Low level of plasminogen increases risk for mortality in COVID-19 patients

David Della-Morte,Renato Massoud,Nicola Di Daniele,Stefania Proietti,Mariannina Iozzo,Francesca Pacifici,Valentina Rovella,Stefano Bonassi,Camillo Ricordi,Davide Lauro,Sergio Bernardini

doi:10.1038/s41419-021-04070-3

Abstract

The pathophysiology of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and especially of its complications is still not fully understood. In fact, a very high number of patients with COVID-19 die because of thromboembolic causes. A role of plasminogen, as precursor of fibrinolysis, has been hypothesized. In this study, we aimed to investigate the association between plasminogen levels and COVID-19-related outcomes in a population of 55 infected Caucasian patients (mean age: 69.8 ± 14.3, 41.8% female). Low levels of plasminogen were significantly associated with inflammatory markers (CRP, PCT, and IL-6), markers of coagulation (D-dimer, INR, and APTT), and markers of organ dysfunctions (high fasting blood glucose and decrease in the glomerular filtration rate). A multidimensional analysis model, including the correlation of the expression of coagulation with inflammatory parameters, indicated that plasminogen tended to cluster together with IL-6, hence suggesting a common pathway of activation during disease’s complication. Moreover, low levels of plasminogen strongly correlated with mortality in COVID-19 patients even after multiple adjustments for presence of confounding. These data suggest that plasminogen may play a pivotal role in controlling the complex mechanisms beyond the COVID-19 complications, and may be useful both as biomarker for prognosis and for therapeutic target against this extremely aggressive infection.

Highlights

Since emerging in Wuhan, China, in late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), has spread rapidly worldwide [1,2,3]
[27], we aimed to evaluate whether factors, such as alteration in in the present study, we aimed to analyze the plasminogen levels, that generate the “blood clots storm” may be association between plasminogen levels and the main COVID-19- predictive markers
Increase in mortality compared to COVID-19 patients with normal or high levels of plasminogen

Summary

Introduction

Since emerging in Wuhan, China, in late 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), has spread rapidly worldwide [1,2,3]. The primary mechanism of transmission of SARS-CoV-2 is through infected respiratory droplets occurring by direct or indirect contact with nasal, conjunctival, or oral mucosa. Factors directly related to virus, such as viral load kinetics, host immune-system defense mechanisms, and crossreactive immune memory from previous exposure to other coronaviruses, may influence history of the disease that ranges from absence of symptoms to a mild infection, to a severe disease accompanied by high mortality [10]. In COVID-19 patients with high rate of mortality, a state of hyperfibrinolysis, characterized by increased fibrin degradation products, such as D-dimer and reduced platelets, is significantly present [21]

Objectives

Methods

Conclusion