SARS-CoV-2 AY.4.2 variant circulating in Italy: Genomic preliminary insight.

The appearance of emerging variants of SARS-CoV-2 carrying mutations into the spike protein has recently raised concern with respect to tracking their transmission and mitigating the impact in the evolving pandemic across countries. AY.4.2, a recently detected Delta variant sublineage, is considered a new variant under investigation (VUI) as it carries specific genetic signatures present in the spike protein, called Y145H and A222V. Here, using genomic epidemiology, we provide the first preliminary insight regarding the circulation of this emerging VUI in Italy.

Epstein-Barr virus, Cytomegalovirus, and Herpes Simplex-1/2 reactivations in critically ill patients with COVID-19.

OBJECTIVES: To assess the incidences of Herpes Simplex-1 and 2 (HSV-1, HSV-2), Cytomegalovirus (CMV), Epstein-Barr Virus (EBV) reactivations in critically ill COVID-19 patients. To determine the association between viral reactivation and in-hospital mortality, Intensive Care Unit Bloodstream infection (ICU-BSI), ventilator-associated pneumonia (VAP). DESIGN: Observational retrospective cohort study. SETTING: COVID-19 Intensive Care Unit. PATIENTS: From November 2020 to May 2021, one hundred and twenty patients with COVID-19 severe pneumonia were enrolled and tested for HSV-1, HSV-2, CMV and EBV at the admission in ICU and weekly until discharge or death. The presence of VAP and ICU-BSI was evaluated according to clinical judgement and specific diagnostic criteria. MEASUREMENTS AND MAIN RESULTS: One hundred and twenty patients were enrolled. Multiple reactivations occurred in 75/120 (63%) patients, single reactivation in 27/120 patients (23%). The most reactivated Herpesvirus was EBV, found in 78/120 (65%) patients. The multivariate analysis demonstrated that viral reactivation is a strong independent risk factor for in-hospital mortality (OR = 2.46, 95% CI 1.02-5.89), ICU-BSI (OR = 2.37, 95% CI 1.06-5.29) and VAP (OR = 2.64, 95% CI 1.20-5.82). CONCLUSIONS: Human Herpesviruses reactivations in critically ill patients with COVID-19 severe Pneumonia are associated with mortality and with a higher risk to develop both VAP and ICU-BSI.

Fibroblast Growth Factor 21 in Chronic Hepatitis C: A Potential Non-Invasive Biomarker of Liver Status upon Viral Eradication.

Fibroblast growth factor 21 (FGF-21), previously recognized as a marker of liver damage and a potential drug target in non-alcoholic fatty liver disease (NAFLD), has unclear implications in hepatitis C virus (HCV) infections. This study aimed to investigate the relationship between FGF-21 levels and liver health in patients with HCV undergoing direct-acting antiviral (DAA) treatment. Forty-five patients were assessed for liver stiffness, blood chemistry, and other relevant metrics before and after achieving sustained viral response (SVR), defined as the absence of detectable HCV-RNA after 24 weeks of treatment. Post-treatment, all patients showed a decrease in liver stiffness and improved liver enzyme levels (AST and ALT), alongside an increase in FGF-21 levels. Interestingly, the increase in FGF-21 correlated negatively with liver stiffness but showed no correlation with hepatic steatosis. The observed elevation in FGF-21 levels at SVR following DAA therapy for chronic HCV infection can be attributed to the restoration of hepatic function, including its synthetic capabilities. Specifically, the mitigation of liver fibrosis post-HCV eradication is expected to lead to improvements in liver function, such as enhanced albumin and FGF-21 production. This improvement in synthetic function likely drives the increase in FGF-21 levels, rather than changes in liver fat content. We suggest a potential role of FGF-21 as a marker of fibrosis and hepatic cytotoxicity and as a drug target beyond NAFLD, to be confirmed by additional studies.

SARS-CoV-2 Variants in COVID-19 Disease: A Focus on Disease Severity and Vaccine Immunity in Patients Admitted to the Emergency Department.

Tracking SARS-CoV-2 variants along with vaccinations are fundamental for severe COVID-19 disease prevention. A study was performed that focused on 43 patients with the SARS-CoV-2 infection who were admitted to the Emergency Department. RT-PCR-positive nasopharyngeal samples were sequenced using the MiSeq II system for variant detection. The main reason for Emergency Department admission was COVID-19 (67%), followed by other causes (33%); 51% patients were unvaccinated or vaccinated with a single dose and 49% had completed the vaccination course with two or three doses. Among the vaccinated group, 38% were admitted for COVID-19, versus 94.5% of the unvaccinated group. After admission, 50% of the vaccinated group and 36% of the unvaccinated group were discharged and allowed to go home, and 80% of the unvaccinated had no major comorbidities; 63% needed hospital admission and 5% required a stay in the Intensive Care Unit. Of these, 37% were vaccinated with 3 doses, 11% with two doses, 4% with a single dose, and 48% were unvaccinated. The 70% of the vaccinated patients who were admitted to hospital presented major comorbidities versus 38% of the unvaccinated group. Two unvaccinated patients that needed intensive care had relevant comorbidities and died. Genome sequencing showed the circulation of three omicron and two pure sub-lineages of omicron, including 22 BA.1, 12 BA.1.1, and 7 BA.2. Data showed the SARS-CoV-2 national and international migration patterns and how vaccination was useful for severe COVID-19 disease prevention.

Genomic Epidemiology Unveil the Omicron Transmission Dynamics in Rome, Italy.

Since 2020, the COVID-19 pandemic represented an important worldwide burden. Well-structured surveillance by reliable and timely genomic data collection is crucial. In this study, a genomic monitoring analysis of all SARS-CoV-2 positive samples retrieved at the Fondazione Policlinico Universitario Campus Bio-Medico, in Rome, Italy, between December 2021 and June 2022, was performed. Two hundred and seventy-four SARS-CoV-2-positive samples were submitted to viral genomic sequencing by Illumina MiSeqII. Consensus sequences were generated by de novo assembling using the iVar tool and deposited on the GISAID database. Lineage assignment was performed using the Pangolin lineage classification. Sequences were aligned using ViralMSA and maximum-likelihood phylogenetic analysis was performed by IQ-TREE2. TreeTime tool was used to obtain dated trees. Our genomic monitoring revealed that starting from December 2021, all Omicron sub-lineages (BA.1, BA.2, BA.3, BA.4, and BA.5) were circulating, although BA.1 was still the one with the highest prevalence thought time in this early period. Phylogeny revealed that Omicron isolates were scattered throughout the trees, suggesting multiple independent viral introductions following national and international human mobility. This data represents a sort of thermometer of what happened from July 2021 to June 2022 in Italy. Genomic monitoring of the circulating variants should be encouraged considering that SARS-CoV-2 variants or sub-variants emerged stochastically and unexpectedly.