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 Mar. 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 were D- Dimer (odds ratio: 1.13 [95% CI 1.04 - 1.22], p=.005), immune-related metabolic index (6.42 [95% CI 2.66 - 15.48], p<.001), and neutrophil-to-lymphocyte ratio (1.08 [95% 1.03 - 1.13], p<.001). Elderly patients receiving interferon atmotherapy showed an increased probability of survival (0.29 [95% CI
0.17 - 0.51], p<.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 surviving versus the deceased subgroup. This may reflect a key pathogenesis of COVID-19 infection.
Conclusion
Although a high mortality has been reported for elderly patients with COVID-19, in this analysis, several factors such as interferon atmotherapy and activity of metabolic pathways were found to be associated with survival of elderly patients. Based on these findings, the survival algorithm (AlgSurv) was developed to assist the clinical stratification for elderly patients. Deregulation of metabolic pathways revealed in this study may aid in the drug development against COVID-19.