Background
Methods
Results
Epidemiologic studies
Author (year) | Country | Study period | No. of patients (M/F) Age of patients | Fatality rate | Contact/ comorbidity | Index related to infectivity | Index related to severity |
Ahmed (2017) [31] | Saudi Arabia | 2015–2017 | 537 (370/167) 55 ± 17.9 | 218/537 (40.6%) | • Comorbidity: 73.9% • Contacts - Hospital-acquired: 38.7% - Household: 9.9% - Camel: 25.3% - Unknown: 26.1% | • Onset to confirmation: 4 days (IQR: 2–7 days) | |
Alenazi (2017) [12] | Saudi Arabia | 2015 | 130 (66/64) 63.5 (community-acquired), 64.7 (healthcare-acquired), 40.1 (HCW) | 51/130 (39.2%) | • Contacts - Community-acquired: 20% - Healthcare-acquired: 46.9% - HCWs: 33.1% | • R - Hospital-acquired: 0.98 for 2nd, 0.64 for 3rd, 0.23 for 4th generation | |
El- Bushra (2017) [21] | Saudi Arabia | 2015 | 87 n.r. | n.r. | • Contacts - 20 primary, 39 first, 18 s, 7 third, 3 fourth generation | • Secondary attack rate/10,000: 42 (95% CI: 33–54) | |
Kim (2017) | South Korea | 2015 | 186 (111/75) 55 | 38/186 (19.9%) | • Contacts - Hospital (99.4%) - Household (0.6%) - Community (0%) • Comorbidity - 29/38 fatalities had underlying disease | ||
Park (2017) [23] | South Korea | 2015 | 25 (13/12) 71a (IQR: 38–86) | 25/11 (44.0%) | • Attack rate: 3.7% • Incubation period: 6.1 days | ||
Sha (2017) [29] | Middle East area/ South Korea | 2012–2016 | 683 (423/260) 50–60 (fatal), 38–46 (non-fatal) | 182 (26.6%) (Middle East: 25.9%, South Korea: 13.8%) | • Comorbidity - 67.9% in fatal, 22.2% in nonfatal cases | • Incubation period - 4.5–5 days in Middle East area - 6 days in South Korea | • Onset to confirmation - 8 days in fatal, 4 days in nonfatal in Middle East area - 4 days in fatal, 5 days nonfatal in South Korea • Onset to death - 11.5 days in Middle East area - 11 days in South Korea • Onset to discharge - 14 days in Middle East area - 17 days in South Korea |
Sherbini (2017) [32] | Saudi Arabia | 2014 | 29 (20/9) 45 ± 12 | 10 (34%) | • Comorbidities - Diabetes (31%) - Chronic kidney disease (27%) | • Symptoms to hospitalization: 2.9–5 days | |
Assiri (2016) [36] | Saudi Arabia | 2014–2015 | 38 (28/10) 51 (range 17–84) | 21/38 (55.3%) | • Contacts - 13 HCWs - 15 were associated with 1 dialysis unit | • Onset to death/discharge: 17 days (range 1.0–84.0) | |
Cho (2016) [5] | South Korea | 2015 | 82 (53/29) 57 (patients and visitors), 38 (HCW) | n.r. | • Contacts - Patients: 40.2% - Visitors: 50% - HCWs: 9.8% • Comorbidity - 24 (29%) had underlying disease | • Incubation period: 7 days (range: 2–17, IQR: 5–10) • Overall attack rate - Patients in the emergency room: 4% (30/ 675) - Visitors: 6% (38/683) | |
Halim (2016) [33] | Saudi Arabia | 2016 | 32 (20/12) 43.99 ± 13.03 | 14/32 (43.8%) | • From symptom to hospitalization - 5.3 ± 3.3 days • Total length of stay - 15 ± 3.6 days | ||
Liu (2016) | Taiwan | 2012–2015 | 1368 (883/476)a 49 (range: 2–90) | 35.6% (487/1368) • CFR 7.03% for HCW - 36.96% for non-HCW | • Contacts - Patients: 46.2% - Family members or visitors: 34.9% - HCW: 18.9% | • Onset to death - 13 (4–17) days for HCP - 12 (1–52) days for non-HCW • Onset to confirmation - 6 (1–14) days for HCP - 10 (1–21) days for non-HCW | |
Mohd (2016) [40] | Saudi Arabia | 2014–2015 | 80 (48/32) 40a | • 10% (8/80) | • Comorbidity - Not different from non-MERS groups | ||
Park (2016) [24] | South Korea | 2015 | 23 (13/10) 66a (range: 31–87) in hospital A; 74.5a (range: 60–82) in hospital B | 11/23 (47.8%) | • Generation - 23 in 2nd; 3 in 3rd | • Incubation period - 7.8 days (95% CI: 6.0–10.0) • Serial interval - 14.6 days (95% CI, 12.9–16.5) • Secondary attack rate - 15.8% in hospital A - 14.3% in hospital B | • Time to deathc - 12.5 days (IQR: 5.5–19) in hospital A - 11 days (IQR: 9–16) in hospital B |
Virlogeux (2016) [25] | South Korea | 2015 | 170 (98/72) 54.6 ± 16.2 | 36/170 (21%) | Incubation period: 6.9 days (95% CI: 6.3–7.5) | ||
Chowell (2015) [8] | Saudi Arabia, South Korea | 2013–2015 | 973 MERS and 7634 SARS cases n.r. | n.r. | • Contacts - 43.5–100% were linked to healthcare setting in MERS | R0 (95% CI) - MERS: 0.91 (0.36–1.44) - SARS: 0.95 (0.67–1.23) Infection rate of disease among HCWs: - MERS: 13.4–13.5% - SARS: 18.8–57.1% | |
Cowling (2015) [26] | South Korea | 2015 | 166 (101/65) 55.4 (range: 16–87) | 24/166 (14.5%) | • Contacts - 119 cases had contact with a confirmed case - 30/166 (18%) were healthcare personnel | • Incubation period: 6.7 days • Serial interval: 12.6 days. | |
KCDC (2015) [4] | South Korea | 2015 | 186 (111/75) 55a (IQR: 42–66) | 36/186 (19.4%) | • Contacts - 44.1% patients exposed in hospitals - 32.8% caregivers - 13.4% HCWs • Comorbidities - 45.2% | • Incubation period - 6.83 days (95% CI: 6.31,7.36) | |
Ki (2015) [3] | South Korea | 2015 | 186 (111/75) 50s in men and 60s in women | 36/186 (19.4%) | • Generation - 28 in 1st (15.1%); 125 in 2nd (67.2%); 32 in 3rd (17.2%); 2 were not certain • Contacts - Same hospital: 82 (44%) - Family/healthcare aides/visitors: 71 (38%) - HCWs: 31 (17%) • Comorbidities - 77 (41%) had underlying diseases | • Incubation period: 6.5 days (2–16 days). | • From symptom onset to confirmation: 5 days (0–17 days) • From symptom onset to discharge from the hospital: 20 days (8–41 days). • From symptom onset to death: 13 days (1–41 days) |
Ministry of Health, South Korea (2016) [27] | South Korea | 2015 | 186 (111/75) 50s (21.6%), 60s (19.9%) | 38/186 (20.4%) | • Generation - 28 in 2nd, 120 in 3rd, 26 in 4th, 11 in unclear/ unknown • Contacts - 82 patients in hospital - 63 family members/ visitors - 39 HCWs - 2 others | • Incubation period - 6.83 days (95% CI: 6.31–7.36) | |
Noorwali (2015) [37] | Saudi Arabia | 2014 | 261 (171/90) n.r. | 110/261 (42%) | • Contacts - 84 HCWs - 177 non-HCWs | ||
Park (2015) [28] | South Korea | 2015 | 37 (21/16) 51.7 (range: 24–79) | 6/37 (16.2%) | • Generation - 1 in 1st, 25 in 2nd, 11 in 3rd • Contacts - 20 patients - 12 relatives of patients - 3 HCWs - 1 unrelated visitors • Comorbidities - 5/6 in fatal, 3/31 in nonfatal | Incubation period - 6 days (95% CI: 4–7 days) | • Symptom onset to confirmation - 6.5 days (95% CI: 4–9) for all cases - 9 days for second cases - 4 days for third cases |
Drosten (2014) [22] | Saudi Arabia | 2013 | 26 (17/9) 55a (range: 2–83) | 18/26 (69.2%) | • Contacts - 280 household contacts | • Secondary transmission: 4% | |
Assiri (2013) [7] | Saudi Arabia | 2012–2013 | 47 (36/11) n.r. | 28/47 (60%) | • Comorbidities - 45 had underlying comorbid medical disorders (96%) | • Incubation period: 5.2 days | |
Breban (2013) [9] | Multiple areas | 2012–2013 | 64 (44/17) b 56a (IQR 41–68.5) | 38/64 (59.4%) | n.r. | • R0: 0.69 (95% CI 0.50–0.92) | |
Oboho (2012) [38] | Saudi Arabia | 2014 | 255 (174/81) 45a (IQR:30–59) | 93 (36.5%) | • Contacts - 40 of 191 symptomatic were HCWs (20.9%) | n.r. | |
Penttinen (2013) [41] | Multiple areas | 2012–2013 | 133 (51/77) b n.r. | 45% | • Contacts - 14 primary cases, 129 cases on transmission | • Proportion to ICU: 60 cases (45%) | |
Estimating the index of infectivity and severity using secondary data | |||||||
Author (year) | Country | Study period | Indexes related to infectivity | Index related to severity | |||
Chang (2017) [18] | South Korea | 2015 | • R0 - 8.097 | ||||
Choi (2017) [15] | South Korea, Saudi Arabia | 2015 | • R0 - 3.9 in South Korea - 1.9–3.9 in Saudi Arabia (1.9 in Riyadh, 3.9 in Jeddah) | ||||
Eifan (2017) [13] | Saudi Arabia | 2013–2015 | • R - 0.85–0.97 | ||||
Zhang (2017) [17] | South Korea | 2015 | • R - 2.5–7.2 | ||||
Kim (2016) [16] | South Korea | 2015 | • R0 - 5.4 (95% CI: 4.61–6.19) in period 1 - 0.14 (95% CI: 0.04–0.26) in period 2 • Infectivity of hospitalized patients - 22 (95% CI: 18.73–25.27) in period 1 - 1 (95% CI: 0.16–1.84) in period 2 | ||||
Lessler (2016) [39] | Saudi Arabia | 2012–2014 | • CFR: 22% (95% CI: 18, 25) | ||||
Kucharski (2015) [10] | Multiple areas | 2012–2013 | • R0: 0.47 (95% CI: 0.29–0.80) | ||||
Mizumoto (2015) [35] | South Korea | 2015 | • CFR: 20.0% (95% CI): 14.6, 26.2). | ||||
Xia (2015) [19] | South Korea | 2015 | • R0 - 4.422 in early stage - 0.385 with control | from hospitalization to death: 15.16 (0–42) (mean, range) | |||
Cauche-mez (2014) [6] | Multiple areas | 2012–2013 | • Incubation period - 5.5 (95% CI: 3.6–10·2) • R0: 0.8–1.3 | • CFR - 74% (95% CI: 49–91) for first cases - 21% (95% CI: 7–42) for second cases | |||
Chowell (2014) [11] | Saudi Arabia | 2013 | • R overall - 0.45 (95% CI: 0.29, 0.61) under the surveillance-bias scenario - 0.88 (95% CI: 0.58, 1.20) under the differential-transmissibility scenario | ||||
Poletto (2014) [14] | Middle East area | 2012–2013 | • R: 0.50 (95% CI: 0.30–0.77) |
R value
Attack rate
Incubation period
Serial interval
Days from onset to confirmation
Days from onset to hospitalization
Mortality
Days from onset to discharge
Days from onset to death
Risk factors related to mortality
Author (year) | Study period | No. of participants (Total/death) | Country | Predictors | Significant factors |
---|---|---|---|---|---|
Risk factors of infection
| |||||
Alraddadi (2016) [42] | 2014 | 146 (30 cases, 116 controls) | Saudi Arabia | Travel history, animal-related exposure, food exposure, underlying health conditions and behaviors | Direct dromedary exposure in 2 weeks, concomitant with diabetes or heart disease, currently smoking tobacco |
Hastings (2016) [43] | 2014 | 78 | Saudi Arabia | Nationality, sex, age group, hospital setting, outbreak week | Older age, outbreak week, nationality |
Risk factors of transmission (spreader)
| |||||
Kang (2017) [44] | 2015 | 186 | South Korea | Age, sex, comorbidity, symptoms, laboratory test, clinical outcome, phase in transmission, incubation period, symptom onset to isolation, non-isolated in-hospital days, symptom onset to diagnosis | Fever, chest X-ray abnormality in > 3 lung zones, more non-isolated in-hospital days |
Kim (2017) [34] | 2015 | 186 | South Korea | Underlying respiratory disease, cycle threshold value, symptom onset to diagnosis, no. of contacts, hospitalization or emergency room before isolation | Lower cycle threshold value, hospitalization or emergency room visit before isolation |
Majumder (2017) [45] | 2015 | 186 | South Korea | Sex, age, comorbidity, case class (HCW, visitor, patient), case outcome (recovered/deceased) | Deceased case outcome |
Risk factors of severity
| |||||
Zhao (2017) [46] | 2014–2015 | 21 | Saudi Arabia | CD4 T cell, CD8 T cell, PRNT50 | Higher PRNT50, higher CD4 T cell response |
Ko (2016) [48] | 2015 | 45 | South Korea | Demographics (age, sex, BMI, underlying disease), symptoms (fever, myalgia, cough, sputum, diarrhea), laboratory test (white blood cell, hemoglobin, thrombocytopenia, lymphopenia, albumin, bilirubin, aspartate transaminase, alanine transaminase, blood urea nitrogen, creatinine, C-reactive protein, lactate dehydrogenase, threshold cycle value of PCR) | • Pneumonia development: older age, fever, thrombocytopenia, lymphopenia, C-reactive protein ≥2 mg/dL, lower threshold cycle value of PCR < 28 • Respiratory failure: male, hypertension, low albumin concentration, thrombocytopenia, lymphopenia, C-reactive protein |
Feikin (2015) [47] | 2014 | 102 | Saudi Arabia | Age, sex, underlying illness, week of specimen collection, MERS-CoV virus load | • Severity: older age, underlying illness, high MERS-CoV virus load • Mortality: older age, underlying illness, high MERS-CoV virus load |
Saad (2014) [49] | 2012–2014 | 70 | Saudi Arabia | Age, gender, occupation, acquisition of infection, comorbidity, radiological findings, concomitant infections, laboratory abnormalities | • ICU care: concomitant infection, decreased albumin • Mortality: older age |
Risk factors of mortality
| |||||
Adegboye (2017) [50] | 2012–2015 | 959/317 (33%) | Saudi Arabia | Sex, age, comorbidity, animal contact, camel contact, HCW, secondary contact, clinical experience | Older age, comorbidity, non-HCW, fatal clinical experience |
Ahmed (2017) [51] | 2014–2016 | 660/197 (29.8%) | Saudi Arabia | Age, sex, nationality, symptomatic, HCW, severity, source of infection, regions | • 3-day mortality: older age, non-HCW, hospital-acquired infection • 30-day mortality: older age, non-HCW, pre-existing illness, severity, hospital-acquired infection |
Sha (2017) [29] | 2012–2016 | 216/56 (25.9%) in Middle East area, 174/24 (13.8%) in South Korea | Middle East Area/South Korea | Age, sex, exposure to camel or other animals, comorbidity, disease progress (days) | Older age (Middle East, South Korea), high comorbidity (Middle East, South Korea), longer days from onset to confirmation of infection (Middle East), longer hospitalized days (Middle East) |
Sherbini (2017) [32] | 2014 | 29/10 (34.5%) | Saudi Arabia | Sex, symptoms, history of chronic disease, duration of disease before hospitalization, vital signs, temperature, blood pressure | Older age, gastrointestinal symptoms, longer duration of symptoms prior to hospitalization, diabetes mellitus, chronic kidney disease, smokers, lower blood pressure |
Nam (2017) [56] | 2015 | 25/11 (44%) | South Korea | - Epidemiologic (age, sex, hospital, inpatient, staying in the same room as the index case, smoking, preexisting pneumonia, chronic lung disease, incubation period) - Clinical symptom - Laboratory examinations | Male, pre-existing pneumonia, smoking history, incubation period of less than 5 days, leukocytosis, abnormal renal function at diagnosis, respiratory symptoms. |
Yang (2017) [52] | 2012–2016 | 1743/559 (32.1%) | Multiple area | Age, sex, comorbidity, epidemic period, contact pattern, country | Older age, comorbidity, epidemic later period |
Almekhlafi (2016) [57] | 2012–2014 | 31/23 (74.2%) | Saudi Arabia | Age, comorbidity, initial manifestations, procedures (non-invasive ventilation, invasive ventilation, continuous renal replacement therapy), need for vasopressor | Need for vasopressors |
Alsahafi (2016) [53] | 2012–2015 | 924/ 425 (46%) | Saudi Arabia | Age, sex, comorbidities, location of acquisition (household, inpatient, HCW) | Older age, cardiac disease, cancer, household patients, HCW |
Virlogeux (2016) [25] | 2015 | 170/36 (21%) | South Korea | Age, sex, incubation period | Older age, shorter incubation period |
Cha (2015) | 2015 | 30/5 (16.7%) | South Korea | Age, sex, chronic kidney disease, diabetes, hypertension, comorbidity, estimated glomerular filtration rate, mechanical ventilator | None |
Majumder (2015) [54] | 2015 | 159/35 (22%) | South Korea | Five potential covariates were analyzed: sex, age, concurrent health condition status, health care worker status, time from onset to diagnosis | Older age, pre-existing concurrent health conditions |
KCDC (2015) [4] | 2015 | 186/36 (19.4%) | South Korea | Sex, age, case classification, respiratory disease, diabetes, cardiac disease, chronic kidney disease, malignancy | Older age, underlying respiratory disease |
Das (2015) [58] | 2014 | 55/19 (35%) | Saudi Arabia | Age, chest radiographic score, absolute lymphocyte count, no. of comorbidities, congestive heart failure, hypertension, diabetes | Chest radiographic score |
Al Ghamdi (2016) [59] | 2014 | 51/19 (37%) | Saudi Arabia | Beta interferon, alpha interferon, hydrocortisone, Ribavirin, APACHE score | APACHE score |
Choi (2016) [55] | 2016 | 186/33 (17.7%) | South Korea | Age, sex, HCW, coexisting medical condition, symptoms at admission, vital signs at admission, laboratory abnormalities at admission, treatment | Age ≥ 55 years, occurrence of dyspnea during the disease course, presence of concomitant medical conditions including diabetes or chronic lung disease, systolic blood pressure < 90 mmHg at admission, leukocytosis at admission, use of mechanical ventilation |
Factors related to MERS infection
Factors related to MERS transmission
Factors related to MERS severity
Factors related to MERS mortality
Epidemiological index of MERS between the Middle East area and South Korea
Index | Saudi Arabia/Middle East area | South Korea (Study including all Korean cases) |
---|---|---|
Mortality | 22–69.2% (Two of ten studies reported lower mortality than 20%) | 14.5–47.8% (20.4%) |
R-value | 0.45–0.98 (Only one study reported 1.9–3.9) | • 2.5–8.1 • Less than 1 in later period or with control intervention |
Attack rate | 0.42–4% | 3.7–15.8% |
Incubation period | 4.5–5.2 days | 6–7.8 days (6.83 days) |
Serial interval | – | 12.6–14.6 days |
Days from onset to confirmation | 4–8 days | 4–6.5 days (5 days) |
Days from onset to hospitalization | 2.9–5.3 days | – |
Days from onset to discharge | 14–17 days | 17–20 days |
Days from onset to death | 11.5–17 days | 11–13 days |