Table 2.
Characteristics of included MERS-CoV studies (n = 26a).
| Source | Country | Study design | Viral aetiology | Diagnosis | Sample | Reported co-morbidities | Symptoms on admission | Ageb | Intervention | Non-intervention treatments |
|---|---|---|---|---|---|---|---|---|---|---|
| Habib et al. (2019) | Saudi Arabia | Retrospective cohort study (LOE II) | MERS | PCR from respiratory tract samples | 63 | Diabetes, HTN, hepatitis C, chronic renal failure, and chronic heart disease | Fever, Diarrhea, Abdominal pain, Organ failure | M(59.7) S(18.2) | IFN- α (61) | RBV |
| Arabi et al. (2019)† | Saudi Arabia | Retrospective cohort study (LOE II) | MERS | Swab RT-PCR | 349 | DM, Malignancy, CPD, Moderate to severe liver disease, CKD, Chronic Cardiac, Chronic neurological disease, Rheumatological disease | NI | M(IFN and/or RBV (−57.5), No IFN and/or RBV (−58)) I(IFN and/or RBV (47–70), No IFN and/or RBV (41–70)) | Combination of RBV and rIFN (117), rIFN alone (9), (rINF type: α 2a 73, α 2b 22, β-1a 31) | RBV, Oseltamivir, Corticosteroid, NO, Renal replacement therapy, Vasopressors, Neuromuscular blockade |
| Choi et al. (2019) | South Korea | Case report (LOE III) | MERS | Patient 1: RT-PCR of nasopharyngeal aspirate, Patients 2 and 3: RT-PCR | 3 | None | Fever, Cough, Shortness of breath, Phlegm, Sore throat, Myalgia, Headache, Diarrhea | Patient1 38, Patient 2 33, Patient 3 45 | Patient 1: interferon α2a (180 μg/week), Patients 2 and 3: interferon-α2a | LPV, RTV, RBV |
| Alfaraj et al. (2019) | Saudi Arabia | Retrospective cohort study (LOE II) | MERS | RT-PCR of respiratory samples | 314 | NI | Fever, Cough, Shortness of breath, Sore throat | M(48.0), S(17.3) | Yes | RBV, Corticosteroid |
| Shalhoub et al. (2018)† | Mainly Saudi Arabia | Retrospective cohort study (LOE II) | MERS | RT-PCR from a respiratory tract sample (nasopharyngeal swab, sputum, deep tracheal aspirate or BAL | 32 | Diabetes, Chronic cardiac disease, CRD, CPD, Malignancies including leukemia, lymphoma or solid tumors | Fever, Cough, Shortness of breath, Chest tightness, Runny nose, Sore throat, Myalgia, Headache, Fatigue, Nausea, Vomiting, Diarrhea, Altered consciousness, Wheezing, Abdominal pain | M(-39), I(32–48) | Yes (13) | RBV, Oseltamivir, IVIG, Vasopressors, Renal replacement therapy |
| Garout et al. (2018) | Saudi Arabia | Retrospective Cohort (LOE II) | MERS | Swab RT-PCR | 52 | HTN, DM, CRF | NI | R(15–35) for (9), (35–55) for (24), (55–75) for (16), (75–85) for (3) | IFN-α (35) | RBV |
| Al-Tawfiq et al. (2014) | Saudi Arabia | Case report (LOE III) | MERS | Nasopharyngeal dacron-flocked swabs or sputum samples RT-PCR | 3 | Rheumatoid arthritis, DM, Dyslipidemia, Chronic HBV carrier | Fever, Cough, Dizziness, Fatigue, Nausea, Vomiting, Diarrhea, | Patient 1: 56, Patient 2: 52, Patient 3: 53 | Patients 2 and 3: IFN-α 2b | Patients 2 and 3: RBV, Patient 2: Oseltamivir |
| Sherbini et al. (2017) | Saudi Arabia | Retrospective cohort (LOE II) | MERS | Swab RT-PCR | 29 | DM, CKD | Fever, Cough, Shortness of breath, Vomiting, Diarrhea | M(45), S(12) | Yes (19) | RBV, Corticosteroid, Levofloxacin, Meropenem, Linezolid, Piperacillin, Azithromycin |
| Lee et al. (2017) | South Korea | Retrospective case report (LOE III) | MERS | Swab RT-PCR | 1 | HTN, Dyslipidemia | Fever, Myalgia, Chills, Dyspnea, Malaise | Patient 1: 68 | Pegylated IFN-α-2b 180 mcg Daily | RBV, Oseltamivir, IV ceftriaxone, azithromycin Vancomycin, and meropenem, Tigecycline, IV colistin, Amikacin, and Fluconazole |
| Kim et al. (2017) | South Korea | Retrospective case report (selected from a cohort) (LOE II) | MERS | RT-PCR for specimen from the lower respiratory tract (collected sputum and endotracheal aspirates) |
23, 4 were included in further analysis | DM, HTN, CHD, CKD, Bronchiectasis, Malignancy, Psychiatric disorder, Ankylosing spondylitis | Fever, Cough, Shortness of breath, Myalgia, Headache, Nausea, Confusion | M(-46), I(27–46) Patient 1: 55, Patient 2: 43, Patient 3: 46, Patient 4: 38 | Pegylated IFN α -2a S.C (180 μg/week for 2 weeks)(23) | LPV, RTV, RBV, Ceftazidime, Teicoplanin, Meropenem, and Moxifloxacin, Patient2: Antiemetic, Antitussive, and Non-steroidal anti-inflammatory drugs |
| Arabi et al. (2017)† | Saudi Arabia | Retrospective cohort (LOE II) | MERS | RT-PCR | 349 | Diabetes, CKD, chronic liver disease | NI | RBV/rIFN M (−57.5) I(47.0–70.0), No RBV/rIFN M (−58.0) I(41.0–70.0) |
rIFN α-2a (73) rIFN α-2b (22) rIFN-β-1a (31) |
RBV |
| Rhee et al. (2016) | South Korea | Retrospective case-series (LOE II) | MERS | Oropharyngeal swab sputum, and tracheal aspiration RT-PCR | 5 | NI | Fever, Cough, Myalgia, Headache, Diarrhea, Abdominal pain, Loose stool | Patient 1: 46, Patient 2: 47, Patient 3: 65, Patient 4: 27, Patient 5: 35 | Pegylated IFN α -2a SC 180 mg/week for 2 weeks (2) | Patients 1, 2, 3, 4, and 5: LPV, Patients 1, 2, 3, 4, and 5: RTV, Patient 2: RBV, Patient 5: Corticosteroid, Patients 1, 2, 3, 4, and 5: Antibiotic, patient3: Ionotropic, Patient 5: Convalescent plasma |
| Malik et al. (2016) | UAE | Case report (LOE III) | MERS | Nasopharyngeal aspirate RT-PCR | 1 | 32 week pregnant | Fever, Back pain | Patient 1: 32 | Peg IFN-α (180 μg/week) (1) | RBV, Oseltamivir, Vancomycin, Meropenem |
| Kim et al. (2016) | South Korea | Case report (LOE III) | MERS | nasopharyngeal/oropharyngeal, sputum RT-PCR | 1 | HTN, DM, Distal Pancreatectomy due to benign pancreatic neoplasm, Chronic dry cough, and Diagnosed with mycobacterium intracellulare | Fever, Cough, Weakness, | Patient 1: 64 | IFN-α2a SC180 microg/0.5 ml (1) | LPV, RTV, RBV |
| Khalid et al. (2016) | Saudi Arabia | Retrospective cohort (LOE II) | MERS | Swab RT-PCR | 32 (14 final inclusion in further analysis) | HTN, DM, Respiratory diseases, Obesity, CHF, CKD, Dialysis, IHD, Stroke, Immunosuppression | Fever, Cough, Shortness of breath, Chest pain, Sore throat, Myalgia, Headache, Nausea, Vomiting, Diarrhea, Hemoptysis, Abdominal pain | M(-54), R(23–79) | Peg IFN-α-2b (11) | RBV, Oseltamivir, Methylprednisolone, Antibiotic, NO, Neuromuscular Blockade, Renal replacement therapy, Vasopressor |
| Choi et al. (2016) | South Korea | Retrospective cohort (LOE II) | MERS | RT-PCR | 186 | HTN, DM, Malignancy, COPD, CHD, Cerebrovascular disease, CLD, CKD, Hematologic malignancy | Fever, Cough, Shortness of breath, Runny nose, Sore throat, Myalgia, Headache, Nausea, Vomiting, Diarrhea, Sputum, Abdominal pain, Decreased consciousness | M(-55), R(16–86) | Yes (183) | LPV/RTV,RBV, IVIG, Antibiotic, Convalescent serum |
| Cha et al. (2016) | South Korea | Case report (LOE III) | MERS | Urine, stool, and sputum RT-PCR | 1 | HTN | Fever, Cough, Shortness of breath, Myalgia, Weakness, Nausea, Vomiting | 68 | Pegylated IFN- α 180 μg (1) | RBV, Vancomycin, Tigecycline, Colistimethate |
| Al-Hameed et al. (2016) | Saudi Arabia | Prospective cohort (LOE II) | MERS | Swab RT-PCR | 8 | DM, HTN, CHF or IHD, Cirrhosis, G6PD deficiency | Fever, Cough, Shortness of breath, Chest pain, Myalgia, Headache, Diarrhea, Sputum production, Altered mental state | M(-56.5), R(26–94) | IFN- α-2b (8) | RBV, Oseltamivir, Corticosteroid, Antibiotic, Norepinephrine, Renal replacement therapy |
| Al Ghamdi et al. (2016) | Saudi Arabia | Retrospective cohort (LOE II) | MERS | PCR from clinical nasal swabs or nasopharyngeal aspirates | 51 | DM, HTN, End stage renal disease, Coronary artery disease, Immunosuppression, Pregnant | Fever, Cough, Runny nose, Sore throat, Vomiting, Diarrhea | M(-54), I(36.5–58) | IFN-β (23, 10 in combination with RBV, 11 IFN- β alone), IFN-α (8, 5 in combination with RBV, 2 IFN-α alone) | RBV, Oseltamivir, Antibiotic, Mycophenolate mofetil |
| Shalhoub et al. (2015) | Saudi Arabia | Sequential retrospective cohort study (LOE II) | MERS | RT–PCR from a respiratory tract sample | 32, 24 included in further analysis (received IFN) | DM, HTN, Chronic renal impairment, Renal failure on hemodialysis, Low ejection fraction | Fever, Cough, Shortness of breath, Chest pain, Phlegm, Vomiting, Diarrhea, Abdominal pain, Confusion | M(IFNa (−65), IFNb (−67), I(IFNa (33–84), IFNb (25–84)) | IFN-α-2a (180 mg S.C. once a week) combined with RBV (loading dose of 2 g orally followed by 600 mg orally q12 h): 13, IFN-b1a (44 mg S.C. three times a week) combined with RBV, dosed as above: 11 |
RBV |
| Oh et al. (2015) | South Korea | Case Report (LOE III) | MERS | RT–PCR on a sputum specimen | 1 | NI | Fever, Cough | Patient 1: 35 | Pegylated IFN α-2a via S.C. injection at a dose of 180 μg per week for 2 weeks (1) |
RBV, Antibiotic, IV Methylprednisolone 1 |
| Khalid et al. (2015) | Saudi Arabia | Case Report (LOE III) | MERS | Patient 1: RT-PCR (UPE, ORF 1b) Patient 2: RT-PCR Patient Routine clinical laboratory tests for influenza, parainfluenza, respiratory syncytial virus, adenovirus, rhino- virus, enterovirus, Epstein–Barr virus, cytomegalovirus, human metapneumovirus, urinary Legionella antigen and serology for Mycoplasma pneumoniae and Chlamydia pneumoniae (no serological results for MERS-CoV) | 2 | NI | Shortness of breath | Patient 1:52, Patient 2: 42 | Pegylated IFN α-2b (2) | RBV, Corticosteroid (Patient 1: IV methylprednisolone, Antibiotic (Patient 1: Broad-spectrum antibiotics like ceftriaxone and azithromycin), Patient 2: Cefuroxime and Azithromycin) |
| Al-Qaseer (2015) | Kuwait | Case Report (LOE III) | MERS | BAL endotracheal RT-PCR | 3 | DM, HTN, peptic ulcer, DM, HTN, IHD | Fever, Cough, Shortness of breath, Diarrhea, Night sweats, loss of appetite | Patient 1: 47, Patient 2: 52, Patient 3: 60 | Patient 1: IFN-α-2a μg S.C., Patient 2: IFN-α-2b 1.5 μg/kg S.C. | RBV, Patient 1: Oseltamivir, Patient 2: IVIG, Patients 1 and 2: Corticosteroid, Patients 1, 2, and 3: Antibiotic |
| Omrani et al. (2014) | Saudi Arabia | Retrospective cohort (LOE II) | MERS | RT-PCR testing of respiratory tract samples | 44 | CHF, Dementia, COPD, Asthma, Rheumatological disease, CLD, DM, Hemiplegia, CKD, Malignant disorder | NI | M(IFN/RBV: 67·4, No IFN/RBV: 64·0) S(IFN/RBV: 18·5, No IFN/RBV: 18·1) |
Pegylated IFN-α -2a S.C. (180 μg/week for 2 weeks) (20 from treatment group) | RBV, Oseltamivir, Hydrocortisone, Antibiotics, Vasopressor Therapy, IVIG |
| Khalid et al. (2014) | Saudi Arabia | Case-series (LOE II) | MERS | Swab RT-PCR | 6 | IHD, heart failure, Right bundle branch block, Cardiomyopathy heart failure | NI | Patient 1: 74, Patient 2: 84, Patient 3: 76, Patient 4: 54, Patient 5: 48, Patient 6: 17 | IFN-α-2b 180 μg S.C. once per weeks for 2 weeks in CrCl 20–50 ml/min (6) | RBV, Methylprednisolone pulse, Antibiotic |
| Al-Tawfiq et al. (2014) | Saudi Arabia | Case reports (LOE III) | MERS | Swab RT-PCR | 5 | HTN, DM, CKD, Dialysis, Asthma, Obstructive sleep apnea, Coronary artery disease, AF, ESRD | Fever, Cough, Shortness of breath, Respiratory failure | M(-62), R(24–81) Patient 1: 62, Patient 2: 58, Patient 3: 63, Patient 4: 81, Patient 5: 24) | IFN-α-2b 130 μg S.C. (1), 100 μg S.C.(3), 144 μg S.C.(1) | RBV, Oseltamivir, IV Methylprednisolone, Imipenem, Levofloxacin |
Abbreviations: AF: atrial fibrillation, BAL: bronchoalveolar lavage, CHD: coronary heart disease, CKD: chronic kidney disease, CoV: coronavirus, CPD: cephalopelvic disproportion, CRD: chronic respiratory disease, CRF: chronic renal failure, DM: diabetes melitus, ESRD: end stage renal disease, G6PD: Glucose-6-phosphate dehydrogenase, g: grams, HBV: hepatitis B virus, HTN: hypertension, I: interquartile, IFN: interferon, IHD: ischemic heart disease, IVIG: intravenous immunoglobulin, LOE: level of evidence, M: mean, MERS: middle east respiratory syndrome, mL: milliliter, NI: not identified/indicated, NO: nitric oxide, ORF: open reading frame, q12h: every 12 h, RBV: ribavirin, rIFN: recombinant interferon, RT-PCR: reverse transcription polymerase chain reaction, S: standard deviation, SARS: severe acute respiratory syndrome, SC: subcutaneous, μg: microgram, upE: envelope gene.
a
24 distinct studies are listed. The three non-distinct studies are marked as †. Among the studies with common participants (2, 5, 11), Arabi et al. is considered the most complete, and was considered for analyses.
b
Age of participants is reported as reported in each study. Estimated mean values may be found in (supplementary material).