An incredible algae against Covid!

A team of researchers would have confirmed a preventive anti-Covid treatment by nasal route reducing by 80% the risk of contracting the disease! Explanations with two experts.

The nourishing sea: seaweed and its carrageenans

Mother Nature is showering us with its benefits to directly stimulate our immune system through the sun via vitamin D or through candidates for treatment against Covid-19 such as black cumin oil in combination with honey, a cocktail shown to be very promising in a randomized controlled trial conducted in Pakistan.
The candidate molecule is Iota-carrageenan (I-C), a sulfated polysaccharide found in certain species of red algae (Rhodophyceae, Chondrus crispus). Seaweeds are already known and appreciated for their high antioxidant content and their richness in vitamins (B, C, K…) and minerals (Iron, Copper, Zinc, Magnesium). The jelly-like consistency of seaweed is due to the carrageenan molecules. Carrageenans are complex molecules, capable of forming interesting gels to cover a surface. It is indeed this property of “biofilm” that has been used by researchers to create a physical barrier on the surface of the nasal mucosa in order to form a protective screen against pathogens. The mucous membranes of the mouth and nose are one of the entry points for infections and the first line of defence for our immune system.

An antiviral shield of natural origin?

This family of carrageenans has already shown in vitro antiviral activity against different types of respiratory infections including coronavirus OC43 and 229E, herpes simplex 1 and 2, CMV, hepatitis A, papillomavirus and HIV [1]. Pre-clinical efficacy of I-C against influenza [1] and clinical efficacy in the treatment of the common cold by nasal spray have been shown [2,3]. Other complex polymeric molecules have also been evaluated for the development of topical preventive treatment of these viral infections [1,4,5]. In the case of rhinovirus, the authors showed that the use of carrageenans at early stages of infection inhibited many virus serotypes without influencing the appearance of viral variants [5].
These molecules have been used for a long time in various fields (food, cosmetics, pharmaceuticals, etc.). The safety profile of carrageenans is well defined [6,7].

Algal extract with demonstrated antiviral activity

Based on previous results, the antiviral activity of Iota-carrageenans in reducing SARS-CoV-2 infection was first evaluated in vitro [8,9]. I-C demonstrated its ability to inhibit SARS-CoV-2 infection in cell culture: up to 4 log reduction in infectious viral titer [9]. A neutralizing activity comparable to that of serum from a patient with the disease has been observed in vitro [8]. The 50% virus neutralizing dose (IC50) [8] is close to that observed for other viruses causing colds (rhinovirus, coronavirus OC43) or influenza [1].

Prevention in high-risk settings: impressive results

In the context of the COVID-19 epidemic, different avenues of infection prevention have been explored [9] in order to limit the risk of transmission of the disease and to mitigate its severity.
Very recently, the anti-COVID-19 prophylactic effect of an I-C spray has been evaluated in hospital staff caring for COVID-19 patients. The results of a multicenter randomized controlled trial (RCT), registered NCT04521322 on are now available (pre-publication) online [10].
394 hospital workers from 10 hospitals in Argentina were selected between July and December 2020. These participants, with similar characteristics (mean age 38.5±9 years and 75.1% female), were randomly assigned to receive either the active molecule (I-C) or placebo at 4 sprays/day over 21 days. The primary endpoint was clinical COVID-19. Both treatment groups continued to wear dedicated personal protective equipment and observe regular and thorough hand washing.

80% reduction in risk of disease

A significant reduction in the incidence of COVID-19 was observed in the I-C group versus the placebo group (1.0% versus 5.0%). The authors also highlighted a 4-fold reduction in the number of days of absence for the treated group [10], which is undoubtedly of great interest for these essential front-line workers and for the management of this epidemic.
This local I-C treatment showed significant efficacy in preventing SARS-CoV-2 infection in persons at particular risk of the disease, without specific side effects. The authors estimate that this I-C prophylaxis confers an 80% reduction in the risk of contracting the disease, and probably consequently of its transmission.

Other clinical trials underway

Another RCT (NCT04701710) in Argentina on 234 hospital workers recently evaluated an I-C combination with ivermectin as a 4-week preventive treatment decreasing the proportion of COVID-19 and its severity by more than a factor of 6 [11].

Other placebo-controlled RCTs are underway to evaluate this preventive strategy in healthcare workers over a longer period of time in the UK over 6-9 months (NCT04590365), in Austria over 12 weeks (NCT04681001).

A preventive treatment to consider

All these results help to show that the use of an I-C based spray brings a notable improvement in the condition of patients with respiratory infections, even preventing relapses of infections [3] and allows to limit the risk of contracting the disease [10]. This approach should be included in a simple way in a hygiene of the respiratory tract [9], in winter for example, in parallel with a stimulation of immunity (by compensation of the lack of sun exposure and induced vitamin D deficiencies) or to be recommended as soon as the respiratory symptoms begin.
Moreover, in an epidemic situation such as the one we are currently experiencing, preventive oronasal administration should be seriously considered for fragile or particularly exposed individuals, such as front-line healthcare workers, as the expected benefit seems positive [12].

Aure SAULNIER: PhD in virology (personal capacity)
Jean-Michel WENDLING: Scientific advisor for Infodujour
Declaration: The authors declare that they have no interest in the product

1 Leibbrandt A, Meier C, König-Schuster M, Weinmüllner R, et al. Iota-Carrageenan Is a Potent Inhibitor of Influenza A Virus Infection. PLoS ONE Dec 2010 5(12) e14320;
2 Ludwig M, Enzenhofer E, Schneider S, Rauch M, et al. Efficacy of a carrageenan nasal spray in patients with common cold: a randomized controlled trial. Respiratory Research Nov 2013 13;14(1):124; doi: 10.1186/1465-9921-14-124
3 Koenighofer M, Lion T, Bodenteich A, Prieschl-Grassauer E, et al. Carrageenan nasal spray in virus confirmed common cold: individual patient data analysis of two randomized controlled trials. Multidisciplinary Respiratory Medicine Nov 2014 12;9(1):57; doi: 10.1186/2049-6958-9-57
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5 Grassauer, A., Weinmuellner, R., Meier, C., Pretsch, A., et al. Iota-Carrageenan is a potent inhibitor of rhinovirus infection. Virology Journal Sep 2008 5, 107.
6 Hebar A, Koller C, Seifert JM, et al. Non-clinical safety evaluation of intranasal iota-carrageenan. PLoS ONE Apr 2015 10(4) e0122911; doi: 10.1371/journal.pone.0122911
7 Bichiri D, Rente AR, Jesus Â. Safety and efficacy of iota-carrageenan nasal spray in treatment and prevention of the common cold. Medicine and Pharmacy Reports Jan 2021; 94(1):28-34; doi: 10.15386/mpr-1817
8 Morokutti-Kurz M, Fröba M, Graf P, Große M, Grassauer A, et al. Iota-carrageenan neutralizes SARS-CoV-2 and inhibits viral replication in vitro. Iota-carrageenan neutralizes SARS-CoV-2 and inhibits viral replication in vitro. PLoS ONE Feb 2021, 16(2) e0237480;
9 Stathis C, Victoria N, Loomis K, Shaun A Nguyen, et al. Review of the use of nasal and oral antiseptics during a global pandemic. Future Microbiology Jan 2021;16(2):119-130; doi:10.2217/fmb-2020-0286
10 Figueroa JM, Lombardo M, Dogliotti A, Flynn L, et al. Efficacy of a nasal spray containing Iota-Carrageenan in the prophylaxis of COVID-19 in hospital personnel dedicated to patients care with COVID-19 disease. A pragmatic multicenter, randomized, double-blind, placebo-controlled trial (CARR-COV-02). medRxiv 2021.04.13.21255409; doi:

11 Chahla RE, Ruiz LM, Ortega ES, Morales FM, et al. A randomized trial – intensive treatment based in ivermectin and iota-carrageenan as pre-exposure prophylaxis for COVID-19 in healthcare agents. medRxiv 2021.03.26.21254398; doi: (preprint)

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