Home›Infectious Disease› Plasma hyaluronic acid levels predict ARDS and intubation in adult COVID-19 patients
Plasma hyaluronic acid levels predict ARDS and intubation in adult COVID-19 patientsCould a simple blood test help predict who needs breathing support for COVID-19?
Frontiers in MedicinePublished April 17, 2026DOI ↗Editorial oversight: Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease
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Key Takeaway
Consider plasma hyaluronic acid as a complementary biomarker for early risk stratification in adult COVID-19 patients.
This retrospective single-center cohort study included 502 adult patients with COVID-19. The primary exposure was plasma hyaluronic acid (HA) levels, compared against clinical severity scores (APACHE II, SOFA) and a non-ARDS group. The study aimed to assess the utility of HA for ARDS diagnosis, severe ARDS stratification, and intubation risk.
For ARDS diagnosis, HA showed an area under the curve (AUC) of 0.904, with a sensitivity of 81.6% and specificity of 87.5% at a cut-off of 103 µg/L. The study population included 361 patients in the non-ARDS group and 141 in the ARDS group. HA was positively correlated with disease severity.
Discrimination for severe ARDS yielded an AUC of 0.953. For endotracheal intubation risk, the AUC reached 0.890, with a sensitivity of 76.6%, specificity of 90.8%, and a negative predictive value (NPV) of 95.5% at a cut-off value of 140.1 µg/L. Multivariable regression analysis indicated HA was independently associated with ARDS diagnosis (OR = 1.04, P = 0.007), severe ARDS (OR = 1.00, P < 0.001), and intubation risk (OR = 1.00, P = 0.011). Combining HA with clinical scores increased the AUC for predicting severe ARDS from 0.960 to 0.973 (ΔAUC = 0.013).
No safety data, adverse events, or discontinuations were reported in this study. Key limitations include the retrospective, single-center design, which restricts generalizability. The evidence suggests HA may serve as a complementary biomarker for early risk stratification, particularly when used in combination with established clinical severity scores.
Imagine having a way to see who is sliding toward severe lung trouble before it happens. This study looked at 502 adults with COVID-19 to see if a specific substance called hyaluronic acid in their blood could warn doctors of danger. The results showed that higher levels of this substance were tied to worse outcomes, including the need for a breathing tube.
When the researchers checked the numbers, the blood test performed very well at spotting severe lung failure. It correctly identified most people who would get sick and missed very few who would stay stable. Adding this blood test to standard severity scores made the prediction even more accurate.
However, this was a single-center study looking back at past data. This means we do not yet know if the test works in every hospital or if changing the treatment based on the result helps patients live longer. For now, it is a helpful tool to add to the existing checklist of how sick a patient is.
What this means for you:
High blood hyaluronic acid levels were linked to severe lung failure in COVID-19 patients.
BackgroundAcute respiratory distress syndrome (ARDS) is a major complication in hospitalized patients with coronavirus disease 2019 (COVID-19). Early identification of patients at increased risk of ARDS progression and invasive ventilation remains clinically important. This study aimed to investigate whether plasma hyaluronic acid (HA), alone or in combination with established clinical severity scores, could help identify ARDS, stratify severe disease, and assess the risk of endotracheal intubation in patients with COVID-19.MethodsThis retrospective single-center cohort study included 502 adult patients with COVID-19 admitted between September 2022 and February 2023. Plasma HA levels were measured within 24 hours after admission. Demographic characteristics, comorbidities, laboratory findings, clinical severity scores, and outcome data were collected. Receiver operating characteristic analysis, multivariable logistic regression, and nomogram construction were used to evaluate the association of HA with ARDS diagnosis, severe ARDS stratification, and intubation risk.ResultsThis retrospective cohort analysis of 502 COVID-19 patients (361 in the non-ARDS group and 141 in the ARDS group) identified plasma hyaluronic acid (HA) as a potential biomarker for early ARDS diagnosis, severity stratification, and intubation risk assessment. HA levels were positively correlated with disease severity, with concentrations significantly increasing alongside ARDS severity, and showed good discrimination for ARDS (AUC = 0.904; sensitivity 81.6%, specificity 87.5% at a cut-off of 103 μg/L). HA also demonstrated excellent discrimination for severe ARDS, with an AUC of 0.953, comparable to that of the APACHE II and SOFA scores. It also showed good discrimination for endotracheal intubation risk in the overall cohort. The AUC for predicting intubation requirement reached 0.890 (sensitivity 76.6%, specificity 90.8%, NPV = 95.5% at a cut-off value of 140.1 μg/L). Integrating HA with clinical scores further improved model performance; incorporating age, lymphocyte count, CRP, CK, APACHE II, and SOFA into the baseline model increased the AUC for predicting severe ARDS from 0.960 to 0.973 (ΔAUC = 0.013). Furthermore, multivariable regression analysis showed that HA was independently associated with ARDS diagnosis (OR = 1.04, P = 0.007), severe ARDS (OR = 1.00, P < 0.001), and intubation risk (OR = 1.00, P = 0.011).ConclusionPlasma HA was positively associated with ARDS severity and intubation risk in patients with COVID-19. HA may serve as a complementary biomarker for early risk stratification, particularly when used in combination with established clinical severity scores.
