Ah, I get it, your brain is not in your head, it is in your Lymph Nodes - gotcha.
Opinion Long COVID and Cognitive Deficits
Opinion Long COVID and Cognitive Deficits
Eric J. Topol, MD
March 07, 2024
The following first appeared in the Substack of Eric Topol, MD, called Ground Truths.
Two new studies published in the New England Journal of Medicine today address the extent and duration of cognitive deficits after COVID in very large cohorts.
The First Study
Eric J. Topol, MD
In England, in a prospective study nearly 113,000 participants, with or without COVID infections, accepted the invitation to participate and completed a cognitive and memory assessment and after 12 weeks, with or without symptom resolution. The cognitive 8-domain assessment demonstrated that the impact of COVID was mainly seen on memory, executive function and reasoning. The adverse cognitive impact was worst with the original (ancestral) virus and the Alpha variant, compared with subsequent Delta and Omicron variants, and there was some protective effect of vaccination.
The Second Study
In Norway, over 134,000 participants in a nationwide study (of ~188,000 total) with COVID tests completed a 13-item memory questionnaire (EMQ, range of score 1-52 points) at baseline, pre-COVID, and subsequently at several points up to 3 years. The analysis was adjusted for age, vaccination status, co-existing conditions, and many known potential confounding characteristics. About half of the near 112,000 participants with COVID tests were either positive or negative. Before COVID, their baseline scores were the same, but there was significant decline in the participants at every time point assessed in those who tested positive for COVID during extended follow-up.
Both studies have the limitation of ascertainment bias — participants who enrolled and were willing to do the assessments, as compared with those who did not for reasons such as being too sick.
An accompanying editorial by Ziyad Al-Aly and Clifford Rosen provided important context, citing the US Population Survey with more than 1 million Americans reporting having “serious difficulty” remembering, concentrating, or making decisions than any time in the preceding years. The graphic accompanying their editorial, reviewing the different mechanisms that appear to be underpinning brain involvement from COVID, is excellent. This important topic was just reviewed by Michelle Monje in the Ground Truths podcast, as she highlighted the role of microglia activation (the most prominent immune cells in the brain, functioning like specialized macrophages in the brain) as likely playing a/the key role of promoting brain inflammation.
Summary
The 2 new studies are the largest to date to prospectively assess COVID impact on cognitive function, and both are consistent in showing declines as compared with controls without COVID. The assessment of cognition in the cohort from England was more in-depth, but of shorter duration, and demonstrated the favorable effect of symptom resolution. The extrapolation to a loss of 3 to 9 IQ points is difficult contextualize, and the risk of long-term sequelae is unknown. It is worthwhile noting that these IQ score losses represent averages, and there is considerable variability in cognitive deficit. In contrast, the Norwegian study only got into memory but had much longer, serial assessment up to 3 years. None of this is good news for long COVID and the brain, folks.
The findings are aligned with the important UK Biobank study with serial MRIs before and after COVID, and a control group who did not get COVID, along with several other related reports that I previously reviewed.
Unfortunately, there will continue to be people who will attempt to dismiss or discount the important effects of COVID on cognitive function. Just the opposite of denialism is what is needed — to recognize this cognitive impairment is real, that millions of people are affected, and much more needs to be done to find effective treatments of long COVID and understand its longer term impact, particularly neurologic.
Thanks for reading, subscribing, and sharing Ground Truths.
Eric Topol, MD, is executive vice president of Scripps Research - Medscape.
Me: "None of this is good news for long COVID and the brain". So we accept that Long Covid is a brain related issue (re my free salt water cure) so why the Pfizer vaccines this then: Last year we learnt that BioNTech, the company that developed the mRNA vaccine with Pfizer, wanted the mRNA to travel around the body to the lymph nodes.
Virginie Joron, a French MP, tweeted a picture from a presentation she was attending. The speaker was Özlem Türeci, co-founder of BioNTech and her slide was called ‘The Bodyhack - Bringing mRNA to the right cells at the right places’.
The image clearly shows that the cells BioNTech were targeting were dendritic cells in the lymph nodes. Robert Kogon reported that “A passage from The Vaccine, the book that Türeci and her husband, BioNTech CEO Ugur Sahin, wrote with journalist Joe Miller, explains why BioNTech’s platform specifically targets the lymph nodes:
What Ugur learnt was that the location to which a vaccine delivers its ‘wanted poster’ really mattered. The reason for this, the couple’s team in Mainz later realised, was that not all dendritic cells … were created equal. The ones that resided in lymph nodes – of which the spleen is the largest – were particularly adept at capturing mRNA and making sure the instructions it carried were acted upon. These kidney-bean shaped organs, found under our armpits, in our groins, and at several other outposts in the body, are the information hubs of the immune system. (p. 98)
Indeed, Sahin and Türeci were so determined to get their mRNA into the lymph nodes that they had an earlier mRNA construct injected directly into the patient’s lymph nodes in the groin (p. 104).
Ah, I get it, your brain is not in your head, it is in your Lymph Nodes - gotcha.