Worldwide, over 694 million people have been infected with SARS-CoV-2, with an estimated 55–60% of those infected developing COVID-19. Since the beginning of the pandemic in December 2019, different variants of concern have appeared and continue to occur. With the emergence of different variants, an increasing rate of vaccination and previous infections, the acute neurological symptomatology of COVID-19 changed. Moreover, 10–45% of individuals with a history of SARS-CoV-2 infection experience symptoms even 3 months after disease onset, a condition that has been defined as ‘post-COVID-19’ by the World Health Organization and that occurs independently of the virus variant. The pathomechanisms of COVID-19-related neurological complaints have become clearer during the past 3 years. To date, there is no overt — that is, truly convincing — evidence for SARS-CoV-2 particles in the brain. In this Review, we put special emphasis on discussing the methodological difficulties of viral detection in CNS tissue and discuss immune-based (systemic and central) effects contributing to COVID-19-related CNS affection. We sequentially review the reported changes to CNS cells in COVID-19, starting with the blood–brain barrier and blood–cerebrospinal fluid barrier — as systemic factors from the periphery appear to primarily influence barriers and conduits — before we describe changes in brain parenchymal cells, including microglia, astrocytes, neurons and oligodendrocytes as well as cerebral lymphocytes. These findings are critical to understanding CNS affection in acute COVID-19 and post-COVID-19 in order to translate these findings into treatment options, which are still very limited.

全球范围内，已有超过 6.94 亿人感染了 SARS-CoV-2，估计其中 55-60% 的感染者发展为 COVID-19。自 2019 年 12 月大流行开始以来，不同的令人担忧的变体已经出现并继续出现。随着不同变种的出现、疫苗接种率和既往感染率的增加，COVID-19 的急性神经症状发生了变化。此外，10-45% 有 SARS-CoV-2 感染史的个体甚至在发病 3 个月后也会出现症状，这种情况被世界卫生组织定义为“后 COVID-19”，并且是独立发生的病毒变种。在过去 3 年中，与 COVID-19 相关的神经系统疾病的病理机制已变得更加清晰。迄今为止，尚无明显的（即真正令人信服的）证据表明大脑中存在 SARS-CoV-2 颗粒。在这篇综述中，我们特别强调讨论中枢神经系统组织中病毒检测的方法学困难，并讨论导致 COVID-19 相关中枢神经系统影响的免疫（全身和中枢）效应。在我们描述脑实质细胞的变化之前，我们依次回顾了报道的 COVID-19 中 CNS 细胞的变化，从血脑屏障和血脑脊液屏障开始，因为来自周围的系统因素似乎主要影响屏障和导管，包括小胶质细胞、星形胶质细胞、神经元和少突胶质细胞以及脑淋巴细胞。这些发现对于了解急性 COVID-19 和 COVID-19 后的中枢神经系统影响至关重要，以便将这些发现转化为仍然非常有限的治疗方案。