Abstract
Background: Elderly patients infected with COVID-19 are reported to be facing a substantially increased risk of mortality. Clinical characteristics, treatment options, and potential survival factors remain under investigation. This study aimed to fill this gap and provide clinically relevant factors associated with survival of elderly patients with COVID-19.Methods: In this multi-center study, elderly patients (age ≥65 years old) with laboratory-confirmed COVID-19 from 4 Wuhan hospitals were included. The clinical end point was hospital discharge or deceased with last date of follow-up on Jul. 08, 2020. Clinical, demographic, and laboratory data were collected. Univariate and multivariate analysis were performed to analyze survival and risk factors. A metabolic flux analysis using a large-scale molecular model was applied to investigate the pathogenesis of SARS-CoV-2 with regard to metabolism pathways.Results: A total of 223 elderly patients infected with COVID-19 were included, 91 (40.8%) were discharged and 132 (59.2%) deceased. Acute respiratory distress syndrome (ARDS) developed in 140 (62.8%) patients, 23 (25.3%) of these patients survived. Multivariate analysis showed that potential risk factors for mortality were elevated D-Dimer (odds ratio: 1.13 [95% CI 1.04 - 1.22], p = 0.005), high immune-related metabolic index (6.42 [95% CI 2.66–15.48], p < 0.001), and increased neutrophil-to-lymphocyte ratio (1.08 [95% 1.03–1.13], p < 0.001). Elderly patients receiving interferon atmotherapy showed an increased probability of survival (0.29 [95% CI 0.17–0.51], p < 0.001). Based on these factors, an algorithm (AlgSurv) was developed to predict survival for elderly patients. The metabolic flux analysis showed that 12 metabolic pathways including phenylalanine (odds ratio: 28.27 [95% CI 10.56–75.72], p < 0.001), fatty acid (15.61 [95% CI 6.66–36.6], p < 0.001), and pyruvate (12.86 [95% CI 5.85–28.28], p < 0.001) showed a consistently lower flux in the survivors vs. the deceased subgroup. This may reflect a key pathogenic mechanism of COVID-19 infection.Conclusion: Several factors such as interferon atmotherapy and recreased activity of specific metabolic pathways were found to be associated with survival of elderly patients. Based on these findings, a survival algorithm (AlgSurv) was developed to assist the clinical stratification for elderly patients. Dysregulation of the metabolic pathways revealed in this study may aid in the drug and vaccine development against COVID-19.
Highlights
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2) is a non-segmented, single-stranded, and positive-sense RNA virus, recently discovered and categorized as the newest and seventh member of the Coronaviride family (1)
Genetically-based, or acquired, immune impairment worsen the COVID-19 disease course (31, 32), our results further suggest that a dysregulation of metabolism may impair immunity contributing to fatal outcome during COVID-19, especially for elderly patients
Our study investigated an age-specific elderly patient cohort suffering from COVID-19
Summary
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV2) is a non-segmented, single-stranded, and positive-sense RNA virus, recently discovered and categorized as the newest and seventh member of the Coronaviride family (1). Several recent studies identified advanced age as a common potential risk factor associated with the course of the coronavirus disease 2019 (COVID-19) (6–9). Changes of anatomical respiratory structure with aging (10), immunosenescene (11), and inflammaging (12) may represent three major determinants for a higher prevalence and mortality of COVID-19 infection in elderly populations. The role of such metabolic alterations in the pathogenesis of SARS-CoV-2 remains under investigation. Patients infected with COVID-19 are reported to be facing a substantially increased risk of mortality. Treatment options, and potential survival factors remain under investigation. This study aimed to fill this gap and provide clinically relevant factors associated with survival of elderly patients with COVID-19
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