Table 2.
Characteristics of the observational studies introduced in the meta-analysis.
| Source | Country | Primary Outcome | Total Pts (n) | Mean Age | Sex, (Male %) | Oxygen Support | TCZ Administer Route and Dosage | Time from Symptoms Onset to TCZ Start (days) | Time from Hospital Admission to TCZ Start (days) | Death (%) (p Value) |
|---|---|---|---|---|---|---|---|---|---|---|
| Albertini [26] | Europe | Efficacy of TCZ on respiratory clinical conditions | 44 TCZ: 22 ST: 22 |
65 | 70.45 | No-IMV/IMV | 8 mg/kg | 10 | NA | TCZ: 13.6 ST: 9 (p = NA) |
| Ayerbe [27] | Europe | Mortality with Heparin therapy | 2019 TCZ: 421 ST: 1598 |
67.57 | 61.268 | No-IMV/IMV | NA | NA | NA | TCZ: 21.14 ST: 12.33 (p = NA) |
| Balena [28] | Europe | Crude mortality and AdE | 164 TCZ:16 ST:148 |
77.5 | 48 | No-IMV/IMV | 8 mg/kg i.v. | NA | NA | TCZ: 31 ST:23 (p = 0.074) |
| Biran [29] | America | Mortality in patients requiring ICU |
630 TCZ:210 ST:420 |
65 | 58.413 | No-IMV/IMV | 8 mg/kg i.v. | 7 | NA | TCZ: 49 ST: 61 (p = 0.0040) |
| Campochiaro [30] | Europe | Clinical improvement and overall survival | 59 TCZ:32 ST:27 |
62 | 86.154 | No- IMV | 400 mg i.v., repeated after 24 h (n = 9) | 11 | NA | TCZ: 16 ST: 33 (p = 0.15) |
| Canziani [31] | Europe | Mortality | 128 TCZ:64 ST:64 |
63.5 | 73 | No-IMV/IMV | 8 mg/kg i.v., repeated after 24 h (n = 61) | 13 | NA | TCZ: 27 ST: 38 (p = 0.185) |
| Capra [32] | Europe | Mortality | 85 TCZ:62 ST:23 |
66.5 | 75 | No- IMV | 400 mg i.v. 324 mg s.c. |
NA | 4 | TCZ: 3.22 ST: 47.8 (p = 0.004) |
| Colaneri [33] | Europe | ICU admission and 7-day mortality rate | 112 TCZ:21 ST:91 |
63.03 | 73.215 | No- IMV | 8 mg/kg i.v. and repeated after 12 h | NA | NA | TCZ: 24 ST: 21 (p = 0.84) |
| De Rossi [34] | Europe | Survival rate | 158 TCZ:90 ST:68 |
66.95 | 71.52 | No- IMV/IMV | 400 mg i.v. or 324 mg s.c. |
NA | 9 | TCZ: 7.7 ST: 50 (p < 0.001) |
| Eimer [35] | Europe | 30-day death after admission to ICU | 87 TCZ:29 ST:58 |
56.5 | 84 | IMV | 8 mg/kg i.v. | 11 | NA | TCZ: 17.2 ST: 32.8 (p = 0.20) |
| Galvan-Romàn [36] | Europe | Need for IMV, mortality | 146 TCZ: 58 ST: 88 |
63 | 66 | No-IMV/IMV | 8 mg/kg (max 800 mg), repeated after 12 h | NA | NA | TCZ: 24 ST: 18 (p = NA) |
| Garcia [37] | Europe | ICU admission and/or death | 171 TCZ: 77 ST: 94 |
61 | 65.498 | No- IMV | 400 mg/24 h iv (Pts ≤ 75 kg) 600 mg/24 h iv (Pts > 75 kg) with the possibility to repeat the dose every 12 h up to 3 doses. |
NA | 6.5 | TCZ: 10.3 ST: 18 (p = 0.156) |
| Gokhale [38] | Asia | Overall survival | 161 TCZ: 70 ST: 91 |
53.5 | 62.11 | No-IMV/IMV | 400 mg/die i.v. and repeated after 24 h (n = 9) | NA | 12 | TCZ: 47 ST: 67 (p = 0.011) |
| Guaraldi [39] | Europe | IMV requirement and/or death | 544 TCZ: 179 ST: 365 |
67 | 66 | No- IMV | 8 mg/kg i.v., repeated after 12 h, or 324 mg s.c. | NA | 7 | TCZ: 7 ST: 20 (p < 0.001) |
| Hill [40] | America | Clinical improvement | 88 TCZ: 43 ST: 45 |
NA | 69 | No-IMV/IMV | 400 mg i.v. | NA | 2 | TCZ: 21 ST: 33 (p = 0.26) |
| Holt [41] | America | Survival time and mortality |
62 TCZ: 32 ST: 30 |
68.5 | 70.97 | No-IMV/IMV | 400 mg i.v. | NA | 2 | TCZ: 31.25 ST: 30 (p = 0.36) |
| Kewan [42] | North America | Median LOS, ICU LOS, duration of IMV, mortality. | 51 TCZ: 28 ST: 23 |
66 | 61 | No-IMV/IMV | 400 mg i.v. | NA | 2 | TCZ: 11 ST: 9 (p > 0.99) |
| Kimmig [43] | North America | Infection and clinical outcomes (discharged, died) | 60 TCZ:28 ST: 32 |
63.15 | 55.856 | No-IMV/IMV | 400 mg i.v. with possible redosing | NA | NA | TCZ: 35.2 ST: 19.3 (p = 0.020) |
| Klopfenstein [44] | Europe | IMV requirement and/or death | 206 TCZ: 30 ST;176 |
73.75 | 60.7 | No- IMV | 8 mg/kg i.v. (1 or 2 doses) |
12 | NA | TCZ: 26.7 ST: 37.5 (p = 0.253) |
| Klopfenstein [45] | Europe | ICU admission and/or death | 44 TCZ: 19 ST: 25 |
74.95 | NA | No- IMV | NA | 13 | NA | TCZ: 25 ST: 48 (p = 0.066) |
| Martinez-Sanz [46] | Europe | Time to death | 1229 TCZ: 260 ST: 969 |
65.5 | 72.246 | No-IMV/IMV | NA | NA | 4 | TCZ: 23 ST: 12 (p < 0.001) |
| Matthew [47] | America | Overall mortality 30 days from the date of intubation | 115 TCZ: 45 ST: 70 |
58.4 | 69.566 | IMV | 400 mg i.v. | NA | 2.5 | TCZ: 29 ST: 40 (p = 0.23) |
| Menzella [48] | Europe | In-hospital mortality rate | 79 TCZ: 41 ST: 38 |
66.5 | 70.89 | No-IMV/IMV | 8 mg/kg i.v (max 800 mg) or 162 mg s.c |
NA | NA | TCZ: 24 ST: 53 (p = 0.01) |
| Mikulska [49] | Europe | Failure-free survival and overall survival | 95 TCZ: 29 ST: 66 |
69 | 67.35 | No- IMV | 8 mg/kg i.v. 162 mg s.c. |
NA | 7 | TCZ: 14.2 ST: 28.1 (p = NA) |
| Moreno-Pérez [50] | Europe | Death, LOS | 236 TCZ: 77 ST: 159 |
59.5 | 59.746 | No-IMV/IMV | 600 mg i.v., with second or third dose (400 mg i.v.) |
10 | NA | TCZ: 12.9 ST: 1.9 (p = 0.002) |
| Pan-Li [51] | Asia | Improvement and death | 58 TCZ: 39 ST: 19 |
73.9 | 63.8 | No- IMV/IMV | 4–8 mg/kg (max dose of 800 mg) | NA | NA | TCZ: 30.8 ST: 47.3 (p = NA) |
| Patel [52] | America | Clinical outcomes and survival | 83 TCZ: 42 ST: 41 |
67.5 | 50.603 | No-IMV/IMV | NA | NA | 4 | TCZ: 21.4 ST: 26.8 in severe Pts TCZ: 14.2 ST: 28.6 (p = NA) |
| Potere [53] | Europe | Overall survival and survival-free of IMV | 80 TCZ: 40 ST: 40 |
55.25 | 65 | No- IMV | 324 mg s.c. (bid) | NA | 5 | TCZ: 5 ST: 27.5 (p = 0.006) |
| Quartuccio [54] | Europe | Optimal patient selection to be treated with TCZ | 111 TCZ: 42 ST: 69 |
58.3 | 69.4 | No-IMV/IMV | 8 mg/kg i.v. | 8.4 | NA | TCZ: 9.5 ST: 0 (p = NA) |
| Ramaswamy [55] | North America | Mortality | 86 TCZ: 21 ST: 65 |
63.7 | 57 | No- IMV | 400 mg i.v. 8 mg/kg i.v. |
NA | NA | TCZ: 14 ST: 12 (p = 0.81) |
| Rodríguez-Bano [56] | Europe | Intubation or death | 432 TCZ: 88 ST: 343 |
67.5 | 77.702 | No- IMV | 400–600 mg i.v. with second or third dose | 10 | NA | TCZ: 2.3 ST: 11.9 (p = 0.004) |
| Rojas-Marte [57] | North America | Mortality | 193 TCZ = 96 ST = 97 |
60.4 | 71 | No-IMV/IMV | NA | NA | NA | TCZ: 52 ST: 62 (p = 0.09) excluding intubated TCZ: 6 ST: 27 (p = 0.024) |
| Roomi [58] | America | Clinical effectiveness of HCQ and TCZ | 170 TCZ: 134 ST: 36 |
61.8 | 48.83 | No- IMV | NA | NA | NA | TCZ: 4.5 ST: 36 (p = 0.44) |
| Rossotti [59] | Europe | Overall survival and hospital discharge | 222 TCZ: 74 ST: 148 |
59 | 81.532 | No-IMV/IMV | 8 mg/kg i.v. (max dose of 800 mg) with possible second dose | NA | NA | TCZ: 25.7 ST: 60.1 (p = 0.035) |
| Roumier [60] | Europe | IMV requirement and death | 59 TCZ: 30 ST: 29 |
65 | 80 | No- IMV | 8 mg/kg i.v. (renewable once) | 14 | NA | TCZ: 17.2 ST: 18.7 (p = 0.837) unadjusted TCZ: 10 ST: 31 (p = 0.41) |
| Ruiz-Antora’n [61] | Europe | Mortality | 506 TCZ: 268 ST: 238 |
68 | 64.03 | No- IMV | 600 mg (3 doses n = 22, 2 doses n = 92, 1 dose n = 154) |
11 | NA | TCZ: 16,8 ST: 31,5 (28days/ death) (p = 0.001) |
| Somers [62] | North America | Survival probability after intubation |
154 TCZ = 78 ST = 76 |
58 | 66 | IMV | 8 mg/kg i.v. (max 800 mg) | NA | 3.9 | 18% in TCZ 36% in ST (28days/ death) (p = 0.01) |
| Tsai [63] | America | Mortality | 274 TCZ: 84 ST: 190 |
63 | 61.4 | No- IMV | 400 mg i.v. (n = 53) 600 mg i.v. (n = 3) 800 mg i.v (n = 10) (second dose n = 4) |
NA | NA | TCZ: 21.4 ST: 9.4 (p = NA) |
| Van den Eynde [64] | Europe | Mortality | 139 TCZ = 21 ST = 118 |
73.2 | 66.91 | No- IMV | 400 mg or 600 mg (once or twice daily) | NA | NA | TCZ: 33,3 ST: 58,4 (p < 0.001) |
| Wadud [65] | North America | LOS, days on ventilator, in-hospital and ICU, mortality. | 94 TCZ: 44 ST: 50 |
55.5 | NA | IMV | NA | NA | NA | 3TCZ: 8.64 ST: 52 (p < 0.001) |
Pts, Patients; TCZ, Tocilizumab; ST, Standard Therapy; AdE, adverse events; HCQ, hydroxychloroquine; LOS, length of stay; IMV, Invasive Mechanical Ventilation; NA, Not Available. In the Table the p-values statistically significant are reported in bold.