Matschke Jakob, Lahann Henri, Krasemann Susanne, Altmeppen Hermann, Pfefferle Susanne, Galliciotti Giovanna, Fitzek Antonia, Sperhake Jan-Peter, Ondruschka Benjamin, Busch Miriam, Rotermund Natalie, Schulz Kristina, Lohr Christian, Dottermusch Matthias, Glatzel Markus
Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Institute of Medical Microbiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Front Neurol. 2022 Jun 16;13:908081. doi: 10.3389/fneur.2022.908081. eCollection 2022.
The severe acute respiratory syndrome-corona virus type 2 (SARS-CoV-2) is the cause of human coronavirus disease 2019 (COVID-19). Since its identification in late 2019 SARS-CoV-2 has spread rapidly around the world creating a global pandemic. Although considered mainly a respiratory disease, COVID-19 also encompasses a variety of neuropsychiatric symptoms. How infection with SARS-CoV-2 leads to brain damage has remained largely elusive so far. In particular, it has remained unclear, whether signs of immune cell and / or innate immune and reactive astrogliosis are due to direct effects of the virus or may be an expression of a non-specific reaction of the brain to a severe life-threatening disease with a considerable proportion of patients requiring intensive care and invasive ventilation activation. Therefore, we designed a case-control-study of ten patients who died of COVID-19 and ten age-matched non-COVID-19-controls to quantitatively assess microglial and astroglial response. To minimize possible effects of severe systemic inflammation and / or invasive therapeutic measures we included only patients without any clinical or pathomorphological indication of sepsis and who had not been subjected to invasive intensive care treatment. Our results show a significantly higher degree of microglia activation in younger COVID-19 patients, while the difference was less and not significant for older COVID-19 patients. The difference in the degree of reactive gliosis increased with age but was not influenced by COVID-19. These preliminary data warrants further investigation of larger patient cohorts using additional immunohistochemical markers for different microglial phenotypes.
严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)是导致人类冠状病毒病2019(COVID-19)的病原体。自2019年末被发现以来,SARS-CoV-2已在全球迅速传播,引发了一场全球大流行。尽管COVID-19主要被认为是一种呼吸道疾病,但它也包含多种神经精神症状。到目前为止,SARS-CoV-2感染如何导致脑损伤在很大程度上仍然不清楚。特别是,免疫细胞和/或先天性免疫及反应性星形胶质细胞增生的迹象是由于病毒的直接作用,还是可能是大脑对一种严重的危及生命的疾病的非特异性反应的表现,而相当一部分患者需要重症监护和有创通气支持,这一点仍不清楚。因此,我们设计了一项病例对照研究,研究对象为10例死于COVID-?19的患者和10例年龄匹配的非COVID-19对照,以定量评估小胶质细胞和星形胶质细胞的反应。为了尽量减少严重全身炎症和/或有创治疗措施的可能影响,我们仅纳入没有任何脓毒症临床或病理形态学指征且未接受有创重症监护治疗的患者。我们的结果显示,年轻的COVID-19患者中小胶质细胞活化程度显著更高,而老年COVID-19患者的差异较小且不显著。反应性胶质细胞增生程度的差异随年龄增加,但不受COVID-19影响。这些初步数据值得使用针对不同小胶质细胞表型的额外免疫组化标记物对更大的患者队列进行进一步研究。