In a community study of healthy infants reported in 2015 the authors stated that “Our finding of low RSV prevalence in asymptomatic infants suggests that RSV is likely the causative agent when detected in the setting of clinical symptoms of bronchiolitis. By contrast, given the observed prevalence of rhinovirus in infants without ARI, and even in infants without any respiratory symptoms, it remains unclear if rhinovirus detection always reflects current illness.”[1] 

To paraphrase, we don’t think rhinoviruses (RVs) have much of a role in causing bronchiolitis in this study of children who didn’t have bronchiolitis because we found RV more often in healthy kids than we found HRSV (human respiratory syncytial virus).

This topic tends to make me talk loudly, even more quickly than normal, and spit a bit.

Right. Let’s take this from the top.

• “Rhinovirus” is not one virus.
  I went into a bit of detail in my last post. It might have been a bit deep, confusing or just boring for some though. The RVs comprise three species (A, B, C) and about 167 genotypically distinct viruses.[4] While we don’t have serotype data on them all (the discovery of a third species in 2007 was all based on genetics not proteins), before the RV-Cs, we knew that >100 RVs were seen by our immune systems as distinct viruses. This also makes an assumption; that each of the 167 RVs are not continuing to evolve. But they are continuing to evolve. This evolution likely includes changes at their antigenic sites which may help them appear “new” to the memory bits of our immune system.
• RSV consists of at least 2 antigenically distinct viruses (probably more).[2]
  See the earlier post for some detail about antigens.[3]
• This study treated RV and RSV as single viruses. So among these healthy infants RSV (2 or more viruses) was rare and RVs (167 or more viruses) were more often found.
• This study found 16 RVs (14.5% of infants); 6 RV type A viruses, 1 RV-B, 8 RV-C and 1 untypeable RV; at least 4 different genotypes of RV representing all three RV species (A-C) we present.
• The authors didn’t spell this out, but there were probably a few different genotypes from within each species as well
• The authors found that 1.8% of the infants were HRSV positive (2 out of 110). By species, 5.5% were RV-A positive, 0.9% were RV-B positive and 7.3% were RV-C positive. So to follow the logic, HRSV was twice as likely to be found in these healthy infants as an RV-B! What if there were 2 or more distinct RV-Bs? H
  RSV – an agreed upon serious respiratory pathogen of infants, children, adults and the elderly is more often found in healthy infants than the wimpiest of the RVs? Hmmm. Wonder why that didn’t make the title. HRSVs must have a good agent.

ASIDE: RV-Bs are considered by those in the RV world, including at least one of the authors of this study, to be the least often detected (disproportionately so [13]) and least threatening pathogens among the common cold viruses.[6,7,8,9,10,12] It would be interesting to immunologically compare a goodly number of RV-As and -Bs, as was done for a few RVs (grouped in a different way) in a 2009 study. THis might show whether members of the RV-B are less effective at killing their host cells and triggering an immune response that leads to inflammation.[11]. 

This all highlights an important issue. We’ll never understand what RVs are capable of if we only look at them as a group. We’ll understand even less if we don’t include testing for them on samples from ill patients with respiratory signs and symptoms. Testing is expensive of course, so will remain a piecemeal process until there is a treatment or vaccine.

When we comprehend that RVs are a large array of distinct, separately circulating viruses, we will likely find that each infection by a single RV genotype can result in…

• no illness at all or
• mild illness or
• moderate illness or
• severe illness

…at rates similar to any other ‘serious’ respiratory virus be that RSV or an influenza virus.

If we only look at the RVs as a group, we’ll miss these patterns and never learn more.

Given that our understanding remains based on virus detection data from an age of insensitive laboratory methods from decades ago, continuing on as we have would be very short-sighted of us indeed. Not only short-sighted, but it will lead us to the wrong conclusions, like the one in the title above.

By all means leave your thoughts in the comment box below or engage with me on Twitter @MackayIM.

References…

1. Detection of respiratory syncytial virus and rhinovirus in healthy infants.
   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4660840/.
2. Sequence variability of the respiratory syncytial virus (RSV) fusion gene among contemporary and historical genotypes of RSV/A and RSV/B.
   http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0175792
3. Human respiratory syncytial virus: an example of why calling them many usually outweighs calling them few, or one
   https://wp.me/p96NBC-TK
4. http://www.picornaviridae.com/enterovirus/enterovirus.htm 
5. Brief info about on what an antigen is
   https://virologydownunder.com/human-respiratory-syncytial-virus-an-example-of-why-calling-them-many-usually-outweighs-calling-them-few-or-one/#antigen
6. Human Rhinovirus Species and Season of Infection Determine Illness Severity
   https://www.ncbi.nlm.nih.gov/pubmed/22923659
7. Clinical and molecular features of human rhinovirus C
   https://www.ncbi.nlm.nih.gov/pubmed/22285901
8. A novel group of rhinoviruses is associated with asthma hospitalizations
   https://www.ncbi.nlm.nih.gov/pubmed/19027147
9. Do rhinoviruses reduce the probability of viral co-detection during acute respiratory tract infections?
   https://www.ncbi.nlm.nih.gov/pubmed/19376742
10. Assessment of wheezing frequency and viral etiology on childhood and adolescent asthma risk
    http://www.jacionline.org/article/S0091-6749(16)30897-1/fulltext
11. Diversity in the bronchial epithelial cell response to infection with different rhinovirus strains
    https://www.ncbi.nlm.nih.gov/pubmed/19207121
12. From sneeze to wheeze: What we know about rhinovirus Cs
    https://www.ncbi.nlm.nih.gov/pubmed/23714395
13. Newly identified respiratory viruses in children with asthma exacerbation not requiring admission to hospital
    https://www.ncbi.nlm.nih.gov/pubmed/20572080