient profiles and in organizing regular follow-ups to HIV testing were also revealed. This pop-up tool represents an additional means of facilitating the prescription of HIV testing by GPs.

Screening of potential donors for immunoglobulins M and G to new coronavirus infection

This study presents the results of the examination of potential donors of blood and its components for immunoglobulins M and G to patients with coronavirus disease 2019 (COVID-19) living in St. Petersburg. A total of 6782 people aged 18-24 years were evaluated, which accounted for 2.07% of the region's population (326 760 people) of this age group. The study was carried out in the spring and autumn of 2020. A negative result (absence of antibodies) was obtained in 93.5% of the participants. The rates of immunoglobulins M and M + G were 0.58% and 4.18%, respectively, in the spring and autumn. Moreover, the number of participants who had immunoglobulins M and G + M in the autumn period was four times higher than the indicators of the spring period, which indicated greater infection activities in the population during this period. This is most likely due to the active movement of the population in the summer. When comparing the rates of COVID-19 infection and the frequency of occurrence in donors of the same age, markers of human immunodeficiency virus 1 and 2 and hepatitis B and C in 2020 (0.024, 0.012 and 0.13%, respectively) indicate the urgency of the problem of donor selection during blood services, especially during a difficult epidemiological situation because of COVID-19. Along with organizational measures for the selection of donors (e.g., attracting individuals from organized groups in which there are no signs of an unfavorable epidemiological situation to donation), mandatory testing of potential donors for immunoglobulins M and G should be considered.

Rural rates of hepatitis C within an emergency department-based universal screening program

Study Objective: As a consequence of the opioid epidemic, overall Hepatitis C (HCV) infections have increased in the United States. HCV mortality now surpasses more than 60 other infections (eg, HIV, and TB). The CDC now recommends universal HCV screening, for all adults aged =18 years. Several reports highlight the success of large urban EDs to provide screening and linkage to care for HCV but the ability to utilize rural EDs has not been explored. Our objective was to highlight results of an electronic health record (EHR) driven "opt-out," universal HCV screening program in a small rural community ED that serves the economically disadvantaged, rural/mountainous area of SC, including parts of Appalachia.

Advances in acute severe hepatitis of unknown etiology in children

Since the International Health Regulations National Focal Point for the United Kingdom alerted the WHO of ten cases of acute severe hepatitis of unknown etiology in children on April 5, 2022, relevant cases have been reported worldwide. These patients had acute hepatitis (negative for hepatitis viruses A-E) and elevated aminotransferase (AST) or alanine aminase (ALT) exceeding 500 U/L. Furthermore, severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and/or adenovirus type F41 have been detected in some cases. This unknown hepatitis has been hypothesized to be induced by a viral reservoir of novel coronavirus superantigen, which repeatedly stimulates the intestines and leads to a multisystem inflammatory syndrome in children (MIS-C), which causes immune abnormalities in the presence of human adenovirus. Although this hypothesis has not been confirmed by any in vivo experimental or clinical studies, it may provide ideas for possible intervention strategies.

Collaborative Referral Model to Achieve Hepatitis C Micro-Elimination in Methadone Maintenance Treatment Patients during the COVID-19 Pandemic.

Although hepatitis C virus (HCV) prevails in patients receiving methadone maintenance treatment (MMT), most do not receive anti-HCV therapy. This single-center observational study aimed to achieve HCV micro-elimination at an MMT center during the COVID-19 pandemic using a collaborative referral model, which comprised a referral-for-diagnosis stage (January 2020 to August 2020) and an on-site-diagnosis stage (September 2020 to January 2021). A multidisciplinary team was established and all MMT center patients were enrolled. HCV micro-elimination was defined as >90% of HCV-infected patients diagnosed and >80% of HCV-viremic patients treated. A total of 305 MMT patients, including 275 (90.2%) anti-HCV seropositive patients, were enrolled. Among 189 HCV-infected patients needing referral, the accumulative percentage receiving HCV RNA testing increased from 93 (49.2%) at referral-for-diagnosis stage to 168 (88.9%) at on-site-diagnosis stage. Among 138 HCV-viremic patients, the accumulative percentage receiving direct-acting antiviral (DAA) therapy increased from 77 (55.8%) at referral-for-diagnosis stage to 129 (93.5%) at on-site-diagnosis stage. We achieved an HCV RNA testing rate of 92.4% (254/275), an HCV treatment rate of 95.8% (203/212) and a sustained virological response rate of 94.1% (191/203). The collaborative referral model is highly effective in HCV RNA testing and HCV treatment uptake among MMT patients, achieving HCV micro-elimination.

Therapeutic potential of peptidomimetics as antiviral agents: short review on recent progress

The tug of war between viruses and humans existed for millions of years. The defensive mechanisms and rapid evolution of these viruses have made it difficult for researchers to progress in antiviral drug discovery. Therefore, this paper is intended to give an overview on reported drug targets via an insight on viral pathogenesis and the peptidomimetic-drugs reported till date against three most globally prevalent and deadly viruses: SARS-CoV-2, HIV, and HCV. The reason for selective illustration in this review is attributed to the proven record of antecedents reporting wide scope of peptidomimetics in development of antiviral drugs highlighting the ease of rapid mobilization of peptidomimetics for treatment of emerging viruses.

Ensuring the implementation of healthcare policies able to eliminate hepatitis C at both central and regional levels during the COVID-19 pandemic

Viral hepatitis C is an important public health problem and its elimination by 2030, defined by the World Health Organization, is an ambitious goal. The chance of free screening for HCV infection represents an important achievement that requires a successful State-Regions coordination and an effective regional organisation, that guarantees an interdisciplinary course between local and specialized healthcare. A structured communication program to increase the sensitivity of target populations as well as health professionals is the key for success. The implementation of the proactive screening, defined by the Milleproroghe Law, is crucial because it will define the tracks for the whole HCV costeffective screening strategies (1948-1988 birth cohorts) required to achieve the HCV elimination targets in Italy by 2030.

Protecting persons at-risk of viral hepatitis and alcohol-related liver disease during the pandemic and beyond: mitigating the impact of Coronavirus disease 2019 on liver health

Background: Treatment seeking for people with alcohol use disorders (AUD), injecting drug use and viral hepatitis is low, and has worsened during the coronavirus disease 2019 (COVID-19) pandemic. Deferring clinical care and increasing drug and alcohol use exacerbate the risks of progression for individuals with chronic liver disease from viral hepatitis and/or alcohol-related liver disease (ALD). We explored the impact COVID-19 epidemic may have on patients with chronic liver disease and suggested mechanisms to protect this at-risk population during and after the pandemic.

Adherence to personal protective equipment against infectious diseases among healthcare workers in Arak-Iran

Background: Occupational exposure to blood and body secretions poses a significant risk of COVID-19, HIV, HCV, and HBV among healthcare workers (HCWs). Assessment of this exposure is necessary for optimized planning and policy-making measures. This study aimed to assess the exposure to occupational risk factors among emergency HCWs.

Naturally occurring resistance-associated variants to NS3/4A protease and NS5A inhibitors in patients with HIV/HCV co-infection or HCV infection alone. (Theme Issue: Diagnosis and treatment of liver failure in children.) [Chinese]

Objective: To investigate the difference in naturally occurring resistance-associated variants (RAVs) between the patients with HIV/HCV co-infection and those with HCV infection alone by detecting the drug resistance loci associated with HCV NS3/4A protease and NS5A inhibitors.

Vitamin A and viral infection in critical care

Vitamin A is fat-soluble compounds of retinoid derivate, consisting of retinol, retinal, and retinyl esters. Vitamin A also affects cell growth and differentiation, playing a critical role in the normal formation and function of the heart, lungs, kidneys, and other organs. According to the role of vitamin A in enhancing immune function, it is known as an anti-inflammatory agent. Also, vitamin A supplementation by reducing morbidity and mortality in different infectious diseases, such as measles, diarrheal disease, measles-related pneumonia, human immunodeficiency virus infection, and malaria considered as a crucial factor against infection. So vitamin A deficiency can be life-threatening, because of impairing the response to infection and significant risk of development of severe respiratory infections in infants and young children. In this paper, we have discussed the effects of vitamin A in modulating immune responses in viral infections and the direct effects of this vitamin on viral replication by comparing its role during different types of viral infections.

Comorbidity of hepatic cystic echinococcosis with HBV/HCV infection, liver cirrhosis, and hepatocellular carcinoma. (Theme Issue: New advances in the precise diagnosis and treatment of liver cancer.) [Chinese]

Objective: To investigate the comorbidity of hepatic cystic echinococcosis with HBV/HCV infection, liver cirrhosis, and hepatocellular carcinoma, and to lay a foundation for further research on the influence of hepatic cystic echinococcosis on HBV/HCV infection, liver cirrhosis, and hepatocellular carcinoma.

Testing and diagnosis of HIV, hepatitis B and C, and bacterial STI in French STI clinics (CeGIDD) in 2020: individual data from SurCeGIDD surveillance. (S..ropositivit.. au VIH: diagnostic, pr..vention et v..cu au temps de la Covid-19.) [French]

Introduction - The CeGIDDs are centres of information, screening and diagnosis for HIV, viral hepatitis and bacterial sexually transmitted infections (STIs), a network of French free-to-use clinics created in 2016. This article describes the characteristics of CeGIDD visitors as well as the screening and diagnostic activities carried out by the structures for the year 2020, comparing them with 2018. Method - We present a repeated cross-sectional study, based on continuous monitoring data from the SurCeGIDD system, which relies on the secure transmission of individual visitor data according to a predefined format. The socio-demographic and behavioural data of the visitors, and their reasons for consultation, are described. The proportions of visitors tested and the positivity rates for HIV, hepatitis B (HBV) and C (HCV), syphilis, gonococcus (NG), Chlamydia trachomatis (CT) and Mycoplasma genitalium (MG) are described according to sexual practices. Results - In 2020, 336,333 consultations were reported by 50.3% of the 336 CeGIDDs identified in 2020. Attendance at CeGIDDs fell sharply in the second quarter of 2020 (-58% compared to the first quarter). In 2020, the visitors were mostly men (62.1%) and young people under 30 (64.5%). About a quarter (23.5%) of the visitors were born abroad. The proportion of men having sex with men (14.8%) and trans people (0.38%) had increased compared to 2018. The most frequent reasons for consultation remained risk exposure (60.4%) and systematic screening (43.3%). Some reasons for consultation increased between 2018 and 2020, such as initiating or monitoring a post-exposure prophylaxis. An increase in positivity rate between 2018 and 2020 is observed for HIV (from 0.37% to 0.41%), but especially for NG (from 2.8% to 4.0%), undoubtedly related to changes in visitor characteristics. At the same time, positivity rates decreased for HBV (from 1.3% to 0.93%) and HCV (from 0.94% to 0.60%). They are relatively stable for CT (7.0% in 2020), MG (6.8%) and syphilis (1.0%). Conclusion - Despite a drop in consultations in 2020 related to the COVID-19 pandemic, the CeGIDDs continued to carry out their screening/diagnostic missions in a comprehensive sexual health approach. SurCeGIDD surveillance provides elements for monitoring the national sexual health strategy, hence the need to improve the comprehensiveness and completeness of the data collected.

Study on the potential mechanism of Fufang Yinhua Jiedu granules based on network pharmacology in the treatment of novel coronavirus

Objective To explore the potential effect and mechanism of Fufang Yinhua Jiedu Granules against the coronavirus disease 19 (COVID-19) by means of network pharmacology, and then to verify its anti-coronavirus effect through in vitro models.

Optimized cell systems for the investigation of hepatitis C virus E1E2 glycoproteins.

Great strides have been made in understanding and treating hepatitis C virus (HCV) thanks to the development of various experimental systems including cell-culture-proficient HCV, the HCV pseudoparticle system and soluble envelope glycoproteins. The HCV pseudoparticle (HCVpp) system is a platform used extensively in studies of cell entry, screening of novel entry inhibitors, assessing the phenotypes of clinically observed E1 and E2 glycoproteins and, most pertinently, in characterizing neutralizing antibody breadth induced upon vaccination and natural infection in patients. Nonetheless, some patient-derived clones produce pseudoparticles that are either non-infectious or exhibit infectivity too low for meaningful phenotyping. The mechanisms governing whether any particular clone produces infectious pseudoparticles are poorly understood. Here we show that endogenous expression of CD81, an HCV receptor and a cognate-binding partner of E2, in producer HEK 293T cells is detrimental to the infectivity of recovered HCVpp for most strains. Many HCVpp clones exhibited increased infectivity or had their infectivity rescued when they were produced in 293T cells CRISPR/Cas9 engineered to ablate CD81 expression (293TCD81KO). Clones made in 293TCD81KO cells were antigenically very similar to their matched counterparts made parental cells and appear to honour the accepted HCV entry pathway. Deletion of CD81 did not appreciably increase the recovered titres of soluble E2 (sE2). However, we did, unexpectedly, find that monomeric sE2 made in 293T cells and Freestyle 293-F (293-F) cells exhibit important differences. We found that 293-F-produced sE2 harbours mostly complex-type glycans whilst 293T-produced sE2 displays a heterogeneous mixture of both complex-type glycans and high-mannose or hybrid-type glycans. Moreover, sE2 produced in 293T cells is antigenically superior; exhibiting increased binding to conformational antibodies and the large extracellular loop of CD81. In summary, this work describes an optimal cell line for the production of HCVpp and reveals that sE2 made in 293T and 293-F cells are not antigenic equals. Our findings have implications for functional studies of E1E2 and the production of candidate immunogens.