Baseline clinical characteristics, viral load, antibody titre, cytokine/chemokine and outcomes in 30 patients with Middle East respiratory syndrome (MERS)
| Total (n=30) | Survivors (n=24) | Non-survivors (n=6) | p Value | |
| Age (years), mean ± SD | 49±13 | 46±13 | 59±8 | 0.03 |
| Male gender | 19 (63) | 14 (58) | 5 (83) | 0.37 |
| Healthcare workers | 8 (27) | 7 (29) | 1 (17) | >0.99 |
| Generations of secondary infection* | ||||
| Second generation | 2 (7) | 2 (8) | 0 | >0.99 |
| Third generation† | 22 (73) | 17 (71) | 5 (83) | >0.99 |
| Fourth generation | 6 (20) | 5 (21) | 1 (17) | >0.99 |
| Underlying disease | ||||
| None | 19 (63) | 15 (63) | 4 (67) | >0.99 |
| Diabetes mellitus | 4 (13) | 3 (13) | 1 (17) | >0.99 |
| Hypertension | 6 (20) | 4 (17) | 2 (33) | 0.57 |
| Chronic kidney disease | 1 (3) | 1 (4) | 0 | >0.99 |
| Chronic heart disease | 1 (3) | 1 (4) | 0 | >0.99 |
| Chronic lung disease | 1 (3) | 0 | 1 (17) | 0.20 |
| Solid tumour | 8 (27) | 8 (33) | 0 | 0.16 |
| Obesity | 2 (7) | 2 (8) | 0 | >0.99 |
| Smoking | 5 (17) | 4 (17) | 1 (17) | >0.99 |
| Pneumonia severity index, median (IQR) | 49 (37–75) | 46 (36–63) | 119 (47–169) | 0.02 |
| Altered mental status | 2 (7) | 0 | 2 (33) | 0.03 |
| Laboratory finding | ||||
| WBC (/μL), median (IQR) | 3975 (3010–5200) | 3825 (3118–5075) | 4900 (2630–9065) | 0.35 |
| Haemoglobin (g/dL), median (IQR) | 13.7 (13.1–15.3) | 13.8 (13.3–16.1) | 13.3 (10.9–14.8) | 0.24 |
| Platelets (/μL), median (IQR) | 1 40 000 (1 09 500–1 85 000) | 1 48 500 (1 10 800–18650) | 1 20 000 (1 01 800–1 43 500) | 0.15 |
| BUN (mg/dL), median (IQR) | 12 (9–18) | 12 (9–16) | 18 (5–32) | 0.55 |
| Creatinine (mg/dL), median (IQR) | 0.7 (0.6–1.0) | 0.7 (0.6–0.9) | 0.8 (0.7–1.4) | 0.16 |
| Albumin (g/dL), median (IQR) | 3.8 (3.5–4.4) | 3.8 (3.5–4.4) | 3.2 (2.5–3.7) | 0.02 |
| AST (IU/L), median (IQR) | 41 (27–93) | 36 (27–96) | 61 (32–136) | 0.47 |
| ALT (IU/L), median (IQR) | 33 (20–50) | 32 (20–46) | 41 (15–71) | 0.69 |
| C-reactive protein (mg/dL), median (IQR) | 2.2 (1.0–5.3) | 1.9 (0.8–4.0) | 7.0 (1.1–12.7) | 0.15 |
| Time from symptom onset to admission (days), median (IQR) | 5 (4–10) | 5 (3–9) | 6 (5–10) | 0.52 |
| Time from hospital admission to defervescence (days), median (IQR) | 8 (4–14) | 7 (3–12) | 15 (8–22) | 0.06 |
| Time from hospital admission to hospital discharge (days), median (IQR) | 13 (10–17) | 13 (10–16) | 18 (5–20) | 0.48 |
| Time from hospital admission to antiviral therapy (days)‡, median (range) | 0 (0–4) | 0 (0–4) | 0 (0–1) | 0.66 |
| Treatment | ||||
| Interferon-alpha + lopinavir/ritonavir + ribavirin | 30 (100) | 24 (100) | 6 (100) | >0.99 |
| Convalescent plasma therapy | 2 (7) | 1 (4) | 1 (17) | 0.37 |
| IVIG | 3 (10) | 0 | 3 (50) | 0.005 |
| Steroids | 1 (3) | 0 | 1 (17) | 0.20 |
| Broad-spectrum antibiotics | 12 (40) | 7 (29) | 5 (83) | 0.03 |
| Haemodialysis | 2 (7) | 0 | 2 (33) | 0.03 |
| Mechanical ventilation | 8 (27) | 2 (8) | 6 (100) | <0.001 |
| ECMO | 2 (7) | 1 (4) | 1 (17) | 0.37 |
| At admission | ||||
| MERS viral loads (RT-PCR Ct value) from respiratory samples on HD 1–4, median (IQR) | 28.3 (22.6–35.8) | 29.1 (26.2–36.6) | 21.1 (19.3-NA) | 0.12 |
| The presence of MERS viraemia on HD 1–4 | 12/16 (75) | 9/13 (69) | 3/3 (100) | 0.53 |
| IP-10 on HD 1–4 (pg/mL), median (IQR) | 1848 (382–5377) | 856 (290–1994) | 5465 (4729–7076) | 0.001 |
| MCP-1 on HD 1–4 (pg/mL), median (IQR) | 273 (85–1498) | 93 (54–324) | 1565 (1171–2923) | <0.001 |
| IL-6 on HD 1–4 (pg/mL), median (IQR) | 46 (0–287) | 12 (0–64) | 333 (233–617) | <0.001 |
| During the course of disease | ||||
| MERS viral loads (RT-PCR Ct value) of respiratory samples on HD 5–10 (1 week), median (IQR) | 37.0 (30.6–38.0) | 37.6 (36.3–38.1) | 28.1 (23.7-NA) | <0.001 |
| MERS viral loads of (RT-PCR Ct value) respiratory samples on HD 11–16 (2 weeks), median (IQR) | 36.4 (33.9–38.5) | 36.8 (34.6–38.7) | 29.0 (31.8-NA) | 0.11 |
| The presence of MERS viraemia on HD 5–10 (1 week) | 7/17 (41) | 5/14 (36) | 2/3 (67) | 0.54 |
| The presence of MERS viraemia on HD 11–16 (2 weeks) | 3/9 (33) | 2/7 (29) | 1/2 (50) | >0.99 |
| IP-10 on HD 5–10 (1 week) (pg/mL), median (IQR) | 840 (298–2807) | 426 (237–858) | 2991 (1712–4230) | <0.001 |
| MCP-1 on HD 5–10 (1 week) (pg/mL), median (IQR) | 179 (80–526) | 124 (46–219) | 532 (276–656) | 0.005 |
| IL-6 on HD 5–10 (1 week) (pg/mL), median (IQR) | 20 (7–95) | 11 (0–37) | 109 (57–165) | 0.002 |
| IP-10 on HD 11–16 (2 weeks) (pg/mL), median (IQR) | 419 (249–851) | 253 (171–314) | 791 (441–1239) | <0.001 |
| MCP-1 on HD 11–16 (2 weeks) (pg/mL), median (IQR) | 315 (108–888) | 127 (75–181) | 888 (596–1183) | <0.001 |
| IL-6 on HD 11–16 (2 weeks) (pg/mL), median (IQR) | 70 (17–126) | 19 (3–77) | 197 (64–170) | 0.007 |
| Low IFA antibody titre (<1:640) on HD 11–16 (2 weeks) | 7/13 (54) | 3/9 (33) | 4/4 (100) | 0.07 |
| Low pseudovirus neutralisation assay antibody titre (≤1:320) on HD 17–24 (3 weeks) | 9/12§ (75) | 5/8 (63) | 4/4 (100) | 0.49 |
| Low IFA antibody titre (<1:640) on HD 17–24 (3 weeks) | 4/6 (67) | 1/3 (33) | 3/3 (100) | 0.40 |
| Low pseudovirus neutralisation assay antibody titre (≤1:320) on HD 17–24 (3 weeks) | 3/6 (50) | 1/3 (33) | 2/3 (67) | >0.99 |
*The first patient with confirmed MERS who triggered the 186 Korea MERS outbreak was defined as generation zero. The patients infected by this patient zero comprised the first generation, followed by the second generation, third generation and fourth generation.
†One patient could not find any epidemiological link from this patient to the known confirmed MERS-CoV-infected patients in Korea outbreak, although exceptional epidemiological investigations were performed to determine the transmission chain by the Korean government. He was classified as third generation without high confidence.
‡Antiviral therapy includes interferon-alpha, ribavirin, or lopinavir/ritonavir.
§Of the 13 plasma samples, one sample was too small amount for the pseudovirus neutralisation assay and was not included.
ALT, alanine transaminase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; CoV, coronavirus; ECMO, extracorporeal membrane oxygenation; HD 1–4, hospital days 1–4; IFA, immunofluorescent antibody; IL-6, interleukin-6; IP-10, inducible protein-10; IVIG intravenous immunoglobulin; MCP-1, monocyte chemoattractant protein-1; WBC, white blood cells.