Can the Novel Coronavirus ‘Turn off’ Brain Areas That Control Breathing?

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Previously: Does the Coronavirus Affect the Brain?

Quick disclaimer: Take all information about COVID-19 cautiously. A lot of studies are case reports, preliminary data, preprints, and/or not peer-reviewed. That does not mean the information in these papers is wrong, but they could just depict an exemption or be presumptive to begin with. This post relies on the review of Li and Colleagues (2020), which is therefore not cited everywhere.

We know that the novel coronavirus SARS-CoV-2 can cause severe respiratory distress and pneumonia that requires hospitalization. But what if the lungs are not the only target that cause breathing problems? What if the brain is involved, too?

What Research on Other Coronaviruses can Tell us

The novel coronavirus SARS-CoV-2 didn’t get the term ‘novel’ for no reason: It is part of a family of coronaviruses (Coronaviridae) that have been around for a longer time already. Being part of a family, like in humans, means being more closely related to each other than to viruses of other families. Families themselves can get further subdivided though. You might have heard of the Severe Acute Respiratory Syndrome SARS-CoV (SARS) which broke out in 2002, or the Middle Eastern Respiratory Syndrome Mers-CoV (MERS) from 2012. Both of them, just like SARS-CoV-2, belong to the family of Coronaviridae, and also to the same genus of Betacoronaviruses. Only SARS and SARS-CoV-2 belong to the next further subdivision, the subgenus of Sarbecoviruses though, meaning that they are more closely related to eachother than to MERS. These relations and the fact that MERS and SARS have been around and studied for a longer time, might be able to give us valuable input into the mechanisms that SARS-CoV-2 might be engaging (they are still different viruses though and causerelated but different symptomatics!).

A genomic analysis by Yu and colleagues (2020) showed that SARS shares a very similar sequence with SARS-CoV-2. Additionally, they are using the same mechanism to enter into host cells (Lu et al., 2020): The spike proteins (= ‘keys’) on the viruses surface bind to the angiotensin converting enzyme 2 (ACE2, = ‘lock’) on the human cell. Opening the ‘lock’ with the ‘key’ leads to conformational changes, eventually allowing endocytosis (=entry) of the virus into the cell. ACE2 usually plays an important role in the renin-angiotensin-system which is regulating blood pressure. ACE2 can be found in high concentrations in the heart, respiratory system and gastrointestinal tract, however, it can be also found in lower concentrations in the brain and the cells of the blood brain barrier (BBB). However, presence of ACE2 doesn’t necessarily mean that a cell can get infected.

Increasing cases suggest that the coronavirus is able to actually enter the brain (in rare cases). Different pathways have been proposed based on previous findings in MERS and SARS, such as the nose, which is connected to the brain via the olfactory bulb, the vagus nerve, or the blood circulation in combination with a blood brain barrier that has been broken down due to inflammation (Xu et al., 2005, Matsuda et al., 2004, Li et al., 2013, Netland et al., 2008, Li et al., 2016).

What Happens if the Virus Enters the Brain?

The virus will do what it would do in any other cells or tissues in the body, too: it wants to replicate itself. And it makes the cell do it for it. This can lead altered or loss of function, or to the death of the host cell. In case of the brain, this would mean neuronal death. Depending on the extent of neuronal death, this could shut down or alter functions of entire brain areas.

So what if the Virus Kills off Brain Cells in the Breathing Center?

Li and colleagues (2020) propose that this might be a possible reason for why most (89%) of patients in intensive care are not able to breathe spontaneously. The ‘breathing center’ is located in the medulla oblongata and pons, who both belong to the brain stem. It’s most important function is to make us breath regularly without actively needing to think of it. The lack of the urge to breath spontaneously might be indicating that on top of the lungs being affected, the brain stem might be too. Li and colleagues (2020) support this hypothesis with previous findings in SARS, that showed particles of the virus mainly infecting brain stem and thalamus (Netland et al., 2008), and the avian corona virus in mice (Matsuda et al., 2004).

Conclusion

In summary, Li and colleagues (2020) hypothesize that dysfunction in the breathing center of the brain could be a reason for the lost drive to breathe in severe cases of COVID-19. They base this hypothesis mainly on research on other viruses of the coronavirus family. Whether it is really the case in severe COVID-19 cases still needs to be further investigated.