MBL2 Genetic Variants in HCV Infection Susceptibility, Spontaneous Viral Clearance and Pegylated Interferon Plus Ribavirin Treatment Response.

Hepatitis C is disease that damages the liver, and it is caused by the hepatitis C virus (HCV). The pathology became chronic in about 80% of the cases due to virus persistence in the host organism. The standard of care consists of pegylated interferon plus ribavirin; however, the treatment response is very variable and different host/viral factors may concur in the disease outcome. The mannose-binding protein C (MBL) is a component of the innate immune system, able to recognize HCV and consecutively activating the immune response. MBL is encoded by MBL2 gene, and polymorphisms, two in the promoter region (H/L and X/Y) and three in exon 1 (at codon 52, 54 and 57), have been described as functionally influencing protein expression. In this work, 203 Italian HCV patients and 61 healthy controls were enrolled and genotyped for the five MBL2 polymorphisms mentioned above to investigate their role in HCV infection susceptibility, spontaneous viral clearance and treatment response. MBL2 polymorphisms were not associated with HCV infection susceptibility and with spontaneous viral clearance, while MBL2 O allele, O/O genotype, HYO haplotype and DP combined genotype (all correlated with low or deficient MBL expression) were associated with sustained virological response. Moreover, a meta-analysis to assess the role of MBL2 polymorphisms in HCV infection susceptibility was also performed: YA haplotype could be associated with protection towards HCV infection.

Herpesvirus reactivation during severe COVID-19 and high rate of immune defect.

OBJECTIVE: We assessed herpesvirus reactivation in severe SARS-CoV-2 infection. METHODS: Retrospective study including consecutive patients admitted to an onco-hematology intensive care unit (ICU) for severe COVID-19. Replication of EBV, CMV, and HSV was evaluated. Competing risk analyses were used to assess the cumulative risk of viral reactivation, and time-dependent Cox and Fine and Gray models to assess risk factors for viral reactivation. RESULTS: Among 100 patients, 38 were immunocompromised. Sixty-three patients presented viral reactivation (12% for HSV, 58% EBV and 19% CMV). Symptomatic patients received treatment. Overall cumulative incidence of viral reactivation was 56.1% [55.9-56.4] at 10 days. After adjustment, a preexisting hematological malignancy (sHR [95%CI]=0.31 [0.11-0.85]) and solid organ transplantation (sHR [95% CI]=2.09 [1.13-3.87]) remained independently associated with viral reactivation. Viral reactivation (P=0.34) was not associated with mortality. CONCLUSIONS: Incidence of herpesvirus reactivation in patients admitted to the ICU for severe COVID-19 was high, but rarely required antiviral treatment.