Immuno-omics profiling of critically ill patients with COVID-19

Abstract

COVID-19 causes a mild infection, but in some patients, develops into a severe acute respiratory distress syndrome (ARDS) requiring mechanical ventilation. Despite the success of vaccination campaigns globally, the intensive care units still receive severe SARS-CoV-2 cases, and the mortality rate among those patients had not dropped drastically. In this dissertation, 100 critically ill COVID-19 patients under mechanical intubation were investigated in respect to immunological pathways over the course of four weeks of ICU, and the correlates of survival were highlighted based on recovered patients. The viral RNA was captured in circulation for 35% of studied cohort on day 1 of ICU. The RNAemia correlated with AST and Ferritin levels, and not with age, BMI, or duration of ICU and mechanical ventilation. The profile of studied cohort revealed a hyperinflammatory response, a lymphopenic signature, and a high antibody production at the epigenetic and transcriptomic levels since day 1 of ICU. On day 14, a significant improve of lymphocytic effector functions was observed in parallel to a significant decline of inflammatory environment for survived patients compared to deceased patients. Furthermore, the immune functional assays confirmed the lymphopenia, the hyperinflammation and high spike-specific antibody production in selected patients (n=18) since ICU admission. Late stages of ICU showed a decline of cytokines storm and an increase of IFN-gamma producing spike-specific T cells after stimulation with SARS-CoV-2 antigens in survivors only. At the epigenetic level, DNA methylation patterns of apoptotic genes predicted patients’ mortality from day 1 of ICU. At the metabolites level, proposed models predicted mechanical ventilation duration and ICU length of stay from day 1 and day 7 measurements better than APACHE II scores in a small group from our cohort (n=39).

Date of Award	2022
Original language	American English
Awarding Institution	HBKU College of Health & Life Sciences