Some people get really sick from COVID-19, and others don't. Nobody knows why. Now, a study by investigators at the Stanford University of Medicine and other institutions has turned up immunological deviations and lapses that appear to spell the difference between severe and mild cases of COVID-19.

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That difference may stem from how our evolutionarily ancient innate immune system responds to SARS-CoV-2, the virus that causes the disease. Found in all creatures from fruit flies to humans, the innate immune system rapidly senses viruses and other pathogens. As soon as it does, it launches an immediate though somewhat indiscriminate attack on them and mobilizes more precisely targeted, but slower-to-get-moving, "sharpshooter" cells belonging to a different branch of the body's pathogen-defense forces, the adaptive immune system.

"These findings reveal how the immune system goes awry during coronavirus infections, leading to severe disease, and point to potential therapeutic targets," said Bali Pulendran, Ph.D., professor of pathology and of microbiology and immunology and the senior author of the study, which will be published Aug. 11 in Science. Lead authorship is shared by Stanford postdoctoral scholars Prabhu Arnunachalam, Ph.D., and Florian Wimmers, Ph.D.; and Chris Ka Pun Mok, Ph.D., and Mahen Perera, Ph.D., both assistant professors of public health laboratory sciences at the University of Hong Kong.