TreatmentUpdate
236

May 2020 

The brain and nerves in COVID-19

Historically, scientists have thought that coronaviruses generally caused infection of the respiratory tract in people (the wet tissues of the nose, mouth, throat, airways and lungs) and the intestinal tract in animals.

In the outbreak of coronavirus disease that occurred in 2002-03 with severe acute respiratory syndrome (SARS), scientists conducted autopsies of some people who had SARS. They found that the virus that caused SARS, SARS-CoV, was present in many tissues, including brain cells. As this virus is closely related to the virus (SARS-CoV-2) that causes COVID-19, it is possible that SARS-CoV-2 can infect a wide range of tissues, including cells in the brain.

It is not clear how SARS-CoV-2 gains entry to the brain. It is possible that the virus could be transported there via cells of the immune system, as these cells are distributed throughout the body. Cells of the immune system could become infected with SARS-CoV-2 in one location, such as the respiratory tract, and then bring the virus to the brain.

Another possibility is that the virus could get into the brain by infecting nerves that connect different parts of the body to the brain.

Whatever route is used by the virus, it is plausible that in a subset of people, infection with SARS-CoV-2 can affect the functioning of parts of the brain.

Brain inflammation

Viruses that can infect the brain can cause inflammation of this organ. Doctors at a hospital in Qingdao, China, have documented a case of brain inflammation in a 56-year-old man with SARS-CoV-2. The doctors did not provide clinical details but did note that his spinal fluid contained SARS-CoV-2.

In experiments with mice and another coronavirus (called HCoV-OC43) that can infect people, scientists found that mice that survived the infection had traces of the virus in their brains for several months.

Other scientists have noted that infection with SARS-CoV-2 is associated with headache, nausea and vomiting. In some cases, these symptoms may be due to infection of the brain or the nerves that are in the intestine.

The virus that causes SARS can infect the brain stem. This is a part of the brain that is involved in regulating automatic functions such as breathing, heart rate and alertness/consciousness. As breathing difficulties can be a feature of severe COVID-19, some scientists have speculated that SARS-CoV-2 may have the ability to injure nerves in the lungs or brain stem that affect the health of the lungs.

Loss of consciousness

The main function of the lungs is to absorb oxygen from the air and release the waste product carbon dioxide. Since COVID-19 is associated with breathing difficulties in severe cases, it is possible that in some of these cases not enough oxygen can enter the tissues of the lungs and, subsequently, blood vessels that connect the lungs to the rest of the circulatory system. As a result, it is possible that vital organs, such as the brain, do not receive enough oxygen, which causes the brain to malfunction. This lack of sufficient oxygen may be one possible explanation for cases in which people with severe COVID-19 have become unconscious.

Neurological symptoms

Neurologists from three hospitals in China recently reviewed data from 214 people with laboratory confirmed COVID-19. These patients were investigated for possible neurological issues. The doctors found that 36% of these people had symptoms that included at least one of the following:

  • dizziness
  • headache
  • reduced sense of taste
  • reduced sense of smell
  • nerve pain
  • muscle weakness (explained below)

Such symptoms were more likely in people with severe COVID-19.

The doctors stated: “Most neurological manifestations occurred early in the course of illness.”

Some of these patients sought medical attention because of stroke or seizure; initially they did not have what the doctors described as typical COVID-19 symptoms (fever, cough, loss of appetite, diarrhea).

Analyses of blood samples from these patients revealed that many with severe COVID-19 had elevated levels of proteins associated with inflammation, including C-reactive protein, D-dimer, elevated levels of liver enzymes and so on.

To help control muscles, many nerves connect muscles to the brain. People with muscle injury associated with COVID-19 had elevated levels of the enzyme creatine kinase in their blood. It is not clear if the virus directly infects muscle cells or how it might otherwise injure them.

Smell and taste disorders

Doctors in Milan, Italy, interviewed 59 people with COVID-19 about their symptoms. They found that 34% reported “at least one” disorder of taste or smell. In 19% of people, both disorders were reported. Disorders of taste were more common prior to hospitalization. After hospitalization, both disorders could appear with equal frequency.

Note that disorders of a sense of smell can have other causes, such as sinus infections, and by themselves, do not prove that a person has COVID-19.

Due to being overwhelmed by cases of COVID-19, the Italian doctors were unable to conduct further assessments of smell and taste disorders. However, their findings highlight an intriguing consequence of COVID-19, at least in some affected people.

—Sean R. Hosein

REFERENCES:

  1. Wu Y, Xu X, Chen Z, et al. Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain, Behavior, and Immunity. 2020; in press.
  2. Helms J, Kremer S, Merdji H, et al. Neurologic features in severe SARS-CoV-2 infection. New England Journal of Medicine. 2020; in press.
  3. Li YC, Bai WZ, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. Journal of Medical Virology. 2020; in press.
  4. Giacomelli A, Pezzati L, Conti F, et al. Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a cross-sectional study. Clinical Infectious Diseases. 2020; in press.
  5. Mao L, Jin H, Wang M, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurology. 2020; in press.
  6. Chen T, Wu D, Chen H, et al. Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study. BMJ. 2020; in press.
  7. Zhou L, Zhang M, Wang J, Gao J. Sars-Cov-2: Underestimated damage to nervous system. Travel Medicine and Infectious Disease. 2020; in press.
  8. Poyiadji N, Shahin G, Noujaim D, Stone M, Patel S, Griffith B. COVID-19-associated acute hemorrhagic necrotizing encephalopathy: CT and MRI features. Radiology. 2020; in press.