Friday, 26 July 2013

Biggest Middle East Respiratory syndrome coronavirus (MERS-CoV) case study to date

Assiri and colleagues from the Kingdom of Saudi Arabia (KSA) today described, in The Lancet, the clinical characteristics of 47 cases of MERS-CoV. The largest detailed analysis of MERS-CoV cases to date.

This report includes 20 cases more than that 27 reported previously by these authors, along with additional information on the first 27. 

The paper opened by noting that clinical data are scant and suggest that's because of the small number of cases since it appeared 15 months ago. The case numbers include all 90 known MERS-CoV cases. 1 new case was announced today.

Some key points from the paper...
  • Nasopharyngeal swabs, tracheal aspirates and bronchoalveolar lavage specimens were taken by attending doctors
  • Since June 15,  MERS-CoV has been detected in 16 ( 17.5% of the current tally of 91 cases) asymptomatic people as a result of screening contacts
  • The authors note the need for rapid and accurate antibody tests to apply to case-control studies
  • 45/47 (96%) of  cases had 1 or more comorbidities with diabetes, chronic kidney/heart disease and hypertenstion the most common among surviving cases
  • All but 2/47 were citizens of the KSA
  • Fever and cough were found in >83% of cases with shortness of breath in 72%
  • Nausea, vomiting  abdominal pain and diarrhoea were present in 17-26% of cases
  • Runny nose was rare (4%), sore throat (21%) and cough were occasional (dry-47%; productive-36%) and headache, chest pain and coughing blood were present in 13-17% of cases
  • Chest X-Ray was abnormal in all cases
  • Neither blood nor respiratory sample from any case had another virus or bacterium detected. That's an extraordinary finding. Co-detections around 20% or more are the norm, not the exception. This might indirectly flag the extent of the antiviral inflammatory response being mounted to MERS-CoV
  • Time between symptom onset and sampling averaged  about 72-hours
  • Real-time RT-PCR threshold values fro 37/45 samples ranged form 20-40
  • Cellular laboratory findings revealed mostly normal neutrophil counts while just over a third had low platelet and/or white blood cells; lactate dehydrogenase and aspartate aminotransferase levels were raised in half of the cases
  • The authors identify a large number of knowledge gaps and some that require urgent research including finding the host, source of exposure to it, what are the excretion and transmission dynamics, how best to sample, contain and manage patients

The authors write of a current absence of clinical and laboratory features to distinguish MERS-CoV cases from other respiratory infections. We have had very good viral detection methods for a while now, so its unclear which other tests they mean when they say "no tests are available" to exclude MERS (the disease) among patients with fever. That could also be said of any respiratory disease due to virus infection. For example, we know much about HCoV-NL63 and HPIV-3, but if a child presented with croup (associated with both viruses), we could not reliably distinguish which caused the disease using signs and symptoms alone. This is a problem common to all respiratory viral infections, not simply those due to MERS-CoV, and is best addressed using an extended panel of assays. Resources permitting.

Could anything biochemically, haematologically or clinically distinguish a patient as being infected by MERS-CoV rather than any other virus? Surely we are beyond trying to do that?

The paper does not mention whether there are sera available from all these cases to address the stated need for good, and well-validated, antibody-detection (serological) assays. As stated by others previously, KSA has the best sample population to make this happen. Without validation (testing antibody-detection assays using known positive as well as negative patent sera), the delay in producing a reliable assay and in getting a better grasp of who has been previously exposed to the MERS-CoV, what the real proportion of fatal cases is and the efficiency with which an infected person to pass on the virus (basic reproduction number, R0).....remains out of reach.