Relation of Statin Use Prior to Admission to Severity and Recovery Among COVID-19 Inpatients

Daniels, Lori B.; Sitapati, Amy M.; Zhang, Jing; Zou, Jingjing; Bui, Quan M; Ren, Junting; Longhurst, Chris; Criqui, Michael H.; Messer, Karen

doi:10.1016/j.amjcard.2020.09.012

Cited by 150 publications

(164 citation statements)

References 30 publications

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“…Several observational studies have evaluated the potential beneficial role of statins in COVID-19 [ [30] , [31] , [32] , [33] , [34] ] ( Table 1 ). Zhang et al.…”

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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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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“…Several observational studies have evaluated the potential beneficial role of statins in COVID-19 [ [30] , [31] , [32] , [33] , [34] ] ( Table 1 ). Zhang et al.…”

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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“…Recent studies on SARS-CoV-2 identified similar syncytia (Buchrieser et al, 2020;Cattin-Ortolá et al, 2020;Ou et al, 2020;Papa et al, 2020;Xia et al, 2020), which may or may not be relevant to patient pathology (Bryce et al, 2020;Giacca et al, 2020;Rockx et al, 2020;Tian et al, 2020). It remains an open question if syncytia are related to viral and host cell membrane composition, and whether their formation provides mechanistic insights into membrane-targeting therapeutics directed toward enveloped viruses including SARS-CoV-2 (Daniels et al, 2020;Zhang et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 Requires Cholesterol for Viral Entry and Pathological Syncytia Formation

Sanders

Jumper

Ackerman

et al. 2020

Preprint

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SummaryMany enveloped viruses induce multinucleated cells (syncytia), reflective of membrane fusion events caused by the same machinery that underlies viral entry. These syncytia are thought to facilitate replication and evasion of the host immune response. Here, we report that co-culture of human cells expressing the receptor ACE2 with cells expressing SARS-CoV-2 spike, results in synapse-like intercellular contacts that initiate cell-cell fusion, producing syncytia resembling those we identify in lungs of COVID-19 patients. To assess the mechanism of spike/ACE2-driven membrane fusion, we developed a microscopy-based, cell-cell fusion assay to screen ∼6000 drugs and >30 spike variants. Together with cell biological and biophysical approaches, the screen reveals an essential role for membrane cholesterol in spike-mediated fusion, which extends to replication-competent SARS-CoV-2 isolates. Our findings provide a molecular basis for positive outcomes reported in COVID-19 patients taking statins, and suggest new strategies for therapeutics targeting the membrane of SARS-CoV-2 and other fusogenic viruses.HighlightsCell-cell fusion at ACE2-spike clusters cause pathological syncytia in COVID-19Drug screen reveals critical role for membrane lipid composition in fusionSpike’s unusual membrane-proximal cysteines and aromatics are essential for fusionCholesterol tunes relative infectivity of SARS-CoV-2 viral particles

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“…The result of the meta-analysis of these seven studies performed in Western countries are reported in ►Fig. 2, [35][36][37][38][39][40][41] which demonstrate that COVID-19 patients taking statins had nearly 40% lower odds of progressing to the composite endpoint of severe/critical illness or death (OR: 0.59; 95% CI: 0.35-0.99; Cochran's Q p ¼ 0.02; I 2 ¼ 60%). Individually, six of these seven studies reported a reduced OR (i.e., OR < 1; protective effect of statins), [35][36][37][38][39][40] while in only one study was the OR >1 (i.e., OR: 1.60; 95% CI: 0.88-2.92).…”

Section: Resultsmentioning

confidence: 99%

Protective Effects of Statins Administration in European and North American Patients Infected with COVID-19: A Meta-Analysis

Onorato

Pucci

Carpenè

et al. 2021

Semin Thromb Hemost

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Severe acute respiratory syndrome coronavirus 2 has spread rapidly throughout the world, becoming an overwhelming global health emergency. The array of injuries caused by this virus is broad and not limited to the respiratory system, but encompassing also extensive endothelial and systemic tissue damage. Since statins effectively improve endothelial function, these drugs may have beneficial effects in patients with coronavirus disease 2019 (COVID-19). Therefore, this investigation aimed to provide an updated overview on the interplay between statins and COVID-19, with particular focus on their potentially protective role against progression toward severe or critical illness and death. A systematic electronic search was performed in Scopus and PubMed up to present time. Data on statins use and COVID-19 outcomes especially in studies performed in Europe and North America were extracted and pooled. A total of seven studies met our inclusion criteria, totaling 2,398 patients (1,075 taking statins, i.e., 44.8%). Overall, statin usage in Western patients hospitalized with COVID-19 was associated with nearly 40% lower odds of progressing toward severe illness or death (odds ratio: 0.59; 95% confidence interval: 0.35–0.99). After excluding studies in which statin therapy was started during hospital admission, the beneficial effect of these drugs was magnified (odds ratio: 0.51; 95% confidence interval: 0.41–0.64). In conclusion, although randomized trials would be necessary to confirm these preliminary findings, current evidence would support a favorable effect of statins as adjuvant therapy in patients with COVID-19. Irrespective of these considerations, suspension of statin therapy seems highly unadvisable in COVID-19 patients.

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Relation of Statin Use Prior to Admission to Severity and Recovery Among COVID-19 Inpatients

Cited by 150 publications

References 30 publications

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

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

SARS-CoV-2 Requires Cholesterol for Viral Entry and Pathological Syncytia Formation

Protective Effects of Statins Administration in European and North American Patients Infected with COVID-19: A Meta-Analysis

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