Molecular autopsy sheds light on cause of sudden death of a child with COVID-19

Newswise — Tokyo, Japan –

When a child dies unexpectedly and the reason is not clear, it's very sad. Finding out why the child died is important so we can improve healthcare and help the family find peace. Some scientists in Japan used a special way of reading the child's DNA, called whole-exome sequencing, to figure out why a child died after a mild infection.

A group of scientists from Tokyo Medical and Dental University (TMDU) published a research paper this month in a journal called Frontiers in Immunology. They found that a very uncommon genetic disease might have made a young boy more vulnerable to COVID-19. The boy got very sick from COVID-19 and it might have caused his heart to stop working, leading to his death.

Associate Professor Kana Unuma, who led the study, explained that they had a patient who was five years old and had a fever for six days. The child was taken to the hospital in an ambulance but unfortunately, went into cardiac arrest and died, even after the doctors tried to save him by giving him CPR. It wasn't immediately clear why the child died so suddenly.

To find out why the child died, the researchers did an examination of the body after death (called an autopsy). They discovered that the child had a serious condition called anemia, which means there weren't enough healthy red blood cells in the body. They also found that the child had abnormal levels of different types of blood cells, a liver and spleen that were larger than usual, and a coronary artery that was not in the normal position. They also found that the child had been infected with the virus that causes COVID-19 (SARS-CoV-2).

Professor Hirokazu Kanegane, who is one of the authors of the study, said that the abnormalities found in the child's heart and blood suggested that there might have been an underlying disease. To investigate this further, they used WES, a test that looks for differences in genes that could explain the disease. They found a difference in a gene called LZTR1, which has been linked to a rare condition called Noonan syndrome (NS).

Noonan syndrome is a rare disease caused by a genetic mutation. People with this condition usually have unique facial features and physical characteristics, developmental delays, heart problems, and a higher chance of developing blood cancer. After the researchers found the genetic difference in the child, they confirmed that the child had Noonan syndrome based on the child's facial features. However, they did not find any other physical signs of Noonan syndrome in the child's body.

Associate Professor Unuma explains that the child had a relatively mild form of Noonan syndrome, which was not suspected before the study. The cause of the child's cardiac arrest and subsequent death could have been due to a combination of fever, dehydration caused by COVID-19, and the unusual location of the coronary artery. This may have caused fatal problems with the child's heartbeat and blood flow.

The unusual location of the coronary artery found in the child is one of the rarest forms of heart defect and has been linked to several cases of sudden death in children. Although this type of defect may not always be detected, a comprehensive molecular autopsy, like the one done in this study, can identify genetic differences and help explain unexpected sudden death.

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The article, “Case Report: Molecular autopsy underlie COVID-19-associated sudden, unexplained child mortality,” was published in Frontiers in Immunology at DOI: 10.3389/fimmu.2023.1121059.