Sunday, 4 September 2016

There (might be) something in the air tonight... [UPDATE]

UPDATE No.1 06SEPT2016
One of the early pieces of science-based news to come out of the May-2015 Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea was a June-2015 piece asking whether air conditioning may have played one (of many?) key role in facilitating the spread of virus from infectious patients, within healthcare facilities.[1]

In a publication that came out in April 2016 (yes, the literature did not see much detail on the South Korean outbreak for quite some time), authors described a study to collect and test air and swabs from surfaces in and outside patient's rooms, and their restrooms, in 2 hospitals that housed 3 male cases of MERS pneumonia.

Whenever RT-PCR is used for this sort of work, it brings with it the question of whether infectious virus-containing droplets were captured, or only bits of non-infectious RNA viral genome was detected. This group, like those in the last post (who did not collect air samples), attempted to grow infectious virus. They could confirm that it was infectious virus by observing cell changes in infected laboratory cultures which were also RT-PCR positive. Also the same approach as that described by the South Korean study reviewed in the last post.[3] Additionally, the infected cell cultures also reacted to an anti-Spike protein antibody in a fluorescent test and they even saw some actual virus from swab cultures (not captured air samples?) using electron microscopy.

Some interesting findings from the use of these test on air and swabs samples included:

  • All airs samples from both hospitals were RT-PCR positive and these included the detection of MERS-CoV of RNA in room, restroom and common corridor air. Infectious virus was grown in cells from from 4 of 7 (57%) samples.
  • 42 of 68 (62%) surface swab samples tested positive for MERS-CoV RNA by RT-PCR and included elevator button and rails, doorknobs and handrails inside and outside a patient's room, telephone button, toilet seat, call button, patient pillow, nasal prong, toilet seat, TV, keyboard, stethoscope and air exhaust dampers. Infectious MERS-CoV was isolated from 15 swabs of some of these items including an elevator button, nasal prong, patient pillow, TV, bed handrail, keyboard, stethoscope, toilet seat and an air exhaust damper

This study really addresses three big issues. 

Firstly MERS-CoV from very ill patients late in their disease course, thoroughly contaminates a hospital room and its surrounds - not just with detectable genetic material, but with infectious, viable MERS-CoV virus. 

Secondly, surface contamination was detected from swabs collected 3-7 hours after daily room cleaning suggesting either that cleaning was insufficient or that new virus was quickly laid down on cleaned surfaces (with no lasting anti-viral effect from the cleaning solution). 

Thirdly, the capture of infectious virus from the air implies that the virus maybe present in droplets or droplet nuclei with implications for the level of personal protective equipment required for healthcare workers and visitors to an infected person bedside. It also pertains to the distance away from a case that is considered "safe" for an uninfected person to be. Six feet may not be nearly enough distance, at least if that is a prolonged period in a room.

More data to explain how MERS-CoV is associated with hospital outbreaks. Why it has been allowed to get away with this is a matter for infection prevention and control specialists in each and every healthcare facility to address.

UPDATE.

After this was published, Van Kerkhove and colleagues wrote a letter to the editor to make some points about the study noting:

  • an absence of negative control sampling from areas where MERS-CoV patients were not housed.
    Absolutely. I'd even suggest a few different sites in very distant hospital areas from where MERS patients were housed, given the possible human-spread of virus around a facility during and the possibility of silent or subclinical infection in patients admitted to hospitals for other reasons during times of outbreak. This will explore whether false positive laboratory results are occurring.
  • other studies have reported surface contamination that did not yield viable virus. Van Kerkhove note that these negative findings need to be published to balance the literature. Always.
    However, it's well known that virus culture is insensitive compared to RT-PCR methods so it
    may fail to detect infectious virus which may be enough to infect a human . It may also be that infectious virus capable of infecting another person who comes into contact with it is not always present in the air or on surfaces. It may be that the surfaces often simply have non-infectious "bits" of virus detected by RT-PCR -these cannot cause a new infection. But in this study infectious virus was able to be isolated from air and surfaces...unless Van Kerkhove and colleagues are implying contamination of the cultures in some way.
  • the need to replicate these findings in other studies.
    Always.
    But as is often the case, let's not wait on those findings to recognise that infectious droplets and contaminated surfaces now have some more data to support them and that they fit nicely into a picture of hospital transmission. Precautionary principle.
A second letter was also written by Myoung-don Oh,[7] noting:

  • few infected cells in the cultures / slow growth.
    This isn't too surprising, it may just reflect that there was a low amount of virus in the air, added to the cell cultures compared to that used from the control virus (cell adapted?) stock.
    This may mean that the risk from airborne transmission in these rooms is low. However, since we don't know what amount of MERS-CoV is required to start a new human infection, this is a moot point.
  • the sequences of the room samples were too different from each other.
    This is a bit surprising since within an outbreak, MERS-CoV doesn't usually vary much at all. I'll have a look at how much South Korea's MERS-CoV Spike gene sequences varied and come back to this point.

Both letters were replied to.[8]

References...



  1. Did poor ventilation lead to MERS 'superspread' in Korea?
    http://www.sciencemag.org/news/2015/06/did-poor-ventilation-lead-mers-superspread-korea
  2. Extensive Viable Middle East Respiratory Syndrome (MERS) Coronavirus Contamination in Air and Surrounding Environment in MERS Isolation Wards
    http://cid.oxfordjournals.org/content/early/2016/06/08/cid.ciw239.abstract
  3. Korea contamination: Middle East respiratory syndrome coronavirus in the room..
    http://virologydownunder.blogspot.com.au/2016/09/korea-contamination-middle-east.html
  4. Interpreting Results From Environmental Contamination Studies of Middle East Respiratory Syndrome Coronavirus
    http://cid.oxfordjournals.org/content/early/2016/08/09/cid.ciw478.full.pdf
  5. STABILITY OF MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS (MERS-COV) UNDER DIFFERENT ENVIRONMENTAL CONDITIONS
    http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20590
  6. Transmissibility of Middle East Respiratory Syndrome by the Airborne Route
    http://cid.oxfordjournals.org/content/early/2016/08/09/cid.ciw479.full.pdf
  7. Interpreting Results From Environmental Contamination Studies of Middle East Respiratory Syndrome Coronavirus
    http://cid.oxfordjournals.org/content/early/2016/08/09/cid.ciw478.full.pdf
  8. Reply to Kerkhove et al and Oh
    http://cid.oxfordjournals.org/content/early/2016/08/09/cid.ciw480.extract
Update...
  1. Added in detail on letter by Van Kerkhove and colleagues [4], and rebuttal authors [5]