As the largest mass vaccination campaign in human history progresses, the landscape of immunity against SARS-CoV-2 within the U.S. is changing. The vaccine strategy that began with focused protection for some and rapidly expanded to protection for all, continues to serve as the crucial step in decoupling COVID-19 deaths from infections. Approximately 50% of our total population is fully vaccinated, as are 80% of those 65 and older. This “community immunity” has largely deescalated the risk to those most likely to experience severe outcomes, while simultaneously placing those who cannot or will not be vaccinated in the spotlight. As adult vaccinations continue to rise, the totality of COVID-19 risk is diminished.
The focus now shifts to the immunologically naïve, especially children. Children less than 12 years old are unable to be vaccinated in the U.S. at this time. Moreover, concerns regarding post-vaccine myocarditis in younger populations may shift the favorable perception of risk/benefit analysis. These implications are significant as COVID-19 outcomes among younger populations are not always benign. With cases currently surging and the seasonality of the virus, we can expect a continued surge in cases this fall — just in time for a return to school.
So, what measures — both new and old — do we need to take to ensure a safe return to classrooms for all kids?
When considering the protection of our school children, a balanced approach is key. It’s a complicated calculus to weigh the risks of viral infection and masking our children (as the American Academy of Pediatrics recently recommended for all students inside schools) in the long- and short-term while overlaying vaccination. If indeed Delta, Gamma, Lambda, or other variants remain ascendant in the autumn we can reliably fall back on our pillars of infection control. But will these measures be sufficient to allay the fears of concerned parents, teachers, institutions, and communities? Additional strategies need to be considered, especially since we can ill afford to deny our children the much needed in-person educational experience.
One underexplored strategy to better control transmission of SARS-CoV-2 in schools may involve the use of a dilute oral antiseptic gargle or oral rinse. Similar to the two-way protection afforded by masks, treating the mouth with a safe, effective dilute antiseptic can better protect students by reducing spread and preventing infection. The idea is simple. If a child is asymptomatically infected and shedding virus, a before- and after-school oral treatment can potentially diminish the quantity or quality of active virus entering infectious droplets/aerosols making them less infectious. On the other hand, if a child is healthy but exposed to the virus, the treatment might provide prophylaxis against or at least mitigate infection. These ideas are not new, but the science of oral antiseptics and their effects on viral transmission dynamics during the last year has taken a big leap forward.
Gargles have been used for thousands of years dating back to the ancient Romans, Egyptians, and Chinese. Modern gargle science, especially with the use of alcohols, was pulled forward with the discovery of microbes by Antonie van Leeuwenhoek and later 19th century interventions of surgeon Joseph Lister. In Asia, there exists a more developed culture around gargling and its salubrious effects. Early in this millennium a group of Japanese doctors termed “The Great Cold Investigators” began to examine the influence of gargling on upper respiratory tract infections and influenza-like illnesses. What they and other investigators found is significant. A series of randomized controlled trials support the notion that gargling with interventions like water, green tea, and dilute povidone-iodine (PVI) may indeed reduce the incidence of these illnesses. Interestingly, the act of gargling water may reduce oropharyngeal proteases, which are critical to viral infection, and the chlorine present in tap water may be of sufficient concentration to inactivate viruses. Oral gargles do not represent a new frontier in children either. They have been used to prevent and treat dental caries and recalcitrant biofilms. In one landmark study conducted in Japan, middle school children from Yamagata City who routinely gargle with dilute PVI for 3 months during the winter reported less absenteeism secondary to the common cold and influenza.
The amount of scientific information generated during the COVID-19 pandemic has been extraordinary. Gargle science has certainly benefitted, as scientists and clinicians desperately looked for ways to augment infection control mechanisms. Numerous in-vitro reports have highlighted the efficacy of gargle active pharmaceutical ingredients like PVI, chlorhexidine, essential oils, alcohols, and hydrogen peroxide against SARS-CoV-2. The difference this time is that these studies carried over into in-vivo, smaller scale clinical trials.
Of all the studied active pharmaceutical ingredients, perhaps the best data has been generated with dilute PVI. This is a broad-spectrum microbiocide with years of data supporting its ability to decontaminate human tissues and kill contagions capable of pandemic spread. It is safe, makes the World Health Organization list of essential medicines, and has not been implicated in antimicrobial resistance. Importantly, its use is not known to alter healthy, supportive populations of the microbiome. Independent clinical trials in the setting of active COVID-19 have shown that administration of dilute PVI decreases viral RNA quantification, decreases infectious viral titers, decreases active virus in whole mouth fluid and respiratory droplets, speeds viral clearance, and protects against infection.
From the outset of this pandemic, the idea of oral rinses with safe and effective antiseptics was well-founded but lacked supportive data. Given the existence of these expanding reports to better inform, the evidence is supportive that use of dilute oral antiseptics may be a safe way to reduce viral transmission. The relatively small-scale of gargle-based clinical trials leaves them vulnerable to the criticism of being poorly performed and underpowered. While large-scale randomized controlled trials are certainly lacking, there is still much to be gleaned from other types and levels of evidence, especially when backed by millennia of favorable experience and implemented for clinical necessity during a pandemic. The low-cost, safety, and preventative practice of gargling or oral rinsing is also consistent with the precautionary principle and the oath of Hippocrates (do no harm or injustice!) making it perhaps an ideal intervention for our vulnerable children when they return to school, especially in combination with other public health measures. It may strike the right balance between doing something and doing nothing, between showing that we are still thinking, evolving, and considering rather than falling back into the same reactive patterns that ultimately led to school closings.
Jesse Pelletier, MD, is a private practice ophthalmologist in Miami, and co-founder/chief medical officer of Veloce BioPharma. Terrence P. O’Brien, MD, is a professor of ophthalmology and the Charlotte Breyer Rodgers Distinguished Chair at the Bascom Palmer Eye Institute in Miami.