US scientists have found the first direct evidence that coronavirus could infect the human brain and replicate inside its cells, heightening concern about the disease’s poorly understood neurological symptoms.
Thomas Hartung and colleagues at Johns Hopkins University, made the discovery after adding low levels of Sars-Cov-2, the virus responsible for Covid-19, to tiny neuronal balls known as mini-brains that are grown from human stem cells.
The researchers found that the virus infected neurons in the mini-brains via the ACE2 human protein that is known to be an important entry point for Sars-Cov-2. The virus then multiplied within the neurons; within three days the number of copies had increased at least tenfold.
“It is really critical to know that our most precious organ can be directly affected by the virus,” said Prof Hartung, a toxicology expert at Johns Hopkins, adding that it was still unclear how frequently this happened in Covid-19 patients.
Whether the virus can infect the brain is among the biggest questions in a long list of unknowns about the way the disease seems to affect most tissues and organs in the human body.
The study, which is under peer review at the journal Altex but not yet published, follows unconfirmed reports of neurological symptoms in Covid-19 patients, including in the original outbreak in Wuhan. More than a third of coronavirus victims who were hospitalised in the Chinese city exhibited neurological symptoms, including dizziness, headache and seizures.
However, it has never been clear whether the virus affects the brain and nerve cells directly or whether such symptoms are a secondary result caused by damage to the patients’ immune and cardiovascular systems.
For instance, it is not known whether a loss of the sense of smell, a common symptom of the virus, is a result of direct infection of olfactory neurons or a side-effect of infection in other cells involved in olfaction.
Thomas Hartung: ‘It is really critical to know that our most precious organ can be directly affected by the virus’ © Lena Smirnova, Johns Hopkins University
If Sars-Cov-2 can attack the human brain, it has to get past the blood-brain barrier that shields the organ against many viruses and chemicals and often prevents infections.
Although the Johns Hopkins mini-brains show some features of a human brain, including electrical activity and communications between neurons, they lack other features, including the blood-brain barrier.
“Whether or not the Sars-Cov-2 virus passes this barrier has yet to be shown,” Prof Hartung said, “but it is known that severe inflammations, such as observed in Covid-19 patients, make the barrier disintegrate”.
The mini-brains, known as BrainSpheres, were developed four years ago and are mass-produced as standardised organoids for toxicology testing of drugs. They have been used to study the effect of other viruses on the brain, including Zika, dengue and HIV.
One particular concern highlighted by Prof Hartung was over the possible effects of the virus on the foetal brain during pregnancy. Other research has shown that the virus crosses the placenta and that embryos lack the blood-brain barrier during early development.
“To be very clear, we have no evidence that the virus produces developmental disorders,” Prof Hartung emphasised. “But clinicians need to know about this research, because it has consequences about [being] cautious and preventing infection during pregnancy.”
The research has significant implications for attempts to find treatments for the virus. If Sars-Cov-2 does infect the brain, it may complicate efforts to eradicate the infection through drugs, because many medicines cannot get past the blood-brain barrier.