Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Statin use is associated with lower disease severity in COVID-19 infection

Abstract

We aim to study the association of hyperlipidemia and statin use with COVID-19 severity. We analysed a retrospective cohort of 717 patients admitted to a tertiary centre in Singapore for COVID-19 infection. Clinical outcomes of interest were oxygen saturation ≤ 94% requiring supplemental oxygen, intensive-care unit (ICU) admission, invasive mechanical-ventilation and death. Patients on long term dyslipidaemia medications (statins, fibrates or ezetimibe) were considered to have dyslipidaemia. Logistic regression models were used to study the association between dyslipidaemia and clinical outcomes adjusted for age, gender and ethnicity. Statin treatment effect was determined, in a nested case–control design, through logistic treatment models with 1:3 propensity matching for age, gender and ethnicity. All statistical tests were two-sided, and statistical significance was taken as p < 0.05. One hundred fifty-six (21.8%) patients had dyslipidaemia and 97% of these were on statins. Logistic treatment models showed a lower chance of ICU admission for statin users when compared to non-statin users (ATET: Coeff (risk difference): − 0.12 (− 0.23, − 0.01); p = 0.028). There were no other significant differences in other outcomes. Statin use was independently associated with lower ICU admission. This supports current practice to continue prescription of statins in COVID-19 patients.

Introduction

The COVID-19 pandemic continues to grow around the world, with more than 20 million cases worldwide1. The coronavirus infections, COVID-19, SARS and MERS, are all associated with dysregulated immune and inflammatory processes. Severe cases of COVID-19 are characterised by high circulating pro-inflammatory cytokines concentrations, as well as high neutrophil counts and lymphopenia2,3,4. COVID-19 has been associated with hyperinflammatory states, cardiovascular disease and venous thromboembolism5,6,7.

Inflammation has a potential role in the pathogenesis of dyslipidaemia8. Statins are commonly used to treat hyperlipidemia and its pleiotropic effects have been shown to reduce cytokines in various non-infective conditions9,10. Long term statin therapy correlates with better outcome in the setting of bacterial pneumonia11,12 and influenza13. A randomised controlled trial evaluating atorvastatin as a treatment for influenza showed significantly lower levels of inflammatory cytokines with treatment [NCT02056340].

Medical comorbidities such as diabetes, hypertension and cardiovascular diseases have been identified as risk factors for severe COVID-19 in numerous large case series from China, Italy and the United States14,15,16. Dyslipidaemia has not been identified as an independent risk factor17, although it is associated with diabetes and hypertension, and contributes to cardiovascular diseases. We aimed to study the association of dyslipidaemia with COVID-19 associated inflammation and the correlation between long term statin therapy and disease severity.

Methods

We carried out a retrospective cohort study of patients with confirmed COVID-19 hospitalized at the National Centre of Infectious Diseases (NCID), Singapore. NCID is responsible for managing more than 60% of COVID-19 patients admitted to hospital in Singapore. Patients were identified by primary care and emergency doctors based on case definitions informed by evolving epidemiological risk factors, case detection from active contact tracing, enhanced pneumonia surveillance and diagnostic testing based on doctors’ discretion18. Patients were included if they were hospitalized from 22 January 2020 to 15 April 2020. This cohort was previously studied for associations with diabetes and hypertension pharmacotherapy19 but this analysis is restricted towards studying the association of dyslipidaemia with COVID-19 associated inflammation and the effects of the use of statin with disease severity.

Electronic medical records of hospitalised patients with COVID-19 confirmed by PCR performed on respiratory samples were reviewed to extract information on demographic data on age, gender and ethnicity, presence of comorbidities and concomitant medications, laboratory investigations including full blood count, renal and liver function tests, C-reactive protein (CRP) and lactate dehydrogenase (LDH) and clinical outcomes of COVID-19. Clinical outcomes of interest were hypoxia with oxygen saturation ≤ 94% requiring supplemental oxygen, intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) and death. All study procedures and data collections were performed in accordance with institutional guidelines. The study protocol was reviewed and approved by the Singapore, Ministry of health who provided a waiver of informed consent from study participants for data collection under the Infectious Disease Act as part of national public health research.

Continuous and categorical variables are presented as median (interquartile range) and frequency (%), respectively. We used linear regression models to assess the association between each of the complete blood count variables and inflammatory markers with dyslipidaemia status adjusting for age, gender and ethnicity. To assess the possible treatment effect of statin use on these outcomes we used a nested case–control design, wherein after excluding patients with diabetes and hypertension, we estimated the statin treatment effect through logistic treatment models with 1:3 propensity matching for age, gender and ethnicity. All statistical tests were two-sided, and statistical significance was taken as p < 0.05. All statistical analyses were performed using Stata version 15.

Results

Within our cohort of 717 patients, one hundred fifty-six (21.8%) patients had dyslipidaemia. Individuals with dyslipidaemia were older (62.5 years, IQR 55–68 years versus 37 years, IQR 27–52 years) and more likely to be of Malay ethnicity (18.6% versus 8.9%). Approximately 24–59% of patients had coexisting diabetes, hypertension and atherosclerotic cardiovascular disease defined as history of ischemic heart disease, stroke or peripheral vascular disease. In terms of inflammatory markers, those with dyslipidaemia were more likely to have higher CRP, LDH, procalcitonin, white cell count and neutrophil count but lower lymphocyte count. Patients with dyslipidaemia were more likely to require supplemental oxygen, ICU admission and IMV. The risk of death was higher (p < 0.05). See Tables 1 and 2.

Table 1 Baseline characteristics and clinical outcomes of patients.
Table 2 Associations of laboratory markers with hyperlipidemia.

Dyslipidaemia was associated with higher white cell count and neutrophil count but not the other inflammatory markers. See Tables 1 and 2.

Of those who had hyperlipidemia, 151 (96.7%) were on statins, 12 (7.7%) were on fibrates and 10 (6.4%) were on ezetimibe. In the nested case–control analysis after excluding patients with diabetes and hypertension, 40 patients were on statins and 509 were non-statin users. The baseline characteristics of these 40 patients is described in Table 3. Approximately 22.5% (9/40) patients had baseline atherosclerotic cardiovascular disease. None of the patients had renal disease or other comorbid diseases. Logistic treatment models using propensity matching showed a lower chance of ICU admission for statin users when compared to non-statin users (Average treatment effect of statins (ATET) Coeff (risk difference): − 0.12 (− 0.23, − 0.01); p = 0.028). There were no other significant differences in other outcomes (Table 4).

Table 3 Baseline characteristics of patients on statins without comorbid conditions of diabetes or hypertension included in the nested case–control propensity matching analysis.
Table 4 Logistic treatment models with 1:3 propensity matching (age, gender, ethnicity) to assess statin treatment effect on clinical outcomes.

Discussion

We found that statins was associated with better outcomes in COVID-19. Similar results have been reported from a large study from Hubei province, China wherein they found that statin use was associated with a lower risk of mortality in COVID-19 infections20. In another retrospective study, atorvastatin also associated with a lower risk of death in COVID-19 patients admitted to the intensive care unit21. In a study involving nursing home residents, statin use was associated with higher chances of asymptomatic infection22.

Lipids and cholesterol-rich membrane microdomains facilitates the interaction between the surface glycoprotein S of SARS-CoV and the cellular receptor angiotensin-converting enzyme 2 (ACE2)23. Cholesterol has been implicated to have a possible role in the increased risk of infection in the elderly patients wherein higher tissue cholesterol has been shown to increase the endocytic entry of SARS-CoV-2 along with increased trafficking of angiotensin converting enzyme-2 (ACE-2) in a preprint24. After cellular entry, RNA viruses require intracellular cholesterol and fatty acids for further replication. For e.g. it has been demonstrated that during the initial phase of dengue virus infection, there is an increase in intracellular cholesterol concentration. This is associated with an increase in low density lipoprotein (LDL) concentrations in cells and a concomitant increase in the enzymatic activity of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inside the cells25,26. Three decades ago, Mabuchi et al., reported that statins can effectively reduce LDL concentrations through HMG-CoA reductase inhibition27 and in the last three decades statins have become the most widely prescribed lipid lowering medication. In COVID-19, statins may help to reduce viral entry and viral transmission by inhibition of the HMG-CoA reductase in the cells which will make less cholesterol available inside cells and tissues.

In our small observational cohort, we observed a significant trend towards higher white cell counts and neutrophil counts in patients with dyslipidaemia. A key pathological process that leads to cardiovascular disease is inflammation. Statins have been shown to have significant pleiotropic, anti-inflammatory and immunomodulatory effects28,29,30,31,32,33,34,35,36, independent of its ability to reduce low-density lipoprotein36. Even in rheumatological disease statins are known to modulate the inflammatory response37. Additional to its beneficial effects in cardiovascular disease, statins may be beneficial in patients with bacterial sepsis38,39, community acquired pneumonia40 and influenza13. Severe outcomes in COVID-19 is associated with higher markers of inflammation and a “cytokine storm”41,42,43. Statins have the potential to block the molecular mechanisms, including NF-κB and NLRP3 inflammasomes and TLR signalling which are responsible for the "cytokine storm" in severe COVID-19 patients44,45,46.

COVID-19 has been associated with significant cardiovascular complications due to direct effects of SARs-CoV-2 virus with significant effects of the virus on the expression and function of ACE-2 in the vasculature and evidence of coronary endothelial dysfunction and endothelialitis seen in multiple vascular beds in fatal patients with COVID-1947,48. Cases of acute coronary events (acute myocardial infarction and thromboembolism) triggered in patients with no underlying history of ischemic heart disease have been reported worldwide49,50,51. Statins are known to be effective in the prevention of endothelial dysfunction and downstream, atherosclerotic pathways and to prevent coronary artery disease52. It has been suggested that dyslipidaemia patients maybe at higher risk of atherosclerotic events after recovery from COVID-19. Similar exacerbations have been reported in influenza infections. It has been suggested that statins should be intensified to reduce cardiovascular risk post COVID-19 infection53,54.

Hence, we suggest that statins should be continued in dyslipidaemia patients who develop COVID-19 infection . This is especially important in COVID-19 as severe disease is related to cardiovascular comorbidities during infection and increased cardiovascular risk post recovery.

Our study has several limitations. We did not have the quantitative lipid profile on admission to study detailed correlations with the lipid phenotype. We did not have the values of the previous lipid profile including maximum LDL-Cholesterol, so we could not study correlations of cholesterol load with COVID-19 severity. Our cohort was small and adverse outcome rates, were low. This will affect the generalisability of our findings. Lastly, there was a risk of channelling bias as patients on statins were more likely to have more severe cardiovascular disease than those without.

Conclusion

We found dyslipidaemia patients had a significant trend towards a higher innate immune response shown by higher white cell counts and neutrophil counts. Statin use was independently associated with lower requirement for ICU admission. This supports current practice to continue prescription of statins in hyperlipidemia and other metabolic disorders in COVID-19 patients. The effect of statin use and intensification on COVID-19 disease severity and atherosclerotic events after recovery needs to be studied in larger observational studies or ideally in randomised controlled trials.

Data availability

The datasets are available from the corresponding author upon reasonable request.

References

  1. 1.

    Situation Reports [Internet]. Situation Reports. 2020 [cited 2020May12]. Available from: https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200511-covid-19-sitrep-112.pdf?sfvrsn=813f2669_2.

  2. 2.

    Liu, J. et al. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients. EBioMedicine 55, 102763 (2020).

    Article  Google Scholar 

  3. 3.

    Konig, M. F. et al. Preventing cytokine storm syndrome in COVID-19 using α-1 adrenergic receptor antagonists. J. Clin. Invest. 130, 139642 (2020).

    Article  Google Scholar 

  4. 4.

    Chen, X. et al. Detectable serum severe acute respiratory syndrome coronavirus 2 viral load (RNAemia) is closely correlated with drastically elevated interleukin 6 level in critically ill patients with coronavirus disease. Infect. Dis. Clin. https://doi.org/10.1093/cid/ciaa449 (2019).

    Article  Google Scholar 

  5. 5.

    Riphagen, S., Gomez, X., Gonzalez-Martinez, C., Wilkinson, N. & Theocharis, P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet 395, 1607–1608 (2020).

    CAS  Article  Google Scholar 

  6. 6.

    Clerkin, K. J. et al. COVID-19 and cardiovascular disease. Circulation 141, 1648–1655 (2020).

    CAS  Article  Google Scholar 

  7. 7.

    Artifoni, M. et al. Systematic assessment of venous thromboembolism in COVID-19 patients receiving thromboprophylaxis: incidence and role of D-dimer as predictive factors. J. Thromb. Thrombolysis. 50, 211 (2020).

    CAS  Article  Google Scholar 

  8. 8.

    Schonbeck, U. & Libby, P. Inflammation, immunity, and HMG-CoA reductase inhibitors: statins as antiinflammatory agents?. Circulation 109, 18–26 (2004).

    Article  Google Scholar 

  9. 9.

    Wassmann, S. et al. Rapid effect of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition on coronary endothelial function. Circ. Res. 93, e98-103 (2003).

    CAS  Article  Google Scholar 

  10. 10.

    Fang, C. H., Li, J. J. & Hui, R. T. Statins, like aspirin, should be given as early as possible in patients with acute coronary syndrome. Med. Hypotheses 64, 192–6 (2005).

    CAS  Article  Google Scholar 

  11. 11.

    Novack, V. et al. The effects of statin therapy on inflammatory cytokines in patients with bacterial infections: a randomized double-blind placebo controlled clinical trial. Intensive Care Med. 17, 1255–1260 (2009).

    Article  Google Scholar 

  12. 12.

    Mortensen, E. M., Restrepo, M. I., Anzueto, A. & Pugh, J. The effect of prior statin use on 30-day mortality for patients hospitalized with community-acquired pneumonia. Respir. Res. 17, 82 (2005).

    Article  Google Scholar 

  13. 13.

    Vandermeer, M. L. et al. Association between use of statins and mortality among patients hospitalized with laboratory-confirmed influenza virus infections: a multistate study. J. Infect. Dis. 205, 13–19 (2012).

    CAS  Article  Google Scholar 

  14. 14.

    Guan, W. J. et al. Clinical characteristics of coronavirus disease 2019 in China. New Engl. J. Med. 382, 1708–1720 (2020).

    CAS  Article  Google Scholar 

  15. 15.

    Richardson, S. et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA 323, 2052–2059 (2020).

    CAS  Article  Google Scholar 

  16. 16.

    Mancia, G., Rea, F., Ludergnani, M., Apolone, G. & Corrao, G. Renin-angiotensin-aldosterone system blockers and the risk of covid-19. N. Engl. J. Med. 382, 2431–2440 (2020).

    CAS  Article  Google Scholar 

  17. 17.

    Chow, N. et al. Preliminary estimates of the prevalence of selected underlying health conditions among patients with coronavirus disease 2019—United States, February 12–March 28, 2020. MMWR Morb. Mortal Wkly. Rep. 69, 382–386 (2020).

    Article  Google Scholar 

  18. 18.

    Ng, Y. X. et al. Evaluation of the effectiveness of surveillance and containment measures for the first 100 patients with COVID-19 in Singapore—January 2–February 29, 2020. MMWR Morb. Mortal Wkly. Rep. 69, 307–311 (2020).

    CAS  Article  Google Scholar 

  19. 19.

    Dalan, R. et al. The association of hypertension and diabetes pharmacotherapy with COVID-19 severity and immune signatures: an observational study. Eur. Heart J. Cardiovasc. Pharmacother. 2020, 098. https://doi.org/10.1093/ehjcvp/pvaa098 (2020).

    Article  Google Scholar 

  20. 20.

    Zhang, X. J. et al. In-hospital use of statins is associated with a reduced risk of mortality among individuals with COVID-19. Cell Metab. 32, 176–187 (2020).

    CAS  Article  Google Scholar 

  21. 21.

    Rodriguez-Nava, G. et al. Atorvastatin associated with decreased hazard for death in COVID-19 patients admitted to an ICU: a retrospective cohort study. Crit. Care 24, 429 (2020).

    Article  Google Scholar 

  22. 22.

    De Spiegeleer, A. et al. The effects of ARBs, ACEis, and statins on clinical outcomes of COVID-19 infection among nursing home residents. J. Am. Med. Dir. Assoc. 21, 909–914 (2020).

    Article  Google Scholar 

  23. 23.

    Glende, J. et al. Importance of cholesterol-rich membrane microdomains in the interaction of the S protein of SARS-coronavirus with the cellular receptor angiotensin-converting enzyme 2. Virology 381, 215–221 (2008).

    CAS  Article  Google Scholar 

  24. 24.

    Wang, H., Yuan, Z., Pavel, M. A. & Hansen, S. B. Cholesterol and COVID19 lethality in elderly. bioRxiv https://doi.org/10.1101/2020.05.09.086249v2 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Soto-Acosta, R. et al. The increase in cholesterol levels at early stages after dengue virus infection correlates with an augment in LDL particle uptake and HMG-CoA reductase activity. Virology 442, 132–147. https://doi.org/10.1016/j.virol.2013.04.003 (2013).

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Scicali, R., Di Pino, A., Piro, S. & Rabuazzo, A. M. Purrello F (2020) May statins and PCSK9 inhibitors be protective from COVID-19 in familial hypercholesterolemia subjects?. Nutr. Metab. Cardiovasc. Dis. 30, 1068–1069. https://doi.org/10.1016/j.numecd.2020.05.003 (2020).

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Mabuchi, H. et al. Effect of an inhibitor of 3-hydroxy-3-methyglutaryl coenzyme A reductase on serum lipoproteins and ubiquinone-10-levels in patients with familial hypercholesterolemia. N. Engl. J. Med. 305, 478–482 (1981).

    CAS  Article  Google Scholar 

  28. 28.

    Bifulco, M. & Gazzerro, P. Statins in coronavirus outbreak: It’s time for experimental and clinical studies. Pharmacol. Res. 156, 104803 (2020).

    CAS  Article  Google Scholar 

  29. 29.

    Ridker, P. M. et al. Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol and Recurrent Events (CARE) Investigators. Circulation 100, 230 (1999).

    CAS  Article  Google Scholar 

  30. 30.

    McCarey, D. W. et al. Trial of atorvastatin in rheumatoid arthritis (TARA): double-blind, randomised placebo-controlled trial. Lancet 363, 2015 (2004).

    CAS  Article  Google Scholar 

  31. 31.

    Albert, M. A., Danielson, E., Rifai, N. & Ridker, P. M. PRINCE Investigators. Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study. JAMA 286, 64 (2001).

    CAS  Article  Google Scholar 

  32. 32.

    Zhang, J. et al. Statins directly suppress cytokine production in murine intraepithelial lymphocytes. Cytokine 61, 540–545 (2013).

    CAS  Article  Google Scholar 

  33. 33.

    Iwata, A. et al. Inhibitory effect of statins on inflammatory cytokine production from human bronchial epithelial cells. Clin. Exp. Immunol. 168, 234–240 (2012).

    CAS  Article  Google Scholar 

  34. 34.

    van der Meij, E. et al. A clinical evaluation of statin pleiotropy: statins selectively and dose-dependently reduce vascular inflammation. PLoS ONE 8, e53882 (2013).

    ADS  Article  Google Scholar 

  35. 35.

    Duan, H. Y. et al. Effect of atorvastatin on plasma NT-proBNP and inflammatory cytokine expression in patients with heart failure. Genet. Mol. Res. 14, 15739–15748 (2015).

    CAS  Article  Google Scholar 

  36. 36.

    Zeiser, R. Immune modulatory effects of statins. Immunology 154, 69–75 (2018).

    CAS  Article  Google Scholar 

  37. 37.

    Erkan, D. et al. A prospective open-label pilot study of fluvastatin on proinflammatory and prothrombotic biomarkers in antiphospholipid antibody positive patients. Ann. Rheum Dis. 73, 1176–1180 (2014).

    CAS  Article  Google Scholar 

  38. 38.

    Liappis, A. P., Kan, V. L., Rochester, C. G. & Simon, G. L. The effect of statins on mortality in patients with bacteremia. Clin. Infect. Dis. 33, 1352–1357 (2001).

    CAS  Article  Google Scholar 

  39. 39.

    Ma, Y. et al. Systematic review and meta-analysis on the association between outpatient statins use and infectious disease-related mortality. PLoS ONE 7, e51548 (2012).

    ADS  CAS  Article  Google Scholar 

  40. 40.

    Mortensen, E. M., Restrepo, M. I., Anzueto, A. & Pugh, J. The effect of prior statin use on 30-day mortality for patients hospitalized with community-acquired pneumonia. Respir. Res. 6, 82 (2005).

    Article  Google Scholar 

  41. 41.

    Huang, C. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395, 497–506 (2020).

    CAS  Article  Google Scholar 

  42. 42.

    Chen, L. et al. Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia. Zhonghua Jie He He Hu Xi Za Zhi. 43, E005 (2020).

    CAS  PubMed  Google Scholar 

  43. 43.

    Xu, Z. et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir. Med. https://doi.org/10.1016/S2213-2600(20)30076-X (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Rodrigues-Diez, R. R. et al. Statins: could an old friend help in the fight against COVID-19?. Br. J. Pharmacol. https://doi.org/10.1111/bph.15166 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Castiglione, V., Chiriacò, M., Emdin, M., Taddei, S. & Vergaro, G. Statin therapy in COVID-19 infection. Eur. Heart J. Cardiovasc. Pharmacother. 6, 258–259 (2020).

    Article  Google Scholar 

  46. 46.

    Dashti-Khavidaki, S. & Khalili, H. Considerations for statin therapy in patients with COVID-19. Pharmacotherapy 40, 484–486 (2020).

    CAS  Article  Google Scholar 

  47. 47.

    Evans, P. C. et al. Endothelial dysfunction in COVID-19: a position paper of the ESC working group for atherosclerosis and vascular biology, and the ESC council of basic cardiovascular science. Cardiovasc. Res. 2020, cvaa230. https://doi.org/10.1093/cvr/cvaa230 (2020).

    Article  Google Scholar 

  48. 48.

    Ackermann, M. et al. Pulmonary vascular endothelialitis, thrombosis and angiogenesis in COVID-19. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa2015432 (2020).

    Article  PubMed  Google Scholar 

  49. 49.

    Li, G. et al. Cardiovascular disease during the COVID-19 pandemic: think ahead, protect hearts, reduce mortality. Cardiol. J. https://doi.org/10.5603/CJ.a2020.0101 (2020).

    Article  PubMed  Google Scholar 

  50. 50.

    Tedeschi, D., Rizzi, A., Biscaglia, S. & Tumscitz, C. Acute myocardial infarction and large coronary thrombosis in a patient with COVID-19. Catheter. Cardiovasc. Interv. https://doi.org/10.1002/ccd.29179 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Shams, A., Ata, F., Mushtaq, K., Munir, W. & Yousaf, Z. Coronary thrombosis in a young male with COVID-19. IDCases 21, 00923. https://doi.org/10.1016/j.idcr.2020.e00923 (2020).

    Article  Google Scholar 

  52. 52.

    Crunkhorn, S. Statin therapy improves endothelial dysfunction. Nat. Rev. Drug Discov. https://doi.org/10.1038/d41573-020-00137-6 (2020).

    Article  PubMed  Google Scholar 

  53. 53.

    Peretz, A., Azrad, M. & Blum, A. Influenza virus and atherosclerosis. QJM 112, 749–755 (2019).

    CAS  Article  Google Scholar 

  54. 54.

    Vuorio, A., Watts, G. F. & Kovanen, P. T. Familial hypercholesterolaemia and COVID-19: triggering of increased sustained cardiovascular risk. J. Intern. Med. 287, 746–747. https://doi.org/10.1111/joim.13070 (2020).

    CAS  Article  PubMed  Google Scholar 

Download references

Acknowledgements

The study is funded through NMRC COVID-19 research fund (COVID19RF-001). RD is supported in part by Ministry of Health, Clinician Scientist Award [MOH-000014]; and National Medical Research Council Centre Grant [NMRC/CG/017/2013].

Author information

Affiliations

Authors

Contributions

R.D., W.Y.T.T. conceptualized the study, performed data analysis, data interpretation, literature review and wrote the manuscript. D.E.K.C.: data interpretation and critical review of manuscript. D.C.L. and B.E.Y. conceptualized the study, data interpretation and critical review of manuscript. All authors reviewed the final manuscript.

Corresponding author

Correspondence to Rinkoo Dalan.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Tan, W.Y.T., Young, B.E., Lye, D.C. et al. Statin use is associated with lower disease severity in COVID-19 infection. Sci Rep 10, 17458 (2020). https://doi.org/10.1038/s41598-020-74492-0

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing