Novel Concept of Immunologic Resilience Can Accurately Predict Which COVID-19 Patients Will Advance to Severe Disease

A novel concept called “immunologic resilience” can accurately predict which COVID-19 patients will advance to severe disease and which will not.

Researchers from UT Health San Antonio (San Antonio, TX, USA) and the South Texas Veterans Health Care System (San Antonio, TX, USA) who developed the concept define immunologic resilience as the capacity to preserve or restore immune competence and control inflammation in the face of infection or other antigenic challenges. This capacity does not depend solely on age, according to the researchers. In fact, the level of immunologic resilience that precedes COVID-19 and develops during the viral disease is a strong predictor of COVID-19 outcomes regardless of age.


An 18-year-old could have inferior immunologic resilience, resulting in a high risk of severe COVID-19, whereas an 80-year-old with robust resilience could manifest less severe COVID-19. However, with age, the proportion of individuals with capacity to preserve immunologic resilience declines, contributing to the greater burden of COVID-19 in older persons. Conceivably, durability of vaccines may wane in persons with inferior immunologic resilience, say the researchers.

The scientists developed novel metrics to monitor immunologic resilience and evaluated them in 522 COVID-19 patients. Each patient’s level of immunological resilience was assessed on the day of admission and then daily for varying durations. Patients whose infections did not require hospital admission were visited at home for assessments. For comparative purposes, the researchers evaluated metrics of immunologic resilience in 13,461 individuals without COVID-19.

The researchers quantified immunologic resilience through “immune health grades,” which are based on measures of infection-fighting T cells, and blood cell gene expression signatures. An immune health grade of I signifies the best immunity and a grade of IV the worst. The group also analyzed grades from large control groups of otherwise healthy adults. The immune health grades and overall concept of immunologic resilience accurately predicted most patient outcomes, which in addition to mortality included hospitalization, need for advanced respiratory support, and levels of SARS-CoV-2 in the nasopharynx. Those who entered the hospital with the best immune health grades had shorter stays and non-progressive COVID-19, findings showed.

“We applied these immune metrics to every COVID-19 patient who came into the VA hospital. These metrics are highly prognostic. Metrics tracking inferior immunologic resilience predicted up to 19-times higher risk of dying within 30 days, which was the primary outcome of the study,” said the first author of the study, Grace C. Lee, PharmD, PhD, assistant professor, UT Health Science Center San Antonio and The University of Texas at Austin College of Pharmacy, and senior translational research scientist with the Foundation for Advancing Veterans’ Health Research. “Remarkably, irrespective of their COVID-19 status, men have inferior immunologic resilience, which may explain why they are predisposed to worse COVID-19 outcomes.”

“The concept is a useful way to assess the severity levels of patients and understand their potential rate of progression and need for advanced therapies and longer hospitalizations,” said co-author Sandra Sanchez-Reilly, MD, professor of medicine at the health science center and associate chief of service for geriatrics and extended care in the South Texas Veterans Health Care System.

Related Links:
UT Health San Antonio
South Texas Veterans Health Care System