Sluggish’ immune response may contribute to more severe COVID-19

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In a new study, researchers found in severely ill COVID-19 patients, “first-responder” immune cells, which should react immediately to signs of viruses or bacteria in the body, instead respond sluggishly.

The findings may explain the difference between severe and mild cases of COVID-19.

That difference may stem from how our evolutionarily ancient innate immune system responds to SARS-CoV-2, the virus that causes the disease.

The research was conducted by a team at Stanford University and elsewhere.

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.

It also 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.

In the study, the team analyzed the immune response in 76 people with COVID-19 and in 69 healthy people.

They found enhanced levels of molecules that promote inflammation in the blood of severely ill COVID-19 patients.

Past studies have shown that three of the molecules researchers found are associated with lung inflammation in other diseases but they hadn’t been shown previously in COVID-19 infections.

These new findings reveal how the immune system goes awry during coronavirus infections, leading to severe disease, and point to potential therapeutic targets.

The lab is now testing the therapeutic potential of blocking these molecules in animal models of COVID-19.

The scientists also found elevated levels of bacterial debris, such as bacterial DNA and cell-wall materials, in the blood of those COVID-19 patients with severe cases.

The more debris, the sicker the patient—and the more pro-inflammatory substances circulating in his or her blood.

The findings suggest that in cases of severe COVID-19, bacterial products ordinarily present only in places such as the gut, lungs, and throat may make their way into the bloodstream, kick-starting enhanced inflammation that is conveyed to all points via the circulatory system.

But the study also reveals, paradoxically, that the worse the case of COVID-19, the less effective certain cells of the innate immune system were in responding to the disease.

Instead of being aroused by material from viruses and bacteria, these normally vigilant cells remained functionally sluggish.

One author of the study is Bali Pulendran, a professor of pathology and of microbiology and immunology.

The study is published in Science.

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