Summary of the effects of all available interventions compared to standard care

The information presented in the figure below comes from a living network meta-analysis that combines all the available evidence on drug therapies for COVID-19. This statistical approach allows us to obtain estimates of effect for all potential comparisons, even those that have not been compared head-to-head in trials. We present the most trustworthy estimates of absolute effect for all available drug therapies for COVID-19 versus standard care. The colours distinguish between the most beneficial and harmful interventions compared to standard care, while the shading of cells indicates the certainty of the evidence of a particular drug based on the GRADE approach.

High/ moderate certainty

Low certainty

Very low certainty

No Evidence

Baseline risk

Minimal important difference

	Mortality (closest to 90 days)	Mechanical Ventilation (closest to 90 days)	Adverse effects leading to discontinuation (within 28 days)	Admission to hospital (within 28 days)	Venous thromboembolism	Clinically important bleeding	Length of hospital stay (in days)	Time to symptom resolution (in days)	Duration of mechanical ventilation (in days)
Baseline risk	130 per 1,000	116 per 1,000	0 per 1,000	43 per 1,000	32 per 1,000	17 per 1,000	12.8 days	9.9 days	14.7 days
Minimal important difference	10 per 1,000	15 per 1,000	20 per 1,000	10 per 1,000	20 per 1,000	20 per 1,000	1 day	1 day	1 day

(acetyl)cysteine

(hydroxy)chloroquine

ACEi/ARB

antihepaciviral

aspirin

aspirin, statins

azithromycin

azithromycin, hydroxychloroquine

azithromycin, hydroxychloroquine, oseltamivir

azithromycin, lopinavir-ritonavir

azithromycin, NSAID

azithromycin, NSAID, corticosteroid

cefepime

ceftazidime

clarithromycin

colchicine

colchicine, emtricitabine, tenofovir, statins

colchicine, statins

corticosteroids (systemic)

doxycycline

doxycycline, ivermectin

doxycycline, lopinavir-ritonavir

electrolyzed saline

emtricitabine, tenofovir

favipiravir

favipiravir, hydrochloroquine

fluvoxamine

full-dose anticoagulant

GM-CSF inhibitor

IL1 inhibitors

IL6 receptor antagonists with corticosteroids (systemic)

IL6 receptor antagonists without corticosteroids (systemic)

inhaled corticosteroids

interferon alfa (subcutaneous)

interferon beta (subcutaneous)

interferon beta (subcutaneous), lopinavir-ritonavir

intermediate-dose anticoagulant

intranasal corticosteroids

intranasal hypertonic polymer spray

ivermectin

JAK inhibitors

lopinavir-ritonavir

melatonin

methylene blue

molnupiravir

nitazoxanide

omega 3

probiotics

proxalutamide

recombinant human granulocyte colony-stimulating factor

remdesivir

serine protease inhibitors

SGLT2 inhibitors

statins

sulodexide

synthetic VIP

tyrosine kinase inhibitors

umifenovir

vitamin C

vitamin D

Mortality (closest to 90 days)	Mechanical Ventilation (closest to 90 days)	Adverse effects leading to discontinuation (within 28 days)****	Admission to hospital (within 28 days)	Venous thromboembolism	Clinically important bleeding	Length of hospital stay (in days)	Time to symptom resolution (in days)	Duration of mechanical ventilation (in days)
-17 (-74 to 66)	-16 (-64 to 53)	0 (-24 to 23)				0.1 (-2.7 to 3.0)
10 (-9 to 30)	28 (3 to 58)	13 (2 to 24)	0 (-21 to 33)			2.0 (0.0 to 3.9)	-1.2 (-2.3 to 0.1)
-15 (-53 to 35)	1 (-36 to 48)	4 (-19 to 27)				-0.5 (-3.6 to 2.6)
-23 (-52 to 10)	-27 (-64 to 22)	0 (-9 to 8)				-1.2 (-4.4 to 2.0)	-2.7 (-4.2 to -0.9)
-7 (-35 to 21)	-8 (-43 to 32)	9 (-6 to 24)	-42 (-43 to -41)	838 (12 to 968)	21 (-14 to 121)	-0.7 (-5.6 to 4.2)
68 (-52 to 255)	69 (-49 to 251)	0 (-9 to 9)				0.3 (-1.0 to 1.7)
-2 (-25 to 25)	-6 (-35 to 26)	-2 (-24 to 20)	6 (-18 to 48)			0.2 (-3.5 to 3.9)	-4.2 (-5.5 to -2.6)
-28 (-88 to 61)	76 (-10 to 191)	5 (-13 to 23)	14 (-25 to 89)			0.4 (-0.8 to 1.5)
164 (-54 to 517)		55 (12 to 99)				6.8 (-1.1 to 14.8)	2.7 (-2.0 to 9.2)
		-1 (-24 to 23)
24 (-85 to 225)	-56 (-115 to 156)
-27 (-107 to 147)	-8 (-107 to 269)
373 (-130 to 870)							-3.2 (-5.4 to -0.3)
372 (-130 to 870)							-2.7 (-5.1 to 0.4)
							-5.4 (-6.7 to -3.5)
-8 (-39 to 18)	-21 (-51 to 11)	25 (-10 to 59)	-6 (-27 to 30)			-0.5 (-3.8 to 2.8)
-49 (-90 to 15)	-29 (-75 to 45)	32 (3 to 61)				0.1 (-7.1 to 7.3)
-20 (-72 to 56)	10 (-54 to 104)	14 (-8 to 35)				-0.0 (-7.2 to 7.2)
-23 (-40 to -7)	-22 (-45 to 4)					1.0 (-2.1 to 4.2)		-1.4 (-3.4 to 0.6)
243 (-33 to 669)	-44 (-105 to 102)					-1.3 (-2.6 to -0.0)	0.2 (-3.1 to 4.4)
-125 (-130 to -83)		10 (-7 to 27)					-1.8 (-4.5 to 1.9)
		-5 (-27 to 17)
-99 (-127 to -30)		27 (-8 to 62)	-26 (-38 to -1)				-4.2 (-6.2 to -1.4)
-25 (-77 to 53)	-18 (-69 to 61)	22 (-2 to 46)				1.0 (-6.3 to 8.2)
34 (-41 to 141)	47 (-23 to 142)	5 (-9 to 20)				-1.2 (-2.4 to -0.1)	-3.0 (-4.2 to -1.6)
2 (-72 to 117)	16 (-54 to 124)					1.0 (-1.8 to 3.8)	3.3 (-2.3 to 11.5)
-34 (-81 to 35)	-25 (-68 to 39)		-12 (-27 to 9)
-5 (-26 to 18)	-34 (-75 to 24)	-3 (-29 to 22)	-11 (-35 to 46)	-16 (-22 to -7)	20 (6 to 40)	0.3 (-1.4 to 1.9)		-0.3 (-1.5 to 0.9)
-26 (-54 to 6)	-3 (-62 to 89)					0.0 (-1.1 to 1.1)	-0.9 (-2.7 to 1.3)
-29 (-64 to 18)	-18 (-61 to 42)	2 (-8 to 12)				-1.0 (-2.2 to 0.2)	-1.6 (-4.0 to 1.4)
-23 (-36 to -7)	-22 (-39 to -2)	-4 (-13 to 4)				-4.9 (-7.8 to -1.9)	-1.5 (-3.7 to 1.7)	-1.0 (-2.2 to 0.2)
11 (-11 to 34)	-44 (-72 to -5)	-2 (-13 to 9)				0.1 (-3.7 to 3.9)	1.0 (-2.0 to 4.8)	-1.6 (-3.3 to 0.1)
	11 (-67 to 140)						-0.1 (-3.0 to 3.7)
816 (221 to 870)	195 (-94 to 820)					0.1 (-1.0 to 1.2)	-1.2 (-4.2 to 2.9)
2 (-28 to 33)	3 (-28 to 41)	0 (-30 to 31)				-0.1 (-3.4 to 3.1)	-1.3 (-3.0 to 0.6)	1.2 (-0.3 to 2.7)
110 (20 to 223)	57 (-8 to 139)	291 (216 to 366)				5.0 (3.3 to 6.7)	-0.1 (-2.6 to 3.1)
19 (-31 to 83)	19 (-61 to 144)			19 (-10 to 67)	-3 (-14 to 24)
-116 (-130 to -35)		-8 (-25 to 9)	0 (-29 to 56)				0.3 (-3.6 to 5.6)
			43 (-24 to 203)
-41 (-77 to 7)	2 (-50 to 75)	3 (-4 to 9)	-18 (-32 to 7)			-0.2 (-3.8 to 3.4)	-1.8 (-3.5 to 0.3)
-44 (-64 to -20)	-23 (-47 to 4)	5 (-6 to 16)				-1.1 (-1.9 to -0.4)	-0.7 (-2.5 to 1.5)	-3.2 (-5.9 to -0.5)
7 (-13 to 29)	12 (-13 to 39)	49 (27 to 72)	-8 (-31 to 36)			0.4 (-2.2 to 3.0)	-0.8 (-2.5 to 1.3)
-119 (-130 to -87)
-57 (-93 to -5)						-4.4 (-9.68 to 0.89)
-116 (-130 to -76)	179 (-116 to 884)	0 (-2 to 2)	-19 (-29 to -5)				-3.3 (-4.8 to -1.6)
-40 (-112 to 110)		2 (-7 to 10)	-14 (-35 to 32)				0.9 (-2.6 to 5.7)
-108 (-128 to -55)
25 (-98 to 293)		0 (-13 to 13)	709 (-43 to 957)				-2.6 (-5.0 to 0.6)
-111 (-119 to -101)	-107 (-113 to -97)	-2 (-17 to 14)	-41 (-43 to -37)				-7.9 (-8.7 to -6.9)
-98 (-124 to -43)	-95 (-107 to -75)					-0.7 (-2.3 to 1.0)	-0.6 (-3.6 to 3.5)
-10 (-31 to 12)	-22 (-42 to 1)	6 (-6 to 17)	-29 (-40 to -6)			-0.5 (-3.6 to 2.5)	-1.2 (-2.9 to 0.6)	-1.2 (-3.9 to 1.4)
-31 (-95 to 85)	160 (-33 to 497)	-16 (-63 to 33)				-0.3 (-1.7 to 1.0)	-0.2 (-2.8 to 3.0)
-28 (-67 to 23)	-17 (-58 to 38)	-17 (-48 to 13)
44 (-67 to 219)	36 (-65 to 202)	4 (-8 to 17)				-0.5 (-2.0 to 0.6)
-65 (-119 to 48)	-44 (-105 to 93)	14 (-44 to 73)	-17 (-33 to 15)	25 (-29 to 227)	-14 (-17 to 3)
23 (-50 to 132)
-67 (-100 to -19)	-60 (-94 to -3)	62 (19 to 105)				0.7 (-1.0 to 2.3)
-30 (-83 to 53)		5 (-24 to 34)				-1.2 (-3.5 to 1.1)	-0.1 (-2.2 to 2.5)
-38 (-85 to 30)	22 (-42 to 112)					-0.1 (-4.8 to 4.6)	-0.7 (-3.0 to 2.2)
-42 (-88 to 27)		-1 (-26 to 24)				-1.4 (-2.8 to -0.2)

The expected risk of each outcome with standard care is reported in the grey row. For mortality, we used data from the Centers for Disease Control and Prevention on patients who were hospitalised with COVID-19. For mechanical ventilation, duration of invasive mechanical ventilation, and duration of hospitalisation, we used baseline risks from the International Severe Acute Respiratory and Emerging Infection COVID-19 (ISARIC) database. For all other outcomes, we used the median from all studies in which participants received standard of care to calculate the baseline risk for each outcome, with each study weighed equally.