SEVERITY of coronavirus disease (COVID-19) varies massively in patients who become infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), from patients having very mild to life-threatening symptoms and needing mechanical ventilation. Researchers from KAIST, Daejeon, South Korea, have identified key markers that could help predict which patients are at increased risk of developing severe COVID-19, and thus allow attending physicians to produce a more personalised treatment plan for the patient.
Acute respiratory distress syndrome accounts for 70% of the deaths in severe COVID-19 infections by causing extensive damage to the airway as a result of an exaggerated immune response to SARS-CoV-2. To identify those at risk, researchers from KAIST, using a public database, analysed RNA sequencing data extracted from individual airway cells of healthy controls and patients with mild and severe COVID-19.
The researchers found that in severe COVID-19 patients, excessive amounts of neutrophil-recruiting chemicals, namely TNF and CXCL8, were produced by myeloid cells. In addition to the finding of heightened neutrophil recruitment, they found that these neutrophils produced excessive extracellular molecules that usually help overcome the pathogen, but when overproduced, they damage the airway cells.
Additionally, the researchers identified that expression levels of glucocorticoid receptors, targets of the anti-inflammatory drug class glucocorticoids, were decreased and correlated with increased CXCL8 levels and neutrophil recruitment. Glucocorticoids have been used to treat COVID-19 and prevent the worsening of disease severity, but the necessary immune reactions to combat the virus could be suppressed if glucocorticoids are used in early or mild COVID-19. Furthermore, if the airway has already been damaged in severe illness, and thus the expression of glucocorticoid receptors decreased, then the glucocorticoids would be ineffective and potentially do more harm than good.
By using biomarkers such as these to identify which stage of infection the patient is in, and the health of their airway, physicians will be able to better judge if a patient will benefit from a treatment or not. Prof Heung Kyu Lee, KAIST, concluded: “This finding could be used as a biomarker for predicting disease severity in patients and thus selecting a targeted therapy that can help treat them at an appropriate time.”
