👤 Giulio Kleiner

Chronic hepatitis C virus (HCV) infection is associated with hypolipidemia. HCV eradication may, therefore, result in hyperlipidemia and increase cardiovascular disease (CVD) risk. We investigated the impact of HCV eradication on serum lipid and lipoprotein profiles and CVD risk during and following direct-acting antiviral (DAA) therapy. We retrospectively analysed stored sera and plasma from 60 DAA-naïve patients, genotypes 1-4, treated with 12 weeks of sofosbuvir-velpatasvir. Serum lipids, apolipoproteins (apo), and a systemic inflammatory marker, GlycA, were measured serially beginning early on treatment and off treatment. Additionally, NMR LipoProfile analysis was performed on plasma samples. Expression of genes regulating lipid metabolism was assessed from paired liver biopsies obtained before and on treatment. Linear mixed models were used to examine changes in lipid and inflammatory markers; Framingham and ASCVD CVD risk scores were assessed before and after treatment. Decline in HCV viremia was associated with a rapid, significant increase in TChol, HDL-C, LDL-C, ApoA-1 and ApoB, and GlycA, improvement in ALT, hepatic inflammation, and steatosis but no change in glycemic control (HOMA-IR and HbA1c). Increase in TChol, LDL-C, and ApoB was associated with an increased SREBP1expression. Both ASCVD and Framingham risk scores were significantly increased at week 24 post treatment after adjusting for age (p < 0.0001). Serum lipids and lipoproteins rapidly increase with inhibition of viral replication during DAA therapy, an effect that may be mediated by genes affecting hepatic de novo lipogenesis. Based on lipid changes, HCV eradication may increase CVD risk, but this needs to be investigated prospectively. Show less

A fraction of patients with COVID-19 develops severe disease requiring hospitalization, while the majority, including high-risk individuals, experience mild symptoms. Severe disease has been associated with higher levels of antibodies and inflammatory cytokines but often among patients with diverse demographics and comorbidity status. This study evaluated hospitalized vs. ambulatory patients with COVID-19 with demographic risk factors for severe COVID-19: median age of 63, >80% male, and >85% black and/or Hispanic. Sera were collected four to 243 days after symptom onset and evaluated for binding and functional antibodies as well as 48 cytokines and chemokines. SARS-CoV-2-specific antibody levels and functions were similar in ambulatory and hospitalized patients. However, a strong correlation between anti-S2 antibody levels and the other antibody parameters, along with higher IL-27 levels, was observed in hospitalized but not ambulatory cases. These data indicate that antibodies against the relatively conserved S2 spike subunit and immunoregulatory cytokines such as IL-27 are potential immune determinants of COVID-19. Show less