Reference
Gilles S, Blume C, Wimmer M, et al. Pollen exposure weakens innate defense against respiratory viruses. Allergy. 2020;75(3):576-587.
Design
A 3-part study that combined data from human cell cultures, mouse models, and human cohorts to test the authors’ hypothesis that pollen exposure weakens immune defense against viral infection
Participants
The human portion of this study had several portions, including both prospective observational and interventional controlled experiments, along with a large retrospective study. For the observational and interventional portions, the researchers recruited healthy non-allergic volunteers in Augsburg, Germany and enrolled them into several cohorts. Eight participants were monitored for symptom intensity over the 2016 allergy season to gauge community exposure to birch pollen. The researchers enrolled 2 groups of 9 participants each (again non-allergic subjects) as an experimental group to be challenged with either pollen exposure or as a control group treated with placebo.
The retrospective human study examined nasal swabs from 20,062 participants collected at Sahlgrenska University Hospital in Gothenburg Sweden from 2010 to 2013. This last cohort enrolled all age groups, including children. The paper provided no further demographic details for these participants.
In vitro portion
For the cell culture portions of the research, primary bronchial epithelial cells were obtained via bronchoscopy from healthy individuals and expanded in appropriate growth media and induced to differentiate. Nasal epithelia were also obtained from healthy volunteers who were undergoing nasal surgeries or from nasal brush biopsies and cultured in appropriate media.
In vivo portion
Six-week-old female mice were used in the initial ex vivo section of the experiments.
Study Intervention
In the small human experimental study, the 18 subjects were subjected to 3 nasal lavage challenges with either a placebo of saline solution or birch pollen extract (n=9). Unilateral curettage biopsies were taken before and after the study. Eight participants were evaluated for ongoing ambient exposure to pollen in the same community as the intervention and control cohorts.
In vitro portion
The cultured bronchial and epithelial tissues were stimulated with pollen extracts and then exposed to human rhinovirus 16 (RV16) viral cultures.
In vivo portion
Six-week old female mice were infected with respiratory syncytial virus (RSV) and then exposed to ragweed pollen by intranasal instillation on 3 successive days.
Results
Observational group
Among the 20,062 participants from Gothenburg, 5,782 rhinovirus‐positive cases occurred over a 3-year period during allergy season. In these human volunteers, nasal symptoms were positively correlated with airborne birch pollen abundance. Time series analysis revealed a significant correlation between rhinovirus‐positive cases, airborne birch pollen concentrations, and precipitation (P=0.005). There was a positive nonlinear relationship between rhinovirus and pollen comparing the RSV cases with pollen counts, whereas the association was negative between rhinovirus/pollen and precipitation. (In other words, if it rained and pollen levels decreased, the risk of RSV cases went down rather than up.)
Interventional group
The data from the 8 nonallergic volunteers who tracked their symptoms during 2016 were used to establish that their nasal symptoms correlated with pollen concentrations. Time series analysis revealed a significant cross-correlation between nasal symptoms and birch pollen with a lag effect of up to 9 days, though the strongest correlation of symptoms was to pollen levels the day prior. In the 9 volunteers who were challenged directly with birch pollen, the exposure led to downregulation of type-I and -III interferons in nasal mucosa compared to those treated with control saline.
In vitro and in vivo results
In the culture and animal portions of this study, pollen exposure significantly diminished interferon-λ and pro-inflammatory chemokine responses of airway epithelia to rhinovirus and viral mimics and decreased nuclear translocation of interferon regulatory factors. In mice infected with RSV, co-exposure to pollen weakened expression of antiviral genes and increased pulmonary viral titers.
Key point
In non-allergic human volunteers, nasal symptoms were positively correlated with airborne birch pollen abundance, and nasal birch pollen challenge led to downregulation of type-I and -III interferons in their nasal mucosa. In the large patient cohort, numbers of rhinovirus positive cases were correlated with airborne birch pollen concentrations.
Clinical Implications
This combination of tissue culture, mouse, and human data creates a compelling argument that pollen exposure weakens innate immune defense against viral infection. What is of particular note is that the participants in this study were not allergy patients—meaning these findings apply to everyone, not just sensitive individuals. Pollen levels, of course, vary seasonally, and we are generally made aware of these concentrations by individuals who do display symptoms. Pollen concentrations are also carefully monitored by health departments, and these levels can easily be accessed online either on government or commercial sites. The knowledge that increasing pollen levels may leave us more susceptible to viral infection is of special concern this year during the Covid-19 pandemic.
A news story broadcast by Radio Sweden on March 29, 2020, quotes one of the authors of this study, Dr. Åslög Dahl who heads the pollen laboratory at Gothenburg University. She has announced preliminary findings from a new study. Using Covid-19 data from the World Health Organization, “Dahl says that areas with the highest mortality rates from the coronavirus have been shown to have the highest pollen levels too.” Although she points out these results have been hastily assembled and require further study, Dahl suggests that everyone—whether they have allergies or not—should currently follow the advice given to those sensitive to pollen and allergies.
This is best summarized in the abstract of the paper: “The ability of pollen to suppress innate antiviral immunity, independent of allergy, suggests that high-risk population groups should avoid extensive outdoor activities when pollen and respiratory virus seasons coincide.”
Even though the observation of Covid-19 rates with pollen counts is still preliminary, taken together with this current study, it is compelling enough that we should encourage patients to follow it. There is no risk in lowering pollen exposure.
Mayo Clinic offers this advice to allergy sufferers:
- Stay indoors on dry, windy days. The best time to go outside is after a good rain, which helps clear pollen from the air.
- Delegate lawn mowing, weed pulling, and other gardening chores that stir up allergens.
- Remove clothes you've worn outside and shower to rinse pollen from your skin and hair.
- Don't hang laundry outside—pollen can stick to sheets and towels.
- Wear a pollen mask if you do outside chores.
If this study’s findings hold up to further validations, the advice given to allergy sufferers may be applicable to everyone, particularly during an outbreak of viral infection.
