Rhinovirus rampant or testing triumphant?

Turns out, this physical distancing thing actually works as advertised. Who would have thought that keeping the things viruses need for their survival – hosts full of cells – far enough apart, would mean fewer illnesses? Well, lot’s of people actually. But some viruses – a really big group of individual viruses – are snubbing their non-enveloped protomers at us. These rhinoviruses (RVs or “rhinos”) may soon be coming to a nose near you.

Physical distancing and flu

It should be no surprise that when we keep humans apart to stop the spread of severe acute respiratory syndrome virus (SARS-CoV-2) that causes coronavirus disease (COVID-19), the beneficial effects extend to other infections.

Influenza virus detections in Australia fell through the floor once restrictions (see the graph below) were applied to travel and close and prolonged interactions at workplaces and sports events and schools in March.

This graph is Figure 5 from the document, COVID-19, Australia: Epidemiology Report 17:
Fortnightly reporting period ending 24 May 2020
.[6] Key restrictions on travel and gatherings started rolling into place from mid-March along with messages about how to avoid infection. NOTE: Week 12 = week starting 16MAR2020; Week 20 = week starting 11MAY2020

Except where I’ve pointed out, this blog post is based on weekly public data produced by diagnostic testing from the Sullivan Nicolaides Pathology private referral labs, with collection centres all over Queensland and in northern New South Wales.

Also called the common cold viruses, the RVs have been evolving alongside us for quite some time! [1,2] They know us well. They spread through all the routes and are some of the earliest human respiratory viruses to get a lot of research attention. RVs are with us all year ’round but often peak in spring and autumn (“pollen season” in some parts), usually on either side of peak influenza (flu) virus activity; the two don’t seem to play well together. RVs usually cause mild quick onset upper respiratory tract illnesses (URTIs) with signs and symptoms which we generally call the “common cold”. They are also the most common viral cause of acute wheeze and asthma exacerbations, or attacks.

Let’s nose our way through some local (mostly Queensland) data from a private pathology lab.

A virus for all seasons

Some respiratory viruses are expected to be in the community right now – flu, respiratory syncytial virus (RSV; it’s starting to come back now), parainfluenza viruses (PIVs) and maybe a little human metapneumovirus (hMPV). And of course the RVs, human adenoviruses (hAdVs) and maybe some enterovirus (EVs).

You can see from the testing results below – from samples from people generally sick enough to go to a doctor – that different viruses peak and trough at different times of the year. This seasonality varies with climate and school holidays and so the patterns below may be different if you live elsewhere.

A crude way to compare what virus numbers from the same labs (Sullivan Nicolaides Pathology) look like over the past four years. Lots of variation but never so many RV positives as we see right now (below; note the y-axes vary a lot). Although also never before a pandemic where testing has been pushed to occur so frequently – ideally, no matter what the symptoms are.

In 2020 its worth noting that we are getting tested for milder illnesses than normal so it is expected that we may see more of the pathogens that cause milder illness. And it’s also worth noting that every known respiratory virus, even SARS-CoV-2, can be associated with a spectrum of illness severity from no symptoms through to severe illness and death. How often different viruses cause mild or severe illness overall does differ, but all viruses can cause the signs and symptoms we call “the common cold“.

A knockout blow for the flu

Influenza viruses began 2020 – as they did 2019 – with an unusually high level of confirmed activity in the Australian summer (pink line below). When we distanced from mid-March, those numbers plummeted and disappeared.

Flu was KO’d as humans physically distanced in Australia during March (starting ahead of official pronouncement in some instances). The same pattern can be seen in each jurisdiction around the country.

What about the other respiratory viruses?

There are over 200 “respiratory viruses”. Some have defined seasons, but they can all tick along year-’round.

Intriguingly, many non-flu viruses – RSV (just starting to come back now), PIVs and hMPV – for example – are nowhere to be seen in our example data from Sullivan Nicolaides Pathology below.[5] But they had been present coming into winter and were expected to continue on as they usually do.

Sullivan Nicolaides Pathology weekly respiratory virus report for week 24 (ending 13JUN2020). Over 7,000 HRVs in a week is a record number of laboratory detections. But what could be causing this and how did the HRVs and hAdVs remain active even when other viruses didn’t, during physical distancing?

Meanwhile, other viruses – namely the RVs (purple) and hAdVs (lime green) retained a solid foothold throughout the physical distancing restrictions which officially started from around Week 12 and started a phased easing from May, or around Week 20.

In particular, the RVs were the last to drop and the first to rise again.

If we compare RV detections over the past few year’s of data kindly provided by Dr Jenny Robson from Sullivan Nicolaides Pathology we can see that in May, RVs made up more than 50% of the viruses identified in all samples tested. Cleary, in Australia and according to these data, you are much more likely to be ill due to an RV infection than infection by any other respiratory virus right now.

NOTE: RV testing only began part-way through 2016 at Sullivan Nicolaides Pathology,m hence the partial line (blue)

If we have a look at age and sex, we can also see that the RVs disproportionately hit the young which is not unusual for RV infections. RVs love kids! There are so many distinct viruses against which kids don’t yet have immunity, but adults do (from their childhood infections).

Over 40% of samples from those aged under one year up to ten years were positive for an RV. From 10 to 40 over 20% of samples were RV positive.

Graph from Report to Week24, 2020, via Sullivan Nicolaides Pathology.[5]

What might be happening here?

New versions of RV?

We have no evidence to suggest there is anything different, or not different, about the RVs circulating. Or even that there is more than one RV around. I know from previous work that 70 or more distinct RVs can co-circulate in one season.[11,12]

I personally doubt we’re seeing anything dramatically different from a virus point of view. We’ll need a little sequencing work to confirm that though.

The level of testing?

In Australia, we accidentally approaching eradication of COVID-19 transmission (and by inference, SARS-CoV-2). It wasn’t the stated policy but we’re awfully close to it nonetheless (….😒…Victoria). We’ve been encouraged to get tested no matter what sort of respiratory illness we have. And we’re now seeing testing numbers for a single virus that are truly gobsmacking.

Thankfully for the suppression/eradication fo COVID-19, we’ve sort of dialled down the “fever and..” reason for presenting for a test. Now, any new signs and symptoms are test-worthy, and with good reason as we see below. The red circles highlight all the non-fever related signs and symptoms combinations and permutations among Australia’s confirmed COVID-19 cases.

Graph from Coronavirus disease (COVID-19) epidemiology reports, Australia, 2020, Report No. 16.[6] This brilliant presentation of complex data clearly highlights the full spectrum of signs and symptoms associated with COVID-19 in Australia. Here, the majority of lab-confirmed cases have been classified as “mild” respiratory infections and you can see a number of cases that had no fever attached to them. This graph and Australia’s data also highlight the futility of relying on fever if your aim is to chase down cases of COVID-19 by finding infected people and isolating them from susceptible people.

The type of testing

The rhinoviruses love the nasal passage and nasopharynx so it isn’t inconceivable that we are enriching our data for them.[9,10] I don’t think this is a major driver of numbers though.

Better to be naked?

The RVs and also the hAdVs are two large and distinct groups of viruses which differ from each other in many ways. They are differently sized; have different structures; their genetic material is made up of RNA or DNA respectively; their genomes have very different genetic sequences; and they use different receptors to attach to cells. But they also share a couple of important features: there are many of them that can infect us, and none of the viruses in these groups has a lipid envelope – they are naked.

There is no “rhinovirus” or adenovirus” – there are dozens of them; more than there are distinct influenza viruses at any given time, or RSVs or MPVs or PIV-1s etc. I’d wager there are some enteroviruses out there as well – another well-endowed group – but we don’t test for them much in Australia.

The naked versus enveloped issue is interesting because the viruses that seem to have been pushed out of circulation, do have an envelope, and the ones that have hung on, don’t.

The hands have it?

Perhaps the RVs are more easily spread via contact with contaminated surfaces and the hands while the SARS-CoV-2 and its enveloped ilk spread more effectively in droplets combined with close and prolonged contact?

Historical studies have found the RVs need some time to infect susceptible people, but that shared items can effectively spread infection in a group.[7]

This could be a difference in fragility when a virus is exposed to the filthy and dusty real world. The enveloped viruses may not survive surfaces for as long (ignoring those perfect-world lab studies of virus stability for this thought) whereas the naked viruses may manage better.

What’s special about the wrapper?

The lipid envelope can be disrupted with soaps and detergents and this renders a virus effectively unable to attach to its cells. This spells doom for these viruses. Can’t attach? Can’t make more clones. With no shelter to be found a virus left out in the open will be destroyed by an immune system or degrade.

But naked viruses with a protein shell (a “capsid”) and no envelope are more resistant to the effects of handwashing and perhaps surface degradation and this may play some role in how hAdVs and HRVs seem to have survived better than influenza and other enveloped viruses.[3,4]

Children are festy transmission factories

When many things closed down, infection and instances of physical proximity were dramatically reduced. However, childcare was not told to shut.[8] Childcare was considered essential to afford frontline workers – including healthcare and supermarket workers – the ability to keep working (thank you to all those who had to go out day after day treating our illnesses and keeping the food shelves stocked!).

As all parents will know, physical distancing is non-existent among young children. So the idea that the RVs may have “hidden out” at childcare, using it as a nexus to carry RVs back into households and keep the RV fires burning until we started mixing again, is an interesting one.

It’s just too hard to prevent the household spread of respiratory viruses.

Sightseeing and homebody viruses

We know that influenza viruses are injected into countries and distributed all over the world via travel hubs (the US and China especially), all the time. Every season is a soup of flu viruses.

Perhaps this lack of travel is yet another factor in why flu viruses have been impacted relatively heavily by our distancing and shutdown measures – lots of us have developed immunity to those that were around in our neighbourhood (through infection or vaccination) and we now need an injection of divergent viruses to kickstart their widespread circulation again. Plus there’s the physical distancing thing.

Another enveloped but generally though of as homebody virus – RSV – also comprises only a few distinct viruses. But it’s starting to show signs of stirring. Perhaps the childcare hideout theory applies to them as well as they also thrive among the young.

Lots of testing, no enveloped viruses but plenty of naked ones

While we can say physical distancing has reduced our flu season – we also expect it should have reduced the presence of common cold viruses to the same extent. All things being equal. Even with massive testing of all types of illness, we’d expect to find flu and RSV and PIV among those cases, if they were around. But they aren’t. And yet RVs and hAdVs are.

While there is no clear-cut answer for the question of what the rampant rise in rhinovirus detection really means, it’s pretty clear that if we ever see a brand new RV turn up, to which we have no immunity…we’ll have even more trouble containing it than we have SARS-CoV-2. And there’s no guarantee it would “only” causes common colds. Rhinoviruses know us well, perhaps even better than we know them.

Here we have yet another fascinating question arising from this pandemic. It hints at how much research – basic and not very complex research on the respiratory viruses we have live with every day, from birth until death for hundreds or more years – simply has yet been done.

Something for the future: sort sharp shutdowns?

Here’s an idea floated to me by two people recently (thanks Kat and Judy). What if once this pandemic is over, we were to instigate an annual multiweek shutdown of international travel to reduce the size and harm of flu season? We could schedule it around the time of school exams, (some number of) months out from the traditional flu season’s start in temperate countries. I think we’ve shown that this can be done, it’s more about whether it can be done with a reduced economic impact as well.

References

  1. The Big Bang of picorna-like virus evolution antedates the radiation of eukaryotic supergroups
    https://www.nature.com/articles/nrmicro2030
  2. Origins and evolution of viruses of eukaryotes: The ultimate modularity
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5898234/
  3. Inactivation of Coxsackievirus B4, Feline Calicivirus and Herpes Simplex Virus Type 1: Unexpected Virucidal Effect of a Disinfectant on a Non-Enveloped Virus Applied onto a Surface
    https://www.karger.com/Article/FullText/350556
  4. Survival of Enveloped and Non-Enveloped Viruses on Surfaces Compared With Other Micro-Organisms and Impact of Suboptimal Disinfectant Exposure
    https://pubmed.ncbi.nlm.nih.gov/18602193/
  5. Infectious disease reports | Respiratory virus reports
    https://www.snp.com.au/clinicians/results-and-reporting/infectious-disease-reports/
  6. Coronavirus disease (COVID-19) epidemiology reports, Australia, 2020
    https://www1.health.gov.au/internet/main/publishing.nsf/Content/novel_coronavirus_2019_ncov_weekly_epidemiology_reports_australia_2020.htm
  7. Transmission of viral respiratory infections in the home
    https://journals.lww.com/pidj/Fulltext/2000/10001/Transmission_of_viral_respiratory_infections_in.2.aspx
  8. Early childhood education and service operations | Victoria
    https://www.education.vic.gov.au/childhood/Pages/coronavirus_ec_serviceoperations.aspx
  9. Human Rhinoviruses: The Cold Wars Resume
    https://pubmed.ncbi.nlm.nih.gov/18502684/
  10. Rhinoviruses Replicate Effectively at Lower Airway Temperatures
    https://pubmed.ncbi.nlm.nih.gov/10223554/
  11. Community-Wide, Contemporaneous Circulation of a Broad Spectrum of Human Rhinoviruses in Healthy Australian Preschool-Aged Children During a 12-Month Period
    https://academic.oup.com/jid/article/207/9/1433/927248
  12. Genotypic diversity, circulation patterns and co-detections among rhinoviruses in Queensland, 2001
    https://www.microbiologyresearch.org/content/journal/acmi/10.1099/acmi.0.000075?crawler=true

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