Effect of statins on SARS-CoV-2 infection

Zapatero-Belinchón, Francisco J.; Moeller, Rebecca; Laßwitz, Lisa; Ham, Marco van; Becker, Miriam; Brogden, Graham; Rosendal, Ebba; Bi, Wenjie; Carriqui, Belen; Islam, Md. Kamrul; Lenman, Annasara; Gunesch, Antonia P.; Kirui, Jared; Pietschmann, Thomas; Överby, Anna K.; Jaensch, Lothar

doi:10.1101/2020.07.13.20152272

Cited by 10 publications

(12 citation statements)

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“…The effect of statins on cell membrane cholesterol content is debated. Some investigators believe that statins, by reducing endogenous synthesis of cholesterol, deplete cell membranes of their cholesterol content [ 23 ]. On the contrary, the other investigators have suggested that reduced circulating cholesterol levels increase upregulation of low-density lipoprotein receptors on cell surfaces, thereby increasing cholesterol uptake from the circulation [ 24 ].…”

Section: Resultsmentioning

confidence: 99%

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Statins and SARS-CoV-2 disease: Current concepts and possible benefits

Minz

Bansal

Kasliwal

2020

Diabetes & Metabolic Syndrome: Clinical Research & Revi

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Background and aims Inflammation-mediated tissue injury is the major mechanism involved in the pathogenesis of coronavirus disease 2019 (COVID-2019), caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2). Statins have well-established anti-inflammatory, anti-thrombotic and immuno-modulatory effects. They may also influence viral entry into human cells. Methods A literature search was done using PubMed and Google search engines to prepare a narrative review on this topic. Results Statins interact with several different signaling pathways to exert their anti-inflammatory and vasculoprotective effects. They also variably affect cholesterol content of cell membranes and interfere with certain coronavirus enzymes involved in receptor-binding. Both these actions may influence SARS-CoV-2 entry into human cells. Statins also upregulate expression of angiotensin-converting enzyme 2 receptors on cell surfaces which may promote viral entry into the cells but at the same time, may minimize tissue injury through production of angiotensin [1-7]. The net impact of these different effects on COVID-19 pathogenesis is not clear. However, the retrospective clinical studies have shown that statin use is potentially associated with lower risk of developing severe illness and mortality and a faster time to recovery in patients with COVID-19. Conclusions Early observations suggest beneficial effect of statin use on the clinical outcomes in COVID-19. Prospective randomized studies as well as well-designed laboratory studies are required to confirm these observations and to elucidate the mechanisms of such benefits, if proven.

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Section: Resultsmentioning

confidence: 99%

“…These opposing theories regarding the impact of statins on the cholesterol content of the cell membranes create uncertainty. Nevertheless, studies employing human respiratory epithelial cell cultures have demonstrated that statins such as Fluvastatin successfully inhibit SARS-CoV-2 entry into the cells [ 23 ].…”

Section: Resultsmentioning

confidence: 99%

Statins and SARS-CoV-2 disease: Current concepts and possible benefits

Minz

Bansal

Kasliwal

2020

Diabetes & Metabolic Syndrome: Clinical Research & Revi

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“…While there is not enough evidence to suggest that a reduced cholesterol level is the direct contributory factor in, or cause of, SARS-CoV-2 susceptibility, calls to examine cholesterol as a therapeutic target are gaining momentum [ 177 , 178 ]. Stemmed from retrospective analyses that showed COVID-19 patients on statins had better outcome [ 179 , 180 ], a yet to be peer-reviewed in vitro study by Moeller et al suggests a decreased rate of SARS-CoV-2 infection under statin treatment, possibly due to reduced membrane cholesterol impacting ACE2-viral spike protein interactions [ 181 ].…”

Section: Covid-19-associated Dyslipidaemiamentioning

confidence: 99%

Dissecting lipid metabolism alterations in SARS-CoV-2

Casari

Manfredi

Metharom

et al. 2021

Progress in Lipid Research

101

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the COVID-19 pandemic that has infected over sixteen million people globally. There have been more than two million deaths recorded worldwide, with no end in sight until a vaccine is developed. Current research has centred on different aspects of the virus interaction with cell surface receptors, but more needs to be done to further understand its mechanism of action in order to develop a targeted therapy and a method to control the spread of the virus. Lipids play a crucial role throughout the viral life cycle, and viruses are known to exploit lipid signalling and synthesis to affect host cell lipidome. Emerging studies using untargeted metabolomic and lipidomic approaches are providing new insight into the host response to COVID-19 infection. Indeed, metabolomic and lipidomic approaches have identified numerous circulating lipids that directly correlate to the severity of the disease, making lipid metabolism a potential therapeutic target. Circulating lipids play a key function in the pathogenesis of the virus and exert an inflammatory response. A better knowledge of lipid metabolism in the host-pathogen interaction will provide valuable insights into viral pathogenesis and to develop novel therapeutic targets.

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“…Moreover, selective statins ( uvastatin was more e cient than other statins) reduced SARS-CoV-2 cell entry and inhibited infection of human respiratory epithelial cells by either the low pathogenic (coronavirus 229E) or highly pathogenic (2019-nCoV) coronavirus. It was contributed with mild attenuation of SARS-CoV-2 infection in vitro [62]. This study also showed that statin therapy did not cause any additional risk to these patients and that some statins may have a mild bene cial effect on COVID-19 outcome [62].…”

Section: Discussionmentioning

confidence: 63%

“…It was contributed with mild attenuation of SARS-CoV-2 infection in vitro [62]. This study also showed that statin therapy did not cause any additional risk to these patients and that some statins may have a mild bene cial effect on COVID-19 outcome [62].…”

Section: Discussionmentioning

confidence: 63%

Statins in Patients with COVID-19: A Retrospective Cohort Study in Iranian COVID-19 Patients

Peymani

Dehesh

Aligolighasemabadi

et al. 2020

Preprint

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Background: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has profoundly affected the lives of millions of people. To date, there is no approved vaccine or specific drug to prevent or treat COVID-19, while the infection is spreading at an alarming rate globally. Because the development of effective vaccines or novel drugs could take several months (if not years), repurposing existing drugs is considered a more efficient strategy that could save lives now. Statins constitute a class of lipid-lowering drugs with proven safety profiles and many known beneficial pleiotropic effects. Our previous investigations showed that statins have antiviral effects and are involved in the process of wound healing in the lung. This triggered us to evaluate if statin use reduces mortality in COVID-19 patients. Results: After initial recruitment of 459 patients with COVID-19 (Shiraz province, Iran) and careful consideration of the exclusion criteria, a total of 150 patients, of which 75 received statins, were included in our retrospective study. Cox proportional-hazards regression models were used to estimate the association between statin use and rate of death. After propensity score matching, we found that statin use appeared to be associated with a lower risk of morbidity [HR=0.85, 95% CI=(0.02, 3.93), P=0.762] and lower risk of death [(HR= 0.76; 95% CI=(0.16, 3.72), P=0.735)]; however, these associations did not reach statistical significance. Furthermore, statin use reduced the chance of being subjected to mechanical ventilation [OR=0.96, 95% CI=(0.61–2.99), P=0.942] and patients on statins had a more normal computed tomography (CT) scan result [OR=0.41, 95% CI= (0.07–2.33), P=0.312]. Conclusions: Although we could not demonstrate a significant association between statin use and a reduction in mortality in patients with COVID19 , we do feel that our results are promising and of clinical relevance and warrant the need for prospective randomized controlled trials and extensive retrospective studies to validate the potential beneficial effects of statin treatment on clinical symptoms and mortality rates associated with COVID-19.

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Effect of statins on SARS-CoV-2 infection

Cited by 10 publications

References 60 publications

Statins and SARS-CoV-2 disease: Current concepts and possible benefits

Statins and SARS-CoV-2 disease: Current concepts and possible benefits

Dissecting lipid metabolism alterations in SARS-CoV-2

Statins in Patients with COVID-19: A Retrospective Cohort Study in Iranian COVID-19 Patients

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