Survival Factors and Metabolic Pathogenesis in Elderly Patients (≥65) With COVID-19: A Multi-Center Study

Qi Mei; Amanda Y Wang; Amy Bryant; Yang Yang; Ming Li; Fei Wang; Shangming Du; Christian Kurts; Patrick Wu; Ke Ma; Liang Wu; Huawen Chen; Jinlong Luo; Yong Li; Guangyuan Hu; Xianglin Yuan; Jian Li

doi:10.3389/fmed.2020.595503

Survival Factors and Metabolic Pathogenesis in Elderly Patients (≥65) With COVID-19: A Multi-Center Study

Front Med (Lausanne). 2021 Jan 7:7:595503. doi: 10.3389/fmed.2020.595503. eCollection 2020.

Authors

Qi Mei¹, Amanda Y Wang^{2

3

4}, Amy Bryant⁵, Yang Yang⁶, Ming Li⁷, Fei Wang⁸, Shangming Du⁹, Christian Kurts¹⁰, Patrick Wu¹¹, Ke Ma¹², Liang Wu¹³, Huawen Chen¹³, Jinlong Luo¹³, Yong Li¹⁴, Guangyuan Hu¹, Xianglin Yuan¹, Jian Li¹⁰

Affiliations

¹ Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
² The Renal and Metabolic Division, The George Institute for Global Health, University of New South Wales, Newtown, NSW, Australia.
³ Concord Clinical School, The University of Sydney, Newtown, NSW, Australia.
⁴ Department of Renal Medicine, Concord Repatriation General Hospital, Newtown, NSW, Australia.
⁵ Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, Idaho State University, Meridian, ID, United States.
⁶ Renmin Hospital of Wuhan University, Wuhan, China.
⁷ Department of Respiratory and Critical Care Medicine, Wuhan Pulmonary Hospital, Wuhan, China.
⁸ Department of Chinese Medicine, Tongji Medical College, Wuhan No. 1 Hospital, Huazhong University of Science and Technology, Wuhan, China.
⁹ Ludwig Maximilian University of Munich, Munich, Germany.
¹⁰ Institute of Experimental Immunology, University Clinic of Rheinische Friedrich-Wilhelms-University, Bonn, Germany.
¹¹ Department of Anaesthesiology, Queen Mary Hospital, Hong Kong, China.
¹² Department and Institute of Infectious Disease, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
¹³ Department of Emergency Medicine, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.
¹⁴ Department of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.

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.

Keywords: COVID-19; clinical stratification; elderly patients; metabolic pathogenesis; mortality; pathway flux; prognostic factors; survival factors.