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To reinforce the proposed association between viral findings on nasopharyngeal swab and AM, none of the patients with acute cardiac disorders other than AM tested positive for a virus. Acute myocarditis (AM) is an acute-onset inflammatory heart disease with heterogeneous clinical presentation, varying from chest pain to cardiogenic shock.1 Viral infections are believed to be associated with AM and indeed typical prodromic symptoms/signs (i.e. fever, flu-like symptoms, sore throat) are frequently reported in AM patients.1,2 Respiratory viruses, such as influenza and corona viruses, identified by real-time polymerase chain reaction (RT-PCR) from nasopharyngeal swabs, have been increasingly recognized as AM triggers.3,4 Nevertheless, no systematic study ever investigated the presence of respiratory viruses in the upper respiratory airways in AM patients. Coherently with the presence of respiratory viruses in the nasopharyngeal mucosa, patients with positive nasopharyngeal swab had a higher prevalence of prodromal respiratory symptoms/signs compared with patients with negative nasopharyngeal swab (88.9% vs. 36.6%, I P i = 0.008). [Extracted from the article]

In early 2020 the new respiratory syndrome COVID‐19 (caused by the zoonotic SARS‐CoV‐2 virus) spread like a pandemic, starting from Wuhan, China, causing severe economic depression. Despite some advances in drug treatments of medical complications in the later stages of the disease, the pandemic's death toll is tragic, as no vaccine or specific antiviral treatment is currently available. By using a systems approach, we identify the host‐encoded pathway, which provides ribonucleotides to viral RNA synthesis, as a possible target. We show that methotrexate, an FDA‐approved inhibitor of purine biosynthesis, potently inhibits viral RNA replication, viral protein synthesis, and virus release. The effective antiviral methotrexate concentrations are similar to those used for established human therapies using the same drug. Methotrexate should be most effective in patients at the earliest appearance of symptoms to effectively prevent viral replication, diffusion of the infection, and possibly fatal complications. Highlights: The COVID‐19 pandemic caused by the SARS‐CoV‐2 virus is a global public health threat causing over 800000 deaths, millions of infected people, and severe economic depression.No vaccine or specific antiviral treatments are currently available.By inhibiting the host‐encoded pathway, which provides ribonucleotides to viral RNA synthesis, the FDA‐approved drug methotrexate efficiently blocks SARS‐CoV‐2 replication. [ABSTRACT FROM AUTHOR]

Background & aims: We investigated the HCV‐RNA amount, variability and prevalence of resistance‐associated substitutions (RASs), in plasma, hepatic tumoral and non‐tumoral tissue samples in patients undergoing liver‐transplant/hepatic‐resection (LT/HR), because of hepatocellular carcinoma and/or cirrhosis. Methods: Eighteen HCV‐infected patients undergoing LT/HR, 94.0% naïve to direct‐acting antivirals (DAAs), were analysed. HCV‐RNA was quantified in all compartments. NS3/NS5A/NS5B in plasma and/or in tumoral/non‐tumoral tissues were analysed using Sanger and Ultra‐deep pyrosequencing (UDPS, 9/18 patients). RASs prevalence, genetic‐variability and phylogenetic analysis were evaluated. Results: At the time of LT/HR, HCV‐RNA was quantifiable in all compartments of DAA‐naïve patients and was generally lower in tumoral than in non‐tumoral tissues (median [IQR] = 4.0 [1.2‐4.3] vs 4.3[3.1‐4.9] LogIU/µg RNA; P = 0.193). The one patient treated with sofosbuvir + ribavirin represented an exception with HCV‐RNA quantifiable exclusively in the liver, but with higher level in tumoral than in non‐tumoral tissues (51 vs 7 IU/µg RNA). RASs compartmentalization was found by Sanger in 4/18 infected‐patients, and by UDPS in other two patients. HCV‐compartmentalization resulted to be associated with HBcAb‐positivity (P = 0.013). UDPS showed approximately higher genetic‐variability in NS3/NS5A sequences in all compartments. Phylogenetic‐analysis showed defined and intermixed HCV‐clusters among/within all compartments, and were strongly evident in the only non‐cirrhotic patient, with plasma and non‐tumoral sequences generally more closely related. Conclusions: Hepatic compartments showed differences in HCV‐RNA amount, RASs and genetic variability, with a higher segregation within the tumoral compartment. HBV coinfection influenced the HCV compartmentalization. These results highlight HCV‐strain diversifications within the liver, which could explain some of the failures occurring even today in the era of DAAs. [ABSTRACT FROM AUTHOR]

Background & Aims The proportion of HCV-infected patients over age 65 years in Western countries is increasing. This growth and the advent of new antiviral therapy bring into the question the real-world efficacy and safety of the combination of sofosbuvir ( SOF) and simeprevir ( SMV) plus a flat dose of 800 mg/d ribavirin ( RBV) in elderly patients with cirrhosis compared to younger patients. Methods Retrospective observational multicentre real-life investigation study of SOF/ SMV/ RBV for a duration of 12 weeks in HCV genotype 1-infected patients with cirrhosis. Results Of the 270 patients enrolled in this study, with compensated cirrhosis, 133 (49.2%) were ≥65 years of age. Sustained virological response at 12 weeks ( SVR12) was achieved by 94.2% (129/137) of those aged <65 years and 97.7% (130/133) of those ≥65 years. Diabetes was the most common comorbidity in patients ≥65 years compared to younger patients (26.3% vs 12.4% P<.003). The most common adverse event ( AE) in elderly patients was a grade 2 anaemia (35.3% vs 19.9% P<.004). Conclusions Sofosbuvir/simeprevir plus a daily flat dose of RBV 800 mg for 12 weeks was highly effective and safe in genotype 1 elderly patients with compensated cirrhosis. [ABSTRACT FROM AUTHOR]

Currently the prevalence of HIV-1 infection in Cameroon is 5.1%, CRF02_AG subtype is responsible for about 50% of infections. Since an HIV-1 drug resistance test is not yet available widely, accurate data on the prevalence of resistant viral strains are missing. The objective of this study was to determine HIV-1 genetic diversity and to characterize HIV-1 mutations conferring drug resistance among antiretroviral therapy (ART)-naïve and ART-treated patients. A cohort of 239 patients infected with HIV were followed-up between January 2007 and July 2010 in Cameroon. Two hundred and sixteen plasma samples were sequenced for phylogenetic analysis and identification of drug resistance mutations in the HIV-1 pol region. A significant genetic diversity was found: Seven pure subtypes (A1, A3, D, F1, F2, G, H), nine circulating recombinant forms (CRFs: 01_AE, 02_AG, 06cpx, 09cpx, 11cpx, 13cpx, 16cpx, 18cpx, 37cpx) and one new unique recombinant form (URF) (G/F2). The rate of transmitted drug resistance (TDR) in naïve patients was 8.2% (4/49). Around 80% of patients failing a first-line ART harbored a virus with at least one resistance mutation to two antiretroviral (ARV) classes, and 36% of those failing a second-line regimen carried a virus with at least one resistant mutation to three ARV classes. The high level of drug resistance observed in the cohort is alarming because this occurred as a result of only few years of treatment. Adherence to therapy, adequate education of physicians, and the appropriate use of genotypic resistance assay are critical points of intervention for the improvement of patient care. J. Med. Virol. 84:721-727, 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background & Aims: Despite the excellent efficacy of direct-acting antivirals (DAA) reported in clinical trials, virological failures can occur, often associated with the development of resistance-associated substitutions (RASs). This study aimed to characterize the presence of clinically relevant RASs to all classes in real-life DAA failures., Methods: Of the 200 virological failures that were analyzed in 197 DAA-treated patients, 89 with pegylated-interferon+ribavirin (PegIFN+RBV) and 111 without (HCV-1a/1b/1g/2/3/4=58/83/1/6/24/25; 56.8% treatment experienced; 65.5% cirrhotic) were observed. Sanger sequencing of NS3/NS5A/NS5B was performed by home-made protocols, at failure (N=200) and whenever possible at baseline (N=70)., Results: The majority of the virological failures were relapsers (57.0%), 22.5% breakthroughs, 20.5% non-responders. RAS prevalence varied according to IFN/RBV use, DAA class, failure type and HCV genotype/subtype. It was 73.0% in IFN group vs 49.5% in IFN free, with the highest prevalence of NS5A-RASs (96.1%), compared to NS3-RASs (75.9% with IFN, 70.5% without) and NS5B-RASs (66.6% with IFN, 20.4% without, in sofosbuvir failures). In the IFN-free group, RASs were higher in breakthrough/non-responders than in relapsers (90.5% vs 40.0%, P<.001). Interestingly, 57.1% of DAA IFN-free non-responders had a misclassified genotype, and 3/4 sofosbuvir breakthroughs showed the major-RAS-S282T, while RAS-L159F was frequently found in sofosbuvir relapsers (18.2%). Notably, 9.0% of patients showed also extra target RASs, and 47.4% of patients treated with ≥2 DAA classes showed multiclass resistance, including 11/11 NS3+NS5A failures. Furthermore, 20.0% of patients had baseline-RASs, which were always confirmed at failure., Conclusions: In our failure setting, RAS prevalence was remarkably high in all genes, with a partial exception for NS5B, whose limited resistance is still higher than previously reported. This multiclass resistance advocates for HCV resistance testing at failure, in all three genes for the best second-line therapeutic tailoring., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)