Immunoglobulin G (IgG) is a fork-shaped molecule produced by adaptive immune cells to intercept foreign invaders. Each type of IgG targets a specific type of pathogen.
The IgG for Sars-CoV-2, the virus causing Covid-19, fights off the virus by binding with the virus' unique spike protein to reduce its chance of infecting human cells. They usually appear a week or two after the onset of illness, when the symptoms of most critically-ill patients suddenly get worse.
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A research team led by Professor Menno de Winther from the University of Amsterdam in the Netherlands said they might have found an important clue that may answer why the IgG appears only when patients are ill enough to be admitted to the intensive care unit (ICU).
The scientists found that the blood from Covid-19 patients struggling for their life on ventilators was highly inflammatory. They observed during a series of experiments that it could trigger an overreaction of the immune system, destroy crucial barriers in tissues and cause water and blood to spill over in the lungs.
When Winther and his colleagues compared the blood from Covid-19 patients to those battling other diseases in the ICU, they discovered that Covid-19 patients had a disproportionately large amount of Sars-CoV-2-specific IgG. These antibodies “strongly amplify pro-inflammatory response”, they said in a non-peer-reviewed paper posted on preprint platform bioRxiv.org on Monday.
When Winther applied the pure form of these antibodies directly to healthy blood and tissue cells, nothing happened. But when combined with a giant immune cell called macrophage, which forms when the body senses an infection, the IgGs caused the macrophages to implode, releasing a large amount of inflammatory molecules known as cytokines, causing “striking” destruction, said the researchers.
This could change the fight with the pandemic, according to Winther.
There was once a hope that the blood of recovered patients could be used as a cure to those still fighting the virus. Clinical trials have been launched in some countries to evaluate the effectiveness of plasma therapy. The Dutch study raised a safety alarm.
“It may be wise to omit the [virus-specific] IgGs that are present in severely ill patients,” said Winther and his colleagues.
A Chinese government epidemiologist based in Shanghai said the Dutch paper confirmed “what we suspected for a long time”. Several studies from China have also found the destructive role played by the macrophages in severely ill patients and proposed potential drugs that could suppress the cytokine storm.
But the roles of antibodies could be more complex than what have been described, according to the researcher. For instance, it remains unclear whether vaccine-induced antibodies, which are supposed to contain some highly specific neutralising IgGs, will have the same effect in the very early stage of infection.
“One thing is certain: we cannot put all our bets on antibodies,” he said.
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