Qom University of Medical Sciences Journal

Introduction
After emergence in China in December 2019, the coronavirus disease (COVID-19) rapidly spread throughout the world and caused high rates of mortalities and morbidities. Although COVID-19 mainly characterized by lower respiratory tract infection, the data later showed the involvement of multiple organs in infected patients. Its virus (SARS-CoV) plays an important role in stimulating inflammatory pathways and causing various manifestations. Considering the anti-inflammatory role of statins which can reduce cytokines, this study aims to compare the anti-inflammatory effect of atorvastatin and standard treatment protocol for hospitalized adults with COVID-19.
Methods
This randomized controlled clinical trial was conducted on 74 adults hospitalized due to COVID-19 infection who were selected using the sequential sampling method. Inclusion criteria were: age>18 years, no history of statin use in the past month, oxygen saturation >93% and receiving auxiliary oxygen, normal level of liver enzymes, consent to participate, no any end-stage renal failure, glomerular filtration rate<15, no cardiogenic shock and hemodynamic instability, no allergy to the administrated drugs, no recent acute kidney failure and hemodialysis, no history of kidney transplant, no CT and MR angiography in the past two weeks, not taking nephrotoxic drugs in the past two weeks, and not taking any drugs that have interference with statins according to the FDA guidelines. The exit criteria were: elevated Creatine phosphokinase level three times the normal limit or its high level during admission, and elevated aspartate aminotransferase level (three times the normal limit). Patients were randomly divided into two groups of treatment (n=37, receiving atorvastatin 40 mg daily for 30 days plus standard treatment protocol) and control (n=37, receiving standard treatment protocol only). The standard treatment protocol included the use of hydroxychloroquine 200 mg daily, azithromycin 250 mg daily, and dexamethasone 4 mg every 12 hours for 30 days. During this period, the patients were contacted by phone to follow up their physical conditions and symptoms, or their need for re-hospitalization. After one month, patients in both groups were examined in the clinic in terms of changes in white blood count and levels of lymphocyte, C-reactive protein (CRP), lactate dehydrogenase, and Spo2, the improvement/maintenance of the initial symptoms (e.g., cough and shortness of breath), or re-hospitalization. The data were analyzed in SPSS v.22 software using chi-square test, paired t-test, and ANOVA. P<0.05 was statistically significant.
Results
The two groups were matched for age and clinical characteristics. Their mean age was 49±16.2 years, ranged 19-81 years. Shortness of breath was the most common symptom and hypertension was the most common underlying disease in patients. There was no significant difference in symptoms and common underlying diseases between the two groups. The men length of hospitalization in patients treated with atorvastatin was 4.4 days, while it was 5.6 days in the control group. The difference was significant (P=0.005). Dyspnea remained in 15.2% of atorvastatin-treated patients and in 43.3% of controls after 30 days of contracting COVID, and the difference was significant (P=0.024). In examining the lung CT scan images, most of the patients had moderate lung involvement, and there was no significant difference between the two groups in lung involvement (P=0.4). There was a significant relationship between the use of statins and reduction in the probability of re-hospitalization after discharge (P<0.05). The CRP level in atorvastatin-treated group decreased significantly (P<0.05) and there was a significant difference in CRP level between the two groups after 30 days (P= 0.01). There was no significant difference in Spo2 level between the two groups on the discharge day. No patients in any groups received invasive mechanical ventilation or needed hospitalization in the ICU.
Discussion
The use of atorvastatin along with standard treatment protocol for COVID-19 can significantly reduce the length of hospitalization and CRP level after 30 days in hospitalized patients. Further prospective studies with longer follow-up periods and randomized controlled trials including statin therapy for COVID-19 patients are recommended.
Ethical Considerations
Compliance with ethical guidelines
Ethical approval of this study was received from the Research Ethics Committee of Qom University of Medical Sciences and Health Services (IR.MUQ.REC.1399.176). Also, the study protocol was registered in the Iranian Clinical Trials Center with the code: IRCT20201128049508N1.
Funding
The financial sponsor of this research is Qom University of Medical Sciences and Health Services.
Authors contributions
All authors contributed equally in preparing all parts of the research.
Conflicts of interest
The authors declared no conflict of interest.
Acknowledgements
The authors would like to thank and appreciate the financial and spiritual support of Qom University of Medical Sciences and Health Services for conducting this study.