ABSTRACT
Introduction: At present, vaccines form the only mode of prophylaxis against COVID-19. The time needed to achieve mass global vaccination and the emergence of new variants warrants continued research into other COVID-19 prevention strategies. The severity of COVID-19 infection is thought to be associated with the initial viral load and for infection to occur, viruses including SARS-CoV-2 must first penetrate the respiratory mucus and attach to the host cell surface receptors. Carrageenan, a sulphated polysaccharide extracted from red edible seaweed, has shown efficacy against a wide range of viruses in clinical trials through prevention of viral entry into respiratory host cells. Carrageenan has also demonstrated in-vitro activity against SARS-CoV-2. This clinical trial was designed to investigate the efficacy of carrageenan nasal and throat sprays in reducing the rate and severity of COVID-19 infection. If proven effective, the self-administered prophylactic spray would have wider utility for key workers and the general population. Methods: and analysis: A single centre, randomised, double-blinded, placebo-controlled phase III trial was designed. Participants randomised in a 1:1 allocation to either the treatment arm, verum Coldamaris plus (1.2 mg iota-carrageenan (Carragelose®), 0.4 mg kappa-carrageenan, 0.5% sodium chloride and purified water) or placebo arm, Coldamaris sine (0.5% sodium chloride) spray applied daily to their nose and throat for 8 weeks, while completing a daily symptom tracker questionnaire for a total of 10 weeks.Primary outcome: Acquisition of COVID-19 infection as confirmed by positive PCR swab taken at symptom onset or seroconversion during the study. Secondary outcomes include symptom type, severity and duration, subsequent familial/household COVID-19 infection and infection with non-COVID-19 upper respiratory tract infections. A within-trial economic evaluation will be undertaken, with effects expressed as quality-adjusted life years. Hypothesis: That carrageenan spray will reduce SARS-CoV-2 attachment to the naso- and oropharyngeal mucosal epithelial cells thus reducing the effective viral infective dose preventing COVID19 infection and reducing disease severity where infection is not prevented. Ethics and dissemination : Ethics approval was obtained from Research Ethics Committee 6 South Wales (REC Reference 20/WA/0298; IRAS 283187) on the 18 th November 2020. The results will be submitted for publication in a peer-reviewed journal. Trial registration number: NCT04590365; registered on ClinicalTrials.gov (NCT04590365) on the 19 th October 2020.