1.HOSPITAL OUTBREAK OF MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS JOSE SOCRATES DEE M. EVARDONE YEAR LEVEL I IM DEPARTMENT, CDUH

2. HOSPITAL OUTBREAK OF MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS AUGUST 1, 2013 VOL. 369 NO. 5 PAGES 407-416 ABDULLAH ASSIRI, M.D., ALLISON MCGEER, M.D., TRISH M. PERL, M.D., ET AL JOSE SOCRATES DEE M. EVARDONE YEAR LEVEL I IM DEPARTMENT, CDUH 3. Study Overview A novel coronavirus (MERS-CoV) is causing severe disease in the Middle East. In this report on a hospital outbreak of MERS-CoV infection, 23 confirmed cases and evidence of person-to-person transmission were identified. The median incubation period was 5.2 days. 4. Objectives: To be able to review about Coronaviruses, Basic Epidemiology To be able to understand about MERS Cov 1) Virology 2) Epidemiology 3) Case definitions 4) Clinical manifestations 5) Diagnosis 6) Treatment 7) Prevention 8) Outcomes 9) Travel Recommendations 5. Methods 6. Setting: The governorate of Al-Hasa, eastern Saudi Arabia Serves a mixed urban and rural population of 1.1 million persons. 1) Hospital A is a 150-bed general hospital in the largest urban area (Al- Hufuf). The dialysis unit, which cares for 43 patients in two shifts per day, is an open unit with 16 beds spaced 1.3 to 1.5 m apart. The intensive care unit (ICU) contains two open 6-bed bays. 2)Hospitals B and C are also general hospitals in Al-Hufuf. Hospital D is a regional referral hospital located 160 km from Al-Hufuf. METHODS: The governorate of Al-Hasa, eastern Saudi Arabia Serves a mixed urban and rural population of 1.1 million persons. Hospital A is a 150-bed general hospital in the largest urban area (Al- Hufuf). The dialysis unit: 43 patients, 2 shifts/day, open unit with 16 beds spaced 1.3 to 1.5 m apart. The ICU contains two open 6-bed bays. Hospitals B and Hospital C are general hospitals in Al-Hufuf. Hospital D is a regional referral hospital located 160 km from Al-Hufuf. 7. METHODS: Definitions: Confirmed case of MERS-CoV infection: 1) laboratory evidence of MERS-CoV 2) either fever and at least one respiratory symptom or two respiratory symptoms without another identifiable cause. Probable case of MERS-CoV infection: 1) if he or she was a household, family, or health care contact of a person with a confirmed case 2) if pneumonia developed without another confirmed cause 3) either laboratory testing for MERS-CoV was not performed or a single test was negative and no other specimens were available for testing. 8. METHODS: Definitions: The date of onset: febrile patients: the first day of fever that persisted for more than 48 hours afebrile patients: the first day of new cough or shortness of breath. Exposed patients: had any face-to-face contact with a symptomatic patient who had a confirmed or probable case, 1) Was in the same hospital room or ward as a symptomatic case patient >1hr 2) Moved into a bed vacated by a symptomatic case patient 3) Was being cared for by a health care worker who was also caring for a symptomatic case patient, or 4) Was sharing hospital equipment with a symptomatic case patient. 9. METHODS: Laboratory Surveillance: September 2012, the Saudi Arabian Ministry of Health requested that all patients with pneumonia requiring admission to the ICU be tested for MERS-CoV. Throat-swab (Eurotubo, Deltalab), sputum, tracheal-aspirate, or bronchoalveolar- lavage placed in viral transport medium (Vircell), stored at 28C, and transported within 72 hours to the Ministry of Health regional reference laboratory in Jeddah, Saudi Arabia, where they were subjected to real-time reverse-transcriptasepolymerase- chain-reaction (RT-PCR) assays totest for MERS-CoV.20 For all patients, the results of RT-PCR tests were confirmed by measuring cycle- threshold values for viral load. 10. METHODS: Identification of Clusters, Collection of Case Data, and Assessment of Exposure Hospital A initiated active surveillance for pneumonia on April 20, 2013, and conducted a retrospective review of in-hospital deaths and cases of pneumonia from March 1 through April 19. They also reviewed the medical charts of patients with confirmed MERS-CoV infection to identify symptoms, laboratory findings, and clinical course. The Ministry of Health interviewed household contacts of patients with confirmed MERS-CoV infection and followed them for 14 days after exposure. 11. METHODS: Identification of Clusters, Collection of Case Data, and Assessment of Exposure Mapped confirmed and probable MERSCoV cases in time and in space within health care facilities. For each case, we identified potential exposures, with the assumption that face-to-face contact or time spent in the same area conferred a greater risk than shared caregivers, which in turn conferred a greater risk than shared equipment. No assumptions were made about incubation periods. Three of the authors reviewed potential exposures independently; when more than one potential exposure was possible, the most likely source of exposure was identified by consensus among those authors and an additional author. The corresponding author vouches for the accuracy and completeness of the data. 12. METHODS: Sequencing and Phylogenetic Analysis: Full-genome sequences were obtained from specimens from four patients (Patients I, J, K, and V) 13. METHODS: Statistical Analysis: They calculated empirical cumulative density functions of the incubation period and serial intervals by computing the cumulative fraction of all observations that fell below each observed value in the respective data sets. They estimated the incubation period by identifying the earliest and latest time of possible exposure and the time of symptom onset for each case. Treating these times as interval-censored estimates of the incubation period for each person, we fit a log-normal distribution to these data using maximum-likelihood techniques. We then examined the robustness of our estimates with multiple definitions of onset and with the exclusion of particular cases. 14. METHODS: Statistical Analysis: They estimated the serial interval by identifying the times of symptom onset in the patient and in the person who transmitted the infection (infectedinfector pairs) and then fitting a lognormal distribution to these interval-censored They estimated the medians and 5th and 95th percentiles of the incubation period and the serial interval using the quantiles of the lognormal distribution fit to each data 15. Results 16. RESULTS: Description of the Outbreak April 1 and May 23, 2013, a total of 23 confirmed cases of human infection with MERSCoV were identified in the eastern province of Saudi Arabia 17. RESULTS: A: Illness in Patients at Hospital A 1) Community Introductions 2) Hemodialysis Unit 3) ICU 4) Medical Ward B: Illness in Staff Members at Hospital A C: Illness in Family Members D: Illness with Onset in Other health care facilities 18. RESULTS: 19. RESULTS: Demographic and Clinical Features 20. RESULTS: Demographic and Clinical Features median time from the onset of symptoms to ICU admission = 5 days (range, 1 to 10) median time to the need for mechanical ventilation = 7 days (range, 3 to 11) median time to death = 11 days (range, 5 to 27) 21. RESULTS: Transmission, Incubation Period, and Serial Interval One patient transmitted the infection to seven persons, one patient transmitted the infection to three persons, and four patients transmitted the infection to two persons each. The incubation period of confirmed cases was 5.2 days (95% confidence interval [CI], 1.9 to 14.7); distributions that were fit to our observed data indicated that 95% of infected patients would have an onset of symptoms by day 12.4 (95% CI of 95th percentile, 7.3 to 17.5), whereas 5% would have an onset of symptoms by day 2.2 (95% CI of 5th percentile, 1.2 to 3.1). We estimated that the serial interval was 7.6 days (95% CI, 2.5 to 23.1) (Fig. 3). The distributions that were fit to our observed data indicate that the serial interval was less than 19.4 days in 95% of cases (95% CI of 95th percentile, 11.7 to 27.0) and less than 3.0 days in 5% of cases (95% CI of 5th percentile, 1.8 to 4.2). 22. RESULTS: Sequencing and Phylogenetic Analysis Phylogenetic analysis of the four MERS-CoV genomes showed that the viruses form a monophyletic clade with a bootstrap support of 100% 23. Discussion 24. LABORATORY-CONFIRMED MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS INFECTION, APRIL MAY 2013.Characteristics Patients with confirmed cases (n=23) Male sex no. (%) 17 (74) Age yr Median 56 Range 2494 Age 50 yr no. (%) 17 (74) Age 65 yr no. (%) 6 (26) Obesity no./total no. (%)* 5/21 (24) Underlying Illness no. (%) End-stage renal disease 12 (52) Diabetes mellitus 17 (74) Cardiac disease 9 (39) Lung disease, including asthma 10 (43) Immunosuppressive condition other than renal disease 0 Symptoms before presentation no. (%) Fever 20 (87) Cough 20 (87) Shortness of breath 11 (48) Gastrointestinal symptoms Any 8 (35) Vomiting 4 (17) Diarrhea 5 (22) 25. LABORATORY-CONFIRMED MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS INFECTION, APRIL MAY 2013. 0 39% 43% 52% 74% 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 Immunosuppressive condition other than renal disease Cardiac disease Lung disease, including asthma End Stage Renal Disease Diabetes mellitus Underlying Illness Underlying Illness 26. LABORATORY-CONFIRMED MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS INFECTION, APRIL MAY 2013.Characteristics Patients with confirmed cases (n=23) Male sex no. (%) 17 (74) Age yr Median 56 Range 2494 Age 50 yr no. (%) 17 (74) Age 65 yr no. (%) 6 (26) Obesity no./total no. (%)* 5/21 (24) Underlying Illness no. (%) End-stage renal disease 12 (52) Diabetes mellitus 17 (74) Cardiac disease 9 (39) Lung disease, including asthma 10 (43) Immunosuppressive condition other than renal disease 0 Symptoms before presentation no. (%) Fever 20 (87) Cough 20 (87) Shortness of breath 11 (48) Gastrointestinal symptoms Any 8 (35) Vomiting 4 (17) Diarrhea 5 (22) 27. TABLE 1. CHARACTERISTICS AND SYMPTOMS OF PATIENTS WITH LABORATORY-CONFIRMED MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS INFECTION, APRIL MAY 2013. 17% 22% 35% 48% 87% 87% 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% GI {Vomiting} (4) GI {Diarrhea} (5) GI {Any} (8) Shortness of breath (11) Fever (20) Cough (20) Symptoms before presentation GI {Vomiting} (4) GI {Diarrhea} (5) GI {Any} (8) Shortness of breath (11) Fever (20) Cough (20) 28. TABLE 1. CHARACTERISTICS AND SYMPTOMS OF PATIENTS WITH LABORATORY-CONFIRMED MIDDLE EAST RESPIRATORY SYNDROME CORONAVIRUS INFECTION, APRIL MAY 2013. (CONT..)Characteristics Patients with confirmed cases (n=23) Laboratory testing at presentation no./total no. (%) Abnormal white-cell count 5/23 (22) Abnormal platelet count 5/23 (22) Elevated aspartate aminotransferase 3/13 (23) Oxygen saturation