Carrageenan nasal spray may double the rate of recovery from coronavirus and influenza virus infections: Re-analysis of randomized trial data

Abstract

In this individual patient data meta-analysis we examined datasets of two randomized placebo-controlled trials which investigated the effect of nasal carrageenan separately on children and adults. In both trials, iota-carrageenan was administered nasally three times per day for 7 days for patients with the common cold and follow-up lasted for 21 days. We used Cox regression to estimate the effect of carrageenan on recovery rate. We also used quantile regression to calculate the effect of carrageenan on colds of differing lengths. Nasal carrageenan increased the recovery rate from all colds by 54% (95% CI 15%-105%; p = .003). The increase in recovery rate was 139% for coronavirus infections, 119% for influenza A infections, and 70% for rhinovirus infections. The mean duration of all colds in the placebo groups of the first four quintiles were 4.0, 6.8, 8.8, and 13.7 days, respectively. The fifth quintile contained patients with censored data. The 13.7-day colds were shortened by 3.8 days (28% reduction), and 8.8-day colds by 1.3 days (15% reduction). Carrageenan had no meaningful effect on shorter colds. In the placebo group, 21 patients had colds lasting over 20 days, compared with six patients in the carrageenan group, which corresponds to a 71% (p = .003) reduction in the risk of longer colds. Given that carrageenan has an effect on diverse virus groups, and effects at the clinical level on two old coronaviruses, it seems plausible that carrageenan may have an effect on COVID-19. Further research on nasal iota-carrageenan is warranted.

Keywords: SARS-CoV-2; common cold; iota-carrageenan; meta-analysis; quantile treatment effect; randomized trial; rhinovirus.

FIGURE 1

The effect of nasal iota‐carrageenan on the recovery from common cold episodes caused by any virus (A), coronavirus OC43 or 229E (B), influenza A (C), and rhinovirus (D). The ITT survival curves published in figures 2 and 5 of Ref. [28] were measured and datasets were regenerated for the current analysis; see the Supplementary file. In the curves of the figure, the size of the steps downwards indicates the number of patients who recovered on the particular day. The red horizontal dotted lines indicate the 20th, 40th, 60th, and 80th percentiles of the distribution of common cold duration, starting with the shortest colds from the top downwards; compare with Figure 2

FIGURE 2

The quantile treatment effect of nasal iota‐carrageenan on the duration of virus‐positive colds as days shortened. The horizontal axis shows the distribution of the duration of colds by percentiles for up to the 83th percentile, after which data in the placebo group was censored, that is, patients did not recover by the end of the follow‐up. The red dotted line indicates the null effect level, and the blue dashed line shows the previously calculated 1.9‐day estimate of effect for carrageenan. ²⁸ The red figures at the bottom indicate the lowest percentile level for the indicated common cold duration in the placebo group. For example, 9‐day colds cover the percentile range from 43.0 to 60.9 percentiles, which corresponds to 21 patients as the total number of placebo group patients was 128. The red vertical bar indicates the 95% CI of the treatment effect for the 80th percentile

FIGURE 3

The quantile treatment effect of nasal iota‐carrageenan on the duration of virus‐positive colds as a relative effect in percentages. The horizontal axis shows the distribution of the duration of colds by percentiles from the 60th up to the 83th percentile, after which data in the placebo group were censored, that is, 21 patients in the placebo group did not recover by the end of the follow‐up