Natural History and Management of Hepatitis C in Children: 25 Years Experience of a Reference Center in Northern Italy.

Hepatitis C virus (HCV) infection natural history and management in the pediatric population are still debated. We retrospectively evaluated the outcome of a HCV pediatric population managed at the Pediatric Infectious Disease Unit of Luigi Sacco Hospital (Milan, Italy) from January 1997 to January 2022 (median follow-up 10 years) and we focused on the role of new drugs and transient elastography. Fifty-seven patients were enrolled: 8 (14%) had a spontaneous clearance, 33 were treated (58%), 7 (12%) were not treated because they were under 12 years old and 9 were lost at follow-up. HCV RNA was undetectable in all treated patients at the end of therapy, after 12 weeks (SVR12) and for the rest of their follow-up. All patients treated underwent elastography before and 1 year after therapy. Median stiffness pretherapy was 5.6 kPa, and 9 patients (16%) had abnormal transient elastography (>7 kPa, median 8.7 kPa). Median stiffness after treatment in the abnormal group was 6.8 kPa. Direct-acting antiviral agents are a safe and effective therapy for HCV chronic infection in the pediatric population. Liver elastography is normal in many vertically infected children before 12 years, but, when abnormal, it shows a significant improvement after direct-acting antiviral agent treatment. Further studies are needed to evaluate the role of elastography at diagnosis and follow-up in children.

Humoral and cell-mediated immune responses in HIV-vertically infected young patients after three doses of the BNT162b2 mRNA SARS-CoV-2 vaccine.

Background: Data on the efficacy of three SARS-CoV-2 mRNA BNT162b2 vaccine doses and the role of previous SARS-CoV-2-infection in enhancing vaccine immunogenicity in HIV-vertically-infected people living with HIV (PLWH) are limited, as is the duration of vaccine-induced responses. Methods: SARS-CoV-2 plasma neutralizing activity (NA) against the European (B.1), Delta (B.1.617.2) and Omicron (B.1.1.529) variants and cell-mediated immunity (CMI) were analyzed in 29 ART-treated young PLWH (mean age 27.9 years) and 30 healthy controls (HC) who received three BNT162b2 vaccine doses. Individuals were stratified based on the presence/absence of previous SARS-CoV-2 infection (infected and vaccinated -SIV-; uninfected and vaccinated -SV-). Analyses were performed before vaccination (T0), 25 days from the second dose (T1), the day the third dose was administered (T2), and 3 months after the third dose (T3). Results: In PLWH: i) NA against all variants was higher in SIV compared to SV at T2 and was increased at T3; ii) switched-memory plasmablasts were augmented in SIV alone at T2 and T3; iii) a SARS-CoV-2 specific T cell memory was generated; iv) IFN-γ-secreting CD4+ and CD8+ T lymphocytes were boosted at T3 mainly in SV. CMI magnitude was reduced in PLWH compared to HC. Notably, after the third dose of vaccine viremia was unmodified, but CD4 T cell counts were reduced>20% in 3/29 PHLW. Conclusion: A third dose of BNT162b2 vaccine induces strong humoral and CMI responses in young ART-treated PLWH independently from a previous SARS-CoV-2 natural infection. The lower magnitude of CMI responses should be considered when planning mRNA vaccine booster doses in PLWH.

Congenital CMV, Lights and Shadows on Its Management: The Experience of a Reference Center in Northern Italy.

Congenital cytomegalovirus infection (cCMV) is the most common congenital viral infection, with a consistent rate of morbidity, mortality, and long-term sequelae, especially in the case of late diagnosis. Nevertheless, a universal screening for CMV is not currently recommended, and global awareness about this infection, as well as accurate and shared indications on follow-up and treatment, are still lacking. We reviewed data about 59 suspect cCMV cases who referred to our center from 2014 to 2021. We report 41 cases of confirmed cCMV diagnosed at birth, with clinical or radiological abnormalities in 36.6% of them. Other five patients received a late diagnosis and all presented neurological impairment. Twelve patients received therapy with Valganciclovir within the first month of life, with favorable outcome in nine cases. Therapy after the first month of life was attempted in four patients, with improvement in one case. The overall awareness about cCMV infection was 32.6%. Considering our population, maternal serological screening followed by targeted testing of neonates could be an effective strategy. Some aspects of cCMV infection management should be further investigated, such as indication of treatment after the first month of life or in asymptomatic patients. Awareness about the infection should be improved to implement preventive strategies.

Immunological Characterization of HIV and SARS-CoV-2 Coinfected Young Individuals.

While the risk of SARS-CoV-2 infection and/or COVID-19 disease progression in the general population has been largely assessed, its impact on HIV-positive individuals remains unclear. We present clinical and immunological data collected in a cohort of HIV-infected young individuals during the first wave of COVID-19 pandemic. SARS-CoV-2 RNA, virus-specific antibodies, as well as the expression of factors involved in the anti-viral immune response were analyzed. Moreover, we set up an in vitro coinfection assay to study the mechanisms correlated to the coinfection process. Our results did not show any increased risk of severe COVID-19 in HIV-positive young individuals. In those subjects who contracted SARS-CoV-2 infection, an increase in IL-10 expression and production was observed. Furthermore, in the in vitro coinfection assay, we revealed a reduction in SARS-CoV-2 replication associated to an upregulation of IL-10. We speculate that IL-10 could play a crucial role in the course of SARS-CoV-2 infection in HIV-positive individuals. These results might help defining clinical management of HIV/SARS-CoV-2 co-infected young individuals, or putative indications for vaccination schedules in this population.

Defining the clinical phenotype of COVID-19 in children.

On January 7, 2020, a novel coronavirus (SARS-CoV-2) was identified as the causative agent of a cluster of pneumonia of unknown origin detected in Wuhan City by Chinese authorities. Since SARS-CoV-2 discovery, the corresponding disease (COVID-19) has rapidly expanded throughout the globe, making as a consequence the World Health Organization (WHO) declaring a pandemic. As of May 19, 2020, over 4.806.299 cases of COVID-19 had been confirmed worldwide, with more than 318.599 deaths.