Background Although mass vaccination has reduced the severity of COVID-19, mortality is still high among hospitalized patients. Being a sepsis-like disease, an anti-inflammatory drug as atorvastatin would reduce mortality and severity in COVID-19. Methods We designed a randomized clinical trial that recruited 220 COVID-19 patients admitted in the COVID-19 isolation hospital at Mansoura University, Egypt. One hundred ten cases were assigned to receive 40 mg atorvastatin once daily for 28 days, and 110 were assigned to receive placebo. Delta Pharm company supported the study with the drug and the placebo, which mimics the drug as regards the drug package, the tablet color, consistency, and size. All patients received the standard treatment as per the hospital protocol. The Institutional Review Board approval and the informed consent from all participants were obtained. The primary outcome is the 28-day all-cause mortality. Additionally, we will collect the in-hospital mortality, the need for mechanical ventilation, time to clinical improvement, in-hospital thrombo-embolic events, acute kidney injury, and the hospital and the intensive care duration of stay. We plan to follow the patients up for 6 months for reporting mortality and long-term neurological, psychological, and respiratory consequences. We will report the un-adjusted 28-mortality using χ2. Then, we will report the adjusted odds ratio with a pre-planned multiple logistic regression model. We will report our results using the point estimate and the 95% confidence interval and the P-value. Discussion The additional issue that we would like to discuss is the added workload on the clinicians and the allied healthcare workers who performed research at the time of the pandemic. Therefore, doing research at the pandemic era was, indeed, challenging. Trial registration The study was registered at the Clinical Trial Registry (NCT04952350) on July 1st, 2021.

Background: COVID-19 is an abnormal host response to the SARS-CoV-2 infection, which is associated with endothelial dysfunction and multi-organ failure. Atorvastatin has been proposed to reduce COVID-19 severity and mortality. Methods: This randomized double-blind trial included 220 COVID-19 patients admitted to Mansoura University's isolation hospital in Egypt. One hundred and ten cases were given 40 mg of atorvastatin once daily for 28 days (group A), while 110 received a placebo (group B). All patients received treatment as per hospital protocol. The primary outcome is all-cause mortality at 28 days. We also tracked six-month mortality, time to clinical improvement, the risk of invasive mechanical ventilation, acute kidney injury, potential adverse events, and hospital and intensive care length of stay. Results: The 28-day all-cause mortality was 52/104 (50%) in group A vs. 54/103 (52.4%) in group B, odds ratio (OR) = 0.907 (0.526, 1.565), P = 0.727; adjusted OR = 0.773 (0.407, 1.47), P = 0.433. Six-month mortality occurred in 53/102 (52%) and 59/79 (60.8%) in group A vs. B, respectively, P = 0.208. Among hospital survivors in group A vs. group B, the median time to clinical improvement was 10 days (7–14) vs. 10 (7–15), P = 0.715; the duration of hospital stay was 10 days (7–14) vs. 10 (8–17), P = 0.378. Discontinuation was higher in group B (four vs. one), P = 0.369. Conclusions: In adults with severe or critical COVID-19, atorvastatin did not reduce the risk of 28-day or six-month mortality and did not improve other clinical outcomes. Trial registration: Clinical Trial Registry (NCT04952350) on July 1st, 2021. https://clinicaltrials.gov/ct2/show/NCT04952350

Background: Although mass vaccination has reduced the severity of COVID-19, mortality is still high among hospitalized patients. Being a sepsis-like disease, an anti-inflammatory drug as atorvastatin would reduce mortality and severity in COVID-19. Methods: We designed a randomized clinical trial that recruited 220 COVID-19 patients admitted in the COVID-19 isolation hospital at Mansoura University, Egypt. 110 cases were assigned to receive 40 mg Atorvastatin once daily for 28 days and 110 were assigned to receive placebo. Delta Pharm company supported the study with the drug and the placebo, which mimics the drug as regards the drug package, the tablet color, consistency, and size. All patients received the standard treatment as per the hospital protocol. The Institutional Review Board approval and the informed consent from all participants were obtained. The primary outcome is the 28-day all-cause mortality. Additionally, we will collect the in-hospital mortality, the need for mechanical ventilation, time to clinical improvement, in-hospital thrombo-embolic events, acute kidney injury, and the hospital and the intensive care duration of stay. We plan to follow the patients up for 6 months for reporting mortality and long-term neurological, psychological, and respiratory consequences. We will report the un-adjusted 28-mortality using X2. Then, we will report the adjusted odds ratio with a pre-planned multiple logistic regression model. We will report our results using the point estimate and the 95% confidence interval and the P-value. Discussion: After summarizing the main results of the study, we will discuss the outcomes with the current evidence. In addition to the planned regression model results, we would report any potential effect modifications after the planned subgroup analysis by the disease severity and the invasive mechanical ventilation status. In the end, we will conclude the risk reduction of atorvastatin on the 28-day all-cause mortality and the main secondary outcomes. Trial registration: The study was registered at the Clinical Trial Registry (NCT04952350) on July 1st , 2021. https://clinicaltrials.gov/ct2/show/NCT04952350