A substantial proportion of persons who develop COVID-19 experience postacute sequelae of SARS-CoV-2 infection (PASC). This article reports baseline findings from an ongoing longitudinal cohort study that seeks to characterize the risk factors, clinical findings, laboratory features, and natural history of PASC.
Background
The efficacy of pegylated IFN-α and ribavirin (pegIFN/RBV) in the treatment of Hepatitis C infection is limited by psychiatric adverse effects (IFN-PE). Our study examined the ability of differential gene expression patterns prior to therapy to predict emergent IFN-PE among 28 HIV/HCV co-infected patients treated with pegIFN-α2b/RBV.
Methods
Patients dually infected with HIV and HCV were evaluated at baseline and during treatment by board-certified psychiatrists who classified patients into 2 groups: those who developed IFN-PE and those who did not (IFN-NPE). Gene expression analysis (Affymetrix HG-U133A) was performed using PBMCs before and after initiation of treatment. ANOVA, post hoc analysis based on pair-wise comparisons and functional annotation analysis identified differentially expressed genes within and between groups. Prediction Analysis for Microarrays was used to test the predictive ability of selected genes.
Results
Twenty-four genes (16 up- and 8 down-regulated) that were differentially expressed at baseline in patients who subsequently developed IFN-PE compared to the IFN-NPE group showed the ability to predict IFN-PE with an accuracy of 82%. In 16 patients with IFN-PE, 135 genes (117 up-; 18 down-regulated) were significantly modulated following treatment. Of these, 10 genes have already been shown to be associated with neuropsychiatric illnesses and were significantly modulated only in patients who experienced IFN-PE.
Conclusions
We describe a novel molecular diagnostic biomarker panel to predict emergent IFN-PE in HIV/HCV-co-infected patients undergoing pegIFN/RBV treatment, which may improve the identification of patients at greatest risk for IFN-PE and suggest candidate therapeutic targets for preventing or treating IFN-PE.
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