Plasma protein biomarkers for long COVID-19: Predictors of symptom severity and mortality risk

Long COVID-19 is marked by persistent symptoms beyond the acute phase, necessitating a deeper understanding of mortality risk factors for effective management. Plasma proteins hold promise as prognostic markers, offering insights into disease progression and aiding in mortality risk assessment.

A total of 240 patients and 89 healthy controls were enrolled for this study. Two months post-COVID follow-up, patients were categorized as survivors (n = 212) and non-survivors (n = 28). Plasma samples underwent 2-dimensional Gel Electrophoresis (2DE) for protein separation, followed by LC-MS/MS for protein identification, and validation was performed using ELISA. Proteomic data analysis was conducted using Mascot version 2.3.02 and Samespots software 4.5.1. Statistical analyses were carried out using GraphPad Prism and IBM SPSS.

LC-MS/MS identified fibrinogen (Spot 14; 52.15 kDa/5.32 pI; protein score 2293) and haptoglobin (Spot 08; 45.86 kDa/6.56 pI; protein score 453) as prospective predictive biomarkers. ELISA results confirmed increased plasma levels of fibrinogen and haptoglobin in severe cases (P < 0.001 for both) and non-survivors (P < 0.01 and P < 0.0086, respectively). ROC analysis showed haptoglobin had moderate predictive power for mortality (AUC = 0.68; P = 0.0025), surpassing fibrinogen (AUC = 0.62; P = 0.0374).

Plasma fibrinogen and haptoglobin are promising biomarkers for assessing disease severity and mortality risk in long COVID. These findings highlight their potential for prognostic applications, warranting further research into their mechanistic roles in COVID-19 and broader clinical implications.