The gene profile in the blood predicts the risk of poor outcomes, the death of patients with COVID-19


The lead researcher in the study was Jose Herazo-Maya, MD, associate professor of medicine and associate head of division at USF Health Pulmonary, Critical Care and Sleep Medicine. Credit: USF Health / University of South Florida

A blood gene profile associated with a high risk of dying from severe lung disease may also predict poor outcomes in patients with COVID-19, a multicenter retrospective study led by the University of South Florida Health (USF Health). The 50-gene-based risk profile could help customize how COVID-19 is treated, improve the allocation of limited health resources such as intensive care beds and ventilators, and potentially save lives.

Idiopathic pulmonary fibrosis (IPF), a disease of unknown cause, affects the disease interstitium or the space between the lung sacs and the bloodstream, causing severe lung scarring. Severe COVID-19 can also damage the interstitial lung and cause severe lung scarring.

“Our study identified at the molecular level, a genetic risk profile that predicts worse COVID-19 outcomes before the patient becomes seriously ill,” said lead researcher Jose Herazo-Maya, MD, associate professor and head associate of pulmonary care and sleep medicine at USF Health Morsani College of Medicine. “This means that all patients with COVID-19 could have a blood test to tell us if they have a high or low risk of dying … And if we know in advance who will probably end up in the ICU and who will recover well at home with proper follow-up, we can tailor our interventions to each patient based on their level of risk. ”

The USF Health study appeared online on June 20 a EBioMedicina, a publication of The Lancet. It is based on previous genomic research by Dr. Herazo-Maya and colleagues at the Yale School of Medicine. In 2017 they led a international team that studied and validated a gene expression signature in the blood that reliably predicts the probability of mortality from IPF. (Some patients with lung scars may live well for years, while others develop a worsening of the disease and die quickly from IPF).

As the COVID-19 pandemic developed, “the basic question we had was” Can we reuse the gene signature known to predict mortality in a fibrotic lung disease to predict mortality in those infected with a new coronavirus that can also cause pulmonary fibrosis? “he said EBioMedicina lead author of the paper, Brenda Juan-Guardela, MD, adjunct professor of medicine at USF Health Morsani School of Medicine and medical director of respiratory care services at Tampa General Hospital (TGH). “To our knowledge, this study is the first to compare overlapping immune gene profiles in COVID-19 and IPF, which were remarkably similar.”

The USF Health-led team analyzed 50 gene expression patterns it is 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 and low-risk gene profiles in the five cohorts.

Among his discoveries:

  • In the COVID-19 validation cohorts, a high risk profile of 50 genes was associated with an increased risk of ICU admission, mechanical ventilation, and hospital death.
  • The researchers also performed single-cell gene expression analyzes and identified specific immune cells (monocytes, neutrophils, and dendritic cells) as the primary source of gene expression changes in the COVID gene profile. -19 high risk. This finding suggests that COVID-19 and IPF may share common innate and adaptive immune responses that trigger lung scars.
  • The risk profile of 50 genes in COVID-19 can also predict IPF mortality at the same threshold.

At TGH, Dr. Herazo-Maya treats previously hospitalized COVID-19 patients who attend the Center for Advanced Lung Disease with Severe Pulmonary Fibrosis; some are being evaluated for lung transplantation. “While coronavirus cases are declining, that doesn’t mean all patients are recovering without complications,” he said. “We are beginning to see the long-term detrimental effects in the lungs of some COVID-19 survivors.”

Although more studies are needed, researchers and clinicians will soon be able to apply genetic risk profiles to help advance the care of both COVID-19 and IPF patients, Dr. Herazo-Maya said. His lab is currently developing a blood test based on these genes, which can be easily applied to clinical practice to predict the poor outcomes of the disease.

In addition to predicting outcomes, identifying risk profiles of 50 genes may also have important therapeutic potentials. For example, a ten-day regimen of the steroid dexamethasone, a drug that suppresses the immune system, has been shown to increase the survival of patients hospitalized with COVID-19.

Immunosuppressive drugs have been discontinued essentially for treatment with IPF, as they increase mortality when administered at high doses and in combination for long periods, Dr. Herazo-Maya said. “But perhaps we could investigate the use of dexamethasone or a similar steroid treatment for a short period of time in a subgroup of IPF patients with a high-risk profile of 50 genes, using the principle of precision or personalized medicine. “.

The high-risk profile of 50 genes may also support the justification for investigating the use of targeted IPF antifibrotic drugs, which slow down the rate of lung scars, to prevent short- and long-term sequelae of COVID-19, he added. .

Gaetane Michaud, a doctor of medicine at USF Health, professor of medicine and head of pulmonary medicine, critical care and sleep medicine, was a co-author of the paper. The research was supported by the Ubben Lung Fibrosis Fund-USF Foundation, the National Institute of Health Clinic Science Fellowship, the Mike Bray Lung Fibrosis Action Fellowship, and the National Heart, Lung and Blood Institute.

The genetic risk profile predicts the survival of people with severe lung disease

More information:
Brenda M. Juan Guardela et al, Risk profiles of 50 genes in peripheral blood predict the results of COVID-19: a retrospective multicenter cohort study, EBioMedicina (2021). DOI: 10.1016 / j.ebiom.2021.103439

Citation: Gene profile in blood predicts risk of poor outcomes, death of patients with COVID-19 (2021, June 21) recovered on June 21, 2021 at -gene-profile-blood-poor -outcomes.html

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