People with severe COVID-19 have 3 distinct immune responses

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In a new study, researchers found three distinct immune responses to the COVID-19 infection that could help predict the trajectory of disease in severe COVID-19 patients and may ultimately inform how to best treat them.

The research was conducted by a team from the Penn Institute of Immunology.

The coronavirus triggers different immune responses and symptoms in critically ill patients, but how those two correspond has remained poorly understood, making treatment decisions more difficult.

While recent studies reveal details on the immune’s response to the virus, most have been single-case reports or focused on a small group of individuals.

This is the first study to offer up a comprehensive immune profile of a large number of hospitalized patients.

The researchers applied deep immune profiling to capture individual responses of 163 patients during the course of their infections.

The study included 90 hospitalized patients treated at the Hospital of the University of Pennsylvania, 29 non-hospitalized patients, and 44 healthy donors with no COVID-19 infection.

The immune responses varied among the group, but there were three patterns that hold clinical promise.

Next, researchers combined the clinical data to understand the relationships between immune responses and disease.

The first immunotype was tied to more severe disease that included inflammation, organ failure, and acute kidney disease.

The second linked not with disease severity but instead pre-existing immunosuppression and mortality.

The third type, which had no immune activation, was not linked to specific symptoms or clinical features, though they varied.

Testing the blood samples of 42 infected patients (with moderate and severe disease) and 12 healthy donors, the researchers found a similar heterogeneity in immune adaptive responses.

While the innate responses were also heterogenous, the researchers observed a decrease of CD15 and CD16 molecules on neutrophils and CD16 on NK cells, immature granulocytes, and monocytes, in patients with more severe disease.

These two molecules are known players in the immune response to viral infections that also represent a potential target for immunotherapy.

How they are driving and exacerbating the adaptive responses in the three immunotypes is an important question the labs are working to better understand.

The team says for patients who are hospitalized with COVID-19, there isn’t just one way for the immune system to respond.

They hope to be able to predict the different immune patterns a patient has based on clinical data.

This would allow scientists to start thinking about enrolling patients to different types of clinical trials investigating treatments.

One author of the study is E. John Wherry, Ph.D., chair of the Department of Systems Pharmacology and Translational Therapeutics and director of the Penn Institute of Immunology.

The study is published in Science.

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