Genetic profiles in the blood predict the risk of death and poor outcome in Covid-19 patients

Multi-facility retrospective exhibition Research A recent blood genetic profile, led by the University of South Florida Health (USF Health), associated with an increased risk of dying from severe lung disease has shown that poor outcomes in Covid-19 patients can be predicted.

A risk profile based on 50 genes has the potential to customize Covid-19 treatment methods, improve the allocation of limited medical resources such as intensive care units and ventilators, and save lives. This study was published in the journal EBioMedicine.

Idiopathic pulmonary fibrosis (IPF), an unexplained disease, affects the pulmonary stroma in the space between the sac and the bloodstream, causing severe pulmonary scarring. Severe Covid-19 can also damage the lung interstitium and cause severe lung scarring.

“Our study was identified at the molecular level, a genetic risk profile that predicts that Covid-19 outcomes will worsen before patients become seriously ill,” said Associate Professor and Associate Professor of Pulmonary Emergency and Critical Care. Jose Herazo-Maya, MD USF Health Morsani Medical College in Sleep Medicine.

“That is, every patient with Covid-19 may be able to have a blood test to find out if they are at high or low risk of dying … and who is likely to enter the ICU. With proper monitoring, those who are likely to recover well at home, knowing in advance, can tailor the intervention to their individual patient based on their level of risk. “

The USF Health study was published online on June 20th in THE LANCET’s publication, EBioMedicine. It is based on a previous genomic study by Dr. Herazomaya and a colleague at Yale School of Medicine. In 2017, they led an international team to study and validate gene expression signatures in the blood that reliably predict the likelihood of death from IPF. (Some patients with lung scars can live well for years, while others develop an exacerbating illness and die quickly with IPF.)

As the Covid-19 pandemic unfolded, “the basic question we had was” lung fibers, reusing gene signatures known to predict mortality in fibrotic lung disease. Can we predict the mortality rate of people infected with a new coronavirus that can cause disease? ” Brenda Juan-Guardela, MD, lead author of the EBioMedicine treatise, states that he is an assistant professor at the USF Health Morsani College of Medicine and a medical director of respiratory care services at Tampa General Hospital (TGH). “As far as we know, this study was the first to compare overlapping immune gene profiles in Covid-19 and IPF, and they were significantly similar.”

The USF Health-led team analyzed gene expression patterns for 50 genes known to predict IPF mortality in three Covid-19 cohorts and two IPF cohorts. Researchers used a molecular scoring system to distinguish between high-risk and low-risk gene profiles in all five cohorts.

In their findings:

-In the Covid-19 validation cohort, a high-risk profile of 50 genes was associated with an increased risk of ICU admission, ventilator, and in-hospital mortality.

-Researchers also performed single-cell gene expression analysis to identify specific immune cells (monocytes, neutrophils, dendritic cells) as the leading cause of gene expression changes in the high-risk Covid-19 gene profile. Identified as. This finding suggests that Covid-19 and IPF may share a common innate and adaptive immune response that causes lung scarring.

-The Covid-19 50-gene risk profile can also predict IPF mortality at exactly the same threshold.

At TGH, Dr. Herazo-Maya treats a previously hospitalized Covid-19 patient who came to the Center for Progressive Lung Disease with Severe Pulmonary Fibrosis. Some have been evaluated for lung transplants. “Even if the number of cases of coronavirus is decreasing, that doesn’t mean that all patients will recover without complications,” he said. “The lungs of some Covid-19 survivors are beginning to have harmful, long-term effects.”

More research is needed, but researchers and clinicians may soon be able to apply genetic risk profiles to help advance care for both Covid-19 and IPF patients, Herazo-Maya said. Said the doctor. His lab is currently developing blood tests based on these genes, which can be easily applied in clinical practice to predict poor outcomes of the disease.

In addition to predicting outcomes, identifying risk profiles for 50 genes may also have important therapeutic potential. For example, a 10-day regimen of the immune system-suppressing drug steroid dexamethasone has been shown to increase survival in patients admitted with Covid-19.

Immunosuppressive drugs were essentially discontinued with IPF treatment because of the increased mortality of high-dose, long-term combinations, Dr. Herazo-Maya said. “But perhaps using the principles of precision or personalized medicine, the use of dexamethasone or similar steroid therapy in a subgroup of IPF patients with a high-risk profile of 50 genes can be investigated for a short period of time. “

The high-risk profile of the 50 genes may also support the rationale for investigating the use of targeted IPF antifibrotic agents that slow the rate of lung scarring to prevent short-term and long-term sequelae of Covid-19. He added that there was.

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