Systematic Reviews
Copyright ©The Author(s) 2022.
World J Crit Care Med. Jul 9, 2022; 11(4): 269-297
Published online Jul 9, 2022. doi: 10.5492/wjccm.v11.i4.269
Table 1 Summary of studies addressing interleukin-1 blockers on coronavirus disease 2019
Ref.
Patients
Intervention
Comparison
Outcome
CORIMUNO-19 Collaborative group[74], RCTHospitalized patient with mild-to-moderate pneumonia, non-ICU admittedAnakinra (200 mg twice a day on days 1-3, 100 mg twice on day 4, 100 mg once on day 5) (n = 59)Standard care (n = 55)No difference in NIV/MV/death at day 4. Stopped early following the recommendation of the data and safety monitoring board
Cavalli et al[75], observationalPneumonia with moderate-to-severe ARDS and hyperinflammation (non-MV, non-ICU admitted)Anakinra (high dose: 5 mg/kg twice a day intravenously, n = 29; or low dose: 100 mg twice a day subcutaneously, n = 7)Standard care (retrospective cohort) (n = 16)Survival. High-dose anakinra: 72%, SC: 56%, P = 0.009
Huet et al[76], observationalBilateral pneumonia (non-ICU admitted)Anakinra (100 mg twice daily for 72 h, followed by 100 mg daily for 7 d) (n = 52)Standard care (historical group) (n = 44)Death/MV. Anakinra: HR = 0.22 (95%CI: 0.11-0.41), P < 0.0001. Death. Anakinra: HR = 0.30 (95%CI: 0.12-0.71), P = 0.0063. MV: Anakinra: HR = 0.22 (95%CI: 0.09-0.56), P = 0.0015
Kooistra et al[77], observationalICU admitted pneumonia (MV: 100%)Anakinra (300 mg iv, followed by 100 mg iv/6 h) (n = 21)Standard care (n = 39)No differences in duration of MV, ICU length of stay, or mortality
Table 2 Summary of studies addressing interleukin-6 blockers on coronavirus disease 2019 (randomized clinical trials and observational studies including critically ill patients)
Ref.
Patients
Intervention
Comparison
Outcomes
Overinfection rate
Salama et al[110], RCT377TCZ (8 mg/kg, 1-2 doses)PlaceboMV/ECMO/mortality 28 d; 19.3% TCZ vs 12% placebo, P = 0.004TCZ 10% vs placebo 12.6%
Rosas et al[113], RCT438TCZ (8 mg/kg, 1-2 doses)PlaceboMortality: NS. Hospital LOS: TCZ: 20, placebo: 28 d (P = 0.037). ICU admission: TCZ: 23.6%, SC: 40.6% (P = 0.01). ICU, LOS: TCZ: 9.8, SC: 15.5 d (P = 0.045)TCZ 21% vs placebo 25.9%
Stone et al[90], RCT242TCZ (8 mg/kg, max 800 mg, 1 dose)PlaceboMV or death. TCZ: 10.6%, SC: 12.5% (NS). Clinical worsening. TCZ: 19.3%, SC: 17.4% (NS)TCZ 8.15% vs placebo 17.1%
Salvarani et al[111], RCT123TCZ (8 mg/kg, max 800 mg, 1-2 doses)Standard of careNSTCZ 1.7% vs TE 6.3%
Mariette et al[112], RCT131TCZ (8 mg/kg, max 800 mg, 1-2 doses)Standard of careNIV/MV/death at day 4. TCZ: 19%, SC: 28% (NS). Survival without HFNO/NIV/MV at day 14. TCZ: 24%, SC: 36% (probability: 95%). 28 d mortality. TCZ: 10.9%, SC: 11.9% (NS)TCZ 3.2% vs TE 16.4%
RECOVERY Collaborative Group[115], RCT4166TCZ (different regimes)Standard of care28 d mortality: TCZ: RR = 0.86 (95%CI: 0.77-0.96, P = 0.006)Not available
REMAP-CAP Investigators et al[116], RCT826TCZ (8 mg/kg, max 800 mg, 1-2 doses) (n = 366). Sarilumab (400 mg) (n = 48)Standard of careDays free of respiratory/hemodynamic support at day 21. TCZ: 10 d, sarilumab: 11 d, SC: 0 d. Hospital mortality. TCZ: 28%, sarilumab: 22.2% SC: 35.8% (probability TCZ better: 99.6%, probability sarilumab better: 99.5%)TCZ 0.2% vs TE 0%
Veiga et al[114], RCT129TCZ (8 mg/kg, max 800 mg)Standard of careStopped early due to higher mortality in TCZ patientsPB 15% vs SC 16%
Tleyjeh et al[121], MA9850TCZ (variable regimen)Standard of careMortality: TCZ: OR = 0.58 (0.51-0.66)TCZ: RR = 0.63 (0.38-1.06)
Gupta et al[106], OS3491TCZ (regimen not specified)Standard of careHospital mortality. TCZ: HR = 0.71 (95%CI: 0.56-0.92)TCZ 32.3% vs SC 31.1%
Somers et al[108], OS154TCZ (8 mg/kg, max 800 mg)Standard of careMortality. TCZ: HR = 0.54 (95%CI: 0.35-0.84)TCZ 54% vs SC 26%. Pneumonia 45% vs 20%. Bacteremia 14% vs 9%
Fisher et al[109], OS115TCZ (400 mg)Standard of care30 d mortality. TCZ: OR = 1.04 (95%CI: 0.27-3.75)TCZ 28.9% vs SC 25.7%
Biran et al[102], OS764TCZ (400 mg, 1-2 doses)Standard of careHospital mortality. TCZ: HR = 0.64 (95%CI: 0.47-0.87, P = 0.004)TCZ 17% vs SC 13%
Guaraldi et al[101], OS544TCZ (8 mg/kg, max 800 mg, 2 doses) (n = 179)Standard of careDeath/MV. TCZ: HR = 0.61 (95%CI: 0.4-0.92), P = 0.020TCZ 13% vs SC 4%
Rossotti et al[105], OS222TCZ (8 mg/kg, max 800 mg, 1-2 doses) (n = 74)Standard of careSurvival rate TCZ: HR = 2.004 (95%CI: 1.050-3.817), P = 0.035. Survival rate in critically ill patient. HR = 30.055 (95%CI: 1.420-636.284), P = 0.029TCZ 24.4%; SC: NA
Rojas-Marte et al[107], OS193TCZ (regimen not specified)Standard of careMortality TCZ: 52%, SC: 62%, P = 0.09. Mortality in non-ventilated patients: TCZ: 6.1%, SC: 26.5%, P = 0.024Bacteremia: TCZ 12.5% vs SC 23.7%. Fungemia: TCZ 4.2% vs SC 3.1%
Table 3 Coronavirus disease 2019 patients treated with tocilizumab and corticosteroids
Ref.
Tocilizumab group
Control
Salama et al[110], RCT80.3%87.5%
Rosas et al[113], RCT36.1%54.9%
Stone et al[90], RCT11%6%
Salvarani et al[111], RCT10%7.6%
Mariette et al[112], RCT33%61%
RECOVERY Collaborative Group[115], RCT82%82%
REMAP-CAP Investigators et al[116], RCT> 80%
Veiga et al[114], RCT69%73%
Gupta et al[189], observational18.7%12.6%
Somers et al[108], observational29%20%
Fisher et al[109], observational73.3%78.6%
Biran et al[102], observational46%42%
Guaraldi et al[101], observational30%17%
Rossotti et al[105], observationalNot reported
Rojas-Marte et al[107], observational43%33%
Table 4 Summary of studies using corticosteroids in coronavirus disease 2019
Ref.
Patients
Treatment regimen
Population
Mortality2
ICU administration
In-hospital stay
Secondary infections
RECOVERY Collaborative Group et al[177], RCT11303DXM 6 mg daily × 10 dIn-hospitalDecrease 2.8% RR 0.83NSIncrease discharged 28 d (3.7%)NA
RECOVERY Collaborative Group et al[177], RCT1007DXM 6 mg daily × 10 dMVDecrease 12.1% RR 0.64NAIncreased discharged 28 d (9.7% RR 1.48)NA
Tomazini et al[176], RCT299DXM 20 mg × 5d + DXM 10 mg × 5dICU patientsDecrease 2.4% (alive or ventilator-free)NADXM 21.9% vs 29.1% standard. (7.9% vs 9.5% bacteremia)
Jeronimo et al[178], RCT416MPD (0.5 mg/kg twice daily) × 5dIn-hospitalNSNS (MV)NSNo significant differences
Dequin et al[179], RCT149HCT 200 mg daily × 7d then decrease dose × 7d (14 d)ICU patientsNSNSNA
Angus et al[180], RCT384HCT 50 or 100 mg/6 h × 7 dICU patients93% and 80% of superiority in organ support freeNSNA
Edalatifard et al[181], RCT68MPD 250 mg × 3 dIn-hospitalDecrease 37%No patients on MVDecrease 4.6 d2.9% (1 pt) in MPD vs 0% (0 pt) standard
Corral-Gudino et al[188], RCT185MPD 40 mg/12 h × 3 d, then MPD 20 mg/12 h × 3 dIn-hospitalDecrease 24% composite death, ICU Adm or NIVNSNA
Kim et al[186], MA49569Variable regimensICU patientsOR 0.54 (0.40-0.73)NANSNA
Van Paassen et al[187], MA20197Variable regimensIn- hospitalOR 0.72 (0.57-0.87)RR 0.71 (0.54-0. 97)NSNA
Table 5 Summary of randomized clinical trials and observational studies including critically ill patients addressing intravenous immunoglobulin and hyperimmune immunoglobulin on coronavirus disease 2019
Ref.
Patients
Intervention
Comparison
Outcome
Xie et al[193], observationalSevere/critical pneumonia and. Lymphocyte count < 0.5 × 109/L (18.9% on MV, 13.8% on NIV/HFNC)IVIG (20 g/d)> 48 h after admission (n = 28) vs < 48 h after admission (n = 30)Reduction in 28-d mortality (23% vs 57%, P = 0.009), need for MV (6.67% vs 32.14%, P = 0.001) and LOS (11.5 ± 1.0 vs 16.9 ± 1.6 d, P = 0.005) in the < 48 h group
Tabarsi et al[194], RCTSevere pneumonia (36.9% on MV, 78.6% ICU-admitted)IVIG (400 mg/kg/24 h for 3 d) (n = 52)Standard care (n = 32)No difference in mortality (46.1% vs 43.7%, P = 0.83), need for MV (40.4% vs 31.2%, P = 0.39) or ICU admission (75% vs 84.4 %, P = 0.3)
Gharebaghi et al[195], RCTSevere pneumonia with persisting symptoms or need for supplementary oxygen to maintain SaO2 > 90% after 48 h of treatmentIVIG (20 g daily for three days) (n = 30)Standard care (n = 29) Lower in-hospital mortality (20% vs 48.3%, P = 0.022). Mortality. IVIG: OR = 0.003 (95%CI: 0.001-0.815, P = 0.042)
Agarwal et al[200], RCTModerate pneumoniaConvalescent plasma (200 mL, 2 doses) (n = 235)Standard care (n = 229)Disease progression or mortality: No difference
Li et al[201], RCTSevere/critical pneumonia (NIV/HFNO: 42.7%, MV/ECMO: 24.3%)Convalescent plasma (4-13 mL/kg) (n = 52)Standard care (n = 51)No improvement in time to clinical improvement within 28 d