Specific novel inflammatory biomarkers predict or are associated with greater severity of disease, poor prognoses, and death in COVID-19, according to systematic review and meta-analysis findings published in Therapeutic Advances in Respiratory Disease.
Increasing evidence suggests inflammatory processes may play a role in the progression of COVID-19. Therefore, investigators sought to characterize the role of numerous novel inflammatory biomarkers in the occurrence and prognosis of COVID-19. These biomarkers included endocan, plasma pentraxin 3 (PTX3), soluble CD14 subtype (sCD14-ST), soluble urokinase plasminogen activator receptor (suPAR), soluble receptor for advanced glycation end products (sRAGE), galectin-3, and monocyte distribution width (MDW).
The investigators conducted a systematic review and meta-analysis searching the Cochrane Library, EMBASE, and PubMed databases from December 2019 through mid-May 2023 without language restriction for cross-sectional, case-control, or cohort studies with blood samples taken from patients with COVID-19 at admission to measure levels of each biomarker, and those showing sufficient information on the distribution of biomarkers for case and control groups.
Overall, 90 studies (N=12,059 participants) were included in the current investigation.
“
Of all the biomarkers investigated, sCD14-ST showed the best discrimination of COVID-19-related deaths (AUC: 0.86, 95% CI: 0.71–1.00), which we recommend for the prediction of mortality in COVID-19 patients.
The investigators found higher levels of the novel inflammatory biomarkers galectin-3, sRAGE, suPAR, PTX3, endocan, and MDW in COVID-19 positive groups (ie, those with positive SARS-CoV-2 reverse transcription polymerase chain reaction [RT-PCR] test regardless of disease severity or hospital admission) vs COVID-19 negative groups (ie, healthy control participants and comparable patients without COVID-19).
The researchers also stratified patients according to disease severity at admission and analyzed the presence of biomarkers in the severe and non-severe cohorts. Between the mild/moderate group of COVID-19 patients and the severe group, no significant differences were found for galectin-3 or suPAR. Patients who died compared with survivors typically had higher levels of suPAR, PTX3, MDW, and sCD14-ST at admission.
Using area under the curve analysis (AUC), the investigators determined PTX3 and endocan were not statistically significant in identifying patients with COVID-19, galectin-3 failed to significantly discriminate between COVID-19 severe and moderate groups, and MDW was not a statistically significant predictor of mortality in patients with COVID-19. However, galectin-3 (AUC, 0.87) and MDW (AUC, 0.83) showed good discriminatory ability for COVID-19. The biomarker sCD14-ST showed the best discrimination of mortality related to COVID-19 (AUC, 0.86).
Poorer comprehensive clinical prognoses typically developed among patients with higher levels of galectin-3, suPAR, endocan, MDW, and sCD14-ST, although none of the biomarkers revealed a clear advantage in discriminating patients with poorer clinical prognoses.
No significant publication bias was found.
Significant systematic review and meta-analysis limitations include high levels of heterogeneity in most included studies and unaccounted-for confounding factors including potential comorbidities.
“In summary, we identified two biomarkers that showed good discriminatory ability for COVID-19: galectin-3 (AUC: 0.87, 95% CI: 0.71–1.00) and MDW (AUC: 0.83, 95% CI: 0.72–0.74). Of all the biomarkers investigated, sCD14-ST showed the best discrimination of COVID-19-related deaths (AUC: 0.86, 95% CI: 0.71–1.00), which we recommend for the prediction of mortality in COVID-19 patients,” the study authors concluded. “None of the biomarkers showed a clear advantage in discriminating patients with a poor clinical prognosis, which may be due to the fact that we merged for different clinical outcomes,” the researchers added.
