Table 1 Characteristics of included studies

Declercq et al. [28]

Inpatient

Multicenter in Belgium;

randomized, controlled, open-label

N^Total: 118 (with other interventions: 342)

n^Anakinra: 43^a

n^Control: 72

Median (IQR):

A: 65 (54–70)

C: 63 (56–73)

IMV:

A: 8/43 (19); C: 9/72 (13)

non-IMV:

A: 16/43 (37); C: 23/72 (32)

supplemental oxygen only^b:

A: 19/43 (44); C: 39/72 (54)

Not requiring supplemental oxygen:

A: 0/43 (0); C: 1/72 (1)

100 mg (s.c.) daily for 28 days or until hospital discharge on top of standard of care

If glomerular filtration rate < 30 ml/min per 1,73 m2, the dosing was lowered to 100 mg once every other day

Standard of Care (not specified)

Antibiotics

A: 21 (49%); C: 34 (47%)

Glucocorticoids

A: 29 (67%); C: 43 (60%)

Hydroxychloroquine

A: 7 (16%); C: 8 (11%)

Remdesivir

A: 3 (7%); C: 3 (4%)

Derde et al. [31]

Inpatient

Multicenter in UK, Australia, Netherlands, Ireland, New-Zealand, Canada, Finland, Italy and Saudi Arabia;

randomized, controlled,

open-label

N^Total: 771 (with other interventions: 2216)

n^Anakinra: 373

n^Control: 406

Mean (SD):

Severe State

A: 59.8 (11.9)

C: 61.1 (12.9)

Moderate State

A: 36.0 (17.0)

C: 67.0 (13.7)

IMV:

A: 138/373 (37); C: 122/406 (30)

ECMO:

A: 0/373 (0); C: 1/406 (0)

No respiratory support/supplemental oxygen only:

A: 1/373 (0); C: 2/406 (0)

300 mg (i.v.) as loading dose, followed by

100 mg every 6 h on days 1–14 or until either free from IMV for more than 24 h, or discharge from ICU

If creatinine clearance < 30 ml/min or receiving renal replacement therapy, the dosing interval was increased to 12 h

Standard of Care (not specified)

Remdesivir (n (%))

A: 109 (29.5), C: 105 (26.1)

Steroids (n (%))

A: 317 (85.9), C: 269 (66.9%)

Kharazmi et al. [35]

Inpatient

One center in Iran;

randomized, controlled, open-label

N^Total: 30

n^Anakinra: 15

n^Control: 15

Mean (SD):

A: 49.25 (19.12)

C: 59.00 (1.79)

IMV or ECMO:

A: 2/15 (13); C: 3/15 (20)

non-IMV or high flow oxygen:

A: 10/15 (67); C: 6/15 (40)

low flow supplemental oxygen only:

A: 3/15 (20); C: 6/15 (40)

100 mg (i.v.) daily until discharge or a maximum of 14 days

Standard of Care (not specified)

Corticosteroid

A: 11 (73,3%); C: 8 (53,3%)

Favipiravir

A: 9 (60%); C: 4 (26,67%)

Interferon

A: 14 (93,3%); C: 9 (60%)

Lopinavir/ritonavir

A: 7 (46,67%); C: 12 (80%)

Remdesivir

A: 2 (13,33%); C: 4 (26,67%)

Kyriazopoulou et al

[10]

Inpatient

Multicenter in

Greece and Italy;

randomized, double-blinded, placebo-controlled

N^Total: 594

n^Anakinra: 405

n^Control: 189

Mean (SD):

A: 62 (11.4)

C: 61.5 (11.3)

no supplemental oxygen:

A: 39/405 (10); C: 11/189 (6)

low or high flow supplemental oxygen:

A: 366/405 (90); C: 178/189 (94)

suPAR ≥ 6 ng/ml

100 mg (s.c.) daily for 7–10 days

Placebo:

0.9% sodium chloride daily for 7–10 days

Any glycopeptide

A: 24 (5.9%); C: 19 (10.1%)

Azithromycin

A: 76 (18.8%); C: 35 (18.5%)

β-lactamase inhibitors

A: 23 (5.7%); C: 10 (5.3%)

Ceftaroline

A: 75 (18.5%); C: 32 (16.9%)

Ceftriaxone

A: 155 (38.3%); C: 85 (45.0%)

Dexamethasone enrollment

A: 342 (84.4%); C: 168 (88.9%)

Linezolid

A: 45 (11.1%); C: 22 (11.6%)

Low-molecular-weight heparin

A: 385 (95.1%); C: 175 (92.6%)

Piperacillin/tazobactam

A: 64 (15.8%); C: 36 (19.0%)

Remdesivir

A: 298 (73.6%); C: 141 (74.6%)Respiratory fluoroquinolone

A: 53 (13.1%); C: 24 (12.7%)

Tharaux

[40]

Inpatient

Multicenter in

France;

randomized,

controlled, open-label

N^Total = 114

n^Anakinra = 59

n^Control = 55

Median (IQR):

A: 67 (55.5–74.3)

C: 64,9 (59.5–78.3)

Low flow supplemental oxygen

A: 59/59 (100)

C: 55/55 (100)

2 × 200 mg (i.v.) daily on days 1–3, followed by 2 × 100 mg (i.v.) daily on day 4 and 100 mg (i.v.)/daily on day 5

In the absence of improvement (reduction in oxygen requirement by > 50%) after 3 days, decision by practitioner:

2 × 200 mg(i.v.) daily d4–6, then

2 × 100 mg (i.v.) d7, then

1 × 100 mg (i.v.) d8

Standard of Care:

Antibiotics, antiviral meds, corticosteroids, vasopressors, anticoagulants (practitioner's choice)

Anticoagulants A: 33 (59%); C: 29 (53%)

Azithromycin

A: 11 (19%); C: 14 (25%)

Dexamethasone

A: 1 (2%); C: 0 (0%)

Hydroxychloroquine

A: 2 (3%); C: 4 (7%)

Lopinavir–ritonavir or lopinavir

A: 1 (2%); C: 2 (4%)

Other glucocorticoids

A: 6 (10%); C: 8 (15%)