study of ruxolitinib plus simvastatin in the prevention and treatment of respiratory failure of covid-19.

Conditions: Coronavirus Infection

Summary: covid-19's mechanism to enter the cell is initiated by its interaction with its cellular receptor, the angiotensin-converting enzyme. as a result of this union, a clathrin-mediated endocytosis process begins. this route is one of the therapeutic targets for which available drugs are being investigated in order to treat covid-19 infection. this is one of the mechanisms blocked by drugs like ruxolitinib and chloroquine. various drugs approved for clinical use that block the clathrin-mediated endocytosis pathway have been explored. it has been found that the best in vitro and in vivo results were obtained with statins, which also allowed generating a greater potent adaptive immune response. therefore, statins and specifically simvastatin make it possible to block the entry process used by covid-19, block inflammation by various mechanisms and increase the adaptive immune response. all of these processes are desirable in patients infected with covid-19. statins have been proposed to have beneficial effects in patients infected with mers-cov, another coronavirus similar to covid-19, but there have been no randomized studies supporting the use of statins in patients with covid-19 infection. in this project we propose the combined use of one of these drugs, ruxolitinib with simvastatin, looking for a synergistic effect in the inhibition of viral entry and in the anti-inflammatory effect.


Eligibility criteria:
inclusion criteria: * patients who have given their written informed consent. if it is considered that obtaining written consent could constitute a factor for the transmission of the disease (given the high contagiousness of the sars-cov-2 virus), it will be permitted to obtain duly justified verbal consent in the patient's medical history. * clinical diagnosis or confirmed by analytical tests (pcr of viral rna or detection of antisars-cov-2 antibodies) that requires care in hospital and that are grade 3 or 4 of the who 7-point ordinal scale of severity categorization for covid. * platelets\> 50,000 / ul, neutrophils\> 500 / ul * kidney or liver failure is not a contraindication, dose adjustment will be made according to the smpc * women of childbearing potential who are sexually active, not undergoing a hysterectomy or double adnexectomy, should follow the following indications for contraception: * negative serum or urine pregnancy test in the 72 hours prior to the start of treatment. * use of a medically accepted contraceptive method during: 2 months prior to the start of study treatment, during the study and up to 3 months after the last dose of treatment. exclusion criteria: * documented concomitant severe bacterial or fungal infection * infection with hiv, hcv, hbv * age \<18 years * thrombocytopenia \<50,000 / ul, neutropenia \<500 / ul * women of childbearing age who do not use an effective contraceptive method. * pregnant or lactating women. * patients who do not want or cannot comply with the protocol. * patients with impaired gastrointestinal function or gastric disease that significantly impairs the absorption of ruxolitinib or simvastatin, such as: severe ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, extensive resection (\> 1m) of the small intestine or inability to swallow oral medication. previous partial or total gastrectomy is not an exclusion criterion

Keywords: covid19 simvastatin ruxolitinib