Table 1.

Clinical and experimental effectiveness of combining Ivermectin with other drugs in COVID-19. Studies already published on IVM combinations with other drugs.

Study Population	Combination IVM with:	Results
Sixty-two patients on a triple combination therapy versus fifty-one patients on symptomatic supportive therapy matched for age and sex.	Nitazoxanide and Ribavirin compared to routine supportive treatment.	This study showed that the clearance rates were 58.1% and 0% on day 7 and 73.1% and 13.7% on day 15 in the combined antiviral group compared to the symptomatic support treatment group. Therefore, the combined use of nitazoxanide, ribavirin and ivermectin plus a zinc supplement effectively eliminated SARS-CoV2 from the nasopharynx in a shorter time than symptomatic therapy [57].
Two hundred patients with mild to moderate symptoms of COVID-19 were randomly assigned to the treatment group and two hundred to the placebo group.	Doxycycline versus placebo.	The median time to recovery was seven days (4–10) in the treatment group and 9 (5–12) in the placebo group, while the percentage of patients with a recovery of ≤7 days was 61% and 44%, respectively [62].
In vitro model of RAW264.7 macrophages infected with MHV.	Remdesivir.	The combination of remdesivir and ivermectin showed a highly potent synergism by significantly reducing the 7-log10 of live virus and 2.5-log10 of viral RNA in infected macrophages. This combination also resulted in the lowest IL-6, TNF-a and leukemia inhibitory factors [63].
The intervention group of five hundred and eighty-five patients and control group of five hundred eighty-five patients were treated with a placebo, along with a second control group of one hundred and thirty-seven untreated patients.	Azithromycin plus nitazoxanide or hydroxychloroquine.	Compared with control group 1 and control group 2, the intervention group showed a 31.5 to 36.5% reduction in viral excretion (p < 0.0001), 70 to 85% in the duration of symptoms (p < 0.0001) and 100% in respiratory complications, hospitalization, mechanical ventilation, deaths and post-COVID manifestations (p < 0.0001). For every 1000 confirmed cases of COVID-19, at least 70 hospitalizations, 50 mechanical ventilation and 5 deaths were averted [64].
Four hundred and eighty-one patients with combined therapy and two hundred and eighty-seven with standard treatment.	Azithromycin, montelukast, and acetylsalicylic acid vs. standard therapy.	A total of 85% of cases who received the combined therapy recovered within 14 days, and the total was 59% in the comparison group. The likelihood of recovery within 14 days was 3.4 times greater among the combined therapy group than in the comparison group. Patients treated with the combined therapy had a 75% and 81% lower risk of being hospitalized and death, respectively, than the comparison group [65].
Nine hundred and twenty-two outpatients, of which three hundred and twenty were given a multidrug therapy with ivermectin.	At least two agents with antiviral activity against SARS-CoV-2 (zinc, hydroxychloroquine) and one antibiotic (azithromycin, doxycycline, ceftriaxone).	A total of 320/922 (34.7%) patients were treated, resulting in 6/320 (1.9%) and 1/320 (0.3%) patients hospitalized and who died, respectively. We concluded that early ambulatory (not hospitalized, treated at home) multidrug therapy is safe, feasible and associated with low rates of hospitalization and death [66].
Sixty-six patients were included in the study, with thirty-six in the study group and thirty in the control group.	Reference treatment protocol: hydroxychloroquine + favipiravir + azithromycin. Patients in the control group received only standard treatment with three other drugs, without ivermectin.	At the end of the first 5-day follow-up period, the rate of clinical improvement was 73.3% (22/30) in the study group and 53.3% (16/30) in the control group (p = 0.10). At the end of the follow-up period, the mean peripheral capillary oxygen saturation (SpO2) values of the study and control groups were 93.5 and 93.0%, respectively. PaO2/FiO2 ratios were determined as 236.3 ± 85.7 and 220.8 ± 127.3 in the study and control groups, respectively. At the end of the follow-up period, mortality was recorded for 6 patients (20%) in the study group and 9 (30%) patients in the control group (p = 0.37) [67].