Tuesday, October 23, 2018

AJIC:Intermittent Positive Testing For MERS-CoV


One of the nagging questions regarding the incidence and spread of MERS-CoV on the Arabian Peninsula is just how well surveillance and testing programs are picking up cases.

In the past we've seen some analyses suggesting that only a fraction of MERS cases are likely diagnosed, including:

Last week, in JIDC: Atypical Presentation Of MERS-CoV In A Lebanese Patient, we looked at evidence that the virus can present with non-respiratory symptoms, and two months ago - in Evaluation of a Visual Triage for the Screening of MERS-CoV Patients - we looked at a highly critical review of the screening methods used by the Saudis for selecting patients for MERS testing.

Today we've another study - in press for the American Journal of Infection Control - that finds intermittent (positive-negative-positive) lab results for MERS in a substantial number of cases.
Middle East respiratory syndrome coronavirus intermittent positive cases: Implications for infection control
Sarah H. Alfaraj, MD, Jaffar A. Al-Tawfiq, MD,  Ziad A. Memish, MD, FRCPC, FACP, FRCPE, FRCPL

Middle East respiratory syndrome coronavirus (MERS-CoV) continues to be reported from the Kingdom of Saudi Arabia. Data on the phenomenon of intermittent positive results for MERS-CoV on reverse-transcription polymerase chain reaction (RT-PCR) with negative results in between are lacking.
Here we describe cases with intermittent positive MERS-CoV test results and highlight the required number of tests to rule out or rule in MERS-CoV infection based on a large retrospective cohort of patients with confirmed MERS-CoV.


This analysis included cases admitted between January 2014 and December 2017. The included patients had a minimum of 3 nasopharyngeal MERS-CoV RT-PCR tests for confirmation and needed 2 negative samples for MERS-CoV evaluated 48 hours apart with clinical improvement or stabilization apart to ensure clearance.


A total of 408 patients with positive MERS-CoV test results were treated at the referring hospital. We excluded 72 patients who had only 1 swab result available in the system and were treated in the initial years of the disease. Of the remaining 336 patients, 300 (89%) had a positive result after 1 swab, 324 (96.5%) had a positive result after 2 consecutive swabs, and 328 (97.6%) had a positive result after 3 consecutive swabs.
Of the total cases, 46 (13.7%) had a positive MERS-CoV test then a negative test, followed by positive test results.


Our data indicate that 2 to 3 nasopharyngeal samples are needed to produce the highest yield of positive results for MERS-CoV. In addition, 2 negative results 48 hours apart with clinical improvement or stabilization are needed to clear patients from MERS-CoV. Evaluation of the yield of sputum samples is needed to assess the effectiveness against nasopharyngeal swabs.

The most common (and least invasive) sampling method for respiratory infections  - and the only one cited in this abstract - is via Nasophyaryngeal (NP) swab. Mentioned in the conclusion, however,  is the need to evaluate the comparative effectiveness of sputum samples. 

The CDC's interim recommendations for specimen collection for MERS are more rigorous, calling for `Collection of all three specimen types (not just one or two of the three), lower respiratory, upper respiratory and serum specimens for testing using the CDC MERS rRT-PCR assay is recommended. '
You'll find the CDC's recommendations at the link below.
Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens from Patients Under Investigation (PUIs) for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) – Version 2.1
Inconsistent MERS test results could be the result of a number of factors, including: sub-optimal specimen collection, sensitivity issues with the laboratory test, or perhaps variations in viral shedding by the patient over time. 
In October of 2015, we saw one of South Korea's 180+ MERS patients relapse, and be put back into isolation, two weeks after being released from the hospital (see Korean Govt. Statement On MERS Patient `Relapse’ and Isolation)
While this is the only documented relapse with MERS I'm aware of, I imagine few are retested after leaving the hospital. We have seen patients with other infections - including Ebola & Zika - continue to harbor (and shed) viruses long after testing negative.

A subtle reminder that while `no' should always mean no - sadly - for lab tests, it isn't always so.