Heinicke Ulrike, Talbot Steven R, Thanasis Filippos, Adam Elisabeth H, von Knethen Andreas, Steinbicker Andrea U, Zinn Sebastian, Zacharowski Kai, Flinspach Armin N
Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, Goethe University, University Hospital Frankfurt, Frankfurt am Main, Germany.
Institute for Laboratory Animal Science, Hannover Medical School, Hannover, Germany.
BJA Open. 2025 Jun 5;14:100415. doi: 10.1016/j.bjao.2025.100415. eCollection 2025 Jun.
Orexin A regulates sleep-wake cycles, arousal, and energy homeostasis, linking it to the renin-angiotensin system and substance P. Dysfunction in these pathways occurs in acute and long-term COVID-19, including post-COVID syndrome.
This observational study analysed plasma orexin A, substance P, bradykinin, and des-Arg-bradykinin (DABK) in 78 ICU COVID-19 patients, 14 survivors of severe COVID-19 (2.5-yr follow-ups), and 14 healthy controls.
During acute COVID-19, bradykinin and substance P were significantly reduced, whereas DABK was elevated compared with healthy controls and 2.5-yr follow-ups. Orexin A concentration correlated with ICU survival (Cohen's d=0.4), length of stay (LOS; r=-0.26, =0.02), and sedation concentrations. Intriguingly, substance P plasma concentrations were elevated in 2.5-yr follow-ups. Plasma orexin A, substance P, and bradykinin increased with lower Richmond Agitation-Sedation Score (RASS): a combination of orexin A, substance P, and bradykinin concentrations at RASS -3 to -5 distinguished survivors from non-survivors of COVID-19 when categorised by age.
Changes in the bradykinin axis, affecting substance P and orexin A signalling, are associated with severe COVID-19, ICU LOS, and survival. Elevated substance P concentrations in the 2.5-yr follow-up cohort may be associated with physical, cognitive, and neuropsychological impairments commonly seen in post-ICU syndrome and post-COVID syndrome. The predictive values of orexin A, substance P, bradykinin, and DABK and the complex interplay between the renin-angiotensin system and the orexinergic system in severe, critical illnesses or viral diseases will be investigated in future studies.
食欲素A调节睡眠-觉醒周期、觉醒及能量平衡，使其与肾素-血管紧张素系统和P物质相关联。这些途径的功能障碍在急性和长期新冠肺炎中都会出现，包括新冠后综合征。
这项观察性研究分析了78例新冠肺炎重症监护病房（ICU）患者、14例重症新冠肺炎幸存者（2.5年随访）及14例健康对照者的血浆食欲素A、P物质、缓激肽和去精氨酸缓激肽（DABK）。
在急性新冠肺炎期间，与健康对照者及2.5年随访者相比，缓激肽和P物质显著降低，而DABK升高。食欲素A浓度与ICU生存率（科恩d值=0.4）、住院时长（LOS；r=-0.26，P=0.02）及镇静浓度相关。有趣的是，在2.5年随访中P物质血浆浓度升高。血浆食欲素A、P物质和缓激肽随里士满躁动-镇静评分（RASS）降低而升高：当按年龄分类时，RASS为-3至-5时食欲素A、P物质和缓激肽浓度的组合可区分新冠肺炎幸存者与非幸存者。
缓激肽轴的变化影响P物质和食欲素A信号传导，与重症新冠肺炎、ICU住院时长及生存率相关。2.5年随访队列中P物质浓度升高可能与ICU后综合征和新冠后综合征中常见的身体、认知及神经心理损伤有关。未来研究将探讨食欲素A、P物质、缓激肽和DABK的预测价值以及肾素-血管紧张素系统与食欲素能系统在重症、危重症疾病或病毒性疾病中的复杂相互作用。
