Table 1.
Characteristics of included studies.
| First Author | Country | Date of publication | Type of study | Sample size | Male: Female | Mean age | Nationality | MEDICATIONS | Inclusion criteria | Exclusion criteria | Severity of disease (mild, mod, severe) | Complications | COVID-19 symptoms | Discharge |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Fan et al. (17) | China | 10-Apr-20 | retrospective cohort study | 148 | 73 M, 75 F | 50 | Chinese | lopinavir/ ritonavir | Clinical criteria of discharge and diagnosis were according to the standards for “Diagnosis and Treatment Scheme of New Coronavirus Infected Pneumonia” (trial version 6), history of exposure and most had clinical manifestations including fever or respiratory symptoms | – | severe (10) | – | fever in 127, cough in 67, Diarrhea in 6, Nausea and vomiting in 3, expectoration in 38, asymptomatic in 5, other liver disease in 9 | 92 |
| Grein et al. (20) | USA | 10-Apr-20 | cohort, compassionate-use | 53 | 40 M, 13 F | 64 | United States, Japan, Italy, Austria, France, Germany, Netherlands, Spain, Canada | remdesivir | COVID-19 infection confirmed by RT-PCR, needing O2 support or O2 Sat ≤ 94% while breathing ambient air, creatinine clearance > 30 mL/min, serum AST and ALT levels <5x ULN, patient consent to not use other investigational drugs(agents) for Covid-19. | missing post baseline information, an incorrect remdesivir start date | Severe | DM in 9, HTN in 13, Asthma in 6, Any coexisting condition in 36, Hyperlipidemia in 6 | – | 13 |
| Cai et al. (21) | China | 13-Apr-20 | cross-sectional study | 417 | 198 M, 219 F | 49 | – | Antibiotics, NSAIDs, Ribavirin, Oseltamivir, Herbal medications, Interferon, lopinavir/ritonavir | ≥1 abnormal result of liver test from admission until end of February 2020 | patients with hypertension at admission and found that the prevalence of abnormal liver function tests remained similar | severe (91), mild (326) | DM in 21, HTN in 51, Prior hepatic dysfunction in 19 | fever in 248, cough in 131 | – |
| Sun et al. (22) | China | 20-Apr-2020 | Retrospective cohort study | 217 | 106 M, 111 F | 45.7 | Chinese | lopinavir/ritonavir, umifenovir | Confirmed SARS-CoV-2 patients | – | Severe (50) | In 62 patients (HTN, DM, HIV, CVD, CKD, COPD) | – | – |
| Wang et al. (23) | China | 29-Apr-20 | randomized controlled trial | 158 | 89 M, 69 F | 66 | – | remdesivir | males and non-pregnant females with COVID-19 aged ≥ 18 years with positive RT-PCR test for SARS-CoV-2, confirmed pneumonia by chest imaging, O2 Sat ≤ 94% on room air or a ratio of arterial O2 partial pressure(PaO2) to fractional inspired O2 ≤ 300 mmHg, within 12 days of start of symptoms. | pregnancy or breast feeding; hepatic cirrhosis; ALT or AST > 5x ULN; known severe renal impairment (estimated GFR <30 mL/min per 1·73 m2) or receipt of continuous renal replacement therapy, haemodialysis, or peritoneal dialysis; possibility of transfer to a non-study hospital within 72 h; enrolment into an investigational treatment study for COVID-19 within 30 days before screening | severe | DM in 40, HTN in 72, coronary heart disease in 15 | fever in 56 | Day 28 clinical improvement in 103 of remdesivir group and in 45 of placebo group - Clinical improvement rates at days 14 and day 28 were also not significantly different between the groups, but numerically higher in the remdesivir group than the placebo group |
| Antinori et al. (24) | Italy | 11-May-20 | prospective (compassionate), open-label study | 35 | 26 M, 9 F | 63 | Italian | remdesivir | males or non-pregnant females aged >18 years, with SARS-CoV-2 infection confirmed by RT-PCR of a respiratory tract sample and pneumonia confirmed by a chest X-ray or CT scan, mechanically ventilated or SaO2 level of <94% in room air or a National Early Warning Score (NEWS) 2 of ≥4 |
ALT or AST level >5x ULN, creatinine clearance <30 mL/min | – | DM in 3, HTN in 12, obesity in 3, cancer in 1 | – | At day 28 from starting remdesivir, 14 patients were discharged from IDW, from ICU 6 discharged, 1 was improved but still hospitalized |
| Mangoni et al. (25) | Italy | 16-May-20 | case Report | 4 | 4 M | 52 | Italian | remdesivir | – | – | severe | – | severe pneumonia and respiratory distress | 3 |
| Muhović et al. (26) | Montenegro | 17-May-20 | case report | 1 | 1 M | 52 | Montenegrin | Tocilizomab | – | – | severe | – | fever, cough | – |
| Goldman et al. (27) | US | 27-May-20 | multicenter, randomized, open-label, phase 3 trial | 397 | 253 M, 144 F | 61.5 | United States, Italy, Spain, Germany, Hong Kong, Singapore, South Korea, Taiwan | remdesivir | confirmed SARS-CoV-2 infection, age ≥ 12 years, O2 Sat ≤ 94% while breathing ambient air or O2 support, radiologic evidence of pneumonia | mechanical ventilation or extracorporeal membrane oxygenation (ECMO) at screening, ALT or AST > 5x ULN, creatinine clearance <50 mL/min, receiving simultaneous treatment (within 24 h before the start of trial treatment) with other agents with supposed activity against Covid-19 |
severe | DM in 90, HTN in 198, asthma in 49, hyperlipidemia in 89 | – | 84 |
| Falcão et al. (28) | Brazil | 1-Jun-20 | case report | 1 | 1 F | 29 | Brazilian | HCQ | – | – | severe | – | dry cough, severe dyspnea, weakness, one episode of hemoptysis | – |
| Jiang et al. (29) | China | 23-Jun-20 | Multicenter retrospective, observational study |
131 | 70 M, 61 F | 51.21 ± 6.1 | Chinese | lopinavir/ritonavir | critically ill and non-critically ill | pregnancy, <18 years old, liver function abnormality before treatment | non-severe = mild or moderate (30), severe (22) critically ill (27) | Cardiovascular and cerebrovascular diseases in 37, endocrine system disease in 22, Digestive system disease in 5, Neurological disorders in 4, Immune system in 2 |
– | – |
| Guaraldi et al. (31) | Italy | 24-Jun-2020 | retrospective, observational cohort study | 179 | 127 M, 52 F | 64 | – | tocilizumab | ≥18 years with PCR confirmed COVID-19 on nasopharyngeal swab, eligible for tocilizumab treatment, if presented SaO2 <93% and a PaO2/FiO2 ratio <300 mm Hg in room air or a decline > 30% in them PaO2/FiO2 ratio in the last 24 h during hospitalization. |
Exclusion criteria for tocilizumab use: concurrent infection other than COVID-19; a PaO2/FiO2 ratio > 300 mm Hg; chronic or current use of glucocorticoid; history of severe allergic reactions to monoclonal antibodies; <500 per μL neutrophils or <50 × 109 platelets; active diverticulitis, inflammatory bowel disease, or another symptomatic digestive tract condition that might incline patients to perforation of bowel; severe liver, renal, or hematological function damage. |
– | cancer in 2, renal insufficiency in 2 | – | – |
| Leegwater et al. (32) | The Netherlands | 28-Jun-20 | case report | 1 | 1 M | 64 | Dutch (the Netherlands) | remdesivir | – | – | severe | HTN, hypercholesterolemia | Fever, cough, headache, progressive dyspnea | 1 |
| Dubert et al. (33) | France | 30-Jun-20 | case series | 5 | 5 M | 59.2 | Chinese, French | remdesivir | patients admitted to the Bichat-Claude Bernard University Hospital, Paris, France, between January 24 and March 1, 2020, diagnosed with COVID-19 and treated with remdesivir (GileadSciences), criteria for compassionate-use remdesivir defined by the French national regulatory authorities and French Ministry of Health: signs of severe illness at diagnosis or subsequent clinical worsening (respiratory symptoms or general signs) | – | ICU | Obesity in 1, malignancy in 1, pulmonary disease in 1, chronic kidney injury in 1 | fever in 5, cough in 4, GI symptoms in 1 | 3 |
| Kelly et al. (34) | Ireland | 8-Jul-20 | retrospective study | 82 | 55 M, 27 F | 64.8 | – | HCQ+ azithromycin | – | – | – | – | – | – |
| Lee et al. (35) | Korea | 23-Jul-20 | retrospective case series | 10 | 5 M, 5 F | 52 | Korean (ME: Korea, Philippines, UK) | remdesivir | confirmed diagnosis of SARS-CoV-2-related pneumonia, aged ≥18 years (or 12–18 years if weighed ≥40 kg) and O2 Sat of ≤ 94% in room air | evidence of multi-organ failure, mechanical ventilation > 5 days, serum AST or ALT >5x ULN, creatinine clearance <50 mL/min (Cockcroft-Gault formula if aged ≥18 years and Schwartz formula in aged <18 years), | 3 in ICU | HTN in 3, FLD in 1, other comorbidities in 2 | fever in 8, cough in 5, asymptomatic in 1, other symptoms in 10 | 3 |
| pregnancy or breastfeeding, known hypersensitivity to RDV or its metabolites, participation in another clinical trial | ||||||||||||||
| Zampino et al. (36) | Italy | 28-Jul-20 | case series | 5 | 5 M | 51.2 | Italian | remdesivir | invasive mechanical ventilation, ALT <5x ULN, creatinine clearance >30 mL/ min | Multi-organ failure, a need for vasopressor | – | HTN in 1, asthma in 1 | – | Final outcome positive in 4/5 patients (maybe 4 discharged) |
| Hundt et al. (37) | USA | 29-July-2020 | Retrospective observational cohort | 1,827 | 969 M, 858 F | 64.6 | – | lopinavir/ritonavir (n = 136), hydroxychloroquine (n = 1,469), remdesivir (n = 46), and tocilizumab (n = 772) | patients who tested positive for SARS-CoV-2 by PCR of nasopharyngeal swab | – | Non-severe (n = 1,175) Severe (n = 652) | DM in 712, Obesity in 748 | – | – |
| Carothers et al. (38) | US | 2-Oct-20 | case series | 2 | 2 F | 74 | – | remdesivir | – | – | – | DM in 2, HTN in 2, CAD in 1, hyperlipidemia in 2 | fever in 1, oxygen saturation in the 70s and 82s, systolic blood pressure > 200 mm Hg in 1, chills in 2, fatigue in 2, body aches in 1, low back pain in 1, shortness of breath in 1, difficulty with urination in 1 | 1 |
| Serviddio et al. (39) | Italy | 7-Oct-20 | case series | 7 | 7 M | 59 | – | HCQ+ azithromycin+ lopinavir/ritonavir | – | – | mild (6), severe (2) | – | fever in 7 | 7 |
| Aiswarya et al. (40) | India | 18-Dec-2020 | Observational prospective study | 48 | 38 M, 10 F | 50 | – | remdesivir | patients with CKD needing hemodialysis, who had positive test for SARS-CoV-2 infection from nasopharyngeal swab by RT-PCR with moderate or severe infection, and who received ≥1 dose of remdesivir | Patients with milddisease and underlying chronic hepatic disease | Moderate (21), severe (27) | DM in 20, HTN in 41, all patients (n=48), CKD in all patients. |
– | 38 |
| Yamazaki et al. (41) | Japan | 28-Dec-2020 | Case report | 1 | 1 M | 73 | Japanese | favipiravir | – | – | severe | Alcoholic hepatitis, HTN, hyperlipidemia, gastric ulcer, BPH, anemia | – | – |
HTN, hypertension; CKD, chronic kidney disease; BPH, benign prostatic hyperplasia; FLD, fatty liver disease; DM, diabetes mellitus; CAD, coronary artery disease; CVD, cardiovascular disease; COPD, chronic obstructive pulmonary disease.