Tuesday, June 18, 2013

MERS-CoV: Early Serological Results

Coronavirus

Photo Credit NIAID

 

 

 

# 7406

 

 

During my brief absence yesterday Helen Branswell of the Canadian Press broke the big story of the day, the long awaited results from retrospective testing of suspect cases from Jordan MERS-CoV cluster in April of 2012.

 

If there’s anyone who hasn’t already read her article, I would invite you to do so now.  When you return, I’ll have more:

 

Earliest known MERS outbreak, in Jordan, infected at least 10 people

Helen Branswell The Canadian Press  June 17, 2013

 

 

The serological testing methods employed in testing these Jordanian cases are still in the early stages of development, and have not been fully validated. So, the actual number of contacts in this cluster who may have been infected could eventually go higher.

 

The CDC appears confident that the positive results they’ve returned are truly positive, but negative results are less certain.

 

At least one of the newly identified seropositive cases reports not having been ill during the outbreak while another reported only mild symptoms. These two cases raise new questions over asymptomatic or subclinical infection with the virus.  

 

A topic that Dr. Ian Mackay addresses in his Virology Down Under column overnight.

 

MERS-CoV in the Asymptomatic?

ProMED noted an article by Helen Branswell (here), that reports on serology results we'd previously mentioned were coming from a collaboration between the Jordanian MOH and the US CDC.

 

124 people were tested from the April 2012 outbreak of pneumonia in Zarqa, Jordan - and 8 people were antibody-positive, identifying an immune response to infection by the MERS-CoV.

 

This brings the MER-CoV total up to 72 with 38 deaths and drops the CFR from 59% to 52%; as happens when you raise the denominator.

 

<SNIP>

So, (yet again-seems like only yesterday I was talking about this) there are signs that this respiratory virus, like other before it, may present in a spectrum of clinical situations ranging from severe (where the virus is an opportunistic pathogen among predominantly older males with "underlying medical conditions") through to asymptomatic.

 

It should come as no surprise to readers of this blog, what my next comment will be. We need to test prospectively and not reactively. Not just using serological assays but also by PCR. Otherwise we keep stumbling around in the dark.

 

Perhaps we could even go so far as to start assuming that each virus can travel both stealthily and "loudly", instead of assuming they can't. Just sayin'

(Continue . . . )

 

 

If Ian’s blog isn’t already part of your daily internet infectious disease tour, I would encourage you to add it to your itinerary.

 

Whenever a new virus begins to circulate in humans we tend to only see the `sickest of the sick’ show up at hospitals. This initially skews our perception of just how deadly an outbreak might be.

 

Over time, as better diagnostics are developed and more samples are tested, we usually discover a broader spectrum of clinical illness, which brings down the mortality rates.

 

Mild or asymptomatic infections are a hallmark of nearly every infectious disease, although their incidence varies widely. How a disease presents in an individual depends greatly on the competence of their immune system, previous exposures, age, and other comorbidities.

 

Last year, in The Very Common Cold, we looked at a study of college students that found asymptomatic Rhinovirus infections led symptomatic infections by a whopping factor of 4 to 1.

 

Those with asymptomatic infections showed lower viral loads than those displaying cold symptoms - suggesting that they may be less efficient spreaders of the virus – but we don’t have enough data to know how much of a viral load it takes to spread the virus.

 

In 2011, in EID Journal: Pre-Symptomatic Influenza Transmission, we saw evidence of presymptomatic spread of the H1N1 virus in three clusters in Japan, which also suggests that asymptomatic carriers ought to be able to spread the virus as well.

 

And last year, in  PLoS One: Influenza Viral Shedding & Asymptomatic Infections, we saw a small study that found 21% of adult secondary influenza cases were asymptomatic or subclinical, yet they shed roughly the same quantity of virus as those showing clinical signs of illness.

 

Of course, MERS-CoV isn’t influenza or a Rhinovirus, which makes comparisons difficult. We do, however, have a serology study from the 2003 SARS (coronavirus) epidemic that found a small, but significant percentage of asymptomatic cases as well.

 

Volume 11, Number 7—July 2005
Dispatch

Asymptomatic SARS Coronavirus Infection among Healthcare Workers, Singapore

Annelies Wilder-Smith , Monica D. Teleman, Bee H. Heng, Arul Earnest, Ai E. Ling‡, and Yee S. Leo

Author affiliations: *Tan Tock Seng Hospital, Singapore; †National Healthcare Group, Singapore; ‡Singapore General Hospital, Singapore

 

We conducted a study among healthcare workers (HCWs) exposed to patients with severe acute respiratory syndrome (SARS) before infection control measures were instituted. Of all exposed HCWs, 7.5% had asymptomatic SARS-positive cases. Asymptomatic SARS was associated with lower SARS antibody titers and higher use of masks when compared to pneumonic SARS.

 

<SNIP>

 

Patients with a positive SARS serologic result, fever, respiratory symptoms, and radiologic changes consistent with pneumonia were defined as having pneumonic SARS. SARS-CoV–positive patients with fever and respiratory symptoms without radiologic changes were defined as having subclinical (nonpneumonic) SARS. SARS-CoV–positive patients without fever or respiratory symptoms were defined as having asymptomatic SARS-CoV infection.

 

<SNIP>

 

Of these 80 hospital staff, 45 (56%) were positive by SARS serology. Of the 45 SARS-CoV–positive study participants, 37 (82%) were classified as having pneumonic SARS, 2 (4%) as having subclinical SARS, and 6 (13%) as having asymptomatic SARS-CoV infection (Table 1). Four staff members had fever and cough but negative SARS serologic test results; none of them was diagnosed as having suspected SARS by the hospital's SARS outbreak team. The overall incidence of asymptomatic SARS-CoV infection was 6 (7.5%) of 80.

 


In this study, the incidence of severe disease among those seropositive for the virus was 82%. Only 4% displayed milder symptoms, while surprisingly, 13% were asymptomatic

 

Admittedly, MERS-Cov isn’t SARS either. But it's the closest analogue we have right now.

 

 

It will take validation of the serology tests and more extensive seroprevalence testing before we can get a good idea of how well MERS-CoV spreads among humans, it’s average severity, and the spectrum of disease it produces.

 

But at least the tools needed to do that are beginning to become available.