Effects of Ivermectin-azithromycin-cholecalciferol combined therapy on COVID-19 infected patients: A proof of concept study. Guadalupe Espitia-Hernandez, Levy Munguia, Dylan Diaz-Chiguer, Ramiro Lopez-Elizalde, Fiacro Jimenez-Ponce * Direccion Normativa de Salud, ISSSTE, Mexico City, Mexico Abstract As the world faces COVID-19, the search for effective treatments against the disease and its complications has turned its gaze to drugs that are classically used in other infectious diseases. Some drugs are being examined for the recent evidence on its effects on viral replication and inflammation. The aim of the study was to assess the outcome of Ivermectin-Azithromycin-Cholecalciferol combination therapy on early stages (I-IIa) of COVID-19 patients. This proof of concept study was carried out on confirmed COVID-19 patients in Mexico City, from April 01 to April 20, 2020. Patients who met inclusion criteria were invited to take Ivermectin (6 mg once daily in day 0,1,7 and 8) plus Azithromycin (500 mg once daily for 4 days) plus Cholecalciferol (4000 UI twice daily for 30 days). Treatment outcome was evaluated on the 10th day onward from the first day of the drug intake. Recovery rate of the 28 patients that received the combination therapy was 100%, the mean symptomatic recovery duration was 3.6 days and negative PCR was confirmed on day 10. Imaging findings of patients with pneumonia were improved on day 10. Transient and mild degree of adverse effect like diarrhea and nausea was noted by 3 (10.7%) patients. This study found that the combination treatment might mitigate disease progression without significant adverse effects. Further studies are needed in order to extrapolate these findings to moderate and severe COVID-19. Keywords: SARS-CoV-2, COVID-19, Ivermectin, Azithromycin, Cholecalciferol. Accepted on August 15, 2020 a weak base that could potentially block endocytosis and thereby limiting viral replication, by amplifying host ’ s interferon (IFN) pathway or by interfering with the SARS- CoV-2 spike protein and host receptor ACE2 (angiotensin converting enzyme-2) interaction inhibiting viral entry into the cells [9]. On the other hand, in viral infections, cholecalciferol may decrease pro-inflammatory cytokines associated with the Th1 type response and increase anti-inflammatory cytokines associated with the Th2 type immune response [10]. Therefore, we decided to evaluate the efficacy of the Ivermectin- Azithromycin-Cholecalciferol combination and compare it to the standard therapy provided to patients in early stages of COVID-19. Materials and Methods Eligibility criteria Eligible subjects were; 18 years old and older with a laboratory confirmed diagnosis of SARS-CoV2 using the CDC reverse transcription–polymerase chain reaction SARS-CoV-2 assay, with mild (cough, fever, malaise, myalgias, gastrointestinal symptoms, ageusia and anosmia) or moderate (dyspnea, tachypnea, hypoxemia, and abnormal lung findings) ISSN 0970-938X www.biomedres.info Introduction Currently, the world is in a race against time to curb the human and economic losses for which the SARS-Cov-2 virus is responsible. This virus infection was initially classified as pneumonia of unknown origin to be later recognized as COVID-19 [1]. The symptoms of COVID-19 infection appear after an incubation period of approximately 5 days with a median of 14 days to develop complications and death [2]. The progression depends on age and comorbidities, where a higher speed of progression is observed in patients>70-years old [3]. The spectrum of symptoms includes fever, cough, headache, diarrhea, dyspnea, anosmia and dysgeusia. Imaging studies reveal findings of pneumonia with grand-glass opacities, acute respiratory distress syndrome and acute cardiac injury [4,5]. Scientists around the world are actively exploring drugs that could be potentially effective in combating COVID-19. Recent publications have drawn attention to the possible benefits of ivermectin, azithromycin and cholecalciferol. These drugs have been used for the treatment for infectious diseases since they have anti-inflammatory and antiviral properties [6,7]. The in vitro antiviral activity of Ivermectin has been related to inhibition of IMPα/1-mediated nuclear import of viral proteins [8]. The effect of azithromycin may be due to its properties as Biomed Res 2020 Volume 31 Issue 5 129 Biomedical Research 2020; 31 (5): 129-133