Rhinovirus and asthma: Challenges and opportunities

Abstract

Human rhinoviruses (RVs) are the primary aetiological agent of the common cold. Generally, the associated infection is mild and self-limiting, but may also be associated with bronchiolitis in infants, pneumonia in the immunocompromised and exacerbation in patients with pulmonary conditions such as asthma or chronic obstructive pulmonary disease. Viral infection accounts for as many as two thirds of asthma exacerbations in children and more than half in adults. Allergy and asthma are major risk factors for more frequent and severe RV-related illnesses. The prevalence of RV-induced wheezing will likely continue to increase given that asthma affects a significant proportion of the population, with allergic asthma accounting for the majority. Several new respiratory viruses and their subgroups have been discovered, with various degrees of relevance. This review will focus on RV infection in the context of the epidemiologic evidence, genetic variability, pathobiology, clinical studies in the context of asthma, differences with other viruses including COVID-19 and current treatment interventions.

Keywords: SARS-Cov-2; asthma exacerbations; influenza; rhinovirus.

FIGURE 1

Estimated seasonality pattern related to asthma exacerbations by month. Expected seasonal increase in exacerbations in the fall and early winter compared with the summer months

FIGURE 2

Tree pattern of changes in sequences collected overtime. The tree on the left is a set of sequences collected from a single individual approximately every 6 months who was not on effective therapy. The tree on the right is a selection of N1H1 Influenza viruses where the earliest sequences are from the 1918 Influenza Pandemic and the most recent are from the 2019 to 2020 flu season. Note that both tree shapes appear to shift from one population to the next suggesting that the effective population size at any one time is relatively small. Each of these trees are rooted by the earliest time points

FIGURE 3

Evolutionary rate based off dated tips of rhinovirus A with an estimated divergence rate. Rhinovirus A has very deep evolutionary nodes, indicating that the population has a very high Ne. (a) Dated tip phylogeny can be used to estimate the dates of all the nodes on a tree including the date of the Most Recent Common Ancestor (MRCA). (b) These dates can be used to assess the maximum likelihood estimate of the divergence rate (2.90e‐03). Importantly, recombination events can drive the appearance of extremely high Ne in a phylogenetic context

FIGURE 4

Inflammatory response following viral infection. Rhinovirus (RV) is transmitted mainly through direct contact and aerosolized particles and replicates in ciliated epithelial cells of the upper and lower airways. The viruses attach to unique cellular receptors. After attachment, infected cells recognize RV pathogen‐associated molecular patterns through interaction with two different families of pattern recognition receptors, that is, Toll‐like receptors. These receptors activate transcription factors that promote the expression of type I and type III interferons and several inflammatory cytokine genes. Early innate immune responses, such as type I interferons, occur rapidly after infection. RV induce cytokines, chemokines and growth factors that activate and attract granulocytes, dendritic cells and monocytes at the site of infection and trigger an inflammatory response and induce an asthma exacerbation