One of the big unanswered questions about the MERS coronavirus is what role – if any – do asymptomatically infected individuals play in the spread of the virus? It’s a topic that we’ve looked at repeatedly over the past couple of years, but answers have been slow in coming.
Part of the problem has been that Saudi MOH – by their own admission – doesn’t treat RTPCR positive MERS-CoV cases as `real cases’ unless they are symptomatic.
As discussed previously, there are serious questions over how one defines `symptomatic’. Are `sniffles’ considered symptomatic? Malaise? Is there a specific fever threshold? Are non-respiratory symptoms (gastrointestinal) counted?
And quite frankly, we don’t know what level of symptomology is required for a carrier to be contagious. We’ve seen some evidence to suggest that mildly symptomatic - or even asymptomatic cases - may be able to pass on the virus (see Study: Possible Transmission From Asymptomatic MERS-CoV Case).
Last week, we saw the WHO Statement On The 10th Meeting Of the IHR Emergency Committee On MERS, that chastised the Saudi Response to MERS in unusually blunt terms, specifically mentioning their handling of asymptomatic cases:
The Committee further noted that its advice has not been completely followed. Asymptomatic cases that have tested positive for the virus are not always being reported as required.
Timely sharing of detailed information of public health importance, including from research studies conducted in the affected countries, and virological surveillance, remains limited and has fallen short of expectations.
Inadequate progress has been made, for example, in understanding how the virus is transmitted from animals to people, and between people, in a variety of settings. The Committee was disappointed at the lack of information from the animal sector.
All of which brings us to a new interim guidance document (dated July 27th, but I just discovered it last week), on the management of PRC positive, asymptomatic MERS cases.
Publication date: 27 July 2015
The clinical spectrum of Middle East respiratory syndrome coronavirus (MERS-CoV) infection ranges from asymptomatic infection to severe pneumonia with acute respiratory distress syndrome (ARDS) and other lifethreatening complications. This document provides a standardized approach for public health authorities and investigators at all levels to plan for and conduct investigations around confirmed and probable cases of MERS-CoV infection. It should be read in conjunction with other detailed guidance referenced throughout the text, such as current laboratory testing guidelines and study protocols. It will be updated as necessary to reflect increased understanding of MERS-CoV transmission and control.
You’ll obviously want to download, and review, the entire document (it is very short), but the following excepts illustrate how seriously the WHO treats the potential threat posed by asymptomatic cases.
The potential for transmission from asymptomatic RT-PCR positive persons is currently unknown. One study found that on day 12 after a first positive test, 30% of asymptomatic or mildly symptomatic persons (n=13) that had been in contact with a case remained positive for viral RNA in the upper respiratory tract4. Another study reported prolonged nasal virus RNA detection (more than 5 weeks) from one asymptomatic RT-PCR positive health-care worker5.
If feasible and as a cautious approach during outbreaks in health care settings, WHO recommends that all close contacts of confirmed cases of MERS-CoV infection6, especially health care workers and other inpatient hospital contacts (e.g. non-health-care workers, patients and visitors), be tested for MERS-CoV regardless of the presence of symptoms.
For now, the WHO strongly urges that asymptomatic PCR-positive MERS cases be isolated, and their contacts be monitored as well.
Until more is known, asymptomatic RT-PCR positive persons should be isolated, followed up daily for symptoms and tested at least weekly – or earlier, if symptoms develop – for MERS-CoV.
The place of isolation (hospital or home) shall depend on the health-care system’s isolation bed capacity, its capacity to monitor asymptomatic RT-PCR positive persons daily outside a health-care setting, and the conditions of the household and its occupants8.
Isolation should continue until two consecutive upper respiratory tract samples (e.g. nasopharyngeal [NP] and/or oropharyngeal [OP] swabs) taken at least 24 hours apart test negative on RT-PCR.
The guidance also offers the following advice on the management of Healthcare workers who are asymptomatically infected.
Asymptomatic RT-PCR positive health care workers – isolation and follow up
As noted above, the potential for transmission from asymptomatic RT-PCR positive individuals is still unknown. Therefore, asymptomatic health-care workers who are RT-PCR positive for MERS-CoV should be isolated and should not return to work until two consecutive upper respiratory tract samples (i.e. NP and/or OP swabs) taken at least 24 hours apart test negative on RT-PCR. Tests should be conducted at least weekly until a first negative test and then every 24-48 hours, so as to reduce isolation time for health-care workers.
Over the past five weeks Saudi Arabia has reported more than 2 dozen HCWs infected with MERS. At the same time, we’ve seen 100 cases or more described as having visited, or been admitted to a medical facility where MERS cases were being treated.
Rarely is direct contact with a confirmed symptomatic MERS case cited, with the WHO usually reporting: `Investigation of possible epidemiological links with the MERS-CoV cases admitted to their hospital or with shared health care workers is ongoing.’
How much of a role asymptomatic carriage of MERS-CoV may have played in those hospital acquired cases is unknown - but when large nosocomial outbreaks becomes the norm rather than the exception - it’s probably long past the time for a new game plan.