Epi. Reviews: A Review of Asymptomatic and Sub-Clinical MERS-CoV Infections

Photo Credit NIAID



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More than 7 years have passed since MERS-CoV (originally called nCoV) emerged in Saudi Arabia, and while much as been learned, there remain many unanswered questions over how the virus is transmitted in the community.

The virus - which likely originated in bats - is endemic in camels across the Middle East, Northern Africa, and parts of Asia. Despite large numbers of seropositive camels in neighboring countries, more than 85% of the worlds human infections have originated from Saudi Arabia. 

It is possible that differences in surveillance and testing could account for the paucity of cases outside of KSA. Further complicating matters, a 2016 study (see EID Journal: Estimation of Severe MERS Cases in the Middle East, 2012–2016) suggested that as much as 60% of severe Saudi MERS cases go undiagnosed.

We also now know that asymptomatic and subclinical infections make up a larger portion of cases than was previously understood.

For the first few years the Saudis treated `asymptomatic' but RT-PCR positive MERS-CoV test results (usually discovered while contact testing during a hospital outbreak) as something `less' than a MERS case.

They were rarely reported, and were not included in their official MERS statistics, and were rarely isolated.  

That is until the World Health Organization issued a particularly strong rebuke (without singling out the Saudis) on the handling of asymptomatic cases in their 2015 WHO Statement On The 10th Meeting Of the IHR Emergency Committee On MERS.

Since then, we've seen a substantial jump in the number of `asymptomatic' (or perhaps, mildly symptomatic) cases reported out of Saudi Arabia.

But even with this new awareness, it is likely that most asymptomatic or mildly symptomatic cases go undetected.

Seroprevalence studies have hinted at this (see Presence of Middle East respiratory syndrome coronavirus antibodies in Saudi Arabia: a nationwide, cross-sectional, serological study by Drosten & Memish et al.,), but the rapid loss of detectable MERS antibodies in mildly ill cases likely undermines those estimates (see EID Journal: Antibody Response & Disease Severity In HCW MERS Survivors).

While many human cases report recent camel (or camel product) contact, or had a known exposure to a confirmed case, hundreds of  others are listed as `primary' (community acquired) cases with no known risk exposure. 

The assumption is that some of these cases may be due to unidentified, mildly symptomatic (or asymptomatic) cases, who occasionally transmit the virus on to others in the community. Last year, the WHO listed some of the `milder' symptoms that may be associated with MERS-CoV infection, including:

Low-grade fever, cough, malaise, rhinorrhoea, sore throat without any warning signs, such as shortness of breath or difficulty in breathing, increased respiratory (i.e. sputum or haemoptysis), gastro-intestinal symptoms such as nausea, vomiting, and/or diarrhoea and without changes in mental status (i.e. confusion, lethargy).

And a year ago, we looked at:

Asymptomatic Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection: Extent and implications for infection control: A systematic review

Jaffar A.Al-Tawfiq abc Philippe Gautretd

Conclusions

The proportion of asymptomatic MERS cases were detected with increasing frequency as the disease progressed overtime. Those patients were less likely to have comorbid disease and may contribute to the transmission of the virus.

While a logical conclusion, proving and quantifying the role of asymptomatic transmission of MERS in the community is quite difficult.  While it falls short of `proof', we have a new review of the literature that examines past studies and finds credible evidence to suggest that asymptomatic transmission likely occurs.

A provisional PDF is available, and I've provided the link and Abstract below.

A Review of Asymptomatic and Sub-Clinical Middle East Respiratory Syndrome Coronavirus Infections

Grant R^1,2, Malik MR³, Elkholy A³, Van Kerkhove MD¹.

Author information

1. Department of Infectious Hazard Management, WHO Health Emergencies Programme, World Health Organization, Geneva, Switzerland.
2. Centre for Global Health, Institut Pasteur, Paris, France.
3. Infectious Hazard Management Unit, Department of Health Emergencies, World Health Organization Regional Office for the Eastern Mediterranean, Cairo, Egypt.

Abstract

The epidemiology of Middle East Respiratory syndrome coronavirus (MERS-CoV) since 2012 has been largely characterised by recurrent zoonotic spill-over from dromedary camels followed by limited human-to-human transmission, predominantly in health care settings.

The full extent of infection of MERS-CoV is not clear, nor is the extent and/or role of asymptomatic infections in transmission. We conducted a review of molecular and serological investigations through PubMed and EMBASE from September 2012 to 15 November 2018 attempting to measure sub-clinical or asymptomatic MERS-CoV infection within and outside of health care settings.

We performed retrospective analysis of laboratory-confirmed MERS-CoV infections reported to the World Health Organization to 27 November 2018 to summarize what is known about asymptomatic infections identified through national surveillance systems. We identified 23 studies reporting evidence of MERS-CoV infection outside health care settings, mainly of camel workers, showing ranges of seroprevalence of 0-67% depending on the study location. We identified 20 studies in health care settings, of health care worker (HCW) and family contacts, of which 11 documented molecular evidence of MERS-CoV infection among asymptomatic contacts.

Since 2012, 298 laboratory confirmed cases were reported as asymptomatic to the World Health Organization, 164 of whom were HCW. Viral shedding studies of asymptomatic MERS infections have demonstrated the potential to transmit MERS-CoV to others.

Our results highlight the possibility for onward transmission of MERS-CoV from asymptomatic individuals. Screening of HCW contacts of confirmed MERS-CoV patients is currently recommended, but systematic screening of non-HCW contacts outside of health care facilities should be encouraged.

(Continue . . . )

The good news thus far is - despite nagging questions over the sensitivity of current surveillance and the role of undetected cases in the spread of the disease -  we've seen no signs of any sustained or efficient transmission of the MERS virus in the greater community.

The somewhat less-than-good-news is that the MERS virus continues to evolve, and may adapt more to a human host over time, and what we can say about its behavior now isn't guaranteed to last forever.