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Beta Coronavirus Surveillance Concerns
Recombinomics Commentary 14:00
February 14, 2013

Based on current but limited information, lower respiratory tract specimens (such as tracheal aspirates and bronchoalveolar lavage; see Table 1) appear to have the highest virus titre. Upper respiratory tract specimens are also recommended, especially when lower respiratory tract specimens cannot be collected.

The above comments from the latest (December 21) WHO update on novel betacornavirus sample collection provide some insight into test failures on symptomatic contacts of confirmed cases, and raise serious concerns that the 11 confirmed cases, as well as a similar number of cases which WHO has designated as probable, represent a serious undercount.  7 of the 11 confirmed cases are linked to three clusters.

The cluster involving the largest number of symptomatic hospitalized cases was reported last April in Jordan.  The cases were directly or indirectly linked to an ICU and all but one of the cases was hospitalized.  Two died (45F and 25M) and the SARS-like symptoms of those who survived raised significant concerns.  Samples were sent to labs in France and Egypt, but initial results were negative, since the novel betacornavirus is group 2c and distinct from prior human viruses, which were in group 1, 2a, or 2b and did not cross react with probes for the known isolates.

However, after the initial cases from Saudi Arabia and Qatar were diagnosed as infected with the new betacornavirus, sequences from those two patients were used to create new probes that targeted the novel virus.  Re-testing of samples from the Jordan cluster confirmed the virus in the two fatal cases.  Details on testing failures on the surviving cases have not been released.  However, the WHO guidelines described above raises concerns that the milder cases were negative because samples were collected from the upper respiratory tract, leading to false negatives. Therefore, testing issues and epidemiological data lead to the classification of these cases as probable.

Although WHO has withheld key information on this cluster, including the number of cases, disease onset dates, and precise relationships between the cluster members, media reports indicate that the two confirmed fatal cases died 7 days apart, and one of the symptomatic surviving cases was the son of the fatal index case (45F).

Similar testing issues were associated with the second cluster, which involved four relatives in Riyadh.  Two of the family members died, and initial test results, which involve use of the new probes, identified the virus in two of the cases (one fatal and one surviving).  Eventually, the virus was confirmed in the fatal index case, but the second surviving family member was not confirmed.  Like the negative cluster members in Jordan, the negative Saudi Arabia family member was also classified as a probable case, once again signaling false negative results for symptomatic contacts of confirmed cases.

In addition, contacts of the first confirmed case from Qatar, were also symptomatic.  However, the symptoms were mild and the cases self quarantined at home.  These symptomatic contacts also tested negative.

Thus, all confirmed cases have been severe cases who were hospitalized.  Most had renal failure and five of the eight cases with known outcomes have died.  The other three confirmed cases remain hospitalized, even though the first Qatar case developed symptoms five months ago.  The other two hospitalized cases formed the most recent cluster

Media reports have indicated the cases are a father (60M) and his son.  The father is on life support (connected to an ECMO machine) and the son is reported to have had an underlying condition.  However, the father developed symptoms in January in Saudi Arabia, while the son recently developed symptoms in the UK and had not recently traveled outside of the country, indicating he was infected while caring for his father.  Passengers on the flight from Saudi Arabia to the UK are under investigation as are health care workers linked to the father, but symptoms have not been reported in any contacts.

However, the linkage of most of the confirmed cases to other confirmed cases, as well as a large number of symptomatic contacts, including those classified as probable, raise serious concerns about testing of milder cases.

Milder cases would be expected to have a lower viral load in general and samples would generally be collected from the upper respiratory tract, which WHO has warned may have a lower concentration.  Moreover, testing has been focused on more severe cases with no known etiology.  However, the detection of H1N1pdm09 in the latest cluster index case raises concerns that severe cases would not be tested for the novel coronavirus if they are H1N1pdm09 confirmed. 

Thus, the co-infection has raised questions about the current case definition, which excludes cases with a known etiology.

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