Circulating Levels of PD-L1, TIM-3 and MMP-7 Are Promising Biomarkers to Differentiate COVID-19 Patients That Require Invasive Mechanical Ventilation.

Leslie Chavez-Galan,Gloria Pérez-Rubio,Ramces Falfan-Valencia,Martha Torres,Andy Ruiz,Moises Selman,Karen Martinez-Espinosa,Hiram Aguilar-Duran,Ivette Buendia-Roldan

doi:10.3390/biom12030445

Leslie Chavez-Galan, Gloria Pérez-Rubio + Show 7 more

Open Access

https://doi.org/10.3390/biom12030445

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Journal: Biomolecules	Publication Date: Mar 14, 2022
Citations: 17	License type: CC BY 4.0

Affiliation: Instituto Nacional de Enfermedades Respiratorias

Abstract

Background: COVID-19 is an infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Many COVID-19 patients require invasive mechanical ventilation (IMV) while others, even with acute respiratory failure, do not (NIMV). Therefore, we aimed to evaluate serum levels of MMP-7 and molecules related to exhausted T-cells as potential biomarkers to differentiate between IMV and NIMV patients. Methods: 105 patients diagnosed with COVID-19 and confirmed by RT-PCR for SARS-CoV-2 were divided into two groups according to the requirement for IMV. Serum levels of sPD-L1, sPD-L2, sTIM-3, sGal-9 and sMMP-7 were quantified by ELISA and correlated with clinical data. Twelve patients were followed up after eight months to compare the levels of the biomarkers between acute disease and post-COVID-19. Results: IMV patients experienced a lower PaO2/FiO2 (p < 0.0001) and a longer hospital stay (p < 0.0001), and exhibited higher levels of sPD-L1 (p < 0.05), sTIM-3 (p < 0.01) and sMMP-7 (p < 0.0001) when compared with NIMV patients. According to a ROC analysis, sMMP-7 had the highest sensitivity (78%) and specificity (76%) with a cut point of 4.5 ng/mL, followed by sTIM-3 and sPD-L1. Eight months post-COVID-19, IMV patients displayed a significant decrease in the initially high levels of sPD-L1, sTIM-3 and sGal-9, while sPD-L2 was increased, and sMMP-7 was unchanged. Conclusion: Circulating levels of sPD-L1, sTIM-3 and sMMP-7 are potential biomarkers of disease severity to distinguish patients requiring IMV. MMP-7 could also be a marker for the persistence of lung lesions post-COVID-19.

Highlights

COVID-19 is an infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)
Our results revealed that soluble forms of PD-L1 (sPD-L1), sTIM-3 and sMMP-7 levels are significantly increased in patients with severe COVID-19, and these markers could be helpful for distinguishing patients that need invasive mechanic ventilation (IMV) from those who do not
Since the main aim of this study was to identify serum biomarkers that can differentiate between IMV and non-invasive mechanic ventilation (NIMV), we did not evaluate the functions of myeloid and lymphoid cells that could be altered by the high levels of sPD-L1 and sTIM-3

Summary

Introduction

COVID-19 is an infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Severe pneumonia and acute respiratory distress syndrome (ARDS) are common complications in these patients, and the severity of respiratory failure increases mortality by around 50%. Many of these patients require invasive mechanical ventilation (IMV), while others require only supplemental oxygen through a nasal cannula (NIMV) [3]. Twelve patients were followed up after eight months to compare the levels of the biomarkers between acute disease and post-COVID-19. Eight months post-COVID-19, IMV patients displayed a significant decrease in the initially high levels of sPD-L1, sTIM-3 and sGal-9, while sPD-L2 was increased, and sMMP-7 was unchanged. Conclusion: Circulating levels of sPD-L1, sTIM-3 and sMMP-7 are potential biomarkers of disease severity to distinguish patients requiring IMV. MMP-7 could be a marker for the persistence of lung lesions post-COVID-19

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