Could the COVID-19 Virus Be Neuroinvasive?

Post by Flora Moujaes 

What's the science? 

In late February 2020, a few days before the World Health Organization declared COVID-19 a pandemic, Li and colleagues from Jilin University in eastern China published an article proposing that the COVID-19 virus may be able to enter the brain and spinal cord. The hypothesis that COVID-19 is neuroinvasive suggests that the respiratory distress experienced by COVID-19 patients is not just due to inflammatory structural damage to the lungs, but also due to damage to the respiratory centers of the brain that control breathing. This could help explain why some patients develop acute respiratory failure and others do not. This week in the Journal of Medical Virology, the researchers published a follow-up article outlining the additional evidence for this hypothesis that has emerged in the last month, as COVID-19 continues to spread around the world.  

What’s the theory? 

When Li and colleagues first published their hypothesis that the COVID-19 virus may be neuroinvasive, their theory was mainly based on the evidence that other similar coronaviruses are neuroinvasive. For example, the severe acute respiratory syndrome (SARS) epidemic, which began in the early 2000s and resulted in 774 deaths, was caused by a similar coronavirus to COVID-19. The SARS virus has been found in neurons in the brains of both patients and experimental animals, particularly in the part of the brain known as the medulla, the brain’s primary respiratory control center. If like the SARS virus, the COVID-19 virus is able to invade brain regions such as the medulla, this invasion could be partly responsible for the acute respiratory failure seen in COVID-19 patients. It would also explain why one 24-year-old COVID-19 patient described losing her ability to breathe involuntarily, and why a small number of initial COVID-19 patients reported neurological symptoms such as headaches (8%) and nausea and vomiting (1%). 

What’s new? 

At the time of publishing their initial hypothesis that COVID-19 may be neuroinvasive, there were less than 90,000 confirmed cases worldwide. One month later, Li and colleagues published a follow-up article outlining the additional evidence for the hypothesis that emerged as the number of worldwide cases surged to over 1.5 million:

(1)   A study on 214 COVID‐19 patients in Wuhan found that neurological symptoms were more common than previously thought and that severe patients were more likely to display neurological symptoms: 36.4% of patients showed neurological symptoms while severe patients were more likely to display neurological symptoms such as acute cerebrovascular diseases (5.7%), impaired consciousness (14.8%) and skeletal muscle injury (19.3%). 

(2)   Loss of smell and taste has also been reported in COVID‐19 patients in several countries, and a similar olfactory dysfunction was also reported in SARS patients. While this symptom can commonly be caused by changes in the nasal cavity during illness, loss of smell can also result from damage to the olfactory nerve through which the virus may enter the brain.

(3)   A limited number of individual case studies demonstrated that the COVID-19 virus is able to infiltrate the brain. For example, in Japan a 24-year-old COVID-19 patient showed meningeal irritation: inflammation of the membranes that cover the brain and spinal cord. Meanwhile, in Beijing a 56-year-old COVID-19 patient presented with encephalitis: inflammation of the brain most commonly caused by a viral infection. Cerebrospinal fluid samples from both patients tested positive for the COVID-19 virus.

(4)   It is still unclear why some patients develop respiratory failure and others do not. For example, a study on 81 COVID‐19 patients in Wuhan showed both asymptomatic and symptomatic patients displayed lung lesions. If neuroinvasion of COVID-19 affected an individual’s breathing, it could help explain the differences in disease progression between these two groups of patients.

What’s the bottom line?

There is growing evidence that the COVID-19 virus may be neuroinvasive. If this is the case, lung infections may not be the only contribution to COVID-19-related breathing difficulties; brain infiltration and damage to the key brain structures involved in the control of respiration like the medulla could play a role. More research is needed to confirm this hypothesis, and the current severity of the pandemic limits the capacity to conduct the necessary research. A greater understanding of the potential brain and spinal cord infiltration of COVID-19 could be critical for the prevention and treatment of this virus. In particular, understanding whether the virus is neuroinvasive may help explain why some patients develop respiratory failure while others do not. Neuroinvasion may also explain why complete clearance of the virus may not be guaranteed even after patients have recovered from acute infection.

Li et al. Response to Commentary on “The neuroinvasive potential of SARS‐CoV‐2 may play a role in the respiratory failure of COVID‐19 patients”. Journal of Medical Virology (2020). Access the original scientific publication here.