The Wind of Change is Blowing

Mucus, saliva, blood – we’ve all spent the last few years offering our bodily fluids into tubes, cartridges, and swabs to monitor for potential SARS-CoV-2 infection. With the need for millions to self-administer tests during the pandemic, most people are now intimately aware of how our bodies’ output can be used to track disease.

Some might assume that scientists have exhausted the human body’s available options for disease detection. But there’s a new contender – tissues. Not the kind you find in a lab, but the ones you use to wipe away tears, clean up spills, and – most importantly for our story – blow your nose.

Could a used tissue offer information on the state of someone’s infection? It’s not the first time nose tissues have been considered as a viable testing tool. A 2012 study using a variety of alternative sampling methods found that tissues could detect upper respiratory tract infections at a similar rate to nasopharyngeal and nasal swabs (1). Four years earlier, researchers found that Streptococcus pneumoniae sampling through nose-blowing had a sensitivity of up to 94 percent for children with visible secretions (2).

It’s this promising beginning that inspired Vincent Thibault, Professor of Virology at the University Hospital of Rennes in Brittany, France, to address the question. After he presented his work at this year’s ESCV conference, we caught up with him to find out whether this line of research was blown out of proportion, or whether it is truly nothing to sniff at.

Could you please introduce your work?
 

Basically, we are in charge of all viral analyses for inpatients and outpatients at our hospital. Our expertise includes serological testing, but nowadays, we cover many molecular biology diagnostic approaches, from simple PCR detection up to full viral genome analysis by next-generation sequencing.

What prompted your study into nose tissue diagnostics?
 

I was always impressed by forensic scientists and their ability to detect minute amounts of human DNA on a piece of tissue paper. Using this idea, I started to test for viral infections on family members’ disposable tissues when they felt sick. I was surprised to notice that I was able to easily detect viral genomes on any analyzed tissue using PCR techniques available in our laboratory. As I accumulated compelling data on this approach, I decided to file a patent for the technology, encompassing the entire process from nose-blowing to tissue collection and processing. I then applied this strategy to detecting viruses on tissues collected from young infant communities and was able to identify many circulating viruses throughout the year.

For those who weren’t at ESCV, can you summarize your study and its findings?
 

We demonstrated that it was possible to detect viral genomes and obtain reliable diagnoses from used tissues. We began by collecting used tissues from a daycare center and then from a kindergarten on a weekly basis and analyzing them with our in-house method. In both communities, we were able to document viral circulation and demonstrate that the circulating viruses were different in the different age classes. Moreover, in the first year (2018, well before the COVID-19 pandemic), tissue analysis in the daycare center detected the flu five weeks before it was picked up in the general population.

We believe our approach could be an interesting tool to document the emergence of any epidemic, particularly in infant communities where seasonal viruses mostly propagate. Informing parents about the circulation of one specific seasonal virus may have many benefits. It explains their children’s symptoms, may limit the need for visits to the doctor, and can even reduce the use of unnecessary antibiotics. At the individual level, tissue testing is cheap, easy to perform, does not require a medical professional for sample collection, and is as sensitive as a standard nasal swabbing. Moreover, used tissues can be shipped anywhere through regular mail for remote diagnosis (using appropriate infection control precautions, of course).

What challenges did you face during your study?
 

Curiously, the most difficult thing was collecting used tissues! I think used tissues have a bad reputation to most people. Consequently, most patients were reluctant to send me their tissues after being diagnosed with a respiratory viral infection. When it comes to the laboratory, we had to invent all of the devices needed to process the collected tissues. We got to use all kinds of unexpected tools!

One unexpected problem was the challenge of communicating our results to non-specialists. It might be frightening to hear that your child is infected with a parainfluenza 3 virus! That’s why deploying such a strategy also requires an understanding of how to tailor scientific communications to the public.

Your findings seem like a solid proof of concept. What’s the next step?
 

As mentioned earlier, this approach is almost too simple! It seems that patients expect some kind of medical intervention for diagnosis and, on the face of it, blowing into a tissue seems much less professional than getting a nasal swab. Our data indicate that nasal swabbing may not always be performed perfectly and nose-blowing suffers no more shortcomings than standard methods. Moreover, unlike nasal swabbing, nose-blowing has no side effects. The main difficulty I perceive is in encouraging patients (and doctors) to accept that this approach is as “real” as the current standard of care. One way to convince them is to demonstrate noninferiority via a large-scale study. Performing such an investigation is a big challenge and requires a lot of time and money. To demonstrate the potency of our approach, we must take into account the rate of positivity for a viral infection; it is usually around 20 percent. In other words, to collect 20 positive tissues, we need to test at least 100 patients. That offers an idea of the study size required! A relevant study would be to test 1,000 patients (i.e., approximately 200 positive) who both undergo nasal swabbing and blow into a tissue – not a simple task given all the hurdles of a clinical trial.

Do you see this kind of nose tissue diagnostic being used at scale?
 

Obviously, I will give you a biased answer! Just ask anyone who has undergone nasal swabbing; the vast majority would likely have preferred to blow into a tissue. Think about athletes during multi-day competitions who are tested on a daily basis; wouldn’t blowing into a tissue be simpler and less invasive? Pediatricians, too, are keen to evolve toward this kind of testing.

What problems might prevent this kind of process from taking off?
 

I have not mentioned the extra work needed in the lab. Obviously, nose tissue testing requires some additional work and is not yet automated. I am confident that we could optimize the process to limit the burden for technicians, but it does have to be taken into consideration. However, tissues are much less expensive than nasal swabs and do not require any medical input.

Our data indicate that viral genomes are very stable when dried on a tissue, giving this approach another advantage – albeit one that we will need to formally demonstrate via another large-scale study. I have spread the word about our approach because I firmly believe that it is a robust alternative to swab testing. I hope other scientists will test our strategy and confirm our findings. I also hope that this approach will ease the diagnostic process for patients and professionals. I am convinced that the ability to diagnose more viral infections with greater ease will benefit us all. Staying informed about viral circulation is reassuring for the public, but this noninvasive approach to detection could also help promote preventative measures, limit unnecessary medical attention, and curtail the overuse of antibiotics.