Invincible: viruses are always out there, take EV-D68 for example

Enterovirus species D genotype 68 (EV-D68) will be back in our media streams in 2020 as the biennial peak likely returns to cause more cases of acute flaccid myelitis (AFM) and severe respiratory illness.

In the absence of a vaccine to eradicate them (we’ve almost managed this for poliovirus), members of the hugely successful family of picornaviruses, keep on circulating, mostly causing annoying illnesses.

But occasionally there are bad outcomes. And even less often, really bad outcomes.

EV-D68 has become notorious for its role in the really bad neurological outcomes following on from infection; central nervous system inflammation and AFM in young children.[2]

Before AFM was reported among those often previously infected with EV-D68, this virus was best known for more severe outcomes following respiratory infection. These illnesses included asthma exacerbations, new onset wheezing, bronchiolitis and pneumonia. By the looks of it, these are still the stock-in-trade for EV-D68.

EV-D68 hit Italy in late 2018

A new EV-D68-focussed study from Italy has delved into a late 2018 outbreak of these clinical diagnoses in hospitals in the Lombardy region of northern Italy.[1] From 853 samples collected, 91 were laboratory confirmed to be infected by a rhinovirus or enterovirus. We don’t get to learn what the other 89% were tested for and what was detected.

Respiratory illnesses among the infected

Predictive EV-D68 model. Courtesy of Claire Wang, UQ Child Health Research Centre.

Among the 91 EVs identified, 21 (23%; about 3% of the original 853) were positive for EV-D68 when the lot was screened with a specific PCR tool. These cases were of all ages and included those with febrile wheezing, pneumonia, severe acute respiratory infection (SARI), bronchial asthma as well as runny nose and cough. Some of the SARI cases required intensive care admission. Ten of the patients had an underlying or concurrent condition but none showed signs of neurological effects.

Virology of the EV-D68s

The genetic codes of the EV-D68 viruses detected in Italy were also studied a bit more closely.

Genetic sequencing of a part of the virus genome of 20 EV-D68s revealed two different sub-groups or clades of EV-D68; B and D.

Technically the viruses were further categorised into subclades D1 and B2 but there is as yet zero evidence to support that this level of drilling down really provides any additional knowledge or benefit to the patient or their management. It also isn’t obvious how or if such subcategories reflect changes to the virus that could be useful in predicting how severe the outcome from infection could be. That would be useful to know.

Having said that, genetic sequence is essential for studying virus evolution, transmission, where an outbreak originated and how it is evolving.

From their partial sequences, the authors could say that the Italian strains were most similar to others reported from Taiwan, the United States and France. From all over.

Circulating in Italy and beyond

This is not the first nor will it be the last outbreak of EV-D68 in Italy or anywhere else. So long as an endemic human virus is sought using specific and sensitive laboratory tools, it will be found.

EV-D68 isn’t really an outbreak virus either. It’s a constantly circulating endemic human virus. And that it was found in summer supports that. EVs generally peak during the summer months.

The virus analysis really shows quite nicely that EV-D68’s circulation may be made possible because it doesn’t sit still. It is constantly evolving. Here we see that as a subtle left-to-right movement in a tree representing worldwide EV-D68 sequences over time.

These viruses can also undertake more dramatic change through a process called recombination.

But none of that is meant to sound scarily unique to EV-D68. Much the same evolutionary processes can be described for any successful RNA virus.

What have we learned?

This study shows is that about 3% of respiratory illness during an outbreak might be due to EV-D68 infections. Among these are mild illnesses and more severe illnesses that require admission to an intensive care unit.

The new study supports that there is no obvious difference among the genetic variants of EV-D68 in terms of how their infection might travel in their host. Perhaps this is an indicator that we need to better understand how the host responds to EV-D68 rather than what the virus does to the host. It also highlights that AFM is not a common outcome from EV-D68 infection. It happens. But it’s rare.

For me, this also exemplifies the benefits of creating and using good laboratory tools. Infectious disease investigations really get started with a detection step. In this case, detection of a virus we didn’t really care much about until relatively recently.


  1. Emergence of divergent enterovirus (EV) D68 sub-clade D1 strains, northern Italy, September to October 2018
  2. It’s spooky how much the virus linked to “polio-like illness” isn’t coming from immigrants

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1 thought on “Invincible: viruses are always out there, take EV-D68 for example”

  1. Yes, they might be invincible, until a countermeasure would be devised. As for the italian experience, it may be useful to note however that after the great economic depression, the overall situation of public infrastructures has became critical, especially education (kindergartens, school, universities) with frequent overcrowding, lack of hygiene and knowledge of basic infection prevention measures. Awareness among the public is nearly null(a), without any recognizable behaviour toward respiratory etiquette or handwashing even in institutional settings. More worrying the state of health care services, public or private with extremely overcrowded places, with hundreds people packed for hours even for simple outpatient visits or bloodworks. This drives explosive respiratory pathogens outbreaks year-round. Further, biomolecular testing is uncommon, so the majority of cases went unnoticed at all. It would be interesting to evaluate the contribution of societal disruptions after the Great Depression (2011-2016) and the (re-)emersion of public health threats in Southern Europe countries.

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