Abstract
PurposeCritically ill COVID-19 patients have significantly increased risk of death. Although several circulating biomarkers are thought to be related to COVID-19 severity, few studies have focused on the characteristics of critically ill patients with different outcomes. The objective of this study was to perform a longitudinal investigation of the potential mechanisms affecting the prognosis of critically ill COVID-19 patients.MethodsIn addition to clinical data, 113 whole blood samples and 85 serum samples were collected from 33 severe and critical COVID-19 patients without selected comorbidities. Multi-omics analysis was then performed using longitudinal samples.ResultsObvious transcriptional transitions were more frequent in critical survivors than in critical non-survivors, indicating that phase transition may be related to survival. Based on analysis of differentially expressed genes during transition, the erythrocyte differentiation pathway was significantly enriched. Furthermore, clinical data indicated that red blood cell counts showed greater fluctuation in survivors than in non-survivors. Moreover, declining red blood cell counts and hemoglobin levels were validated as prognostic markers of poor outcome in an independent cohort of 114 critical COVID-19 patients. Protein–metabolite–lipid network analysis indicated that tryptophan metabolism and melatonin may contribute to molecular transitions in critical COVID-19 patients with different outcomes.ConclusionsThis study systematically and comprehensively depicted the longitudinal hallmarks of critical COVID-19 patients and indicated that multi-omics transition may impact the prognosis.Take home messageFrequent transcriptional phase transitions may contribute to outcome in critically ill COVID-19 patients. Furthermore, fluctuation in red blood cell and hemoglobin levels may relate to poor prognosis. The biological function of melatonin was suppressed in COVID-19 non-survivors, which may provide a potential theoretical basis for clinical administration.
Highlights
Coronavirus disease 2019 (COVID-19) was declared a global pandemic by the World Health Organization (WHO) on March 11, 2020
Take home message: Frequent transcriptional phase transitions may contribute to outcome in critically ill COVID-19 patients
Fluctuation in red blood cell and hemoglobin levels may relate to poor prognosis
Summary
Coronavirus disease 2019 (COVID-19) was declared a global pandemic by the World Health Organization (WHO) on March 11, 2020. Despite an overall 2% mortality rate in COVID-19 patients, 53.8–61.5% of critically ill patients deceased within 28 days of admission to intensive care units (ICU) [1,2,3]. Previous longitudinal studies of COVID-19 have primarily focused on the immune response against pathogens [4, 5]. At present, sequencing-based multiscale changes among critical COVID-19 patients and their potential correlation with clinical trajectory remain unknown. Exploration of these molecular changes could contribute to our understanding of COVID-19 and help uncover potential therapeutic targets. Many studies have shown that comorbidities impact the COVID-19 prognosis [6, 7]. We studied patients without selected comorbidities (see Methods)
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