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MERS SARS-CoV-like KSA Surveillance Concerns
Recombinomics Commentary 15:30
June 20, 2013

Description of the Outbreak
Between April 1 and May 23, 2013, a total of 23 confirmed cases of human infection with MERS-CoV were identified in the eastern province of Saudi Arabia (Fig. S1 in the Supplementary Appendix). All confirmed cases and 11 probable cases were part of a single outbreak involving four health care facilities (Figure 1)

The above comments are from a New England Journal of Medicine paper which details a nocosomial MERS-CoV outbreak involving at least four hospitals in Al Hasa in eastern Kingdom of Saudi Arabi (KSA) – see map.  The detail in the paper contains many elements that are strikingly similar to nocosomial outbreaks linked to the SARS coronavirus in 2003 including infections of patients and health care workers (HCWs) by super spreaders which lead to extended transmission chains in multiple hospitals.

In the Al Hasa outbreak the index case (Patient A, 56M) is the likely source of infection of the super spreader (Patient C, 55M), who was hospitalized in an adjacent room, as well as one of his sons (patient O, 33M) and a nurse (patient R, 42F).

The super spread is the likely source for the infection of 7 patients in the dialysis unit (patient D, 59M; patient E, 24M; patient F, 87M; patient G, 77M; patient H, 62F; patient I, 58M) or ICU (patient J; 94M).  Five of these seven cases were the source of onward transmission involving 13 additional confirmed cases in four different hospitals (as depicted in Figure 2).

Although the confirmed cases described above define the spread of MERS-CoV between patients and HCWs in four hospitals, there were at least 9 additional cases which were classified as probable and not lab confirmed (as indicated above).  Although these cases are represented in Figure 1, which includes disease onset date and hospital, the relationship of these 9 cases with each other and the confirmed cases is far from clear, so the hospital transmission chains may be longer than represented in Figure 2 (which had three H2H2H2H2H chains).

Patients A and B are listed as cases which were infected in the community (see Figure 2 and supplement).  However, both cases had been hospitalized for 4 or 6 days, respectively, prior to disease onset, suggesting that they were infected in the hospital by unknown patients or HCWs, which would have extended the hospital transmission chain.

Moreover, neither case A or C were lab confirmed, even though both infections were fatal and case A was in the ICU for 7 days after disease onset (including intubation for the final 5 days) and case C was hospitalized for 8 days after disease onset, including 5 days in the ICU where he was intubated.  Thus, if these two key cases were not linked to additional pneumonia cases, it is likely that they would have never been reported, even though they were fatally infected with MERS-CoV.

In addition to the detail in the paper, more information on the index case and his older son (who was lab confirmed) were available from many media reports and videos (see CNN/Reuters clip in first 26 seconds), including an English language report covered by ProMED.  The confirmed son (Hesham Mohamed Al Bin Sheik) indicated is father (the index case, Mohamed Al Sheik) was infected in the hospital and the son developed symptoms 3 days after his father’s death.  A second son (Abdullah Mohamed Al Bin Sheik) also developed symptoms and was also hospitalized.  Media reports included pictures of both sons in their hospital beds, as well as news conferences when each was discharged.  Media reports indicated a daughter was also symptomatic, but she tested negative and recovered without hospitalization.  Thus, the transmission chain was longer than the linkage between the index cases and his confirmed son, and the number of recovered cases was higher than the one confirmed case.

The older son is one of only seven confirmed MERS-CoV KSA cases who has been discharged.  KSA has reported 32 deaths, which includes the vast majority of confirmed cases from the Al Hasa outbreak, which produces a case fatality rate of 82% for confirmed cases with outcomes (10 of the confirmed cases are hospitalized, but most are in critical condition and on life support).  The two milder unconfirmed cases in the family of the index case would lower this rate if they were confirmed, which is also likely for additional suspect cases cited in the paper.

However, in addition to the cases in the paper, they are likely many more infected cases among the hundreds or thousands of cases which have tested negative because the collection times of the samples were sub-optimal, or collections were limited to the upper respiratory tract, where viral RNA levels may be below detection limits.

The paper clearly shows that MERS-CoV is readily transmitted to patients and HCWs and the number of infected contacts is markedly higher than the small number of confirmed cases.  Many of these additional cases would be identified through antibody testing, as was seen in the Jordan ICU outbreak, which would also significantly lower the CFR, which is much higher in KSA than the Jordan ICU cluster or onward transmission cases outside of the Middle East.

The paper provides dramatic evidence for similarities between the spread of MERS-CoV and SARS-CoV in 2003, and raises serious concerns about potential infections and spread linked to Umrah associated with Ramadan beginning July 9, as well as the Hajj in KSA in October.

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