COVID-19 Immune Response Fits Into 3 Categories With 'Fundamental Differences'

The immune responses of COVID-19 patients fit into three categories, according to a study.

Researchers studied blood samples and health data from 125 COVID-19 patients hospitalized at the University of Pennsylvania, as well as 46 people who had recovered from the disease, and 70 healthy donors.

Most of the patients had symptoms when they were diagnosed with COVID-19, and around 30 percent ended up needing a ventilator to breathe. Eighteen of the participants died over the course of the study, which was published in the journal Science.

The team analysed the blood samples in their entirety, as well as specific white blood cells which are part of the immune system. They tried to find patterns with different immune cells and clinical features, and came up with thousands of different combinations which could be studied mathematically.

By looking for around 200 immune and 50 clinical features in the patients, they identified what they called three "immunotypes" or categories.
The three immunotypes were categorized according to the types and strengths, or lack thereof, of the immune cells that were activated in response to the coronavirus infection. The first two types were related to the activity of white blood cells known as T-Cells.

The third group was characterized by a lack of detectable white blood cells, suggesting this part of the immune system didn't activate in these patients, according to the study.

"These immunotypes may reflect fundamental differences in the ways patients respond to SARS-CoV2 infection," the authors wrote, referring to the name of the COVID-19-causing coronavirus.

Co-author Dr. Nuala J. Meyer, associate professor of medicine at the University of Pennsylvania, told Newsweek patients who were critically ill and needed a ventilator to breathe or very high levels of oxygen support showed all three patterns. The first immunotype showed signs of imbalanced immune responses and some main drivers linked with higher levels of organ failure.

The third immunotype appeared to have a lower risk of becoming seriously ill, she said.

The study draws attention to how different the immune responses of COVID-19 patients are, and starts to identify patients that may be more favorable and unfavorable, Meyer said. She was surprised by "the breadth of abnormalities across the immune system" the virus can set off.

Her team were motivated to profile the immune systems of their sickest patients and those who had recovered from COVID-19 "to lay the foundation for more informed treatment."

"The medical and scientific community faced a very humbling realization that we really didn't understand why patients with SARS-CoV2 were experiencing such severe and dramatic pneumonia, and such a high frequency of severe acute respiratory distress syndrome (ARDS). ARDS is a life-threatening condition where fluid leaks in the lungs," she said.

It has always been thought that severe pneumonia causing ARDS has to do with a problem in the immune response to infection, Meyer said. "And yet the prospect of intervening on the immune response without better knowledge of how the immune reaction was abnormal was frightening, in that we could do more harm than good."

"This virus has the potential to impact almost every part of the immune system yet there are some patients in whom it barely perturbs any aspect," she said.

Meyer said their study is "quite large for this type of very deep immune profiling." But "since humans are so diverse, larger and more diverse populations are always helpful."

It will also be important to understand how treatments modify the immune response, she said.

Professor Daniel Altmann of the Department of Medicine at the U.K.'s Imperial College London, who did not work on the study, told Newsweek the study "is an impressive and important step forward.

The patterns the team found "should be valuable both as a biomarker to predict those patients likely to do badly, and as an inroad into new therapeutic strategies."

Meyer said the team started working on their research "as the pandemic started to affect the West Coast and New York, and enrolled the first subject in mid-March.

"It has been a full-time, around the clock effort for the last four months, and we continue to work on this daily," Meyer said.