Ehler Johannes, Klawitter Felix, von Möllendorff Friedrich, Zacharias Maike, Fischer Dagmar-Christiane, Danckert Lena, Bajorat Rika, Hackenberg Johanna, Bertsche Astrid, Loebermann Micha, Geerdes-Fenge Hilte, Fleischmann Robert, Klinkmann Gerd, Schramm Patrick, Schober Sarah, Petzold Axel, Perneczky Robert, Saller Thomas
Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, Rostock University Medical Center, 18057, Rostock, Germany.
Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, 07747, Jena, Germany.
Infection. 2025 Apr;53(2):593-605. doi: 10.1007/s15010-024-02406-7. Epub 2024 Oct 1.
Compared to intensive care unit patients with SARS-CoV-2 negative acute respiratory tract infections, patients with SARS-CoV-2 are supposed to develop more frequently and more severely neurologic sequelae. Delirium and subsequent neurocognitive deficits (NCD) have implications for patients' morbidity and mortality. However, the extent of brain injury during acute COVID-19 and subsequent NCD still remain largely unexplored. Body-fluid biomarkers may offer valuable insights into the quantification of acute delirium, brain injury and may help to predict subsequent NCD following COVID-19.
In a multicenter, observational case-control study, conducted across four German University Hospitals, hospitalized adult and pediatric patients with an acute COVID-19 and SARS-CoV-2 negative controls presenting with acute respiratory tract infections were included. Study procedures comprised the assessment of pre-existing neurocognitive function, daily screening for delirium, neurological examination and blood sampling. Fourteen biomarkers indicative of neuroaxonal, glial, neurovascular injury and inflammation were analyzed. Neurocognitive functions were re-evaluated after three months.
We enrolled 118 participants (90 adults, 28 children). The incidence of delirium [85 out of 90 patients (94.4%) were assessable for delirium) was comparable between patients with COVID-19 [16 out of 61 patients (26.2%)] and SARS-CoV-2 negative controls [8 out of 24 patients (33.3%); p > 0.05] across adults and children. No differences in outcomes as measured by the modified Rankin Scale, the Short-Blessed Test, the Informant Questionnaire on Cognitive Decline in the Elderly, and the pediatrics cerebral performance category scale were observed after three months. Levels of body-fluid biomarkers were generally elevated in both adult and pediatric cohorts, without significant differences between SARS-CoV-2 negative controls and COVID-19. In COVID-19 patients experiencing delirium, levels of GFAP and MMP-9 were significantly higher compared to those without delirium.
Delirium and subsequent NCD are not more frequent in COVID-19 as compared to SARS-CoV-2 negative patients with acute respiratory tract infections. Consistently, biomarker levels of brain injury indicated no differences between COVID-19 cases and SARS-CoV-2 negative controls. Our data suggest that delirium in COVID-19 does not distinctly trigger substantial and persistent subsequent NCD compared to patients with other acute respiratory tract infections.
ClinicalTrials.gov: NCT04359914; date of registration 24-APR 2020.
与感染新型冠状病毒（SARS-CoV-2）呈阴性的急性呼吸道感染重症监护病房患者相比，感染SARS-CoV-2的患者被认为更频繁、更严重地出现神经后遗症。谵妄及随后的神经认知障碍（NCD）对患者的发病率和死亡率有影响。然而，急性新型冠状病毒肺炎（COVID-19）期间脑损伤的程度以及随后的NCD在很大程度上仍未得到充分研究。体液生物标志物可能为急性谵妄、脑损伤的量化提供有价值的见解，并有助于预测COVID-19后的后续NCD。
在一项多中心观察性病例对照研究中，纳入了德国四家大学医院收治的患有急性COVID-19的住院成人和儿童患者以及表现为急性呼吸道感染的SARS-CoV-2阴性对照患者。研究程序包括评估既往神经认知功能、每日谵妄筛查、神经系统检查和血液采样。分析了14种指示神经轴突、神经胶质、神经血管损伤和炎症的生物标志物。三个月后重新评估神经认知功能。
我们招募了118名参与者（90名成人，28名儿童）。COVID-19患者[61名患者中有16名（26.2%）]和SARS-CoV-2阴性对照患者[24名患者中有8名（33.3%）]的谵妄发生率[90名患者中有85名（94.4%）可评估谵妄]在成人和儿童中相当（p>0.05）。三个月后，改良Rankin量表、简易精神状态检查表、老年人认知能力下降知情问卷和儿科脑功能分类量表所测量的结果没有差异。成人和儿童队列中的体液生物标志物水平普遍升高，SARS-CoV-2阴性对照患者和COVID-19患者之间没有显著差异。在发生谵妄的COVID-19患者中，与未发生谵妄的患者相比，胶质纤维酸性蛋白（GFAP）和基质金属蛋白酶-9（MMP-9）水平显著更高。
与感染SARS-CoV-2呈阴性的急性呼吸道感染患者相比，COVID-19患者中谵妄及随后的NCD并不更常见。同样，脑损伤的生物标志物水平在COVID-19病例和SARS-CoV-2阴性对照患者之间没有差异。我们的数据表明，与其他急性呼吸道感染患者相比，COVID-19患者中的谵妄不会明显引发大量且持续的后续NCD。
ClinicalTrials.gov：NCT04359914；注册日期2020年4月24日。
