On Friday, the Centers for Disease Control and Prevention (CDC) released its weekly flu activity map. The newest map shows that the 2022-2023 flu season is already bad and ramping up especially early. The cumulative hospitalization rate for this past week of the year is currently higher than it was at this point in flu season over the past decade.
Between common colds, the flu, respiratory syncytial virus (RSV), and COVID-19, it’s that the sneezy time of year where people are getting sick left and right. Some of the factors that influence the spread and rise of upper respiratory infections are still puzzling scientists. In fact, it wasn’t too long ago that miasma theory, or the idea that “bad air” caused disease was much more popular. While some diseases are certainly spread through the air, it’s airborne viruses or bacteria, and not the air itself, that makes us sick.
A new study from Massachusetts Eye and Ear Hospital and Northeastern University published today in The Journal of Allergy and Clinical Immunology found that a specific immune response inside the nose that fights off infection-causing upper respiratory viruses, is inhibited by colder temperatures. This then makes infections more likely to occur as temperatures drop.
“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,” Benjamin S. Bleier, director of Otolaryngology Translational Research at Mass. Eye and Ear and a co-author of the study, said in a statement. “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.”
Part of what makes wearing a mask so effective is that it protects and covers the nose. Our nostrils are a likely entry point for germs, since the nose one of the first points of contact between the outside environment and inside the body. If pathogens are inhaled or we place them onto the front of our nose using our hands, they can work their way backwards through the airway and into the body. Once inside, they can infect cells and lead to an upper respiratory infection.
In 2018, a study sought to better understand the mystery of how the airway protects itself from this onslaught of pathogens. It found that an innate immune response was triggered when bacteria is inhaled through the nose. The cells located in the front of the nose detected the bacteria and then released billions of extracellular vesicles (EVs) into the mucus. These tiny fluid-filled sacs surround and attack the bacteria. According to Bleier, the release of this EV swam is similar to “kicking a hornets’ nest.”
The study from 2018 also showed that EV’s can move around protective antibacterial proteins through the mucus from the front of the nose to the back of it along the airway. This mechanism protects other cells against the bacteria before it has a chance to get too far into the body. This research helped set the stage for a closer look into what factors influence this response in the nose.
Other studies have found that EVs are present in the nasal passages of infants infected with RSV and other respiratory infections.
[Related: Is it flu or RSV? It can be tough to tell.]
In this new study, the team examined how the cells and nasal tissue samples responded to three different viruses: a single coronavirus and two of the rhinoviruses that cause the common cold. The samples were collected from the noses of healthy volunteers as well as patients undergoing surgery.
The team found that each virus triggered this EV swam response from nasal cells using a signaling pathway that is different from the one that is used to fight off bacteria. When the EV swarm was released, they acted a bit like decoys, bringing with them receptors that the virus could bind itself to instead of bringing along nasal cells to be infected.
“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,” Di Huang, a research fellow at Mass Eye and Ear and Northeastern, and a co-author of the study, said in a statement.
Temperature is particularly relevant in nasal immunity because the internal temperature of the nose is dependent on the temperature of the air it is inhaling. To see how colder temperatures affected this EV swam response, the team took healthy volunteers from a room temperature environment and then exposed them temperatures of 39.9° F for 15 minutes. After exposure to the cold air, they found that the temperature inside the nose fell by about 9° F. They then performed the same reduction in temperature with the nasal tissue and found that the quantity of EVs secreted by the nasal cells decreased by close to 42 percent and the antiviral proteins in the EVs were also impaired.
According to the team, these findings provide an explanation for the mechanisms behind seasonal variation in upper respiratory infections.
In an interview with PopSci, Director of Pulmonary Research at the University of Kansas Navneet Dhillon also praises this study as a step in better understanding the mechanisms behind the spread.
“I think it’s a good study and one of the novelties in this study is cold exposure,” said Dhillon. “A great next step will be proving that EVs are therapeutic in an actual infection setting, with virus replication. But they have already done a very detailed study with all of their experiments.” Dhillion was not involved with the study.
Rhinologist Zara Patel, a professor of otolaryngology and head and neck surgery at Stanford University School of Medicine in California, told CNN “This is the first time that we have a biologic, molecular explanation regarding one factor of our innate immune response that appears to be limited by colder temperatures.”
She also added “It’s important to remember that these are in vitro studies, meaning that although it is using human tissue in the lab to study this immune response, it is not a study being carried out inside someone’s actual nose. Often the findings of in vitro studies are confirmed in vivo, but not always.” Patel also was not involved in this study.
Next steps include include trying to replicate these findings with other illnesses and also the team also believe that this process can help develop treatments that can induce and strengthen the nose’s innate immune response.
“We’ve uncovered a new immune mechanism in the nose that is constantly being bombarded, and have shown what compromises this protection,” said Mansoor M. Amiji, a professor of pharmaceutical sciences at Northeastern University and co-author, in a statement. “The question now changes to, ‘How can we exploit this natural phenomenon and recreate a defensive mechanism in the nose and boost this protection, especially in colder months?’”