A study led by researchers at Harvard Medical School and Boston Children’s Hospital provides new insights into why the virus that causes COVID-19 can sometimes trigger a storm of inflammation that results in serious, even fatal, disease.
The study, published April 6 in the journal Nature, made the surprising finding that the SARS-CoV-2 virus infects and kills certain immune system cells in the blood and lungs, the medical school and hospital said in statements. As the cells die, they trigger alarms for the immune system.
“We wanted to understand what differentiates patients with mild versus severe COVID-19,” said Dr. Judith Lieberman, professor of pediatrics at Boston Children’s, one of the leaders of the study, in a statement. “We know that people with severe illness have elevated inflammatory markers, and that inflammation is the root of the severity of the disease. But we did not know what was causing the inflammation. “
Researchers found that the virus can infect two types of immune “sentinel cells” that act as early responders to infection: monocytes in the blood and macrophages in the lungs. Once infected, the cells die. Researchers believe that the cells die so quickly that the virus cannot take over and replicate itself. But in the process of dying, they release an explosion of inflammatory molecules, the researchers said.
The “inflammatory cell death … disrupts the production of infectious virus but causes systemic inflammation that contributes to the COVID-19 pathogenesis,” the study’s abstract said.
What happens is “like a small fire. It spreads and explodes, and no fire extinguisher is able to put it out.” That’s what Lieberman told CNN.
That monocytes and macrophages could even become infected with the virus was a surprise. Monocytes do not carry ACE2 receptors, the well-known entry point for the virus, and macrophages have low amounts of ACE2, the statements said.
Researchers also believe that the antibodies that people create when they are infected with COVID-19 can actually aggravate inflammation by helping the virus enter the monocytes, the statements said. They found that the antibodies created by vaccination did not appear to cause the same problem.
Donna Farber, a professor of microbiology and immunology at Columbia University who was not involved in the study, told CNN that it was “really elegant. … They actually put together some pieces that had not been put together before.”
Malik Peiris, a virologist at the University of Hong Kong, said in a news article in Nature accompanying the study that the Boston researchers’ study, as well as a preprint study from Yale, offered a plausible explanation for how serious COVID-19 is progressing. “I do not think it is the only or most important path, but it is certainly interesting,” he said.
Caroline Junqueira, Ângela Crespo, and Shahin Ranjbar of the Boston Children’s Program in Cellular and Molecular Medicine co-authored the paper.
The team, which also included a number of co-authors, was led by Lieberman, Junqueira and Dr. Michael Filbin at Massachusetts General Hospital.
Martin Finucane can be reached at [email protected].