Immune response to the mRNA COVID-19 vaccine in hemodialysis patients: cohort study (preprint)

Background: End-stage renal disease (ESRD) patients experience immune compromise characterized by complex alterations of both innate and adaptive immunity, and results in higher susceptibility to infection and lower response to vaccination. This immune compromise, coupled with greater risk of exposure to infectious disease at hemodialysis (HD) centers, underscores the need for examination of the immune response to the COVID-19 mRNA-based vaccines.Methods: A transcriptomic analysis of the immune response to the Covid-19 BNT162b2 mRNA vaccine was assessed in 20 HD patients and cohort-matched controls. RNA sequencing of peripheral blood mononuclear cells (PBMCs) was performed longitudinally before and after each vaccination dose for a total of six time points per subject. Anti-spike antibody levels were quantified prior to the first vaccination dose (V1D0) and seven days after the second dose (V2D7) using anti-Spike IgG titers and antibody neutralization assays. Anti-spike IgG titers were additionally quantified six months after initial vaccination. Clinical history and lab values in HD patients were obtained to identify predictors of vaccination response.Results: Transcriptomic analyses demonstrated differing time courses of immune responses, with predominant T cell activity in controls one week after the first vaccination dose, compared to predominant myeloid cell activity in HD at this time point. HD demonstrated decreased metabolic activity and decreased antigen presentation compared to controls after the second vaccination dose. Anti-spike IgG titers and neutralizing function were substantially elevated in both controls and HD at V2D7, with a small but significant reduction in titers in HD groups (p < 0.05). Anti-spike IgG remained elevated above baseline at six months in both subject groups. Anti-spike IgG titers at V2D7 were highly predictive of 6-month titer levels. Transcriptomic biomarkers after the second vaccination dose and clinical biomarkers including ferritin levels were found to be predictive of antibody development.Conclusion: Overall, we demonstrate differing time courses of immune responses to the BTN162b2 mRNA COVID-19 vaccination in maintenance hemodialysis subjects (HD) comparable to healthy controls (HC) and identify transcriptomic and clinical predictors of anti-Spike IgG titers in HD. Analyzing vaccination as an in vivo perturbation, our results warrant further characterization of the immune dysregulation of end stage renal disease (ESRD). Funding: F30HD102093, F30HL151182, T32HL144909, R01HL138628This research has been funded by the University of Illinois at Chicago Center for Clinical and Translational Science (CCTS) award UL1TR002003

LncRNAs NEAT1 and MALAT1 Differentiate Inflammation in Severe COVID-19 Patients (preprint)

Hyperactive and damaging inflammation is a hallmark of severe rather than mild COVID-19 syndrome. To uncover key inflammatory differentiators between severe and mild COVID-19 disease, we applied an unbiased single-cell transcriptomic analysis. We integrated a bronchoalveolar lavage (BAL) dataset with a peripheral blood mononuclear cell dataset (PBMC) and analyzed the combined cell population, focusing on genes associated with disease severity. Distinct cell populations were detected in both BAL and PBMC where the immunomodulatory long non-coding RNAs (lncRNAs) NEAT1 and MALAT1 were highly differentially expressed between mild and severe patients. The detection of other severity associated genes involved in cellular stress response and apoptosis regulation suggests that the pro-inflammatory functions of these lncRNAs may foster cell stress and damage. The lncRNAs NEAT1 and MALAT1 are potential components of immune dysregulation in COVID-19 that may provide targets for severity related diagnostic measures or therapy.