Abdullah M. Assiri

BACKGROUND: In September 2012, the World Health Organization reported the first cases of pneumonia caused by the novel Middle East respiratory syndrome coronavirus (MERS-CoV). We describe a cluster of health care-acquired MERS-CoV infections. METHODS: Medical records were reviewed for clinical and demographic information and determination of potential contacts and exposures. Case patients and contacts were interviewed. The incubation period and serial interval (the time between the successive onset of symptoms in a chain of transmission) were estimated. Viral RNA was sequenced. RESULTS: Between April 1 and May 23, 2013, a total of 23 cases of MERS-CoV infection were reported in the eastern province of Saudi Arabia. Symptoms included fever in 20 patients (87%), cough in 20 (87%), shortness of breath in 11 (48%), and gastrointestinal symptoms in 8 (35%); 20 patients (87%) presented with abnormal chest radiographs. As of June 12, a total of 15 patients (65%) had died, 6 (26%) had recovered, and 2 (9%) remained hospitalized. The median incubation period was 5.2 days (95% confidence interval [CI], 1.9 to 14.7), and the serial interval was 7.6 days (95% CI, 2.5 to 23.1). A total of 21 of the 23 cases were acquired by person-to-person transmission in hemodialysis units, intensive care units, or in-patient units in three different health care facilities. Sequencing data from four isolates revealed a single monophyletic clade. Among 217 household contacts and more than 200 health care worker contacts whom we identified, MERS-CoV infection developed in 5 family members (3 with laboratory-confirmed cases) and in 2 health care workers (both with laboratory-confirmed cases). CONCLUSIONS: Person-to-person transmission of MERS-CoV can occur in health care settings and may be associated with considerable morbidity. Surveillance and infection-control measures are critical to a global public health response.

BACKGROUND: Strategies to contain the Middle East respiratory syndrome coronavirus (MERS-CoV) depend on knowledge of the rate of human-to-human transmission, including subclinical infections. A lack of serologic tools has hindered targeted studies of transmission. METHODS: We studied 26 index patients with MERS-CoV infection and their 280 household contacts. The median time from the onset of symptoms in index patients to the latest blood sampling in contact patients was 17.5 days (range, 5 to 216; mean, 34.4). Probable cases of secondary transmission were identified on the basis of reactivity in two reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays with independent RNA extraction from throat swabs or reactivity on enzyme-linked immunosorbent assay against MERS-CoV S1 antigen, supported by reactivity on recombinant S-protein immunofluorescence and demonstration of neutralization of more than 50% of the infectious virus seed dose on plaque-reduction neutralization testing. RESULTS: Among the 280 household contacts of the 26 index patients, there were 12 probable cases of secondary transmission (4%; 95% confidence interval, 2 to 7). Of these cases, 7 were identified by means of RT-PCR, all in samples obtained within 14 days after the onset of symptoms in index patients, and 5 were identified by means of serologic analysis, all in samples obtained 13 days or more after symptom onset in index patients. Probable cases of secondary transmission occurred in 6 of 26 clusters (23%). Serologic results in contacts who were sampled 13 days or more after exposure were similar to overall study results for combined RT-PCR and serologic testing. CONCLUSIONS: The rate of secondary transmission among household contacts of patients with MERS-CoV infection has been approximately 5%. Our data provide insight into the rate of subclinical transmission of MERS-CoV in the home.

BACKGROUND: The Middle East respiratory syndrome (MERS) coronavirus causes isolated cases and outbreaks of severe respiratory disease. Essential features of the natural history of disease are poorly understood. METHODS: We studied 37 adult patients infected with MERS coronavirus for viral load in the lower and upper respiratory tracts (LRT and URT, respectively), blood, stool, and urine. Antibodies and serum neutralizing activities were determined over the course of disease. RESULTS: One hundred ninety-nine LRT samples collected during the 3 weeks following diagnosis yielded virus RNA in 93% of tests. Average (maximum) viral loads were 5 × 10(6) (6 × 10(10)) copies/mL. Viral loads (positive detection frequencies) in 84 URT samples were 1.9 × 10(4) copies/mL (47.6%). Thirty-three percent of all 108 serum samples tested yielded viral RNA. Only 14.6% of stool and 2.4% of urine samples yielded viral RNA. All seroconversions occurred during the first 2 weeks after diagnosis, which corresponds to the second and third week after symptom onset. Immunoglobulin M detection provided no advantage in sensitivity over immunoglobulin G (IgG) detection. All surviving patients, but only slightly more than half of all fatal cases, produced IgG and neutralizing antibodies. The levels of IgG and neutralizing antibodies were weakly and inversely correlated with LRT viral loads. Presence of antibodies did not lead to the elimination of virus from LRT. CONCLUSIONS: The timing and intensity of respiratory viral shedding in patients with MERS closely matches that of those with severe acute respiratory syndrome. Blood viral RNA does not seem to be infectious. Extrapulmonary loci of virus replication seem possible. Neutralizing antibodies do not suffice to clear the infection.