Possible diagnostic biomarkers ID’d for COVID-19 complicated by PH

Study findings focus on activity of 2 inflammation-related genes

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Researchers have identified two inflammation-related genes — SELE and CCL20 — whose activity could serve as diagnostic biomarkers for the development of pulmonary hypertension (PH) in people with COVID-19.

Further, the team also identified molecules that target these biomarkers as possible therapeutic approaches for managing the complication.

Overall, the findings offer “new insights into the prediction and treatment of COVID-19 complicated with PH in clinical practice,” the researchers wrote.

The study, “Potential therapeutic targets for COVID-19 complicated with pulmonary hypertension: a bioinformatics and early validation study,” was published in Scientific Reports.

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Seeking to know more about the biological pathways shared by PH, COVID-19

SARS-CoV-2, the virus that causes COVID-19 infection, is a respiratory virus that leads to symptoms like fever, cough, and shortness of breath. While many patients recover from infection with only mild symptoms or no symptoms at all, others will experience more serious complications, particularly cardiovascular ones.

Pulmonary hypertension or PH, where the pressure in the arteries carrying blood from the heart to the lungs is elevated, is one such potential complication. It increases the likelihood of needing intensive care unit care or dying from COVID-19. As such, early detection of PH as a COVID-19 complication is critical for improving prognosis.

In this study, the researchers sought to learn more about the biological pathways that are shared between COVID-19 and PH. This can help not only in the identification of possible diagnostic biomarkers, but also in finding therapeutic targets for managing the complication.

Two genetic datasets were analyzed: one comparing healthy people with individuals with a type of PH, and another that compared healthy individuals with those with COVID-19. In each, the scientists looked for genes that had different activity levels between the disease state and healthy people. This is called a differentially-expressed gene, or DEG.

Next, the team looked for DEGs that overlapped between the PH and COVID-19 datasets. Such shared genes could potentially offer a “genetic connection” between the two diseases, according to the scientists.

Overall, 62 DEGs were found in common between the two conditions. Among them were a number of genes with increased activity that were involved in immune responses and inflammation.

“These results strongly suggest that immune inflammation is a driving force in the emergence and progression of COVID-19 coupled with PH,” the researchers wrote.

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SELE, CCL20 genes ID’d as potential diagnostic biomarkers

Artificial intelligence-based algorithms then pulled out two genes in particular believed to be able to best predict PH progression in COVID-19 patients. One was SELE, which encodes the production of the E-selectin protein, and the other was CCL20, a gene that encodes a protein of the same name. Both are related to immune function and were elevated in the two conditions.

A model taking into account activity of these two genes was found to be accurate for predicting PH and COVID-19 using additional genetic datasets.

Having established the role of these two genes as possible predictive biomarkers, the scientists further explored how they might be linked to the two diseases. To do so, the team used a range of different predictive algorithms.

Both genes were predicted to be associated with activated immune responses and the release of pro-inflammatory molecules, promoting the growth of pulmonary artery smooth muscle cells that promotes PH. They also were directly related to the activity of a number of different immune cell types.

Altogether, the researchers believe that COVID-19 likely leads to a strong “storm” of inflammatory molecules that ultimately damages the cells lining blood vessels and contributes to the structural changes that drive PH.

The scientists also identified other molecules that might interact in a network with these genes to influence PH-complicated COVID-19.

Finally, prediction models were used to identify existing molecules that could target these newly identified biomarker genes and possibly offer therapeutic benefits.

A few candidates were identified, one being fenretinide. This synthetic molecule has been investigated for a number of medical purposes, including the treatment of cancer. It could potentially have therapeutic benefits in PH associated with COVID-19, according to the scientists, but its mechanisms remain to be fully understood.

Further studies are needed to verify these findings and further explore the role of these candidate genes and therapeutic molecules in COVID-19 complicated by PH, according to the researchers.

A Conversation With Rare Disease Advocates