Infection but not sickness

Asymptomatic infections are those where we can detect the virus using reliable laboratory methods, but the infected person doesn’t show any signs or symptoms of a disease; we’ve been infected but not made ill. This outcome is common 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]

A recent study

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). Infection 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 were 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 a 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 was positive.

The good

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

The not so good

I deliberately wrote “done well” because that wasn’t clear. There were a few annoying omissions, perhaps to the study design or perhaps just to the write-up of it…

1. What was sampled? Upper respiratory tract samples are not ideal for detecting MERS-CoV in those with the disease. How much trust can we put in the reliability of the results?
2. Was the index HCW 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 known positive didn’t mount an antibody response, this test is useless as an indicator of past infection by MERS-CoV among this group.
3. 45 of the 82 HCW permitted sampling and 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 the virus in healthy 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.

We need better studies to answer questions posed by mild or asymptomatic viral infections. Questions that need answering include 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

Updates

1. 02JAN2019. Updates to spelling and layout.