A new study showed a link between COVID-19 and neurological disorders. Researchers found that maternal immune response could elevate a cytokine, which might alter gene expressions related to autism and schizophrenia.
The association between COVID-19 and neurological disorders was unveiled by researchers led by King's College London. They identified a cytokine type that could alter gene expression. This alteration could increase the risk of a baby to develop autism spectrum disorder or schizophrenia later in life. The study suggested that a mother's immune response to the coronavirus might influence the cytokine's adverse effects on the baby's brain. They published their findings in the journal Science Advances.
Autism Spectrum Disorder Rates in the US and Other Countries
Autism spectrum disorder or ASD refers to a broad range of conditions characterized by specific challenges, such as issues communication and social skills, and repetitive behaviors. As such, the presentation differs in every case. While the exact cause is unknown, experts have determined factors that increase the risk of ASD. Some of the risk factors include medications, pollutants, pregnancy complications, and viral infections. Thus, doctors recommend pregnant women to avoid these risk factors during pregnancy.
According to Statista, a German portal for statistics, as of April 2020, Hong Kong at the highest prevalence rate of ASD in the world at 372 per 10,000 children. It was followed by South Korea at 263 per 10,000 children, the US at 222, Japan at 181, Ireland at 153, Switzerland at 145, and Canada at 106. Below the 100 per 10,000 children prevalence rate, Denmark was the highest at 69. It was followed by Singapore at 67, Belgium and Estonia at 60 each, Finland at 54, Norway at 51, the Netherlands at 48, Germany at 38, China at 23, Taiwan at five, and Poland at three per 100,000 children.
In the US, the prevalence of autism was increasing steadily from 2000 to 2014. In 2014, the rate was 16.8 per 1,000 children. It was higher than the 14.6 in 2012, 14.7 in 2010, 11.3 in 2008, nine in 2006, eight in 2004, 6.6 in 2002, and 6.7 in 2000. Simplified, the rates translated to one in 59 children in 2014, one in 68 children in 2012 and 2010, one in 88 children in 2008, one in 110 children in 2006, one in 125 children in 2004, and one in 150 children in 2002 and 2000.
Can COVID-19 Raise Autism Risk in Children?
When it comes to the complications of COVID-19, most doctors look for signs of respiratory distress, system-wide inflammation, and organ failure. They have to control these signs to prevent patients from succumbing to the disease. But due to little knowledge, no one is sure what else SARS-CoV-2 can do inside the human body. There is a possibility that the virus can attack the brain, heart, liver, and the kidneys, whether or not it has penetrated the lungs.
King's College London researchers and collaborators investigated if COVID-19 could be associated with neurological disorders. The investigation was inspired by other studies that linked viral illnesses to ASD. Influenza was a particular viral illness connected to autism. One study suggested an almost three-fold risk of autism in newborns if mothers had a severe influenza infection. But COVID-19 is more virulent and may have a greater impact.
"One of the conundrums surrounding the link between viral illness and autism is its longevity. We have all suffered viral illness and been bed-ridden for a few days, but the trauma passes. We get well, and as long as the sickness was not too profound - no scarring of the lungs, for example - we carry on as before. Mum might not even remember the illness. Why, therefore, might her baby be impacted to such an extent that two or three years later, a behavioral disturbance erupts?" said Dr. Jack Price, the senior author of the study and professor of developmental neurobiology at King's College London.
Their theory is the possible role of interferon-gamma, a cytokine, in the link. Lymphocytes can be stimulated by interferon-gamma, and when they do, they turn into antiviral agents to eliminate virally-infected cells. The stimulation requires activating specific genes and cellular pathways to lead lymphocytes to correct targets. The first stimulation can take some time, but after that, lymphocytes can react quickly. This is because immune cells tend to remember what stimulated them.
In the brain, a type of cell can respond to interferon-gamma. The adult brain can be affected by the cytokine because of glial cells. But early fetal brain lacks glial cells due to neurons being the top priority. Even in the third trimester of pregnancy, only a few glial cells can be found in the fetal brain. But there is another cell that may be reactive to the cytokine. This cell is a neural precursor of glia.
To determine its reactiveness to interferon-gamma, researchers applied a cellular model of human brain development. Their analysis showed that the precursor responded to the cytokine. It even remembered being stimulated in that manner. Moreover, neurons generated by the precursors carried the memory of that stimulation. Neurons from stimulated precursors remembered what their predecessor witnessed before: a viral encounter.
Researchers examined the behavior of the said neurons. The cells behaved closely to neurons derived from people with ASD. The cells' behavior was significantly different from neurons of neurotypical people – individuals without ASD or mental illness. Simply put, the exposure of glial cell precursors to interferon-gamma altered their eventual cellular behavior. The altered behavior was characterized by less efficiency in communicating with other brain cells.
To make their discovery useful, researchers studied the mechanism behind the alteration. They noted that in lymphocytes, structures called PML nuclear bodies inside the nucleus store the interferon-gamma stimulus. The same structures were detected in primed neurons. The structures were found located next to the interferon-gamma response genes. Although the accumulation of the structures could be reversed, it would be difficult to assess therapies in patients.
The risk of autism from COVID-19 still varies. Using data in England, the recent daily new infections is about 2,400 per 10,000 population. That is roughly 72,000 new cases per month or 0.13% of the country's population. From that figure, the risk of COVID-19 infection is 0.13% per month but pregnant women get 0.4% cumulative risk due to their condition. With an assumed average of 2% of pregnant women being hospitalized, the population at risk is narrowed to 56 hospitalized pregnancies. If the autism risk from this sample rose from 1% to 3%, then one single ASD diagnosed may be a result of COVID-19 infection.
Nevertheless, pregnant women are strictly advised to avoid any viral infection. This is to shield their unborn baby from potential complications.