The common cold and influenza

We've talked aplenty about how much we still need to understand about influenza. Not just its basic biology but its dynamics. How does it spread over space and time and how existing infection rates affect future infection rates and how each are related to the number of susceptibles in the population. It's even more than that. There are other viruses perhaps competing for or perhaps cooperating with the flu virus in its sole job, to make copies of itself, using the host's (i.e., our own) biological machinery. You can imagine a scenario whereby once a lot of cells are infected by one virus, monopolizing the protein and genetic replication machines of an infected cell, gives another virus a harder time getting a purchase. Maybe that's how an influenza strain becomes dominant in a flu season. It got there first or was more efficient. And now a new idea has been broached, still highly speculative but no less intriguing for all that: maybe one of the forms of the "common cold" is somehow protective against getting influenza. This was suggested last month in a short communication by researchers at the Swedish Institute for Infectious Disease Control to the periodical Eurosurveillance (hat tip Deborah MacKenzie, New Scientist):

All cases of influenza were made reportable in Sweden on 13 May 2009. Samples were taken from all suspected cases until 16 July, when the strategy was changed from containment to mitigation.


Since the number of samples sent for influenza analysis was increasing until week 36 while the proportion of samples positive for pandemic H1N1 influenza was already decreasing, we hypothesised that some other virus infection may have interfered with the spread of the influenza pandemic. (Linde et al., Eurosurveillance Volume 14, Issue 40, 08 October 2009; cites omitted)

The "other virus infection" in question is rhinovirus, one of the principal agents of an upper respiratory infection belonging to a group often referred to as "the common cold" or "head cold." Like influenza, a rhinovirus has genetic material that is RNA instead of DNA, but it is positive sense, not negative sense (meaning the rhinovirus genetic material can be immediately translated into protein). It also has only one genetic segment (influenza has 8, but that is very unusual; the rhinovirus model is the way most virus genetic molecules are arranged, in one long segment). Rhinovirus is also very small (a quarter the size of the flu virus) and makes only 4 proteins versus influenza's 11. Moreover it's possible to be infected with a rhinovirus several times a year. When the virus infects host cells they respond in a general way, releasing chemical alarm signals (chemokines and cytokines). Thus people infected with rhinovirus have an immediate generic defense reaction already in motion. Does this protect people against an attack by the flu virus if it occurs in close relation with it? Maybe.

Laboratories in Sweden conducting extended viral diagnosis on samples sent for influenza examination were asked what viruses they found in the influenza-negative samples, and the answer was unanimous: rhinoviruses dominated, with sporadic findings of other respiratory viruses, such as enteroviruses and adenoviruses.


As shown in Figure 2, there was an increase in the proportion and number of rhinovirus diagnoses roughly in parallel with the decrease of influenza diagnoses.

A simple but likely explanation for the sudden interruption of the spread of influenza could thus be the increase in the spread of above all rhinoviruses. It is well known that a major rhinovirus epidemic always occurs soon after school has started.(Linde et al.; cites omitted)

Now a letter to Eurosurveillance from French doctors, makes a similar suggestion:

The A(H1N1)v circulation in France, like in other European countries (Sweden), is still reported as sporadic. The incidence of A(H1N1)v infections monitored in the community by the French National Influenza Centre has remained stable for 6 weeks from week 37 to week 42 (159 cases per 100,000 inhabitants). This is right above the epidemic cut-off of 114 cases per 100,000 inhabitants two months after the start of the new school year. This delay in the A(H1N1)v outbreak expansion is puzzling. At the same time, we report a high rhinovirus activity (34.5 % of samples positive for rhinovirus) in the community and in the hospital (unpublished data). (Casalegno et al., Letter, Eurosurveillance, Volume 14, Issue 44, 05 November 2009)

Interesting. But also very complicated. Influenza virus isn't the only respiratory virus around. Far from it. Respiratory syncytial virus (RSV) is one of the big ones and may interact with rhinovirus the same way flu does. At least that's what the French suggest:

This year, rhinovirus detection started on week 37, peaked on week 40 and decreased on week 43. At that moment, we can report the first detection of RSV and an increasing activity of A(H1N1)v. Regarding what was observed during last winter on the circulation of rhinovirus, RSV and A(H3N2) virus , it will be of much interest to follow the impact of the A(H1N1)v pandemic on the coming RSV peak. In other words, which respiratory virus between RSV or A(H1N1)v, will win the race for second place? (Casalegno et al.)

What all this says is we still don't know some of the most important aspects of respiratory disease dynamics. It's an amazingly complicated mechanism with many moving parts. And we don't even know what they all are, much less how they work with each other or against each other.

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Very interesting. One bit I was taught back in residency and which has seemed to be true in my two decades of practice is that RSV and influenza rarely share the stage. Most years one pushes the other off. I've never quite understood why but these thoughts suggest some explanations.

In any case, my troublesome side has me automatically thinking of this: assume rhinovirus is protective - it has little risk of serious morbidity or mortality so we'd want more people to have it - rhinovirus spreads well by aerosol and by both direct and indirect contact - influenza minimally spreads less well by those means. If so we'd want to do that which encourages the spread of rhinovirus over influenza which means less handwashing! Okay, I don't believe it, but it does logically follow.

It also gets me thinking about what I've asked a revere about before - why we almost always see a decrease in the rate of percent office visits for ILI in January before the ILI rate takes off in Feburary. One speculative answer is that during the holidays rhinovirus pushes influenza off the stage.

I dunno. Some of my patients have had dual rhinovirus/H1N1 untypable infections via PCR testing (rapid flu tests are unreliable and we don't use them now.) And they have been ill enough to be in the hospital. We are still checking out the significance.

And then there is also this…

>>Neither the federal government nor the states track rhinoviruses in the way they do "surveillance" for influenza, based on samplings of doctor diagnoses, emergency-room visits, and lab reports. Children's Hospital of Philadelphia is one of the few institutions that routinely checks for them whenever it tests for influenza and other viruses.

Rhinovirus - named after the Greek word for nose - is known to circulate year-round, and typically to peak shortly before and after flu season. Children's recorded rising numbers in September, right on schedule. Then they kept rising.

"The rate of activity was unbelievably high," Richard L. Hodinka, director of the clinical virology laboratory, said yesterday. "What got my attention was not only the numbers we were seeing in the laboratory, but physicians saying there was severe disease." ...

... Besides the sheer numbers of rhinovirus, Coffin was surprised that it was causing more problems - wheezing, pneumonia, fever, and lower-respiratory-tract infections - than are normally associated with the common cold, which typically infects the upper respiratory tract. That has led her to suspect that a strain not seen here before may be responsible. The CDC's lab will attempt to identify the strain. ...

... And doctors in Louisville, Ky., at least, noticed a similar phenomenon: serious illness (in both children and adults) that did not test positive for influenza. They, too, were surprised to find rhinovirus.

"We haven't thought of it as something that causes kids to be really sick and need to be admitted to the ICU," said Kris Bryant, hospital epidemiologist at Kosair Children's Hospital.

Scientists who specialize in rhinovirus are used to their chosen microbe being underestimated, and lauded Children's just for testing for it.>>

So back to handwashing!

1. Would it not occur for rhinovirus to be living in the upper resp, H1N1A in the lower resp, tract in a given person? 2. These Louisville and Philadelphia reports are seriously scary (unless some "mitigating" factors, like most the kids tested being homeless in the rain or the like).

It's an appealing argument. My concern would be the immediate post-rhinovirus immunosuppression making one once again vulnerable.

Although that said, I had a rhinovirus immediately before my husband came home with influenza, and I somehow managed to avoid getting his bug.... so n=1 but that might be an explanation. Or I might be lucky.