Abstract

Background: Since the SARS-CoV-2 pandemic emerged in December 2019, it has triggered 4.4 million deaths and strained health systems across the world. Yet more than a year and a half since the pandemic emerged, therapeutic drugs to treat COVID-19 disease are limited.

Purpose: To investigate the therapeutic potential of a nicotinic Cholinergic Agonists Mixture (CAM), delivered daily as oral drops and as nasal spray, in alleviating ten common COVID-19 related symptoms in 80 symptomatic human adults with confirmed SARSCoV- 2..

Methods: This randomized open-label pilot trial recruited 80 symptomatic adults with confirmed SARS-CoV-2 infection after RTPCR+ test less than five days. Participants were recruited from databases of several Colombian hospitals and were randomly assigned to the control group, which received the Standard of Care (SOC) treatment (outpatient treatment), or the intervention group, which received SOC combined with the Cholinergic Agent Mixture (CAM + SOC). Both groups received their treatment for a total of 14 days. The duration of symptoms was compared across the 14-day period.

Results: This study found statistically significant reductions in symptom duration for 5 out of 10 symptoms, including dyspnea (reduction of 4.43 days [95% CI: 2.70; 6.15], p < 0.0001), cough (reduction of 3.18 days [95% CI: 1.29; 5.06], p = 0.0089), cephalea (reduction of 3.13 days [95% CI: 1.53; 4.72], p = 0.0019), muscle fatigue (reduction of 4.18 days [95% CI: 2.03; 6.32], p = 0.0019) and general malaise (reduction of 5.98 days [95% CI: 4.20; 7.76], p < 0.0001).The study found no significant reductions in the duration of the following symptoms: fever, ageusia, anosmia, chest tightness, and nasal congestion.

Conclusion: In comparison to the control group, the intervention group witnessed statistically significant and clinically relevant reductions in the duration of 5 out of 10 common COVID-19 disease symptoms within two weeks.

This includes a reduction of approximately 4.4 days in the duration of dyspnea, a symptom that appears to be strongly correlated to severe COVID-19 disease and admission to Intensive Care Units.

Further studies are needed to confirm these preliminary findings and to evaluate whether this specific nicotinic cholinergic agonists mixture could have implications for public health.

Keywords: Cholinergic Agonists; Cholinergic System; COVID-19; Nicotine; Nicotinic Acetylcholine Receptors; nAChR; SARS-CoV-2; Human Trial; Anti-Inflammatory Cholinergic Pathway; Long Covid; Post-Covid Syndrome

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