新冠长期后遗症脑雾症状的新疗法？

KEY POINTS
要点

Breathlessness, chronic fatigue, and other long-COVID symptoms may slowly improve. However, brain fog may worsen with time.
呼吸困难，长期疲劳以及其他新冠长期后遗症（长期新冠）症状可能会缓慢好转，但脑雾却会逐渐恶化。

Although brain fog in long COVID may look like ADHD, Mild Cognitive Disorder, or other neurological disorders, the underlying mechanisms differ.
尽管新冠长期后遗症中的脑雾症状看起来可能像是ADHD（注意力缺陷多动障碍，多动症），轻微认知障碍或其他神经障碍，底层机制却并不相同。

An ADHD medication, Guanfacine, and antioxidant, NAC, were used on a small sample to treat long-COVID brain fog.一种ADHD药物，胍法辛和抗氧化剂NAC在一个小规模样本中被用于治疗新冠长期后遗症脑雾症状。

Future treatments should target brain inflammation to address the currently known causes of long-COVID cognitive deficits.
在应对新冠后遗症认知缺陷症状的当前所知原因方面，未来治疗方案应围绕大脑炎症来治疗。

Sufferers of long COVID experience symptoms that may persist for weeks, months, or even years after contracting the COVID virus. Some researchers and clinicians have listed as many as 200 long COVID symptoms. The most frequently reported symptoms are breathlessness, chronic fatigue, and brain fog. The breathlessness, chronic fatigue, and other symptoms may slowly improve; however, brain fog may worsen with time.

新冠长期后遗症患者所表现出的症状可能会延续数周、数月甚至数年。一些研究人员和临床医生已经列出了高达200种新冠长期后遗症症状。人们报告最多的症状是呼吸困难、长期疲劳和脑雾。前两种和其他症状可能会缓慢好转，但脑雾症状却可能会逐渐恶化。

Brain fog is a foggy term. It is not specific, which makes it challenging to study. Another way of describing the commonly reported cognitive issues is cognitive impairment or deficits. I also don't believe that conceptualizing the post-COVID brain changes as impairments, deficits, or dementias is accurate. Post-COVID cognitive changes may look like other neurological disorders, such as dementia, ADHD, or traumatic brain injury. But it is important to keep in mind that the underlying biological mechanisms may not be identical. This is an important consideration for treatment.

脑雾，是一个并不明确和具体的术语，因此对这一症状的研究也就充满挑战。对于普遍报告的认知问题，另一种描述词汇是认知损伤或缺陷。但我也不认为将新冠后的大脑变化定义为损伤、缺陷或痴呆是精准的。新冠后认知能力变化可能看起来像是其他的神经障碍，如痴呆，ADHD或创伤性大脑损伤等。但需要记住其底层生物机制可能并不相同。这是治疗中的一个重要考量因素。

Many people who suffer from neuro-long COVID indeed perform like those with mild cognitive impairment on neuropsychological assessments. This is certainly concerning enough for researchers to find mechanisms and treatments based on this understanding.

受神经性新冠长期后遗症困扰的人的确在神经心理评估中表现得类似轻微认知损伤患者。这足以引起重视，研究人员需要基于这一发现来寻找致病机制和治疗方案。

These long-COVID symptoms can look like attention deficit disorder (ADHD). The hallmark symptoms of ADHD are difficulty focusing, short attention span, difficulty multitasking, and executive dysfunction. One can use the vague term "brain fog" to also describe a person's experience with ADHD. Pathologies in the brain's dopamine and norepinephrine systems have been proposed as the underlying mechanisms of ADHD. Hence, the management of ADHD symptoms has focused on amplifying the dopamine and norepinephrine brain signals.

这些新冠长期后遗症症状看起来会像是ADHD（注意力缺陷障碍）。ADHD的标志症状是难以集中精力、注意力集中时间短，难以同时处理多项工作以及执行功能障碍（大脑控制情绪、行为和想法的功能存在障碍，其中包括难以规划、启动和完成需要达成某种目标的活动等）。人们也可以用脑雾这一模糊术语来描述ADHD的患病体验。大脑多巴胺和去甲肾上腺素系统疾病被认为是ADHD的底层机制。因此，对ADHD症状的管控一直是基于放大多巴胺和去甲肾上腺素大脑信号这一方法。

A new study
一项新研究

To connect all these observations, a study on a very small sample size tested a currently used ADHD medication for long COVID (N=12).1 Guanfacine was approved for the treatment of ADHD in 2009. It was developed in the lab of Amy Arnsten, one of the authors of this report. The medication is combined with N-acetylcysteine (NAC-600 mg), an antioxidant for treating Traumatic Brain Injury (TBI). Eight out of the 12 patients studied reported improvements in memory, organizational skills, and ability to multitask. No objective tests were used to verify the patients' reported improvements. Two patients were unavailable for follow-up; the other two discontinued the medication due to intolerable side effects, such as low blood pressure and dry mouth.

为将这些发现联系起来，一项在小规模样本(12人)中开展的研究测试了将当前所用的一种ADHD药物用于治疗新冠长期后遗症。2009年，胍法辛被批准用于治疗ADHD。该药物由 Amy Arnsten 的实验室研发。Amy Arnsten也是本报告的作者之一。该药物与N-乙酰半胱氨酸（NAC-600mg）（用于治疗创伤性脑损伤的一种抗氧化剂）共同使用。12位受试者中有8位报告了记忆力、组织能力和多任务处理能力有所改善。但并未开展客观性测验来确认患者所报告的这些改善。两位患者无法参加后期追踪，另外两位因为无法忍受的副作用，比如低血压和口干症而终止服用药物。

This is not a placebo-controlled study and is considered anecdotal. Double-blind and placebo-control studies with much larger samples should be conducted before prescribing ADHD medications to long COVID sufferers. Also, one of the report's authors receives royalties from the U.S. sales of Intuniv (extended-release guanfacine).

该研究并无安慰剂对照组，被认为只是基于主观观察和汇报。在将ADHD药物用于新冠患者之前，需要在更大样本中开展双盲测试和安慰剂对照研究。另外，本报告的作者之一也是美国Intuniv（缓释胍法辛）销售市场中专利使用费受益人之一。

As explained earlier, the proposed mechanism of ADHD cognitive symptoms (attention, focus, and memory) is dopaminergic/adrenergic pathologies. We have begun to understand the underlying mechanisms of long COVID. A recent paper proposed six underlying mechanisms of long-COVID cognitive changes:

如前所述，ADHD认知症状（注意力、聚焦力和记忆力）的致病机制被认为是多巴胺/肾上腺素疾病。我们对新冠长期后遗症的致病机制也开始有了一定理解。一项近期的论文提出了新冠长期后遗症认知能力变化的6种底层机制：

1. Immune system's response to the virus increases molecules such as cytokines and chemokines, which can put the brain on fire (neuroinflammation).

免疫系统对病毒的反应增加了细胞因子和趋化因子等分子数量，这些分子会引发大脑炎症（神经炎症）

1. The virus itself can directly infect the brain.

病毒本身会直接感染大脑。

1. The virus can give rise to an autoimmune response where the brain attacks its own cells.

病毒会引发一种自身免疫反应，让大脑攻击自己细胞。

1. The virus can wake up dormant herpesviruses, like the Epstein-Barr virus, damaging the brain and leading to cognitive impairments.

病毒会唤醒潜伏的疱疹病毒，如EB病毒，这会损伤大脑，引发认知受损。

1. The virus and the resulting biological response can impair blood circulation, which provides the conduit of nourishments to brain cells.

病毒和其所导致的生物反应会损伤血液循环，从而影响对大脑细胞的营养输送。

1. Multi-organ dysfunctions in severe COVID cases can cause hypoxemia (a below-normal level of oxygen in your blood, specifically in the arteries) and metabolic disturbances that deprive brain cells of oxygen and nourishment and, in turn, provoke cell death.

新冠重症患者种的多器官功能障碍会引发低血氧（血液中，尤其是动脉中氧含量低于正常水平）和新陈代谢紊乱，从而导致大脑细胞缺乏氧分和营养物质，从而引发细胞死亡。

Where can we go from here
未来可以依循怎样的研究方向

It would be more beneficial to target the currently known mechanisms of brain changes in long COVID to search for efficient and effective treatments. Specifying the exact brain changes in long COVID using sensitive neuropsychological tests is crucial. The symptoms reported by long COVID patients, such as memory problems, might result from dysfunctions in other faculties, such as attention, default mode network, processing speed, neuroplasticity, neuro-inflammation, etc. Also, following the trajectory of these cognitive symptoms is essential. Cognitive deficits do not always lead to dementia or permanent decline.

建议在寻找高效和有效治疗方法时，应着眼于新冠长期后遗症大脑变化的目前已知致病机制。通过敏感神经心理测试来明确界定新冠长期后遗症中的大脑变化，这一点至为关键。新冠长期后遗症患者所报告的症状，比如记忆问题等，可能来自于其他机能的功能失调，比如注意力、默认模式网络、处理速度，神经可塑性，神经炎症等。另外，追踪这些认知症状的发展轨迹也至关重要。认知缺陷并非都会导致痴呆或永久退化。

As a sufferer of long COVID since 2020, the problem with my long-COVID brain is not one of memory deficit. It is more like the time scale used by the brain is much slower than the actual time. By the time the next moment begins, I am still processing the previous one. Or I stop processing the previous one in favor of hoping to catch the next one fully.

作为自2020年以来新冠长期后遗症患者，我的新冠后大脑的问题并非是记忆缺陷，而更像是我的大脑所采用的时间标尺要比实际时间缓慢。在下一时刻开始之前，我还依旧在处理之前时刻的信息。或者我会为了充分赶上下一时刻，而直接终止对之前信息的处理。

Also, the long-COVID brain struggles with multitasking, tasks requiring a long attention span, and intense focus. The byproduct of this slowing of brain machinery is memory deficits. While using strategies to improve memory would help, addressing the more direct mechanism would be better.

另外，新冠长期后遗症患者大脑会难以同时处理多项任务，或者需要长时间集中注意力的任务，或者精力的高度集中。大脑机器变得迟缓所带来的副产品是记忆缺陷。尽管一些记忆提升策略会有帮助，但如果能针对其更为直接的产生机制，则会更有效。