Highlight
- •This is the first study comparing tocilizumab to standard of care in severe COVID-19
- •Tocilizumab in severe COVID-19 patients did influence 28-day clinical outcomes
- •Tocilizumab safety was satisfactory except for ICU-admitted patients
Abstract
Background
Methods
Results
Conclusions
Keywords
1. Introduction
- Dong E
- Du H
- Gardner L
- Grasselli G
- Zangrillo A
- Zanella A
- et al.
- Kaur S
- Bansal Y
- Kumar R
- Bansal G
- Ruan Q
- Yang K
- Wang W
- Jiang L
- Song J
- Liu B
- Li M
- Zhou Z
- Guan X
- Xiang Y
- Luo P
- Liu Y
- Qiu L
- Liu X
- Liu D
- Li J
- Xu X
- Han M
- Li T
- et al.
- Di Giambenedetto S
- Ciccullo A
- Borghetti A
- et al.
2. Methods
2.1 Patients and setting
2.2 Eligibility criteria
2.3 Treatment
2.4 Study population
2.5 Outcomes
- Cao B
- Wang Y
- Wen D
- et al.
WHO | Coronavirus disease (COVID-2019) R&D. https://www.who.int/blueprint/priority-diseases/key-action/novel-coronavirus/en/. Accessed April 19, 2020.
2.6 Monitoring of adverse events
2.7 Statistical analysis
3. Results
3.1 Baseline patients’ characteristics
Patients features | Tocilizumab (32 patients) | Standard treatment (33 patients) | p-value |
---|---|---|---|
Age (years), median (IQR) | 64 (53 – 75) | 60 (55 – 75.5) | 0.52 |
Sex (male), n (%) | 29 (91) | 27 (82) | 0.47 |
Duration of symptoms (days), median (IQR) | 11 (8 – 14) | 9 (8 – 10) | 0.14 |
PaO2:FiO2 ratio, median (IQR) | 107 (82 – 181) | 124 (91 – 172) | 0.40 |
NIV, n (%) | 25 (78) | 20 (61) | 0.18 |
FiO2, median (IQR) | 60 (60 – 80) | 80 (50 – 80) | 0.96 |
Body temperature (°C), median (IQR) | 37.6 (37.0 – 38.3) | 38.2 (37.3 – 38.6) | 0.06 |
CRP (mg/L), median (IQR) | 156 (100 – 208) | 169 (98 – 226) | 0.63 |
LDH (U/L), median (IQR) | 469 (362 – 548) | 479 (394 – 591) | 0.26 |
Ferritin (ng/mL), median (IQR) | 1400 (1027 – 2777) | 1448 (793 – 4131) | 0.88 |
Comorbidities, n (%) | 20 (62) | 20 (61) | |
Smoking | 0 | 2 (6) | 0.49 |
CKD | 3 (9) | 5 (15) | 0.71 |
Arterial hypertension | 12 (37) | 16 (48) | 0.32 |
COPD | 1 (3) | 2 (6) | 0.61 |
Cancer | 2 (6) | 1 (3) | 0.61 |
T2DM | 4 (12) | 6 (18) | 0.51 |
CAD | 4 (12) | 6 (18) | 0.51 |
3.2 Tocilizumab treatment
3.3 Survival and clinical outcome

Clinical status | Baseline TCZ | Baseline ST | Day 28 TCZ | Day 28 ST |
---|---|---|---|---|
1. Discharged from hospital, n (%) | 0 | 0 | 20 (63) | 16 (48) |
2. Hospitalization, not requiring supplemental O2, n (%) | 0 | 0 | 2 (6) | 2 (6) |
3. Hospitalization, requiring supplemental low-flow O2, n (%) | 0 | 0 | 2 (6) | 2 (6) |
4. Hospitalization, requiring NIV and/or high-flow supplemental O2, n (%) | 32 (100) | 33 (100) | 3 (9) | 1 (3) |
5. Hospitalization, requiring invasive mechanical ventilation or ECMO, n (%) | 0 | 0 | 0 | 1 (3) |
6. Death, n (%) | 0 | 0 | 5 (16) | 11 (33) |

3.4 Safety and adverse events
3.5 Predictors of survival and clinical improvement in tocilizumab-treated patients
Survived (27 patients) | Dead (5 patients) | p-value | |
---|---|---|---|
Age (years), median (IQR) | 61 (53 – 73) | 77 (74 – 81) | 0.003 |
Sex (male), n (%) | 25 (93) | 4 (80) | 0.41 |
PaO2:FiO2, median (IQR) | 118 (86 – 181) | 69 (65 – 94) | 0.034 |
Body temperature (°C), median (IQR) | 37.5 (38.9 – 38.2) | 38 (37.5 – 38) | 0.85 |
CRP (mg/L), median (IQR) | 139 (88.5 – 204) | 185 (146 – 185) | 0.46 |
LDH (U/L), median (IQR) | 439 (357 – 546) | 443 (438 – 456) | 0.94 |
NIV, n (%) | 20 (74) | 5 (100) | 0.56 |
Duration of symptoms (days), median (IQR) | 11 (7 – 14) | 12 (9 – 15) | 0.36 |
CKD, n (%) | 3 (9) | 0 | 0.99 |
Arterial hypertesion, n (%) | 11 (34) | 1 (20) | 0.63 |
COPD, n (%) | 0 | 1 (20) | 0.16 |
Cancer, n (%) | 2 (7) | 0 | 0.99 |
T2DM, n (%) | 3 (11) | 1 (20) | 0.51 |
CAD, n (%) | 2 (7) | 2 (40) | 0.10 |
Re-treatment, n (%) | 8 (30) | 1 (20) | 0.99 |
Improved (22 patients) | Not improved (10 patients) | p-value | |
---|---|---|---|
Age (years), median (IQR) | 59,5 (51 – 72) | 74 (69.5 – 78) | 0.009 |
Sex (male), n (%) | 22 (100) | 7 (70) | 0.024 |
PaO2:FiO2, median (IQR) | 137 (90 – 185) | 86 (68 – 103) | 0.008 |
Body temperature (°C), median (IQR) | 37.6 (36.5 – 38.3) | 37.5 (37.4 – 38.1) | 0.77 |
CRP (mg/L), median (IQR) | 128 (69 – 187) | 186 (137 – 2702) | 0.038 |
LDH (U/L), median (IQR) | 429 (354 – 552) | 446 (426 – 564) | 0.54 |
NIV, n (%) | 16 (73) | 9 (41) | 0.39 |
Duration of symptoms (days), median (IQR) | 11 (7 – 14) | 11.5 (10 – 14) | 0.28 |
CKD, n (%) | 2 (9) | 1 (10) | 0.99 |
Arterial hypertension, n (%) | 7 (32) | 5 (50) | 0.44 |
COPD, n (%) | 0 | 1 (10) | 0.31 |
Cancer, n (%) | 1 (4) | 1 (10) | 0.53 |
T2DM, n (%) | 3 (14) | 1 (10) | 0.99 |
CAD, n (%) | 2 (9) | 2 (20) | 0.57 |
Re-treatment, n (%) | 5 (23) | 4 (40) | 0.41 |


4. Discussion
Qin C, Zhou L, Hu Z, et al. Dysregulation of immune response in patients with COVID-19 in Wuhan, China [published online ahead of print, 2020 Mar 12]. Clin Infect Dis. 2020;ciaa248. doi:10.1093/cid/ciaa248.
U.S. National Library of Medicine, ClinicalTrials.gov(www.clinicaltrials.gov) accessed on 06 May 2020.
- Luo P
- Liu Y
- Qiu L
- Liu X
- Liu D
- Li J
- Xu X
- Han M
- Li T
- et al.
- Di Giambenedetto S
- Ciccullo A
- Borghetti A
- et al.
- Y Shu H
- Xia J
- Liu H
- et al.
- Grasselli G
- Pesenti A
- Cecconi M
- Cavalli G
- De Luca G
- Campochiaro C
- et al.
5. Conclusions
Declaration of competing interest
Acknowlegments
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- Tocilizumab for severe COVID-19: A promising intervention affecting inflammation and coagulationEuropean Journal of Internal MedicineVol. 76
- PreviewThe COVID-19 pandemic is causing significant morbidity and mortality worldwide. Although most patients experience predominantly a respiratory tract infection, a proportion of patients progresses to a more severe and systemic disease, characterised by treatment-resistant pyrexia, acute lung injury with adult respiratory distress syndrome (ARDS), shock, and multiple organ dysfunction, associated with substantial mortality [1,2].
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