Abstract
Coronavirus disease 2019 (COVID-19) is currently a worldwide emergency caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In observational clinical studies, statins have been identified as beneficial to hospitalized patients with COVID-19. However, experimental evidence of underlying statins protection against SARS-CoV-2 remains elusive. Here we reported for the first-time experimental evidence of the protective effects of simvastatin treatment both in vitro and in vivo. We found that treatment with simvastatin significantly reduced the viral replication and lung damage in vivo, delaying SARS-CoV-2-associated physiopathology and mortality in the K18-hACE2-transgenic mice model. Moreover, simvastatin also downregulated the inflammation triggered by SARS-CoV-2 infection in pulmonary tissue and in human neutrophils, peripheral blood monocytes, and lung epithelial Calu-3 cells in vitro, showing its potential to modulate the inflammatory response both at the site of infection and systemically. Additionally, we also observed that simvastatin affected the course of SARS-CoV-2 infection through displacing ACE2 on cell membrane lipid rafts. In conclusion, our results show that simvastatin exhibits early protective effects on SARS-CoV-2 infection by inhibiting virus cell entry and inflammatory cytokine production, through mechanisms at least in part dependent on lipid rafts disruption.
Highlights
Coronavirus disease 2019 (COVID-19) is currently a worldwide emergency caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) [1]
Viral load measurements performed on the sixth day post-infection revealed a lower number of viral genome copies (Figure 1A) in the lungs of animals in the simvastatin group alongside lower tissue damage inferred through Lactate dehydrogenase (LDH) levels bronchoalveolar lavage (BAL) (Figure 1B)
Despite simvastatin not completely reversed the diffuse alveolar damage (DAD) and edema in SARS-CoV-2 infected mice, the treatment led to an important decrease in tissue hemorrhage and inflammation
Summary
Coronavirus disease 2019 (COVID-19) is currently a worldwide emergency caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) [1]. The susceptibility to developing severe COVID-19 is determined by various preexisting conditions, such as old age, obesity, diabetes mellitus, and cardiovascular diseases [4, 5]. Since hypercholesterolemia is often observed in obesity, diabetes mellitus, and cardiovascular diseases, many people at high risk of developing severe COVID-19 use statins regularly to lower their cholesterol levels [6, 7]. The pre-existing statin therapy has been associated with lower mortality and improved clinical parameters in COVID-19 compared to patients without statin therapy [2]. Patients who remained on statins during hospitalization exhibited a lower mortality rate compared to patients who stopped receiving statins after hospital admission [15]. A recent updated meta-analysis including twenty-five cohorts and 147.824 patients concluded that the use of statins is associated with a lower risk of mortality in COVID-19 patients [16]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
