Efficacy and Durability of Dolutegravir- or Darunavir-Based Regimens in ART-Naïve AIDS- or Late-Presenting HIV-Infected Patients.

BACKGROUND: Since limited data are available, we aimed to compare the efficacy and durability of dolutegravir and darunavir in advanced naïve patients. METHODS: Retrospective multicenter study including AIDS- or late-presenting (def. CD4 ≤ 200/µL) HIV-infected patients starting dolutegravir or ritonavir/cobicistat-boosted darunavir+2NRTIs. Patients were followed from the date of first-line therapy initiation (baseline, BL) to the discontinuation of darunavir or dolutegravir, or for a maximum of 36 months of follow-up. RESULTS: Overall 308 patients (79.2% males, median age 43 years, 40.3% AIDS-presenters, median CD4 66 cells/µL) were enrolled; 181 (58.8%) and 127 (41.2%) were treated with dolutegravir and darunavir, respectively. Incidence of treatment discontinuation (TD), virological failure (VF, defined as a single HIV-RNA > 1000 cp/mL or two consecutive HIV-RNA > 50 cp/mL after 6 months of therapy or after virological suppression had been achieved), treatment failure (the first of TD or VF), and optimal immunological recovery (defined as CD4 ≥ 500/µL + CD4 ≥ 30% + CD4/CD8 ≥ 1) were 21.9, 5.2, 25.6 and 1.4 per 100 person-years of follow-up, respectively, without significant differences between dolutegravir and darunavir (p > 0.05 for all outcomes). However, a higher estimated probability of TD for central nervous system (CNS) toxicity (at 36 months: 11.7% vs. 0%, p = 0.002) was observed for dolutegravir, whereas darunavir showed a higher probability of TD for simplification (at 36 months: 21.3% vs. 5.7%, p = 0.046). CONCLUSIONS: Dolutegravir and darunavir showed similar efficacy in AIDS- and late-presenting patients. A higher risk of TD due to CNS toxicity was observed with dolutegravir, and a higher probability of treatment simplification with darunavir.

Performances of Dried Blood Spots and Point-of-Care Devices to Identify Virological Failure in HIV-Infected Patients: A Systematic Review and Meta-Analysis.

To broaden access to HIV viral load monitoring (VLM), the use of blood samples from dried blood spots (DBS) or point-of-care (POC) devices, could be of great help in settings where plasma is not easily accessible. The variety of assays available makes the choice complex. This systematic review and meta-analysis aims to estimate the sensitivity and specificity of DBS and POC devices to identify patients in virological failure using World Health Organization (WHO) recommendations (viral load ≥1000 copies/mL), compared with plasma, for the assays currently available. Four databases were searched for articles, and two reviewers independently identified articles reporting sensitivity and specificity of DBS and/or POC to identify patients in virological failure. We excluded articles that used other thresholds as well as articles with a total number of participants below 50 to avoid reporting bias. Heterogeneity and factors associated with assays' performances were assessed by I2 statistics and metaregression. The protocol of this review follows the PRISMA guidelines. Out of 941 articles, 47 were included: 32 DBS evaluations and 16 POC evaluations. Overall, when using DBS, the Abbott RT HIV-1, Roche CAP-CTM, NucliSENS BioMerieux and Aptima assays presented sensitivity and specificity exceeding 85%, but reported results were highly heterogeneous. Factors associated with better performances were high volume of blood and the use of the same assay for DBS and plasma VLM. Regarding the POC devices, SAMBA I, SAMBA II, and GeneXpert devices presented high sensitivity and specificity exceeding 90%, with less heterogeneity. DBS is suitable VLM, but performances can vary greatly depending on the protocols, and should be performed in trained centers. POC is suitable for VLM with less risk of heterogeneity but is more intensive in costs and logistics.

Detection of Enteroviruses and SARS-CoV-2 in Tunisian Wastewater.

Monitoring the circulation of enteric viruses in environmental wastewater is a valuable tool for preventing the emergence of waterborne and food-borne diseases in humans. The detection of viruses was performed in five Tunisian wastewater treatment plants, three located in the Grand Tunis City (WWTP 1, WWTP 2, WWTP 3) and two in the Sahel of Tunisia (WWTP 4, WWTP 4), known as very developed and crowded zones, to assess the effectiveness of three biological wastewater treatment procedures namely natural oxidizing lagoons, rotating biodisks procedure, activated sludge procedure, and one tertiary sewage treatment using UV-C254 reactor for this enteric viruses' removal. Thus, 242 sewage samples were collected between June 2019 and May 2020 from different lines of wastewater treatment procedures implemented in the five wastewater treatment plants investigated. SARS-CoV-2 was analyzed using real-time multiplex reverse-transcription polymerase chain reaction (multiplex real-time RT-PCR) and enteroviruses using reverse-transcription polymerase chain reaction (RT-PCR). The enteroviruses detection showed 93% and 73% respective high frequencies only in the two WWTPs of the Grand Tunis (WWTP 1 and WWTP 2). SARS-CoV-2 was detected in 58% of the all wastewater samples collected from the five studied WWTPs with a respective dominance of N gene (47%), S gene (42%), RdRp gene (42%) and at last E gene (20%). These enteroviruses and SARS-CoV-2 detection were revealed in all steps of the wastewater treatment procedures, so poor virological quality is found at the exit of each biological and tertiary step of treatment investigated. For the first time in Tunisia, these results highlighted the enterovirus and SARS-CoV-2 detection with high rates, and the ineffectiveness of the biological and UV-C254 treatment implemented to remove these viruses. The preliminary results of SARS-CoV-2 circulation in Tunisian wastewater confirmed the wide positivity rate underlined by other works worldwide and allowed showing a move towards integrating wastewater as a way for this virus to spread in different areas and environments. So, this last result about SARS-CoV-2 circulation allowed us to caution about the strong probability of diffusion of this hazardous virus through water and sewage; despite its enveloped character and nature, as a labile and sensitive virus in these environments. Thus, establishing a national surveillance strategy is needed to improve the sanitary quality of treated wastewater and prevent public health problems related to these viruses in treated wastewater.

Coronavirus disease 2019 rebounds following nirmatrelvir/ritonavir treatment.

Nirmatrelvir/ritonavir (NMV-r) is an effective anti-SARS-CoV-2 agent and has been recommended in the treatment of nonhospitalized patients with COVID-19. In rare occasions, some patients experience virologic and symptomatic rebound after initial resolution, which we call COVID-19 rebound after NMV-r. Although COVID rebound can also occur after molnupiravir treatment or even no antiviral treatment, we have more serious concern about the rebound after NMV-r, which remains the most effective antiviral. Due to a lack of information about its frequency, mechanism, outcomes, and management, we conducted this review to provide comprehensive and updated information to address these questions. Based on the limited evidence, the incidence of COVID-19 rebound after NMV-r was less than 2%, and most cases developed 5-15 days after initiating NMV-r treatment. Almost all reported cases had mild symptoms, and the clinical condition gradually subsided without additional treatment. Overall, the clinical outcome was favorable, and only a small number of patients required emergency department visits or hospitalization. Regarding virologic rebound, culturable SARS-CoV-2 with possible transmission was observed, so re-isolation may be needed.

Evaluating virological outcomes in people with HIV on stable antiretroviral therapy with reduced frequency of HIV viral load monitoring during the COVID-19 pandemic.

OBJECTIVES: In response to the COVID-19 pandemic, HIV outpatient attendances were restricted from March 2020, resulting in reduced frequency of HIV viral load (VL) monitoring (previously 6-monthly) in clinically stable and virologically suppressed people living with HIV (PLWH). We investigated virological outcomes during this period of reduced monitoring and compared with the previous year, prior to the COVID-19 pandemic. METHODS: People living with HIV with undetectable VL (<200 HIV RNA copies /mL) on antiretroviral therapy (ART) were identified from March 2018 to February 2019. We determined VL outcomes during the pre-COVD-19 period (March 2019-February 2020) and the COVID-19 period (March 2020-February 2021) when monitoring was restricted. Frequency and longest durations between VL tests in each period were evaluated, and virological sequelae in those with detectable VL were determined. RESULTS: Of 2677 PLWH virologically suppressed on ART (March 2018-February 2019), VLs were measured and undetectable in 2571 (96.0%) and 2003 (77.9%) in the pre-COVID and COVID periods, respectively. Mean (SD) numbers of VL tests were 2.3 (1.08) and 1.1 (0.83) and mean longest duration between VL tests was 29.5 weeks (SD 8.25, 3.1% were ≥12 months) and 43.7 weeks (12.64, 28.4% were ≥12 months), in the pre-COVID and COVID periods, respectively. Of 45 individuals with one or more detectable VL during the COVID-19 period, two developed new drug resistance mutations. CONCLUSION: Reduced VL monitoring was not associated with poorer virological outcomes in the majority of stable individuals receiving ART. One in 20 individuals had not returned for VL testing after ≥31 months and the risk of harm in these individuals is unknown.

Viral load decrease in SARS-CoV-2 BA.1 and BA.2 Omicron sublineages infection after treatment with monoclonal antibodies and direct antiviral agents.

The efficacy on the Omicron variant of the approved early coronavirus disease-2019 (COVID-19) therapies, especially monoclonal antibodies, has been challenged by in vitro neutralization data, while data on in vivo antiviral activity are lacking. We assessed potential decrease from Day 1 to Day 7 viral load (VL) in nasopharyngeal swabs of outpatients receiving Sotrovimab, Molnupiravir, Remdesivir, or Nirmatrelvir/ritonavir for mild-to-moderate COVID-19 due to sublineages BA.1 or BA.2, and average treatment effect by weighted marginal linear regression models. A total of 521 patients (378 BA.1 [73%], 143 [27%] BA.2) received treatments (Sotrovimab 202, Molnupiravir 117, Nirmatrelvir/ritonavir 84, and Remdesivir 118): median age 66 years, 90% vaccinated, median time from symptoms onset 3 days. Day 1 mean VL was 4.12 log2 (4.16 for BA.1 and 4.01 for BA.2). The adjusted analysis showed that Nirmatrelvir/ritonavir significantly reduced VL compared to all the other drugs, except versus Molnupiravir in BA.2. Molnupiravir was superior to Remdesivir in both BA.1 and BA.2, and to Sotrovimab in BA.2. Sotrovimab had better activity than Remdesivir only against BA.1. Nirmatrelvir/ritonavir showed the greatest antiviral activity against Omicron variant, comparable to Molnupiravir only in the BA.2 subgroup. VL decrease could be a valuable surrogate of drug activity in the context of the high prevalence of vaccinated people and low probability of hospital admission.

Assessment of clinical and virological outcomes of rural and urban populations: COVID-19.

Objective: To assess the clinical and virological status in urban and rural populations. Methods: A cross-sectional study was conducted in a tertiary care hospital, Postgraduate Institute of Medical Sciences, Rohtak for a period of six months. Upper respiratory tract (URT) specimens including nasopharyngeal and oropharyngeal swabs were collected from the patients and their contacts and processed by RT-PCR technique for COVID-19 detection. Further, clinical and virological response in both the population were assessed and compared. Results: A total of 37,724 URT samples were tested, out of which 20,144 (53%) samples were from the rural population and 17,580 (47%) from the urban population. Out of the total samples from urban and rural population, COVID-19 positivity was 13.9% in urban population and 6.2% in rural population. Around 86% patients or contacts were asymptomatic in both the rural and urban population and rests were symptomatic 14%. Among the symptomatic patients, sore throat was seen as the most common presenting symptom (95-100%) followed by fever (80-83%), dry cough (55-61%), nasal discharge (18-23%), and breathlessness (3-5%) in both the rural and urban population. Conclusion: Our outcomes provide novel facts that the COVID-19 epidemic severely affected both rural and urban populations but with few differences. In our study, positivity rate in case of urban population was 13.9% as compared to 6.2% in rural population. There are two foremost facets that contributed variation in positivity in both the population. First, better immune response in rural population as compared to urban population which can be due to the fact that rural people in India are more exposed to various pathogens during their early lifetime thus, improving their immune status. Second, factor could be elevated population densities in urban areas which can contribute to increased infectiousness thus higher positivity rate. In addition, people living in urban population have to commute more for their work and are exposed to more people throughout the day thus, having more possibility to get infection of COVID-19 as compared to the rural population. To the best of our knowledge, there are no studies conducted on COVID-19, among rural population of Haryana. Hence, this study will allow us to fill the gap in knowledge about the variation in contagion spread and immune response in both rural and urban populations.

Clinical outcomes, virological efficacy and safety of nitazoxanide in the treatment of patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: This study investigated the clinical outcomes, virological efficacy and safety of nitazoxanide in the treatment of patients with COVID-19. RESEARCH DESIGN AND METHODS: The PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases were searched for relevant articles written before August 23, 2022. Only randomized controlled trials (RCTs) that assessed the usefulness and safety of nitazoxanide in patients with COVID-19 were included. RESULTS: Five RCTs were included. The overall mortality of COVID-19 patients receiving nitazoxanide (study group) was 1.3% (9/670), which was lower than the control group (1.8%, 12/681), but this difference did not reach statistical significance (risk difference [RD], 0.00; 95% CI: -0.01 to 0.01; P =0.97). However, nitazoxanide was associated with a higher virological eradication rate than placebo or standard care (RD, 0.09; 95% CI: 0.01 to 0.17; P = 0.03). Compared with the placebo or standard care, nitazoxanide were associated with a similar risk of any adverse event (RD, -0.02; 95% CI: -0.07 to 0.03; P = 0.44). CONCLUSIONS: Although nitazoxanide can help virological eradication and is also tolerable, it does not provide additional clinical benefits. Based on these evidences, the use of nitazoxanide in the treatment of patients with COVID-19 is not recommended.

Feasibility of At-Home Virological and Serological Testing for SARS-CoV-2 in Children.

Longitudinal virological and serological surveillance is essential for understanding severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) transmission among children but requires increased test capacity. We assessed the uptake of serial at-home testing in children (2-17 years) via mailed SARS-CoV-2 antibody and molecular tests. Completion rates demonstrated the feasibility and sustainability of at-home testing across age groups.

Epidemiological and virological surveillance of influenza viruses in China during 2020-2021.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, seasonal influenza activity declined globally and remained below previous seasonal levels, but intensified in China since 2021. Preventive measures to COVID-19 accompanied by different epidemic characteristics of influenza in different regions of the world. To better respond to influenza outbreaks under the COVID-19 pandemic, we analyzed the epidemiology, antigenic and genetic characteristics, and antiviral susceptibility of influenza viruses in the mainland of China during 2020-2021. METHODS: Respiratory specimens from influenza like illness cases were collected by sentinel hospitals and sent to network laboratories in Chinese National Influenza Surveillance Network. Antigenic mutation analysis of influenza virus isolates was performed by hemagglutination inhibition assay. Next-generation sequencing was used for genetic analyses. We also conducted molecular characterization and phylogenetic analysis of circulating influenza viruses. Viruses were tested for resistance to antiviral medications using phenotypic and/or sequence-based methods. RESULTS: In the mainland of China, influenza activity recovered in 2021 compared with that in 2020 and intensified during the traditional influenza winter season, but it did not exceed the peak in previous years. Almost all viruses isolated during the study period were of the B/Victoria lineage and were characterized by genetic diversity, with the subgroup 1A.3a.2 viruses currently predominated. 37.8% viruses tested were antigenically similar to reference viruses representing the components of the vaccine for the 2020-2021 and 2021-2022 Northern Hemisphere influenza seasons. In addition, China has a unique subgroup of 1A.3a.1 viruses. All viruses tested were sensitive to neuraminidase inhibitors and endonuclease inhibitors, except two B/Victoria lineage viruses identified to have reduced sensitivity to neuraminidase inhibitors. CONCLUSIONS: Influenza activity increased in the mainland of China in 2021, and caused flu season in the winter of 2021-2022. Although the diversity of influenza (sub)type decreases, B/Victoria lineage viruses show increased genetic and antigenic diversity. The world needs to be fully prepared for the co-epidemic of influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus globally.

Current Trend of Virology in the Post COVID-19 Era with Related Topic-Based Tweet Analysis

In light of current trends in virology, we performed social media analysis of 13 main topics in the area of virology and ranked these topics with metrics such as users, posts, engagement, and influence. These metrics were monitored against the 13 keywords on Twitter for the same period (i.e., from 27 November to 6 December 2021) for benchmarking purposes. The 13 main topics were "virological Science", " preventive vaccines", "therapeutic vaccines", "viral pathogenesis", "viral immunology", "antiviral strategies", "virus structure", "virus expression", "viral resistance", "emerging viruses", "interspecies transmission", "viruses and cancer" and " viral diseases". "viral diseases" recorded the highest number of users (i.e., 905 users) and the highest number of post (i.e., about 1K posts). The second-highest number of posts were monitored to be on "therapeutic vaccines" with 729 posts from 691 users. In terms of engagement, "viral diseases" (3.4 K) were found to be on the top followed by "viruses and cancer" (3.1K). Lastly, in terms of influence, "viral diseases" recorded 9.0 million influences followed by 6.6 million influences on "emerging viruses". In summary, "viral diseases" was found to be the most engaging and influential topic highest with the highest number of posts from most of the tweet users. In relation to trending hashtags in virology, #COVID19 recorded the highest number of hashtags, followed by # omicron, #sarscov2, #publichealth, #omicronvarient, #wuhan, #originofcovid, #fauci and #epidemiology. Word clouds showing the main area of discussion were also generated for these 13 main topics.

Real-world effectiveness of sofosbuvir/velpatasvir for the treatment of hepatitis C virus in prison settings

Plain language summary Achievement of elimination of HCV as a major public health threat requires focus on vulnerable populations such as people in prison. The prison population is at high risk of HCV infection but their treatment is complicated by social issues such as mental health disorders and drug use. Simple and effective treatment regimens are required to increase access to treatment and improve cure rates. This real-world analysis across Europe and Canada analyzed data from 20 prison populations. HCV-infected individuals were treated with sofosbuvir/velpatasvir, a once daily treatment which requires minimal monitoring. This regimen achieved high cure rates in the prison population despite the existence of complicating social issues. Background: People in prison are at high risk of hepatitis C virus (HCV) infection and often have a history of injection drug use and mental health disorders. Simple test-and-treat regimens which require minimal monitoring are critical. Methods: This integrated real-world analysis evaluated the effectiveness of once daily sofosbuvir/velpatasvir (SOF/VEL) in 20 prison cohorts across Europe and Canada. The primary outcome was sustained virological response (SVR) in the effectiveness population (EP), defined as patients with a valid SVR status. Secondary outcomes were reasons for not achieving SVR, adherence and time between HCV RNA diagnosis and SOF/VEL treatment. Results: Overall, 526 people in prison were included with 98.9% SVR achieved in the EP (n = 442). Cure rates were not compromised by drug use or existence of mental health disorders. Conclusion: SOF/VEL for 12 weeks is highly successful in prison settings and enables the implementation of a simple treatment algorithm in line with guideline recommendations and test-and-treat strategies.

The RIO trial: rationale, design, and the role of community involvement in a randomised placebo-controlled trial of antiretroviral therapy plus dual long-acting HIV-specific broadly neutralising antibodies (bNAbs) in participants diagnosed with recent HIV infection-study protocol for a two-stage randomised phase II trial.

BACKGROUND: Antiretroviral therapy (ART) has led to dramatic improvements in survival for people living with HIV, but is unable to cure infection, or induce viral control off therapy. Designing intervention trials with novel agents with the potential to confer a period of HIV remission without ART remains a key scientific and community goal. We detail the rationale, design, and outcomes of a randomised, placebo-controlled trial of two HIV-specific long-acting broadly neutralising antibodies (bNAbs): 3BNC117-LS and 10-1074-LS, which target CD4 binding site and V3 loop respectively, on post-treatment viral control. METHODS: RIO is a randomised, placebo-controlled, double-blinded prospective phase II study. Eligible individuals will have started ART within 3 months of primary HIV infection and have viral sequences that appear to be sensitive to both bNAbs. It will randomise 72 eligible participants 1:1 to the following arms via a two-stage design. In Stage 1, arm A participants are given dual long-acting (LS-variants) bNAbs infusions, followed by intensively monitored Analytical Treatment Interruption (ATI) (n = 36); in arm B, participants receive placebo infusions followed by ATI. The primary endpoint will be time to viral rebound within 36 weeks after ATI. Upon viral rebound, the participant and researcher are unblinded. Participants in arm A recommence ART and complete the study. Participants in arm B are invited to restart ART and enroll into Stage 2 where they will receive open-label LS bNAbs, followed by a second ATI 24 weeks after. Secondary and exploratory endpoints include adverse events, time to undetectable viraemia after restarting ART, immunological markers, HIV proviral DNA, serum bNAb concentrations in blood, bNAb resistance at viral rebound, and quality of life measures. DISCUSSION: The two-stage design was determined in collaboration with community involvement. This design allows all participants the option to receive bNAbs. It also tests the hypothesis that bNAbs may drive sustained HIV control beyond the duration of detectable bNAb concentrations. Community representatives were involved at all stages. This included the two-stage design, discussion on the criteria to restart ART, frequency of monitoring visits off ART, and reducing the risk of onward transmission to HIV-negative partners. It also included responding to the challenges of COVID-19. TRIAL REGISTRATION: The protocol is registered on Clinical. TRIALS: gov and EudraCT and has approval from UK Ethics and MHRA.

Preclinical Validation of a Novel Injection-Molded Swab for the Molecular Assay Detection of SARS-CoV-2.

During the COVID-19 public health emergency, many actions have been undertaken to help ensure that patients and health care providers have timely and continued access to high-quality medical devices to respond effectively. The development and validation of new testing supplies and equipment, including collection swabs, has helped to expand the availability and capability for various diagnostic, therapeutic, and protective medical devices in high demand during the COVID-19 emergency. Here, we report the initial validation of a new injection-molded anterior nasal swab, ClearTip™, that was experimentally validated in a laboratory setting as well as in independent clinical studies in comparison to gold standard flocked swabs. We have also developed an in vitro anterior nasal tissue model which offers a novel, efficient, and clinically relevant validation tool to replicate the clinical swabbing workflow with high fidelity, while being accessible, safe, reproducible, and time- and cost-effective. ClearTip™ displayed greater inactivated virus release in the benchtop model, confirmed by its greater ability to report positive samples in a small clinical study in comparison to flocked swabs. We also quantified the detection of biological materials, as a proxy for viral material, in multi-center pre-clinical and clinical studies which showed a statistically significant difference in one study and a reduction in performance in comparison to flocked swabs. Taken together, these results emphasize the compelling benefits of non-absorbent injection-molded anterior nasal swabs for COVID-19 detection, comparable to standard flocked swabs. Injection-molded swabs, as ClearTip™, could have the potential to support future swab shortages, due to its manufacturing advantages, while offering benefits in comparison to highly absorbent swabs in terms of comfort, limited volume collection, and potential multiple usage.

How a virus changes language-Observations in Russian

The COVID-19 pandemic has challenged people's thinking worldwide. Russia, too, has seen experts writing reports on the causes and consequences of the pandemic and citizens commenting on the restrictions on their lives, which they accepted or rejected. None of this would have been possible, if words had not been adopted, borrowed, modified, revisited, fitted into grammatical structures, or varied in their meanings. This article provides a first overview of such changes in Russian. © 2021 Walter de Gruyter GmbH, Berlin/Boston.

Surveillance for Severe Acute Respiratory Infections among Hospitalized Subjects from 2015/2016 to 2019/2020 Seasons in Tuscany, Italy.

In Italy, the influenza season lasts from October until April of the following year. Influenza A and B viruses are the two viral types that cocirculate during seasonal epidemics and are the main causes of respiratory infections. We analyzed influenza A and B viruses in samples from hospitalized patients at Le Scotte University Hospital in Siena (Central Italy). From 2015 to 2020, 182 patients with Severe Acute Respiratory Infections were enrolled. Oropharyngeal swabs were collected from patients and tested by means of reverse transcriptase-polymerase chain reaction to identify influenza A(H3N2), A(H1N1)pdm09 and B. Epidemiological and virological surveillance remain an essential tool for monitoring circulating viruses and possible mismatches with seasonal vaccine strains, and provide information that can be used to improve the composition of influenza vaccines.

An experience using historical hepatitis C data to Re-Engage: Possibilities and pitfalls during the COVID-19 pandemic.

OBJECTIVES: Public Health England (PHE) aims meet the WHO target to eliminate hepatitis C as a public health concern by 2030. One aspect of this strategy is to use historical surveillance data of anti-HCV positive patients identified by PHE to re-engage with offers of PCR testing and treatment if RNA-positive. Operational Delivery Networks (ODN), who deliver Hepatitis C treatment across 22 regions in England, are responsible for enacting this initiative. This study aims to evaluate the effectiveness of using this data with regional PCR results to re-engage HCV-infected persons in the West Midlands region of England. STUDY DESIGN: A longitudinal prospective study using historical surveillance data. METHODS: A dataset of historical anti-HCV positive antibody patients provided to the ODN by PHE was cross-referenced with HCV RNA data from 01/01/1996 to 01/01/2019 from five laboratories across the West Midlands. Letters were sent to the general practitioner and to the patients who were HCV RNA positive to invite them for repeat testing and treatment to achieve cure. RESULTS: From a dataset of 4540 anti-HCV antibody results, 31.7% (n=1440) had a PCR result: 48.1% (n=693) were PCR positive for HCV RNA. 693 letters were sent to GPs with responses from 14.2% (n=99). By May 2021, only 212 patient letters were sent (due to significant interruption by the COVID-19 pandemic) and 11.3% (n=24) replied, 17 presented for PCR testing and 4 were found to be viraemic. To date, one patient has achieved cure and three have completed treatment awaiting confirmation of cure. CONCLUSION: The use of historical anti-HCV antibody results can be used to successfully re-engage people into testing and treatment for hepatitis C, albeit with modest gains.

Immunological Assessment of Pediatric Multisystem Inflammatory Syndrome Related to Coronavirus Disease 2019.

BACKGROUND: Recently, cases of multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) have been reported worldwide. Negative polymerase chain reaction (RT-PCR) testing associated with positive serology in most of the cases suggests a postinfectious syndrome. Because the pathophysiology of this syndrome is still poorly understood, extensive virological and immunological investigations are needed. METHODS: We report a series of 4 pediatric patients admitted to Geneva University Hospitals with persistent fever and laboratory evidence of inflammation meeting the published definition of MIS-C related to COVID-19, to whom an extensive virological and immunological workup was performed. RESULTS: RT-PCRs on multiple anatomical compartments were negative, whereas anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin A (IgA) and immunoglobulin G (IgG) were strongly positive by enzyme-linked immunosorbent assay and immunofluorescence. Both pseudoneutralization and full virus neutralization assays showed the presence of neutralizing antibodies in all children, confirming a recent infection with SARS-CoV-2. The analyses of cytokine profiles revealed an elevation in all cytokines, as reported in adults with severe COVID-19. Although differing in clinical presentation, some features of MIS-C show phenotypic overlap with hemophagocytic lymphohistiocytosis (HLH). In contrast to patients with primary HLH, our patients showed normal perforin expression and natural killer (NK) cell degranulation. The levels of soluble interleukin (IL)-2 receptor (sIL-2R) correlated with the severity of disease, reflecting recent T-cell activation. CONCLUSION: Our findings suggest that MIS-C related to COVID-19 is caused by a postinfectious inflammatory syndrome associated with an elevation in all cytokines, and markers of recent T-cell activation (sIL-2R) occurring despite a strong and specific humoral response to SARS-CoV-2. Further functional and genetic analyses are essential to better understand the mechanisms of host-pathogen interactions.

Efficacy of chloroquine and hydroxychloroquine in treating COVID-19 infection: A meta-review of systematic reviews and an updated meta-analysis.

OBJECTIVE: To synthesize findings from systematic reviews and meta-analyses on the efficacy and safety of chloroquine (CQ) and hydroxychloroquine (HCQ) with or without Azithromycin for treating COVID-19, and to update the evidence using a meta-analysis. METHODS: A comprehensive search was carried out in electronic databases for systematic reviews, meta-analyses and experimental studies which investigated the efficacy and safety of CQ, HCQ with or without Azithromycin to treat COVID-19. Findings from the reviews were synthesised using tables and forest plots and the quality effect model was used for the updated meta-analysis. The main outcomes were mortality, the need for intensive care services, disease exacerbation, viral clearance and occurrence of adverse events. RESULTS: Thirteen reviews with 40 primary studies were included. Two meta-analyses reported a high risk of mortality, with ORs of 2.2 and 3.0, and the two others found no association between HCQ and mortality. Findings from two meta-analyses showed that HCQ with Azithromycin increased the risk of mortality, with similar ORs of 2.5. The updated meta-analysis of experimental studies showed that the drugs were not effective in reducing mortality (RR 1.1, 95%CI 1.0-1.3, I2 = 0.0%), need for intensive care services (OR 1.1, 95%CI 0.9-1.4, I2 = 0.0%), virological cure (OR 1.5, 95%CI 0.5-4.4, I2 = 39.6%) or disease exacerbation (OR 1.2, 95%CI 0.3-5.9, I2 = 31.9%) but increased the odds of adverse events (OR 12,3, 95%CI 2.5-59.9, I2 = 76.6%). CONCLUSION: There is conclusive evidence that CQ and HCQ, with or without Azithromycin are not effective in treating COVID-19 or its exacerbation. REGISTRATION: PROSPERO: CRD42020191353.