Objective To establish the therapeutic action of a nicotinic cholinergic agonist agent composition in synergy with other non-cholinergic molecules (CA) in the COVID-19 symptoms in a group of human patients infected with SARS-CoV-2 vs. control group. Methods Randomized open-label trial pilot study where 80 patients were randomly assigned to receive standard of care (SOC) treatment as outpatient treatment after PCR+ test; SOC plus CA was administered in the intervention group (40 patients). SOC was administered in the control group (40 patients). Basic Odds Ratio study (95% confidence interval) in 40 patients for intervention group and 40 patients for the control group. The evaluation in the groups was carried out during 15 days assessing the improvement or worsening of each symptom daily. Results: Fever (OR=0.897), Cough (OR = 0.571), Dyspnea (OR = 0.460), Muscle fatigue (OR = 0.250), Cephalea (OR = 0,570), Ageusia (OR = 0.150), Anosmia (OR = 0.650), General malaise (OR = 0.316), Nasal congestion (OR= 0.890), are less than 1 converting the use of the cholinergic agent in a protective and therapeutic factor showing therefore improvement of these symptoms, after its use, compared to the control group. Conclusions: The positive results obtained on the symptoms caused by COVID-19 by delivering mixture of cholinergic agonists molecules and other non-cholinergic supportive molecules (CA) with special oral and nasal route of administration and specific pharmacological design against COVID-19 in humans infected by SARS-CoV-2 versus the control group is a (novel) promising therapeutic approach to fight SARS-COV-2. Larger multicentrical trials in humans are encouraged.