Blood Test for 50-Gene High Risk Profile Can Predict Poor Outcomes and Help Customize Treatment for COVID-19 Patients

A previously validated gene profile in blood that predicts idiopathic pulmonary fibrosis (IPF) mortality was repurposed to assess the likelihood of COVID-19 survival, which means every patient with COVID-19 could potentially get a blood test that could tell if they are at high or low risk of dying.

A multicenter retrospective study led by the USF Health (Tampa, FL, USA) has demonstrated that a blood gene profile associated with a high risk of dying from a severe lung disease can also predict poor outcomes in patients with COVID-19. The risk profile based on 50 genes could help customize how COVID-19 is treated, improve allocation of limited health care resources such as intensive care beds and ventilators, and potentially save lives. IPF, a disease of unknown cause, affects the lung interstitium or the space between the lung sacs and the bloodstream, leading to severe lung scarring. Severe COVID-19 can also damage the lung interstitium leading to severe lung scarring.

The USF Health-led team analyzed gene expression patterns of 50 genes known to predict IPF mortality in three COVID-19 cohorts and two IPF cohorts. The researchers used a molecular scoring system to distinguish between high versus low-risk gene profiles in all five cohorts. The researchers found that in the COVID-19 validation cohorts, a 50-gene high risk profile was linked to greater risk of ICU admission, mechanical ventilation, and in-hospital death. The researchers also performed single-cell, gene expression analyses and identified specific immune cells - monocytes, neutrophils, and dendritic cells - as the primary source of gene expression changes in the high-risk, COVID-19 gene profile. This finding suggests COVID-19 and IPF may share common innate and adaptive immune responses that trigger lung scarring. The 50-gene risk profile in COVID-19 can also predicts mortality in IPF at the exact same threshold.

While more studies are needed, researchers and clinicians may soon be able to apply the gene risk profiles to help advance the care of both COVID-19 and IPF patients. The team is currently developing a blood test, based on these genes, that can be easily applied in clinical practice to predict poor disease outcomes. Besides outcome prediction, the identification of 50-gene risk profiles may also have significant therapeutic potentials. For example, a 10-day regimen of the steroid dexamethasone, a drug that suppresses the immune system, has been shown to increase survival of patients hospitalized with COVID-19. Immunosuppressant drugs have been essentially discontinued for IPF treatment because they increase mortality when given at high doses and in combination over long periods. The 50-gene high risk profile may also support the rationale to investigate the use of targeted IPF antifibrotic medications, which slow the rate of lung scarring, to prevent short and long-term sequelae of COVID-19.

“Our study identified at the molecular level, a gene risk profile that predicts worse COVID-19 outcomes before the patient becomes severely ill,” said principal investigator Jose Herazo-Maya, MD, an associate professor and associate chief of pulmonary, critical care and sleep medicine at the USF Health Morsani College of Medicine. “That means every patient with COVID-19 could potentially get a blood test that could tell us if they are at high or low risk of dying… And if we know in advance who will likely end up in the ICU and who will likely do well recovering at home with appropriate monitoring, we can tailor our interventions to individual patients based on their level of risk.”

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