Clinical and prognostic implications of hyaluronic acid in patients with COVID-19 reinfection and first infection

Objective: Previous research has shown that human identical sequences of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) promote coronavirus disease 2019 (COVID-19) progression by upregulating hyaluronic acid (HA). However, the association of HA with mortality and long COVID in SARS-CoV-2 reinfection and first infection is unclear. Methods: Patients with COVID-19 at Beijing Ditan Hospital from September 2023 to November 2023 were consecutively enrolled. SARS-CoV-2 reinfections were matched 1:2 with first infections using a nearest neighbor propensity score matching algorithm. We compared the hospital outcomes between patients with COVID-19 reinfection and first infection. The association between HA levels and mortality and long COVID in the matched cohort was analyzed. Results: The reinfection rate among COVID-19 hospitalized patients was 25.4% (62 cases). After propensity score matching, we found that reinfection was associated with a better clinical course and prognosis, including lower levels of C-reactive protein and erythrocyte sedimentation rate, fewer cases of bilateral lung infiltration and respiratory failure, and shorter viral clearance time and duration of symptoms (p < 0.05). HA levels were significantly higher in patients with primary infection [128.0 (90.5, 185.0) vs. 94.5 (62.0, 167.3), p = 0.008], those with prolonged viral clearance time [90.5 (61.5, 130.8) vs. 130.0 (95.0, 188.0), p < 0.001], and deceased patients [105.5 (76.8, 164.5) vs. 188.0 (118.0, 208.0), p = 0.002]. Further analysis showed that HA was an independent predictor of death (AUC: 0.789), and the risk of death increased by 4.435 times (OR = 5.435, 95% CI = 1.205-24.510, p = 0.028) in patients with high HA levels. We found that patients with HA levels above 116 ng/mL had an increased risk of death. However, the incidence of long COVID was similar in the different HA level groups (p > 0.05). Conclusion: Serum HA may serve as a novel biomarker for predicting COVID-19 mortality in patients with SARS-CoV-2 reinfection and first infection. However, HA levels may not be associated with long COVID.