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The aim of this study was to evaluate the potential transmission of HCV strains between HIV-positive men who have sex with men (MSM) and HIV-negative MSM. Since 2000, an ongoing epidemic of HCV infections is observed among HIV-positive MSM in high-income countries. However, HCV infections in HIV-negative MSM are investigated to a lesser extent due to the lack of follow-up in this population and only limited information is available on the risk of HCV transmission between HIV-positive MSM and HIV-negative MSM. We enrolled 49 MSM of which 43 were HIV-positive and 6 HIV-negative, including 4 being enrolled or waiting for enrolment in a preexposure prophylaxis (PrEP) program. All patients were diagnosed with acute HCV infection at the Infectious Disease Unit at the Hospices Civils de Lyon from 2014 to 2016. Risk factors for HCV infection were similar in both groups and included IV or nasal drug use, and rough sex practices. Typing and phylogenetic cluster analysis of HCV variants were performed by NS5B sequencing. Several clusters of infections were identified (genotype 1a: 3 clusters and 1 pair; genotype 4d: 1 cluster and 2 pairs), suggesting that several transmission events occurred within the study population. Every HCV strain identified in HIV-negative MSM was included in a cluster with HIV-positive MSM. Chronological analysis of contagiousness suggested the transmission of HCV from HIV-positive to HIV-negative patients. We conclude that recommendations for HCV surveillance should not be confined to HIV-positive MSM but should be extended to HIV-negative MSM with similar risk factors.

Background Sexually transmitted acute hepatitis C virus (HCV) infections (AHIs) have been mainly described in human immunodeficiency virus (HIV)–infected men who have sex with men (MSM). Cases in HIV-negative MSM are scarce. We describe the epidemic of AHI in HIV-infected and HIV-negative MSM in Lyon, France. Methods All cases of AHI diagnosed in MSM in Lyon University Hospital from 2014 to 2017 were included. AHI incidence was determined in HIV-infected and in preexposure prophylaxis (PrEP)–using MSM. Transmission clusters were identified by construction of phylogenetic trees based on HCV NS5B (genotype 1a/4d) or NS5A (genotype 3a) Sanger sequencing. Results From 2014 to 2017, 108 AHIs (80 first infections, 28 reinfections) were reported in 96 MSM (HIV-infected, 72; HIV-negative, 24). AHI incidence rose from 1.1/100 person-years (95 confidence interval [CI], 0.7–1.7) in 2014 to 2.4/100 person-years (95 CI, 1.1–2.6) in 2017 in HIV-infected MSM (P = .05) and from 0.3/100 person-years (95 CI, 0.06–1.0) in 2016 to 3.4/100 person-years (95 CI, 2.0–5.5) in 2017 in PrEP users (P < .001). Eleven clusters were identified. All clusters included HIV-infected MSM; 6 also included HIV-negative MSM. All clusters started with ≥1 HIV-infected MSM. Risk factor distribution varied among clusters. Conclusions AHI incidence increased in both HIV-infected and HIV-negative MSM. Cluster analysis suggests initial transmission from HIV-infected to HIV-negative MSM through chemsex and traumatic sexual practices, leading to mixed patterns of transmission regardless of HIV status and no overlap with the general population.

Since the beginning of the COVID-19 outbreak, SARS-CoV-2 whole-genome sequencing (WGS) has been performed at unprecedented rate worldwide with the use of very diverse Next Generation Sequencing (NGS) methods. Herein, we compare the performance of four NGS-based approaches for SARS-CoV-2 WGS. Twenty four clinical respiratory samples with a large scale of Ct values (from 10.7 to 33.9) were sequenced with four methods. Three used Illumina sequencing: an in-house metagenomic NGS (mNGS) protocol and two newly commercialized kits including a hybridization capture method developed by Illumina (DNA Prep with Enrichment kit and Respiratory Virus Oligo Panel, RVOP) and an amplicon sequencing method developed by Paragon Genomics (CleanPlex SARS-CoV-2 kit). We also evaluated the widely used amplicon sequencing protocol developed by ARTIC Network and combined with Oxford Nanopore Technologies (ONT) sequencing. All four methods yielded near-complete genomes (>99%) for high viral loads samples, with mNGS and RVOP producing the most complete genomes. For mid viral loads, 2/8 and 1/8 genomes were incomplete (<99%) with mNGS and both CleanPlex and RVOP, respectively. For low viral loads (Ct ≥25), amplicon-based enrichment methods were the most sensitive techniques yielding complete genomes for 7/8 samples. All methods were highly concordant in terms of identity in complete consensus sequence. Just one mismatch in two samples was observed in CleanPlex vs the other methods, due to the dedicated bioinformatics pipeline setting a high threshold to call SNP compared to reference sequence. Importantly, all methods correctly identified a newly observed 34-nt deletion in ORF6 but required specific bioinformatic validation for RVOP. Finally, as a major warning for targeted techniques, a default of coverage in any given region of the genome should alert to a potential rearrangement or a SNP in primer annealing or probe-hybridizing regions and would require regular updates of the technique according to SARS-CoV-2 evolution.

ObjectivesType-I interferons (IFNs-I) have potent antiviral effects. IFNs-I are also overproduced in patients with systemic lupus erythematosus (SLE). Autoantibodies (AAbs) neutralising IFN-α, IFN-β and/or IFN-ω subtypes are strong determinants of hypoxemic COVID-19 pneumonia, but their impact on inflammation remains unknown.MethodsWe retrospectively analysed a monocentric longitudinal cohort of 609 patients with SLE. Serum AAbs against IFN-α were quantified by ELISA and functionally assessed by abolishment of Madin-Darby bovine kidney cell protection by IFN-α2 against vesicular stomatitis virus challenge. Serum-neutralising activity against IFN-α2, IFN-β and IFN-ω was also determined with a reporter luciferase activity assay. SARS-CoV-2 antibody responses were measured against wild-type spike antigen, while serum-neutralising activity was assessed against the SARS-CoV-2 historical strain and variants of concerns.ResultsNeutralising and non-neutralising anti-IFN-α antibodies are present at a frequency of 3.3% and 8.4%, respectively, in individuals with SLE. AAbs neutralising IFN-α, unlike non-neutralising AAbs, are associated with reduced IFN-α serum levels and a reduced likelihood to develop active disease. However, they predispose patients to an increased risk of herpes zoster and severe COVID-19 pneumonia. Severe COVID-19 pneumonia in patients with SLE is mostly associated with combined neutralisation of different IFNs-I. Finally, anti-IFN-α AAbs do not interfere with COVID-19 vaccine humoral immunogenicity.ConclusionThe production of non-neutralising and neutralising anti-IFN-I antibodies in SLE is likely to be a consequence of SLE-associated high IFN-I serum levels, with a beneficial effect on disease activity, yet a greater viral risk. This finding reinforces the recommendations for vaccination against SARS-CoV-2 in SLE.

Objective: A new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) emerged in China during late 2019 and resulted in the coronavirus disease 2019 (COVID-19) pandemic which peaked in France in March–April 2020. Immunodeficiency, precariousness and promiscuity could increase the risk of COVID-19 in HIV-infected patients and in preexposure prophylaxis (PrEP) users. No epidemiological data are available in these two populations. We report COVID-19 attack rate in HIV-infected patients and in PrEP users in the Rhône department, France, and compared it with the general population. Design: Retrospective analysis of a laboratory database. Methods: COVID-19 testing strategy in France was centered on symptomatic infections, hospitalized patients and symptomatic healthcare workers while most asymptomatic cases were not confirmed. SARS-CoV-2 positivity rate on PCR assays and COVID-19 attack rate were determined in HIV-infected patients and in PrEP users. COVID-19 attack rate in the general population was estimated from health authorities’ database and demographic data. A corrected attack rate taking into account the laboratory representativeness was calculated. Results: From March to April 2020, 24 860 samples from 19 113 patients (HIV-infected 77, PrEP users 27, others 19 009) were assessed for SARS-CoV-2 PCR assay. The positivity rate appeared similar in HIV-infected patients (15.6%), in PrEP users (14.8%) and in other patients (19.1%). The crude/corrected COVID-19 attack rate appeared similar in HIV-infected patients (0.31/0.38%) and in PrEP users (0.38/0.42%), and of the same order as the estimated attack rate in the general population (0.24%). Conclusion: The risk of symptomatic COVID-19 in France appeared similar in HIV-infected patients and in PrEP users compared with the general population.

Since 2016, an increase in the number of hepatitis A cases affecting mainly men who have sex with men (MSM) has been reported in low endemic countries in Europe. We calculated the attack rate in Lyon, France, in populations considered at high-risk: HIV-infected MSM and HIV-negative MSM receiving HIV pre-exposure prophylaxis (PrEP). In these populations, high level of immunity did not prevent the outbreak, indicating that vaccination should be reinforced, particularly in younger individuals.

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