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©The Author(s) 2021.
World J Methodol. May 20, 2021; 11(3): 95-109
Published online May 20, 2021. doi: 10.5662/wjm.v11.i3.95
Published online May 20, 2021. doi: 10.5662/wjm.v11.i3.95
Ref. | Country | Type of study | No. of pts | Median follow up (d) | Male/Female, % | Median age (yr) | CV Comorbities, % | Respiratory/diabetes % | Other/cancer, % | Other medications, % | Ventilatory status (Baseline to end of follow up, %) | ICU admission %/time to ICU admission (d) |
Alattar et al[11], 2020 | Quatar | Retrospective | 25 | 14 | 92/8 | 58 | 12 HTN | -/48 | CKD 16/4 | HCQ (100), AZITRO (96), lopinavir/ritonavir (96), ribavirin (88), and INF 1-α2a (60) | 56 (invasive) | 100/1 |
Alberici et al[12], 2020 | Italy | Retrospective | 6 | 4 | - | - | - | -/- | -/- | Steroids, antivirals, HCQ | 33 (16 worsened) | -/- |
Capra et al[13], 2020 | Italy | Retrospective (with ctr arm1) | 82 (n = 62 TCZ) | 9 | 73/27 | 63 | 63 HTN | -/16 | -/- | HCQ (100), lopinavir/ritonavir (100) | 35.2 (27% worsened) | 4.8/- |
Colaneri et al[14], 2020 | Italy | Retrospective with prop. score | 112 (n = 21 TCZ) | 7 | 90/10 | 62.3 | 47.6 HTN | 0/9.5 | 19/4.7 | HCQ, AZITRO, steroids (100) | - | 14/- |
Hassoun et al[15], 2020 | United States | Retrospective | 9 | - | 66/33 | 60 | 55 HTN | 11/11 | 66/- | HCQ, AZITRO (100) steroids (33), antibiotics (66) | - | 89/- |
Klopfenstein et al[16], 2020 | France | Case control | 45 (n = 20 TCZ) | - | - | 76.8 | 55 HTN/70 CVS disease | 20/25 | -/35 | HCQ or lopinavir/ritonavir + antibiotics ± steroids (100) | - | 0/- |
Luo et al[17], 2020 | China | Retrospctive | 15 | - | 80/20 | 73 | 66 HTN | -/26.6 | -/- | Steroids (53) | 6.6 (33.3% worsened) | -/- |
Quartuccio et al[18], 2020 | Italy | Retrospective (with ctr arm1) | 111 (n = 42 TCZ) | 17.8 | 78.6/21.4 | 62.4 | 47.6 HTN | -/- | -/- | Antivirals (100), HCq (92.9) steroids (40); antibiotics (28.6) | 65 (invasive) | 57/- |
Sciascia et al[19], 2020 | Italy | Prospective | 63 | - | 89/11 | 62.6 | 45 | 4.7/9.5 | - | Lopinavir/ritonavir (71), darunavir/cobicistat (29) | 95 | 7.9/- |
Toniati et al[20], 2020 | Italy | Prospective | 100 | 10 | 88/12 | 62 | 62 | 9/17 | 11/6 | HCQ, lopinavir/ritonavir or remdesivir, antibiotic, steroids | 69 (n = 23 worsened) | 43/- |
Xu et al[21], 2019 | China | Retrospective | 21 | - | 86/14 | 56.8 | 57.2 | 9.6/23.8 | CKD 4.8/- | Lopinavir/ritonavir, IFN-α, ribavirin, steroids (100) | 100 | -/- |
Ramaswamy et al[22], 2020 | United States | Case control | 86 (n = 21 TCZ) | - | 61.9/38.1 | 63.2 | 14.3 HTN/heart disease, AF or stroke 19.1 | 28.6/14.3 | -/0 | HCQ (81), AZITRO (23.8), steroids (42.9) | - | 47.6/- |
Rimland et al[23], 2020 | United States | Retrospective | 11 | 17 | 82/18 | 59 | 73 HTN/18 CVS | 27/36 | Renal or liver 18/9 | HCQ (36), AZITRO (64) | 54 (10% worsened) | 73/- |
Sanchez-Montalva et al[24], 2020 | Spain | Prospective | 82 | - | 63/37 | 59.1 | 39 HTN/6.1 heart failure/12.2 AF | 23.5/19.5 | Liver 1.2/- | HCQ (98.9), lopinavir/ritonavir (76.8), AZITRO (96.3), darunavir/cobicistat (25) | 53 (52% worsened) | 2.9/- |
Wadud et al[25], 2020 | United States | Case control | 94 (n = 44 TCZ) | - | -/- | 55.5 | - | -/- | -/- | - | - | - |
Campochiaro et al[26], 2020 | Italy | Retrospective | 65 (n = 32 TCZ) | 28 | 91/9 | 64 | 37 HTN/12 CAD | 3/12 | CKD 9/6 | HCQ, AZITRO, lopinavir/ritonavir (100) | 91 | 0/- |
Morena et al[27], 2020 | Italy | Prospective | 51 | 30 | 78.4/21.6 | 60 | 29.4 HTN/49 CVS disease | 9.8/11.8 | 5.9/5.9 | HCQ (98), antibiotics (76), lopinavir/ritonavir (82), remdesivir (42) | 66.6 (33% worsened) | 11.8/- |
Kimmig et al[28], 2020 | United States | Retrospective (with ctr arm) | 60 (n = 28 TCZ) | - | 46.8/53.2 | 63.8 | 53.6 HTN/43 other | 35.7/14.3 | 14/14.3 | - | - | - |
Roumier et al[29], 2020 | France | Compassionate use | 59 (n = 30 TCZ) | 8 | 80/20 | 50 | 20 HTN/13 CVS | 13/23 | 33/- | HCQ (6.6), steroids (6.6) | - | 23.3/- |
Ip et al[30], 2020 | United States | Retrospective | 547 (n = 134 TCZ) | 30 | 78/22 | 62 | 71.6 HTN and coronary arthery disease | 15/35 | 15/9 | HCQ + AZITRO (92), steroids (66) | - | 100/- |
Perrone et al[31], 2020 | Italy | Phase 2 and expansion cohort | 1221 (n = 708 TCZ3) | 30 | 82/18 | 61% > 60 | 68 heart disease or HTN | -/15 | -/- | HCQ (75), anti-retroviral (65), antibiotics (50), steroids (28) | - | 16 invasive ventilation/- |
Perez-Tanoira et al[32], 2020 | Spain | Cohort study | 562 (n = 36 TCZ) | - | -/- | - | - | -/- | -/- | - | - | - |
Somers et al[33], 2020 | United States | Observational | 154 (n = 78 TCZ) | 47 | 68/32 | 55 | 85 HTN or heart failure | 54/13 | CKD 35/- | HCQ (26), steroids (29), remdesivir (3) | 56 (18 and worsened) | 100/41 < 24 h, 36 > 48 h |
Heili-Frades et al[34], 2020 | Spain | Cohort study | 4712 (n = 366 TCZ)2 | - | -/- | - | - | -/- | -/- | - | - | 40.7/- |
Issa et al[35], 2020 | France | Retrospective | 10 | - | 100/0 | 66 | 60 HTN | -/30 | -/- | HCQ (100), steroids (30) | 50 | 70/7 d |
Garcia et al[36], 2020 | Spain | Retrospective | 171 (n = 77 TCZ) | - | 58.8/51.2 | 61.5 | 61 HTN or heart disease | 10.3/15.6 | -/- | Antivirals (100, steroids (50) | 90 | 10.3/- |
Ayerbe et al[37], 2020 | United Kingdom | Retrospective | 2075 (n = 421 TCZ) | 8 | -/- | - | - | -/- | -/- | - | - | -/- |
Borku Uysal et al[38], 2020 | Turkey | Retrospective | 12 | 22 | 50/50 | 65.8 | 58 HTN | 16/58 | CKD 8/16 | HCQ and antivirals (100), AZITRO (50), antibiotics (58) | 82 | 17/- |
Fernandez-Cruz et al[39], 2020 | Spain | Retrospective | 463 (n = 189 TCZ) | - | -/- | - | - | -/- | -/- | Steroids (100), other not available | - | -/- |
Garibaldi et al[40], 2020 | United States | Cohort study | 832 (n = 39 TCZ) | - | -/- | - | - | -/- | -/- | - | - | -/- |
Martínez-Sanz et al[41], 2020 | Spain | Cohort study | 1229 (n = 260 TCZ) | - | 73/27 | 65 | 17 HTN, 8 CAD, 2 heart failure | 18/15 | CKD 4/- | - | - | 19/6 d |
Petrak et al[42], 2020 | United States | Retrospective | 145 | - | 64/36 | 58.1 | - | - | - | Corticosteroids (60), HCQ + AZITRO (98.6) | - | -/- |
Rossi et al[43], 2020 | France | Case control | 246 (n = 106 TCZ) | 28 | 66/34 | 64 | 60 HTN, 23.6 CVS | 16/45 | -/5.7 | Antibiotics (100), HCQ (83), steroids (40), lopinavir/ritonavir (0.9) | - | -/- |
Ref. | Fever (baseline) °C/% | O2 sat. % | Cough % | Dyspnea % | Leucocytes 109/L | Lymphocites/Neutrophil 109/L | PLT 109/L | Hb g/dL | LDH | Liver tests IU/L | CRP mg/L | PCT ng/L | D-dimer | IL6 ng/L | Imaging % |
Alattar et al[11], 2020 | 38/92 | - | 84 | 72 | 6.0 | 0.9/5.0 | 208 | - | - | 46/30 | 95.2 | 0.38 | - | - | Infiltrates and ground glass opacities 100 |
Alberici et al[12], 2020 | -/- | - | - | - | - | -/- | - | - | - | - | - | - | - | - | - |
Capra et al[13], 2020 | 38/- | - | - | - | - | -/- | - | - | - | - | 123 | 0.6 | - | - | Bilateral pulmonary opacities 100 |
Colaneri et al[14], 2020 | -/- | - | - | - | - | 0.6/8.4 | 303 | - | 445 | 38/72 | 21.3 | 0.24 | - | - | Interstitial lung disease 100 |
Hassoun et al[15], 2020 | -/- | - | - | - | - | -/- | - | - | - | -/- | - | - | - | - | - |
Klopfenstein et al[16], 2020 | -/- | 90 | - | - | - | 0.67/- | - | - | - | -/- | 158 | - | - | - | ≥ 50% lung involvement 60 |
Luo et al[17], 2020 | -/- | - | - | - | - | -/- | - | - | - | -/- | 96 | - | - | 71 | - |
Quartuccio et al[18], 2020 | -/- | - | - | - | 5540 | 0.68/4.5 | 157 | - | 625 | -/- | 79.05 | - | 835 | 63.5 | - |
Sciascia et al[19], 2020 | < 38/39.7 | - | - | - | - | - | - | - | - | - | - | - | - | - | Bilateral pulmonary infiltrates |
Toniati et al[20], 2020 | > 37.5/85 | - | 55 | 73 | 6 | 0.78 | 177 | 13.6 | 413 | 55/39 | 97 | - | 525 | 41 | Ground glass opacities and consolidation, bilateral pulmonary infiltration |
Xu et al[21], 2019 | -/100 | - | 66.7 | - | 6.3 | 0.97 | 170 | - | 370 | 31/29 | 75 | 0.33 | 0.8 | 153 | Ground glass opacities and focal consolidation, peripheral and subpleural |
Ramaswamy et al[22], 2020 | -/- | - | - | - | - | 1.1/6.7 | 200 | - | - | 60/43.5 | 15.9 | 2.2 | 2900 | 371 | - |
Rimland et al[23], 2020 | -/- | - | - | - | 8.5 | -/0.8 | 230 | - | 1203 | 51/35 | 197.3 | - | 343.5 | 30.65 | - |
Sanchez-Montalva et al[24], 2020 | 37.7/91.5 | 94 | 86.6 | 65.9 | 9.2 | 0.86/ | 199 | 13.3 | 446 | 53/41 | 17.98 | - | 295 | 74.8 | - |
Wadud et al[25], 2020 | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - |
Campochiaro et al[26], 2020 | 37.6/- | - | - | - | - | -/- | - | - | 469 | -/- | 156 | - | - | - | - |
Morena et al[27], 2020 | 74.5/- | - | 62.7 | 54.9 | 9.1 | 0.8/7.3 | 230 | - | 470 | 48/39 | 189 | - | 1706 | 116 | Bilateral pulmonary opacities 100 |
Kimmig et al[28], 2020 | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - |
Roumier et al[29], 2020 | - | - | - | - | - | - | - | - | - | - | 189 | - | 3712 | - | - |
Ip et al[30], 2020 | 80 | - | 78 | 80 | - | -/- | - | - | - | -/- | - | - | - | - | |
Perrone et al[31], 2020 | -/- | - | - | - | - | -/- | - | - | - | -/- | 30 | - | - | - | - |
Perez-Tanoira et al[32], 2020 | -/- | - | - | - | - | -/- | - | - | - | -/- | - | - | - | - | - |
Somers et al[33], 2020 | -/- | - | - | - | 12.1 | 0.9/- | - | - | 627 | 50/76 | 185 | - | 2400 | - | - |
Heili-Frades et al[34], 2020 | -/- | - | - | - | - | -/- | - | - | - | -/- | - | - | - | - | - |
Issa et al[35], 2020 | -/100 | - | - | - | - | -/- | - | - | - | -/- | 246 | - | 1354 | - | Ground glass opacities |
Garcia et al[36], 2020 | -/98.7 | - | 83 | 43 | - | 0.87/- | - | - | - | -/- | 97 | - | 918 | - | - |
Ayerbe et al[37], 2020 | -/- | - | - | - | - | -/- | - | - | - | -/- | - | - | - | - | - |
Borku Uysal et al[38], 2020 | -/92 | 92 | 100 | 67 | 6.1 | 1.09/4.3 | 180 | 13.8 | 259 | 33/39 | 54 | - | 599 | - | Ground glass opacities |
Fernandez-Cruz et al[39], 2020 | -/- | - | - | - | - | -/- | - | - | - | -/- | - | - | - | - | - |
Garibaldi et al[40], 2020 | -/- | - | - | - | - | -/- | - | - | - | -/- | - | - | - | - | - |
Martínez-Sanz et al[41], 2020 | 36.8/- | 91 | - | - | - | 0.89/5.4 | - | - | 669 | -/32 | 113 | - | 809 | 70 | - |
Petrak et al[42], 2020 | - | - | - | - | - | - | - | - | 538 | - | 53.3 | - | 1.3 | - | - |
Rossi et al[43], 2020 | 37.5/- | 94 | - | - | - | 1.128/- | - | - | - | - | 168 | - | - | - | - |
Ref. | N° TCZ administered (median doses) | Death % | Dismissed % | Median hospitalization (d) | TCZ AEs % | Comparison with other medications or no TCZ | NOS Scale | ROBIN risk |
Alattar et al[11], 2020 | 1 | 12 | 36 (from ICU) | - | Anemia 64; ALT ↑ 44 | HR for discharge from ICU 0.64 (0.37-1.11) | 8 | Low |
Alberici et al[12], 2020 | 1 | 33 | 16 | - | - | - | 6 | Moderate |
Capra et al[13], 2020 | 1 | 8 | 92 | 12.5 | - | OR for OS 0.036 (0.07-0.18)° | 7 | Low |
Colaneri et al[14], 2020 | 2 | 23.8 | 85.7 (from ICU) | 2 | 0 | OR for OS 0.78 (0.06-9.34); OR for ICU 0.11 (0-3.38) | 7 | Low |
Hassoun et al[15], 2020 | 1 | 22 | 55 | 13.5 (n = 7) | - | - | 5 | Low |
Klopfenstein et al[16], 2020 | 1 or 2 | 25 | 55 | 13 | - | OR for OS and ICU admission 0.36 (0.1-1.3) and 0.03 (0.002-0.56); OR for mechanical vent 0.05 (0.003-0.93) | 5 | Low |
Luo et al[17], 2020 | 1 | 20 | - | - | - | - | 5 | High |
Quartuccio et al[18], 2020 | 1 | 9.5 | 28.5 | - | - | OR for OS 14.5 (0.76-278.3); OR for ICU admission 220.9 (12.7-3826.1) | 8 | Moderate |
Sciascia et al[19], 2020 | 1 (2 in 82.5%) | 11 | - | - | - | - | 6 | Moderate |
Toniati et al[20], 2020 | 1 (2 in 87%) | 20 | 15 | - | Septic shock (n = 2), GI perforation (n = 1) | - | 8 | Low |
Xu et al[21], 2019 | 1 (2 in 14.3%) | 0 | 100 | 15.1 | - | - | 5 | Moderate |
Ramaswamy et al[22], 2020 | 1 (2 in 38%) | 14.3 | - | - | - | HR for OS 0.25 (0.07-0.9) | 5 | Moderate |
Rimland et al[23], 2020 | 1 | 27 | 18 | 18 | - | - | 7 | Low |
Sanchez-Montalva et al[24], 2020 | 1 | 26.8 | 41.5 | - | - | - | 6 | Low |
Wadud et al[25], 2020 | - | 38.6 | - | - | - | OR for OS 0.58 (0.25-1.32) | 6 | Moderate |
Campochiaro et al[26], 2020 | 1 (2 in 28%) | 15 | 63 | 13.5 | SAEs (25) | OR for OS 0.38 (0.11-1.27); OR for ICU admission 0.33 (0.13-8.5) | 8 | Low |
Morena et al[27], 2020 | - | 27 | 61 | - | AST/ALT ↑ 29, PLT 14, neutropenia 6, rash 2 | - | 8 | Low |
Kimmig et al[28], 2020 | 1 (2 in 10.7%) | 42.9 | 25 | - | Infections 71.4 | OR for OS 2.25 (0.75-2.24) | 6 | Moderate |
Roumier et al[29], 2020 | 1 | 10 | 20 | - | - | OR for OS 0.25 (0.05-1.03); OR for ICU 0.17 (0.06-0.48) | 7 | Low |
Ip et al[30], 2020 | 1 (78%) | 46 | - | - | Bacteriemia (13), secondary pneumonia (9) | OR for OS 0.66 (045-0.99) | 8 | Low |
Perrone et al[31], 2020 | 1 (59.8), 2 (54.5) | 20 | - | - | 26.4 G3-5; 14.4 G1-2 | OR for 30-d OS 0.7 (0.41-1.22) and 1.22 (0.86-1.92) in phase 2 and validation cohort | 8 | Low |
Perez-Tanoira et al[32], 2020 | - | 27.7 | - | - | - | OR for OS 1.015 (0.47-2.18) | 5 | Moderate |
Somers et al[33], 2020 | 1 | 18 | 56 | 20.4 | Superinfection (54) | OR 0.39 (0.18-0.82) | 8 | Low |
Heili-Frades et al[34], 2020 | - | 22.4 | - | - | - | - | 6 | Moderate |
Issa et al[35], 2020 | 1 | 10 | - | 11 (ICU) | - | - | 5 | High |
Moreno-Garcia et al[36], 2020 | - | 10.3 | 84.4 | - | - | OR for ICU 0.3 (0.12-0.71) and OR for OS 0.52 (0.21-1.29) | 5 | Moderate |
Ayerbe et al[37], 2020 | - | 21.1 | - | - | - | OR for OS 1.9 (1.44-2.51) | 5 | High |
Borku Uysal et al[38], 2020 | 2 | 0 | 100 | - | - | - | 6 | Moderate |
Fernandez-Cruz et al[39], 2020 | - | - | - | - | - | OR for OS 0.69 (0.41-1.19) | 5 | High |
Garibaldi et al[40], 2020 | - | 5 | - | - | - | OR for OS 1.14 (0.46-2.81) | 5 | Moderate |
Martínez-Sanz et al[41], 2020 | 1 | 23 | - | 13 | - | OR for OS 2.19 (1.54-3.1) | 5 | Low |
Petrak et al[42], 2020 | 1 (84.8), 2 (15.2) | 28.3 | 48.3 | - | - | - | 5 | Moderate |
Rossi et al[43], 2020 | 1 | 28.9 | - | - | - | HR for OS 0.29 (0.17-0.49) | 8 | Low |
- Citation: Petrelli F, Cherri S, Ghidini M, Perego G, Ghidini A, Zaniboni A. Tocilizumab as treatment for COVID-19: A systematic review and meta-analysis. World J Methodol 2021; 11(3): 95-109
- URL: https://www.wjgnet.com/2222-0682/full/v11/i3/95.htm
- DOI: https://dx.doi.org/10.5662/wjm.v11.i3.95