MASPs at the crossroad between the complement and the coagulation cascades - the case for COVID-19.

Valéria Bumiller-Bini,Marcia Holsbach Beltrame,Camila De Freitas Oliveira-Toré,Miguel Angelo Gasparetto Filho,Letícia Boslooper Gonçalves,Nina De Moura Alencar,Tamyres Mingorance Carvalho,Gabriela Canalli Kretzschmar,Angelica Beate Winter Boldt

doi:10.1590/1678-4685-gmb-2020-0199

Valéria Bumiller-Bini, Marcia Holsbach Beltrame + Show 7 more

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https://doi.org/10.1590/1678-4685-gmb-2020-0199

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Abstract

Components of the complement system and atypical parameters of coagulation were reported in COVID-19 patients, as well as the exacerbation of the inflammation and coagulation activity. Mannose binding lectin (MBL)- associated serine proteases (MASPs) play an important role in viral recognition and subsequent activation of the lectin pathway of the complement system and blood coagulation, connecting both processes. Genetic variants of MASP1 and MASP2 genes are further associated with different levels and functional efficiency of their encoded proteins, modulating susceptibility and severity to diseases. Our review highlights the possible role of MASPs in SARS-COV-2 binding and activation of the lectin pathway and blood coagulation cascades, as well as their associations with comorbidities of COVID-19. MASP-1 and/or MASP-2 present an increased expression in patients with COVID-19 risk factors: diabetes, arterial hypertension and cardiovascular disease, chronic kidney disease, chronic obstructive pulmonary disease, and cerebrovascular disease. Based also on the positive results of COVID-19 patients with anti-MASP-2 antibody, we propose the use of MASPs as a possible biomarker of the progression of COVID-19 and the investigation of new treatment strategies taking into consideration the dual role of MASPs, including MASP inhibitors as promising therapeutic targets against COVID-19.

Highlights

The emergence of a new infectious agent late in 2019 brought back the attention of the world to the Coronaviridae family
Since MBLassociated serine proteases (MASPs)-2 strictly depends on MASP-1 for LP activation, and given its important role linking the LP to the coagulation cascade and association with many of the factors/comorbidities increasing the risk for severe COVID-19 disease, we strongly suggest both as major candidates for further functional and genetic association studies in coronaviral diseases
Increased levels of MASPs are associated with comorbidities of COVID-19 (CVD, Chronic kidney disease (CKD), diabetes, Chronic obstructive pulmonary disease (COPD) and cerebrovascular diseases), and are associated with exacerbated inflammation and activity of the coagulation cascade

Summary

Introduction

The emergence of a new infectious agent late in 2019 brought back the attention of the world to the Coronaviridae family (reviewed by Hui et al, 2020; Malik, 2020). MASP1 and MASP2 polymorphisms are associated with protein levels and with the susceptibility to different viral infections (reviewed by Beltrame et al, 2015) (Tables 1 and 2).

Results

Conclusion