Blood test may identify COVID survivors at risk for ongoing lung disease

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Abnormally high levels of lung-injury biomarkers in the blood after COVID-19 infection may flag patients at risk for ongoing lung disease, an Imperial College London–led study suggests.

The team analyzed concentrations of lung-injury biomarkers in the plasma of 957 COVID-19 survivors participating in the observational Post HOSPitalisation-COVID study five months after hospital admission. Patients had similar COVID-19 severity on hospitalization.

“Long term respiratory symptoms are reported following recovery of acute COVID-19 infection and residual lung abnormalities (RLA) on follow-up thoracic computed tomography (CT) after COVID-19 hospitalisation have been observed,” the study authors noted. “It is unknown whether RLA are associated with epithelial lung injury.”

The researchers published their findings last week in eBioMedicine.

Damage to lining of the lungs

Of the 957 patients with dysfunctional gas exchange and an abnormal chest radiograph who had been hospitalized for their infections, 11.6% underwent follow-up CT, with 85 (76.6%) of them showing RLAs of at least 10%. In total, 12.2% of the 846 patients who didn’t undergo follow-up CT were identified as at-risk due to high levels of certain biomarkers in the blood.

These findings could pave the way for simple blood tests to determine which individuals might have ongoing lung problems, and help us decide on the best course of treatment for them.

Rachael Evans, MD, PhD

Concentrations of the biomarkers Krebs von den Lungen-6 (KL-6) and matrix metalloproteinase 7 (MMP-7) were significantly higher in patients with RLA involvement of 10% or more than in those at low risk. High levels of these molecules have previously been linked to damage to the epithelial cells that line the lungs, potentially affecting lung function over time, the authors said.

“The biomarkers we’ve observed in the blood samples in this study tell us that there is damage to this lining, and this is contributing to ongoing symptoms and restrictive lung function in some people with long-COVID,” coauthor Rachael Evans, MD, PhD, of the University of Leicester, said in a university news release. “These findings could pave the way for simple blood tests to determine which individuals might have ongoing lung problems, and help us decide on the best course of treatment for them.”

Risk of ongoing symptoms, restrictive lung function

While levels of surfactant protein-D (SP-D) and surfactant protein-A (SP-A) didn’t reach significance, they were tied to the extent of reticulation, or pattern of fine lines resembling a web, on CT (3.22%).

“The results suggests that pro-fibrotic signalling cascades contribute to persistent epithelial lung injury observed in some people recovering from COVID-19, which may contribute to ongoing symptoms and restrictive lung function,” the researchers wrote.

“Further research and surveillance are required to address the longitudinal association of epithelial lung injury biomarkers and radiological patterns following COVID-19 in order to understand whether fibrotic features are stable, resolving or progressive in the long-term,” they added.

Lead author Iain Stewart, PhD, of Imperial College London, said the high-quality data in the study allowed the team to identify signs of ongoing lung damage in a relatively small group of patients. “The fact that this damage may have life‑long consequences means that finding reliable markers to identify people at risk is crucial,” he said.