Scientists believe they may have an explanation for the swathe of neurological symptoms seen in long COVID patients, and it could be to do with the elimination of connections within the brain. Based on the findings of a new study, a reduction in synapses – that is, the gaps between neurons that signals pass through – could be to blame as to why many experience “brain fog” associated with COVID recovery. 

Long COVID is a mysterious condition in which people who got infected with COVID-19 appear to have symptoms for often many months after recovering from the initial illness. Symptoms vary, but a common theme is a “brain fog”, in which people have problems with cognition, sleep, and memory. The name comes from a foggy feeling in the brain, making you sluggish and struggling to make decisions. 

The brain fog is difficult to study, particularly because we can’t open up living brains and have a look inside. All we can do is use cadavers and look back in retrospect, or use tiny brain organoids to simulate what is happening at a larger brain scale. 

That is exactly what a new study by the Karolinska Institutet, Sweden, did. Taking tiny brain organoids, they infected them with SARS-CoV-2 and watched as the organoids developed to see what happened. 

Immediately, the virus particles initiated neuronal cell death, which has been widely characterized in the past. More interestingly, however, was the loss of connections between neurons. It wasn’t the virus that was directly doing this though. Instead, immune cells called microglia, which typically clear synapses as part of daily housekeeping within the brain, were clearing them at a much higher rate than normal.  

The loss of synapses, which provide crucial communication between brain cells, could explain why people have cognitive troubles while suffering from long COVID. The profile of these errant microglia is extremely similar to other neurodegenerative conditions like Parkinson’s and Alzheimer’s, which incidentally, also have significantly higher risks after COVID-19 infection. Genes switched on or off during COVID-19 infection mimic the changes seen in these conditions, contributing to a similar outcome of synapse loss, and this may go towards explaining why COVID-19 infection may increase the risks of neurological conditions. 

This is now just the starting point for the researchers and they hope to search for drug candidates to inhibit the changes seen in their models. They already have an antibiotic candidate that has been shown to reduce synapse loss via microglia, and the next move will be to use it on their organoids during COVID-19 infection to see if it helps. 

The study was published in Molecular Psychiatry.