How can COVID-19 affect the brain?

By Mahesh Jayaram and Christos Pantelis

COVID-19 has transformed everyone’s lives globally. Early on in the pandemic, our research team became interested in the symptom of anosmia (loss of smell) as an early clinical feature of COVID-19 infection. “Why does this occur?” we wondered, and began exploring further to see if the virus impacted the brain, mental health or had consequences for pregnant women and newborns. Our recently published findings suggest that COVID-19  can indeed have serious impacts on the brain, causing not only loss of smell and taste but also confusion, headaches, fluctuating consciousness and, more seriously, strokes and thrombosis (blood clots). It also causes significant mental health issues such as depression, anxiety, fatigue and sleep disorders. Although pregnant women and some newborn infants tested positive for COVID-19, there have been no reports of significant birth complications, however risk of clotting for the mother remains high.

It is not only difficult to keep up with COVID-19 literature, which is being published at ‘warp speed’, but also challenging to evaluate the quality of these studies. In our paper, we synthesised key scientific information to enable healthcare professionals to identify specific clinical features. We also used our research expertise in animal models to inform mechanisms of action of the virus and mapped out future research prioritisation.

We found that although COVID-19 commonly affects the respiratory system, it impacts the central nervous system (CNS) and brain surprisingly more commonly than thought (up to 84%). There are 3 possible pathways for this:

  1. Direct neuronal effect - the virus could invade the nervous system directly e.g. via the olfactory nerve and enter the brain. This was thought to cause anosmia, although other recent research indicates this is less likely. The next two options are more likely

  2. Inflammation mediated damage – severe COVID-19 infections lead to activation of microglia and macrophages – the cells that normally clear up debris in the brain, however in this instance potentiate a ‘cytokine storm’, an overreaction of the body’s immune system causing significant damage, which can be detected by MRI scans.

  3. Coagulation induced damage – the virus provokes a cascade of changes causing increased risk of clotting, which results in strokes in both the large and small blood vessels in the brain, thereby causing neurological symptoms.

“Does COVID-19 cause ‘brain fog’?”  

More people are talking about this worrying but as yet ill understood phenomenon. Brain fog describes a constellation of symptoms - fatigue, memory issues, confusion and difficulty focussing and can continue to occur for months after the acute infection has resolved. This seems to occur regardless of the severity of initial infection. We noted the increasing likelihood of depression, anxiety and Post Traumatic Stress Disorder (PTSD) which can also cause fatigue, insomnia, difficulty concentrating, mood fluctuations and thereby contribute to ‘brain fog’. Specific parts of the brain such as the amygdala, hippocampus have been involved which can mediate intense states of fear and emotion. It is now becoming apparent that these symptoms continue for months (well over 100 days post infection) and has the potential to become a chronic health issue, thereby significantly affecting quality of life.

“Does COVID-19 impact pregnancy and newborns?”

This question vexes every impending parent. The good news so far is that no major abnormalities have been reported in neonates or their mothers who were COVID-19 positive. Whether infection in critical earlier trimesters causes neurological development is an issue we are yet to uncover. Mothers who test positive are at increased risk of clotting. Antibodies such as IgG and inflammatory markers (cytokines) have crossed the placenta and were found in infants. Notably, larger antibodies such as IgM which could not have crossed the placenta were found in newborns suggesting that these were produced by the infant in response to viral exposure within the womb. One study reported infants less than 3 months experienced neurological symptoms. These issues suggest the need to monitor infants carefully to evaluate if other neurodevelopmental issues may emerge years later. Fifteen years from now, whilst taking a developmental history, we will need to ask if infants were born to COVID-19 positive mothers.

For now, in the absence of a cure, we need to do our best to avoid infection and if we do get it, we need to monitor for neurological, neuropsychiatric and pregnancy related sequalae. We are urging clinicians to be aware of these complications as they can occur both during the acute and post recovery phase of COVID-19 infection.

Article Details

Neurological, neuropsychiatric and neurodevelopmental complications of COVID-19
Christos Pantelis, Mahesh Jayaram, Anthony J Hannan
First Published October 1, 2020 Research Article
DOI: 10.1177/0004867420961472
Australian & New Zealand Journal of Psychiatry

About the Authors