Upper respiratory tract infections spike in winter and now we know why

A popular explanation for why we see a spike in upper respiratory tract infections in winter has been left out in the cold. Researchers in the US have discovered that an immune response within the nose is responsible for fighting off many of the viruses that cause cold and flu – and it’s temperature-sensitive.

The breakthrough might lead to more therapies to help the nose do its work in preventing colds and flu.

“Conventionally, it was thought that cold and flu season occurred in cooler months because people are stuck indoors more where airborne viruses could spread more easily,” says Dr. Benjamin Bleier, a specialist in sinus, nasal, skull base and orbital surgery at Massachusetts Eye and Ear in Boston, in the US.

“Our study, however, points to a biological root cause for the seasonal variation in upper respiratory viral infections we see each year, most recently demonstrated throughout the COVID-19 pandemic.”

Transmission electron micrograph (tem) of a section of nasal lining.
Transmission electron micrograph (TEM) of a section of nasal lining through cilia (green) covering the epithelial lining of the nasopharyx, the part of the throat behind the nasal cavity. Cilia are microscopic hair-like structures that are covered with a sticky mucus, and trap dust and other inhaled particles. Co-ordinated wave-like beating of the cilia propels the mucus backwards towards the throat, where it is swallowed. Also seen are microvilli (blue), which increase the cell’s surface area. Magnification: x6000 when printed at 10 centimetres wide. Credit: Steve Gschmeissner/Getty Images

One of the many reasons we are told to breathe through our noses is that little hairs, known as ‘cilia’, filter out small particles and pathogens, shuffling them along the nasal passageways, down the throat and into the stomach – avoiding the lungs.

In 2018, Bleier and colleagues discovered another reason: at the first sign of inhaled bacteria, small cells at the front of the nose release billions of sacs into the nasal passages. Known as ‘extracellular vesicles’, or ‘EVs’ (previously, exosomes), these tiny fluid—filled sacs swarm and attack the microbes.

The study also revealed that by shuttling antibacterial protons through mucus in the nasal passageways, the EVs were able to effectively ‘arm’ the rest of the cells in the airways – preparing the whole respiratory system to defend itself against the pathogen.

Now, Bleier’s team has turned its attention to viruses causing some of the most common upper respiratory tract infections – one coronavirus and two rhinoviruses.

The researchers obtained cell and nasal tissue samples from both healthy volunteers and patients undergoing surgery. By analysing and comparing the response of the samples to the common cold viruses, the researchers were able to uncover the role EVs play in fighting off viral invasion.

Like the response to bacteria, EVs swarmed from nasal cells upon first detection of the virus.

In response to the virus, though, the EVs acted like decoys by carrying receptors to which the virus would attach, rather than binding to the nasal cells.

“The more decoys, the more the EVs can mop up the viruses in the mucus before the viruses have a chance to bind to the nasal cells, which suppresses the infection,” says Dr. Di Huang, an otolaryngology (commonly known as ‘Ear, Nose, Throat’, or ‘ENT’) expert and first author of the study.

Upper respiratory tract infections are the result of coronaviruses and rhinoviruses (cartoon of structures).
Coronaviruses and rhinoviruses can cause common cold and upper respiratory tract infections. Credit: Shonyjade/Getty Images

Having uncovered the important role EVs play in tackling viruses, the researchers set out to better understand how this process was impacted by temperature – hopefully giving insight into the connection between spikes in respiratory tract infections and the season.

Crucially, the researchers discovered that quantity of EVs released is dependent on temperature.

The temperature inside the nose is dependent on the temperature of the air being inhaled, so to emulate winter conditions, the researchers exposed healthy volunteers originally in a room temperature environment to 4.4°C temperatures for 15 minutes, finding that the interior nasal temperature dropped by 5°C.

Applying this temperature to nasal tissue samples, the researchers found that the secretion of EVs dropped by 42%. The cooler temperature also resulted in a reduced ability of the EVs to act effectively as decoys and combat the virus.

“Combined, these findings provide a mechanistic explanation for the seasonal variation in upper respiratory infections,” said Dr. Huang.

The researchers hope to continue studying the role played by EVs in combatting nasally-introduced pathogens, including replication with animal model or human studies.

There is also hope that the research could result in new therapeutic methods such as sprays to boost the natural immune mechanisms of nasal cells.

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