COVID-19 in the Brain?

There is news circulating about COVID-19 and the brain that is worth a closer look. I first saw this in multiple news reports that did not cite the original article. A quick search pulled up a university press release that linked to the published article that studied the SARS-CoV-2 virus and inflammation in brains of infected mice.

Mice are often used to model human disease to study the source of the disease (viral, genetic, bacterial, etc.) and the pathology of disease (how it affects the body). This is often a good way to learn more about something, although great care has to be taken to develop a model that can be roughly translated to what happens in humans.

In this case, the mice, K18-hACE2, were made to express the human ACE2 receptor, the target of SARS-CoV and SARS-CoV-2. To mimic how this receptor is expressed in humans, it was given an epithelial promoter. Promoters tell a gene where it should be expressed. In this case, the promoter tells the gene to express in epithelial cells, which places the human receptor in the mice’s airways to allow the virus to infect cells similar to how it infects cells in a human. The specific promoter used is form keratin 18 (KRT18), which does have slightly broader expression than ACE2, but it’s a close approximation. Worth noting is that KRT18 does have low levels of expression in the brain, whereas ACE2 is undetectable.

Why go into so much detail about the mice model used in the study? The brains of these mice likely have more ACE2 receptors than a human brain would have. That does not invalidate the results of the study, but is a reason to give pause when comparing humans to the animal model. Also, this study doesn’t go into whether SARS-CoV-2 lingers in the brain because all of the mice died within six days. This is how a hypothesis is formed for further study. It is difficult, however, because you are limited to studying the virus in brains of people that died suddenly due to COVID-19 or from other causes, like car accidents, during an infection.

Something also worth noting is how scientific articles are summarized in press releases and news reports. University press offices put out these releases because it’s good publicity. They are often well written, but sometimes they overstate findings. In this case, the press release did include a quote from the researcher about the virus hiding in the brain, but the news reports are where statements about the virus later reactivating were inserted.

Viral reactivation typically refers to a virus that is coded in DNA and integrates into the host genome. This happens with the varicella-zoster virus (chickenpox that reactivates to cause shingles) and HSV1 (the virus that reactivates to cause cold sores). RNA viruses such as SARS-CoV-2 never get converted into DNA and do not have a dormant (lysogenic) part of their lives. It is possible that a virus may take longer to eliminate from certain organs or tissues, but this is not the same as reactivation that can occur months, years, or decades later.

Does this mean we should be worried about SARS-CoV-2 in the brain? The only immediate thing it would change is whether the disease adversely affects the parasympathetic nervous system and some treatments could better maintain things like breathing and heart rate. Does it mean that we have a possible avenue to explore to help explain long-term damage caused by COVID-19? Yes.

In short, I don’t see any changes in the short-term based on these findings, but it does encourage more research into these areas.

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