Background: Covid-19 infection is a multifactorial disease where the virus mainly enters through the nasal cavity, grows, triggers inflammation, and destroys nasal mucosa cells, allowing systemic virus entry and infection of other organs. When symptoms appear, the disease physiopathology is already established. The immune system tries to control the infection but if the infection persists, it gets tired, fatigued, stressed, and finally, there is burnout. Therefore, an effective treatment should be multi-targeted and should not focus only on one parameter. Minimizing virus concentration, reducing nasal mucosa inflammation, and keeping the nasal surface clean should lessen systemic infection and the probability of developing severe respiratory distress. We evaluated clinical efficacy and safety of an osmotic nasal surface cleaning, virus and cytokine trapping polymeric film, in early-stage Covid-19 positive symptomatic patients. Methods: A randomized, multicentric, observational study was performed to evaluate the efficacy and safety of the osmotic film in 213 patients, randomized in 2 equal arms, and confined for 14-days just after the RT-PCR+ test. Due to ethical reasons, all patients received symptomatic treatments (ST). In addition, the patients in Arm-1 received the test product (ST+TP, 2-3 sprays, 4-5 times/ day) for 14-days. Leicester Cough Questionnaire, Visual Analogue Scale, and Covid-19-associated symptoms such as fever, pain, taste, smell, and headache were evaluated daily. Home-confined patients were immediately hospitalized in case of aggravation of any life-threatening clinical sign. Results: Among 213 patients, 98 in the ST and 102 in the ST+TP group completed the study. Thirteen patients did not complete the study as 8 in the ST group and 5 in the ST+TP group were hospitalized during the study due to low blood oxygen levels or sudden health deterioration and were excluded from the study. In the remaining control standard treatment group (n=98), clinical signs sharply aggravated on day 1-2 followed by stabilisation between days 3-6 and progressive reduction thereafter. In the test product group (n=102), symptoms were stabilized just after the first application and improved progressively. Only 42/102 patients in the test product group presented nasal discharge or irritation due to the osmotic properties of the product. Conclusion: The continuous multi-target approach of detaching and neutralizing virus particles and pro-inflammatory cytokines from the nasal surface to minimize systemic virus exposure is a very logical and efficient approach to avoid Covid-19-induced systemic pathology.