When MERS means detection but not disease…

An asymptomatic infection is one where we can detect the virus using reliable laboratory methods, but the infected person doesn’t show any signs or symptoms of disease; we have been infected but not made ill. This outcome is common – to some extent – to pretty much every virus wherever it’s been sought; from the highly transmissible norovirus [2] to the scary forest-dwelling Ebola virus.[3,4]

Back in May we read about a study to see if one such asymptomatic person, a healthcare worker (HCW) in South Korea who became infected with Middle East respiratory syndrome coronavirus (MERS-CoV). This occurred during unprotected respiratory exposure to an infected patient. The study looked at whether the HCW went on to infect other people they were in contact with.[1]

Antibody tests were conducted on blood samples taken from 45 of 82 HCW contacts who consented. These samples were collected 2-weeks, and again at 4-weeks, after the HCWs were variously exposed to the infected nurse. None showed a rise in MERS-CoV specific antibodies.

When a contact became obviously ill during  2-week period during which all 82 contacts were isolated at home, they were also sampled (nature of the sample was not described) and tested for virus using a commercial kit-based RT-PCR. Presumably this was the same kit that initially detected MERS-CoV in the original asymptomatic HCW. None of the 82 samples tested positive for MERS-CoV.

At the end of the 2-week isolation period, another sample (also not described) was taken and RT-PCR performed. None of these samples were positive.

This case provides interesting data that are essential to know when dealing with an emerging virus infectious disease outbreak. If asymptomatic cases can transmit virus and cause new cases, then they must be isolated; as was done in this study. But potentially removing many healthcare workers from duty during an outbreak or epidemic can very quickly leave a healthcare facility without the staff it needs to run and thus unable to manage new cases as they arrive. So this sort of study needs to be done, done early in our understanding of an emerging virus, and done well.  

I say that last point because it’s not clear if this study was done well. There were a few annoying omissions, perhaps to the study or perhaps just to the write-up of it…

  1. what sample was taken? It is known that upper respiratory tract samples are not ideal for detecting MERS-CoV in those with disease. How much trust can we put in the reliability of the reuslts?
  2. there is no mention made of whether the index HCW was also sampled and tested for the presence of MERS-CoV antibodies. This is a major omission. We need to know whether an RT-PCR positive asymptomatic case triggered an immune response. If they did not, the antibody results for the other 82 HCWs are meaningless. If a know positive didn’t mount an antibody response, this test is useless as an indicator of past infection by MERS-CoV among this group.
  3. Only 45 of the 82 HCW gave permission to be sampled for antibody testing; 45% did not. So what happened in nearly half of the HCWs?
  4. Only 4 HCWs were symptomatic during the isolation period – and all tested negative for MERS-CoV RNA. Aside from the issues in Point 1 above, waiting for 2 weeks before testing for virus in well humans, guarantees a negative result. It was pointless. It would have been more useful (and innovative) to test them every few days from the day of known exposure for 2 weeks. There has been a distinct lack of cohort studies in MERS-CoV – and among many other new, “known”, emerging or re-emerging viruses. We’re missing vital information by not following and sampling humans in the community, during outbreaks or across relevant seasons of highest virus activity.

There need to be better studies to answer questions posed by mild or asymptomatic viral infections. Questions such as whether they have a role in transmission, how long do they persist and do our antibody detection assays work on asymptomatic cases?  

References…

  1. Infectivity of an Asymptomatic
    Patient With Middle East Respiratory
    Syndrome Coronavirus Infection
    https://www.ncbi.nlm.nih.gov/pubmed/28444154.
  2. Re-assessing the total burden of norovirus circulating in the United Kingdom population
    https://www.ncbi.nlm.nih.gov/pubmed/28094075
  3. Ebola Virus Persistence in Breast Milk After No Reported Illness: A Likely Source of Virus Transmission From Mother to Child.
    https://www.ncbi.nlm.nih.gov/pubmed/27940938
  4. Asymptomatic infection and unrecognised Ebola virus disease in Ebola-affected households in Sierra Leone: a cross-sectional study using a new non-invasive assay for antibodies to Ebola virus
    https://www.ncbi.nlm.nih.gov/pubmed/28256310

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