Covid: really scary brain changes in mild cases

 A preprint, pre-peer reviewed study was done in the UK finding important changes in brain scans after Covid-19 infections, even after mild ones (see ​​covid brain mri changes medrix2021 in dropbox, or doi.org/10.1101/2021.06.11.21258690 ) 

 

Details: 

-- over 40,000 volunteers had MRI scans done prior to the Covid pandemic, stored in the UK Biobank 

-- mean age 60, 43% male, 97% white, blood pressure 115/80, BMI 26 

-- researchers reviewed 782 scans of people who had prior MRIs in the Biobank and second scans done on average 37 months after the initial ones:

    -- 394 people with 2 scans later tested positive for Covid, and these people were matched for age, sex, ethnicity, and interval between the scans with people who did not have Covid

-- 15 of these Covid patients had been hospitalized (2 in the critical care unit, 3 with ventilatory support), 379 had non-hospitalizable infections 

-- the study compared the 1st and 2nd scans of individuals who did vs did not have symptomatic Covid and compared their pre- and post-covid scans for MRI changes, vs the same assessment for people who did not have symptomatic covid

 

Results: 

-- those with Covid vs without: significant effects of Covid in the brain with a loss of gray matter in the left parahippocampal gyrus, the left lateral orbitofrontal cortex, and the left insula. There were  also changes in the anterior cingulate cortex, supramarginal gyrus, and temporal pole. All results were localized to the left hemisphere 

-- there were comparatively similar findings in the Covid-19 group who were hospitalized vs the non-hospitalized, though with a greater loss of gray matter in the cingulate cortex, central nucleus of the amygdala, and hippocampal cornu ammonis in the latter

 

Commentary: 

-- this study had the huge benefit of individual data from people pre-and post- Covid infection, as compared to controls without clinical SARS-CoV-2 infection 

    -- prior studies had found significant brain related pathologies, but this study is able to show specific changes in the same individuals before and after infection 

-- there is evidence of symptomatic neurologic complications of Covid in a large number of patients, with neurologic symptoms in more than 80% of severe cases

-- the loss of gray matter in the limbic cortical areas are consistent with the clinical changes in the olfactory and gustatory systems; also the limbic region is involved in supporting longterm memory of events and emotional behaviors (ie, damage to these areas might well translate not only to the common symptoms of loss of smell/taste, but perhaps also “brain fog” and memory issues…..) 

-- there has been speculation in the past that the olfactory mucosa and the olfactory bulb were the entry point of the virus into the brain, consistent with the above findings 

    -- there is a question of reverse causation: were the cerebral changes found a result of direct viral invasion or from nasal changes that led to disrupted connection with the central nervous system, decreased stimulation, and resultant cerebral atrophy.  

    -- However, coronavirus itself has been found in the central nervous system in prior studies 

-- one interesting finding was that comparing Covid patients and controls, the biggest difference was in the volume of the thalamus. BUT, since they had high quality scans prior to infection, it turned out that this effect “entirely disappears when taking into account the baseline scans”. So, this raises the rather intriguing issue: is there a baseline difference in brain anatomy/physiology that predisposes some people to getting more neurologic damage?? And, it also confirms the real importance of looking at changes in imaging in individuals and not just making observations/conclusions based on single scans of people who were infected with SARS-CoV-2… 

-- it is also not clear why the findings were much more in the left hemisphere, though there is an apparent asymmetry in the olfactory system itself, and the left hemisphere is more involved in the emotional aspects of olfactory memory (the right hemisphere is more involved with the longterm memory processes) 

    -- and, it is concerning that some of these findings are found with Alzheimer’s disease/other dementias, including this left sidedness of the olfactory effect. Will there be really long-term increases in dementia in those with Covid-19? Even mild cases? Will it show up early as “brain fog”? will it be silent for years and then manifest itself as early dementia???? 

-- what about people with asymptomatic disease? Will they have neurologic issues (including increased dementia) that manifest themselves clinically over time?? 

 

Limitations: 

-- this was a preprinted and pre-peer reviewed article, and there may be significant changes as in some other similar articles after more detailed peer evaluation 

-- there are no real granular data on psychosocial issues that might affect brain development, evolution, or function, such as stress, diet, exercise, socioeconomic issues, psych issues etc, etc.  

    --and, no data on the specifics of the clinical covid infection, eg oxygen saturation levels (though we do know that the vast majority had “mild” infections)

-- those in the Biobank were volunteers. Were they different in important ways from the general population??? (which would limit generalizability of their conclusions…) 

-- as an observational study, one cannot prove causality, only an association 

-- it is a bit of a logical leap to translate gross scan data into functional equivalences on a neuronal and clinical level. There are studies suggesting that grey matter thickness or volume are very sensitive markers or neurodegenerative processes, which provides some support, but still not totally clear 

-- does the brain recover? it does in some diseases (eg: studies have shown that stress or depression dramatically decreases hippocampal neuronal density and memory. but this recovers over time). would be important to rescan these people later to see if changes are long-term

 

So, this article confirms a significant effect of the virus on peoples’ brains (with the benefit of being able to compare pre- and post-infection scans), that it happens even in those with mild cases, and it provides a plausible physiologic mechanism for the post-covid, long covid, sequelae-of-covid syndrome. There are lots of unanswered questions, including in comments above, but this is all pretty scary stuff… 

 

And, yet again and again: vaccinate, vaccinate, vaccinate.  And make vaccine-hesitant patients aware that there may be profound, long-lasting consequences of even mild Covid-19 infections 

geoff

 

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