Multi-Omics integration analysis of respiratory specimen characterizes baseline molecular determinants associated with COVID-19 diagnosis.

Rapid diagnosis and precise prognostication of SARS-CoV-2 infection remains a major challenge. A multi-omic approach was adopted, and in the discovery phase, global proteome/metaproteome/metabolome were analysed in the respiratory specimens of SARS-CoV-2 positive [n=20], negative [n=20], and H1N1 positive [n=5] cases. We identified MX1 (MX Dynamin Like GTPase 1) and WARS (Tryptophan--tRNA ligase) as clues to viral diagnosis and validated in 200 SARS-CoV-2 suspects. MX1 >30pg/ml and WARS >25ng/ml segregated virus positives patients [(AUC=94%CI(0.91-0.97)]. Distinct increase in SARS-CoV-2 induced immune activation, metabolic reprograming and a decrease in oxygen transport, wound healing, fluid regulation, vitamin and steroid metabolism was seen (p<0.05). Multi-omics profiling correlated with viraemia and segregated asymptomatic COVID-19 patients. Additionally, the multiomics approach identified increased respiratory pathogens [Burkholderiales, Klebsiella pneumonia] and decreased lactobacillus salivarius (FDR<0.05, p<0.05) in COVID-19 specimens. ConclusionNovel proteins [MX1 and WARS] can rapidly and reliably diagnose SARS-CoV-2 infection and identify asymptomatic and mild disease.

Predictors of steroid non-response and new approaches in severe alcoholic hepatitis

Severe alcoholic hepatitis (SAH) remains a disease with high mortality. Steroid is the main stay and has been shown to give modest 28-day survival benefit in carefully selected patients, but no 90-day survival benefit. Since non-responders have high incidence of infections and increased mortality, it would be worthwhile to identify them before starting steroid therapy. A high and rising bilirubin, urinary acetyl carnitine >2,500 ng/mL, high asiloglycoprotein positive microparticles, and specific features in liver biopsy could predict steroid non-response at baseline. There is an ever-growing need to find new and effective therapies for SAH patients. Besides aggressive nutrition, granulocyte colony stimulating factor, fecal microbiota transplantation, and plasma exchange appear promising therapies and provide a hope for steroid ineligible or steroid non-responsive patients. Suppression of hepatic inflammation, preventing new bacterial or fungal infections, and enhancing liver regeneration will remain the key targets for next generation therapies.