A tiresome SPAT

I’m surprised that we can’t stop arguing about the modes of SARS-CoV-2 transmission, despite the fact that most experts (including our friends at WHO) agree on the important issues. Our colleague Jorge Salinas very nicely summarized these issues (and their implications) in this post.

The latest kerfuffle: media coverage of 239 experts who are upset that the WHO is not acting as decisively as they’d like on an evidence base that the experts themselves admit is far from definitive.

As we’ve outlined here and here, a major problem plaguing this discussion is the false dichotomy between “droplet” and “airborne” transmission that we use in healthcare settings (for simplicity of messaging, and because it has served us well for several decades—for reasons I’ll get back to later). This dichotomy divides application of transmission-based precautions between those pathogens spread via respiratory droplets, all of which must absolutely fall to the ground within 6 feet of the source, and those pathogens which become airborne, meaning they travel long distances on air currents, remain in the air for very long periods of time, and most importantly, can cause infection after their airborne sojourns if they find the right mucosal surface.

But we know (and WHO experts know) that there is no such dichotomy—it’s more of a continuum. At the very least there is a middle category, let’s call it Small Particle Aerosol Transmission (or SPAT). Many respiratory viruses (not just SARS-CoV-2) can remain suspended in aerosols and travel distances > 6 feet. As Jorge outlined, it’s probable that transmission events occur when these aerosols are concentrated in closed, poorly ventilated spaces or in very large amounts (e.g. a 2+ hour choir practice, a 3 hour indoor birthday party, a crowded bar). This may explain the superspreading events that drive a lot of SARS-CoV-2 transmission.

It’s important to distinguish SPAT from “classic airborne transmission” (let’s call it CAT). The CAT pathogens (TB, measles, VZV) have very different transmission dynamics than SPAT pathogens, as I outlined here (R0s of >10, household transmission rates of 50-90%). The distinction is important because for most healthcare epidemiologists, using the term “airborne” implies a common set of “one-size fits all” interventions to prevent transmission, interventions that require resource-intensive engineering controls and PPE requirements. It is not at all clear that such interventions are required to prevent transmission of SPAT pathogens. In fact, most evidence (and real world experience) suggests that they are not. This is why the droplet-airborne dichotomy has served us fairly well over the years—either because droplet precautions appear to be pretty effective at preventing SPAT, or because SPAT is rare even among those viruses capable of it.

I could say more about my feelings about aerosol-scientists criticizing epidemiologists and clinicians for having an “overly medicalized view” of the evidence, but I don’t want to be CAT-ty. I just want to end the SPAT.

So let’s redirect the discussion instead to: with the limited information we have, what additional interventions should WHO and/or CDC recommend for transmission prevention during the pandemic? Masks in crowded indoor spaces? Sure, but avoiding such spaces is preferred. Improved ventilation in all indoor environments? Absolutely, let’s get to work on that. N95s in the community? Don’t make me laugh, it might generate aerosols.* N95s for all patient care? Fair to consider, but by now we’ve gathered quite a lot of experience safely delivering care using existing WHO recommendations. And as Jorge aptly pointed out, “a debate only centered on whether respirators or medical masks are needed can distract us from the bigger challenges.” Indeed.

*Clarification as this comment, made in jest, has been misinterpreted.  N95 masks do not generate aerosols. They are unrealistic for community use, as they must be fit-tested and worn properly (even if we had an unlimited supply, which we do not). Nor are they, in my opinion, necessary for community protection. Face shields or medical/cloth masks are preferred for community use.

Airborne vs Droplet: Turbulent Gas Clouds of Opinion!

There’s much about the COVID-19 pandemic that is unprecedented, at least in my lifetime. One aspect is very familiar, though: arguments about the primary mode(s) of transmission of a newly emerging respiratory virus.

Much of the problem stems from our need to divide transmission modes into simple categories in order to apply prevention measures effectively. When someone calls the infection prevention program to ask about precautions recommended for virus X on the respiratory viral panel, it's not helpful to begin the conversation by saying, 

“well, you know, droplet and airborne transmission is not really a dichotomy, it’s more like a continuum, and there are a lot of factors at play—can we talk in more detail about the patient’s condition, what procedures they might be undergoing, and whether they might break out in song during routine patient care activities?”

One recent review you may find useful was published in Current Opinions in Infectious Diseases in August of 2019 by Shiu, Leung and Cowling (talk about great timing…). A very important point made in this piece is that viral nucleic acids and (less often) viable virus can be found in air samples--including from healthcare environments--for influenza, RSV, adenovirus, rhinovirus, and other coronaviruses. So reports about airborne SARS-CoV-2 (which will keep coming out in both pre-print and peer-reviewed literature) are not surprising. Nor do they answer the most important practical question about SARS-CoV-2 transmission:

Is airborne transmission a major mode of COVID-19 spread in community and in routine (i.e. no aerosol-generating procedure (AGP)) clinical settings?

My view is that we should consider the epidemiology of COVID-19 thus far in the pandemic, to determine if transmission patterns are more consistent with that of other common respiratory viral pathogens, or more consistent with that of the agents we classically consider to be transmitted by the airborne route (measles, VZV and M. tuberculosis). We could compare, for example, attack rates in various settings (household, healthcare, public), and the infamous R0 (expected ‘average’ number of secondary cases from a single infected individual in a susceptible population).

For COVID I’ll point to two careful contact investigations—this one of the over 400 close contacts of the first 10 travel-related COVID-19 cases in the US, and this study from Guangzhou, China, which was ten-fold larger (4950 close contacts to confirmed cases). The US study examined symptomatic secondary attack rates, and the study in China did serial RT-PCR on all contacts in addition to monitoring for symptoms. The findings are remarkably similar: highest attack rates are among household contacts (10.5% in US, 10.2% in Guangzhou), with extremely low rates of transmission among healthcare or community contacts (zero in US study, 1% among healthcare contacts and 0.1% among public transport contacts in Guangzhou). As for the R0, which of course varies as a population begins prevention approaches, the best estimate in my opinion is the tragic natural experiment performed on the unfortunate passengers of the Diamond Princess: during the early stage of the outbreak the R0 was 2.3.

For measles, the R0 is 12-18 and the secondary household attack rates are >= 90%. 

For VZV, the R0 is ~10 and the secondary household attack rate is 85%.

For TB, the R0 for smear-positive untreated TB is up to 10 (per year) and the secondary household attack rate has been reported to be >50%.

Based upon the above, I’m confident that SARS-CoV-2 transmission is similar to that of other respiratory viruses we are used to encountering—for which experience suggests droplet + contact spread to be the primary route of transmission. The trick is determining under what conditions a higher-risk aerosol might be produced (i.e. what is our list of AGPs? See here and here, if you dare!).

Does this mean that every respiratory droplet falls to the ground immediately and within 6 feet of a coughing patient? No. Dr. Lydia Bourouiba has an excellent piece in JAMA about the role of “turbulent gas clouds” in allowing droplets to travel further, and to remain in the air longer, than our traditional “droplet-airborne” dichotomy considers. In my view, this kind of droplet + "gas cloud" production mostly contributes to the extensive surface contamination that results in the highest risk of transmission being among close household contacts.

Eye Protection and Seasonal Influenza

At the last HICPAC meeting, Drs. Bryan Christensen and Ryan Fagan led an excellent discussion of the following question: should eye protection be included in droplet precautions for seasonal influenza and other respiratory viruses? 

Eye protection is one aspect of Standard Precautions, of course, to be used whenever there is a risk for splashes or sprays of blood and body fluids (BBF), or during aerosol-generating procedures. However, there is no recommendation for routine use of eye protection as part of Droplet Precautions—it’s an “unresolved issue”. 

Nonetheless, whenever CDC has had to issue interim guidance for new respiratory viral threats (SARS, MERS, novel influenza A viruses, etc.), they’ve included the routine use of eye protection. But seasonal influenza kills far more people annually than any of the novel threats, and there’s little reason to believe that seasonal flu strains can’t use the eye as a portal of entry (in addition to rarely causing direct ocular disease). The same applies to various of the other respiratory viruses (adeno, RSV, rhinovirus, hMPV, etc.). 

As is so often the case, we don’t have much published data to help answer this question: some work done in the 80’s suggested that eye protection was important for RSV transmission prevention, and Dr. Werner Bischoff demonstrated in an experimental system (air chamber into which live attenuated influenza vaccine virus was aerosolized) that the eyes could serve a portal of entry for influenza. So definitely wear goggles if Werner invites you to enter an airtight test chamber.

Anyway, thanks to Bryan and Ryan for their review (I will link to it when the transcript is out), and to HICPAC members for the lively discussion that followed…so what do you think? Does your center use eye protection routinely for droplet precautions for seasonal flu?

E is for...Enterovirus 68

Never a dull moment. Just as facilities have begun wrapping up their Ebola preparation plans, there's gathering evidence that several US states may be facing large clusters of acute respiratory illness associated with human enterovirus 68 (EV68).

Last week the Missouri Department of Health released an Alert describing increased cases in St. Louis and an outbreak of over 300 acute respiratory illnesses in a Kansas City pediatric hospital with 15% requiring ICU care. 19 of 22 specimens sent to the CDC from the Kansas City outbreak were positive for EV68. Many St. Louis cases were positive for enterovirus but specific typing is pending. Denver is seeing severe respiratory illness in very young children and children with asthma. Children's Hospital Colorado has treated 900 children and admitted 86 since August 18th, but so far the specific viral pathogen has not been confirmed. CDC reports similar cases have appeared in at least 10 states -- Missouri, Kansas, Illinois, Kentucky, Iowa, Colorado, Ohio, Oklahoma, North Carolina, and Georgia.

There are a few publications over the last 5 years describing EV68 associated outbreaks including an MMWR covering 2008-2010 clusters and individual reports from the EV68 emergence in the Netherlands, and an Indian Health Services (IHS) outbreak in children (both were already covered in MMWR). The Netherlands has seen the majority of cases in September to November (Figure above) with the highest prevalence in patients ages 50-59, while the IHS outbreak occurred in August-September in children with a median age of 4.8 years.

Clinical Findings: Signs and symptoms include cough, tachypnea, hypoxemia, and wheezing, particularly new-onset. In the Arizona IHS outbreak, at least half of the children had infiltrates on CXR and short hospital stays (median 1.5 days). The clinical presentations of the 18 IHS patients are listed in the table below.

Diagnosis: There are commercially available, FDA-approved, multi-pathogen detection systems including Luminex xTAG RVP, Idaho Technologies FilmArray Respiratory Panel. However, these non-specifically identify pathogens as "entero-rhinovirus" or "human rhinovirus/enterovirus." Most facilities can't currently perform enterovirus typing. Identification of EV68 requires partial sequencing of the structural protein genes, VP4-VP2 or VP1.

Treatment: There is no specific treatment for EV68. Care is usually supportive and only a minority of patients require brief hospitalization. Currently, there are no vaccines available.

Infection Prevention: The CDC currently (2007) recommends Standard Precautions for enteroviral infections but recommends "Contact Precautions for diapered or incontinent children for duration of illness and to control institutional outbreaks." However, most of the data that informed these recommendations were not derived from respiratory EV68 outbreaks. Recommendations from Hong Kong are very similar. 

I contacted a hospital epidemiologist in one of the states experiencing an outbreak, who has graciously shared their current protocol. Currently, they use symptoms to drive precautions so their respiratory patients are placed on droplet plus contact isolation for the duration of their hospitalization. In addition, they started their usual winter respiratory visitation restrictions last week so that children under 13 yo cannot visit and increased their focus on year-round routine screening of all visitors/family members for illness. Finally, they noted that this was the earliest they've ever started respiratory visitation restrictions.