# The Predictive Role of C-Reactive Protein, Leukocyte Cell Count, and Soluble Urokinase Plasminogen Activator Receptor for Pulmonary Sequelae in Hospitalized COVID-19 Survivors: A Prospective Single-Center Cohort Study

## TL;DR

This study finds that certain biomarkers, especially suPAR, can predict lung function issues in hospitalized COVID-19 survivors, potentially reducing unnecessary follow-ups.

## Contribution

The study identifies suPAR as a strong predictor of DLCO impairment and highlights the value of combining biomarkers for high negative predictive value.

## Key findings

- DLCO impairment was the most common pulmonary function issue in post-COVID-19 patients.
- suPAR at admission showed the strongest correlation with DLCO impairment.
- Combining biomarkers improved prediction accuracy with a high negative predictive value of 0.93.

## Abstract

What is already known on this topic?

There is an urgent clinical need for biomarkers to predict pulmonary deterioration among acutely admitted patients with COVID-19. Patients with COVID-19 present with a wide range of clinical outcomes, from mild illness to respiratory failure. Identifying patients who are at risk of deterioration early on can guide clinical management, resource allocation, and targeted interventions.

What does this study add?

This study shows that the most commonly affected pulmonary function parameter during follow-up was DLCO impairment. Among the biomarkers studied, soluble urokinase Plasminogen Activator Receptor (suPAR) at admittance demonstrated the strongest correlation with DLCO impairment, and a low suPAR cut-off value showed the highest negative predictive value (NPV) for DLCO impairment.

How might this study affect research, practice, or policy?

This study could assist physicians in reducing the number of patients requiring follow-up at pulmonary outpatient clinics, particularly due to the high negative predictive value (NPV) of the biomarkers in forecasting DLCO impairment. This could potentially be of benefit for individual patients and, at the same time, alleviate the pressure on the healthcare system.

What is already known on this topic?

There is an urgent clinical need for biomarkers to predict pulmonary deterioration among acutely admitted patients with COVID-19. Patients with COVID-19 present with a wide range of clinical outcomes, from mild illness to respiratory failure. Identifying patients who are at risk of deterioration early on can guide clinical management, resource allocation, and targeted interventions.

What does this study add?

This study shows that the most commonly affected pulmonary function parameter during follow-up was DLCO impairment. Among the biomarkers studied, soluble urokinase Plasminogen Activator Receptor (suPAR) at admittance demonstrated the strongest correlation with DLCO impairment, and a low suPAR cut-off value showed the highest negative predictive value (NPV) for DLCO impairment.

How might this study affect research, practice, or policy?

This study could assist physicians in reducing the number of patients requiring follow-up at pulmonary outpatient clinics, particularly due to the high negative predictive value (NPV) of the biomarkers in forecasting DLCO impairment. This could potentially be of benefit for individual patients and, at the same time, alleviate the pressure on the healthcare system.

Background: Pulmonary function impairment significantly affects quality of life, work ability, and healthcare utilization. Among patients with COVID-19, respiratory symptoms vary in severity. This study aimed to assess whether biomarkers related to respiratory function and inflammation at emergency department (ED) admittance can predict long-term pulmonary function impairment in COVID-19 survivors. Methods: This prospective single-center study recruited patients 4–5 months post-COVID-19 infection using consecutive sampling. All attendees at the respiratory outpatient clinic were invited to participate. Pulmonary function tests, including diffusing capacity of the lungs for carbon monoxide (DLCO), total lung capacity (TLC), forced expiratory volume in the first second (FEV1), and forced vital capacity (FVC), were performed, with DLCO < 80% as the key indicator of impairment. Baseline biomarkers—C-Reactive Protein (CRP), leukocyte counts, and soluble urokinase Plasminogen Activator Receptor (suPAR)—were correlated with post-discharge DLCO values. Results: This study enrolled 110 patients with COVID-19; 58.2% were female, the median age was 61.5, and the average BMI was 27.2. Smoking history showed that 53.7% were never smokers, 43.5% were former smokers, and 2.8% were current smokers. A diffusion deficit (DLCO < 80%) was present in 48.6% of patients. Leukocyte counts and suPAR had the highest sensitivity (>0.80) for predicting DLCO impairment but showed low specificity and a positive predictive value (PPV) of around 0.50. However, combining all biomarkers improved prediction accuracy, with a negative predictive value (NPV) of 0.93. Conclusions: The chosen inflammatory biomarkers by themselves had a limited ability to predict long-term pulmonary function impairment in COVID-19 survivors. However, when combined, they demonstrated a high negative predictive value (NPV) for identifying DLCO impairment. This strategy could help clinicians better tailor follow-up care for patients with COVID-19.