生物与医学2021thelancet.com
新冠康复者的认知缺陷
Cognitive deficits in people who have recovered from Covid-19
进阶 · 约 25 分钟读完前置知识：基础统计与假设检验、认知测试/智商评分常识、横断面研究设计
导读
这项发表在《柳叶刀·EClinicalMedicine》的研究基于大规模在线认知测试（英国智力测试），比较了曾感染新冠并康复的人群与未感染者在认知表现上的差异，发现感染者存在认知缺陷，且缺陷程度随病情严重程度递增——从非住院者的约0.4个智商点，到住院并使用呼吸机者的约7个智商点。需要注意这是横断面组间比较，而非同一批人感染前后的纵向对比。
HN 关注点：HN读者一方面关注其方法学局限（横断面设计、社会经济混杂因素），另一方面讨论即使是很小的认知损伤，放到庞大感染人群上也可能有可观的公共卫生影响。
后来怎么样
该研究成为长新冠认知影响领域被广泛引用的早期大规模证据之一，推动了后续纵向队列与神经影像研究对感染后认知障碍的关注，但其横断面设计导致的因果推断局限也常被同行引用讨论。
HN 评论精选
这几条评论里：质疑 2 补充 2
质疑研究是横断面组间比较而非同一人前后对比，且未控制早期感染在社会经济层面的分布差异；作者本可复测275名感染后个体却错失机会。
这项研究至少存在一个明显的方法学缺陷：他们并没有对同一批人在感染前后进行测评，而是把既往感染者和未感染者作为两组人群来比较。虽然他们尝试校正了年龄等部分社会经济因素，但数据无法纳入早期新冠病例分布中的社会经济差异——早期感染绝大多数冲击的是需要直接面对客户的服务业从业者，而有研究生学位的人比没有高中同等学历的人更可能自我隔离、居家办公。让我觉得遗憾的是，这些研究者其实有条件复测原测试者中的一个子集：超过10%的人在2020年12月完成了随访调查，其中出现了275名在首次参与研究后感染新冠的个体。复测这275人以及另外8000多名新冠状态未变的人（以控制年龄增长、因重复做测试而分数提高等因素），数据集足够大，至少能确认或排除较大的效应量。
bijant查看英文原文
This Study suffers from at least one significant methodological flaw. They did not evaluate the same individuals pre- and post Covid infection but instead evaluated people as a group who were either previously infected or not. While they did try to correct for some socio-economic factors such as age their data did not allow them to factor in the socio-economic discrepancies in the distribution of early Covid cases which overwhelmingly hit service industry workers with direct customer exposure. People with Graduate Degrees were much more frequently able to self isolate and work from home than people without a high school equivalent degree. What I find to be quite sad, is the fact that these researchers were actually in a position to retest a subset of the original test takers as more than 10% completed a follow up survey in December 2020 which surfaced 275 individuals who had contracted Covid after their first participation in the study. Retesting those, as well as the >8000 individuals who had no change in Covid status to control for increase in age, increase in points due to getting better at the test with repeated exposure etc, would have been a sufficiently large dataset to actually confirm or rule out at least large effect sizes.
补充按病情严重程度分层，智商损失从0.4到7个点不等。
结果：研究显示，未住院的新冠患者智商约下降1个点。完整表格：新冠、无呼吸困难：损失0.4个智商点；新冠、有呼吸困难、无需家庭协助：损失1个点；新冠、有呼吸困难、需家庭协助：损失2个点；新冠、住院、未使用呼吸机：损失4个点；新冠、住院、使用呼吸机：损失7个点。
codesections查看英文原文
Results: The study shows ~1 IQ point decline for non-hospitalized Covid patients. Full table: Covid, no respiratory difficulty: 0.4 IQ point loss Covid, respiratory difficulty, no home assistance: 1 IQ point loss Covid, respiratory difficulty, with home assistance: 2 IQ point loss Covid, hospitalized, without ventilation: 4 IQ point loss Covid, hospitalized, with ventilation: 7 IQ point loss
补充结合英国脑成像研究，认为新冠的长期神经影响值得警惕，即使风险比例很小，在人群尺度上后果也可能很大。
我认为对新冠保持远比“只是大号流感”和“终将变成地方性流行病”阵营所认为的更谨慎的态度是合理的。英国那项脑成像研究也是朝这个方向的一个数据点（样本小、尚未同行评审）：https://www.medrxiv.org/content/10.1101/2021.06.11.21258690v2 。似乎有迹象表明新冠可能带来严重的长期神经影响。考虑到已经感染的海量人数（以及若变成地方性流行病会波及的人数），即便是相对小的风险因子（比如个位数百分比）之于路易体痴呆和帕金森病，也可能对公共卫生造成巨大影响。值得提醒自己的是，关于新冠的中长期影响，我们只有大约两年窗口的数据。
glangdale查看英文原文
I think it's reasonable to be way more cautious about COVID than the "just a flu" and "it'll become endemic" (for some value of 'endemic') crowd seem to think. The UK brain imaging study is a (small, not-yet-peer-reviewed) data point in that direction also: https://www.medrxiv.org/content/10.1101/2021.06.11.21258690v2 There seems to be somewhat of suggestion that COVID may have serious long-term neurological effects. Given the massive numbers that it has affected already (and how many it would affect if it becomes endemic), even relatively small risk factors (i.e. single digit percentages) for things like Lewy body dementia and Parkinsons could have huge effect on public health. It's worth reminding ourselves that we don't have any data on the mid-to-long term effects of COVID beyond about a 2 year window.
质疑0.2个标准差仅约3个智商点，接近测试本身的重复测量波动，小效应量难以可信测量。
挺有意思。重症感染的认知变化看起来是可信的，但我对较小的变化有些怀疑。0.2个标准差的下降只有3个智商点（随所用测试/量表略有差异）。如果只是用测试分数来推断他们之前的智商，这么小的降幅似乎很难测出来。智商测试本身就不太稳定，我连续做智商测试，波动都可能超过3个点。
giantg2查看英文原文
Kind of interesting. The changes with the more severe infections seems legitimate. I'm a little skeptical about the ones with smaller changes. A .2 sd reduction is just 3 IQ points (varies slightly on which test/scale is used). That seems like a very small decrease to measure when only looking for markers to evaluate their previous IQ. Testing IQ in general is a fickle thing. I could take IQ tests back to back and have it vary by more than 3 points.
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