Systematic review with meta-analysis of the epidemiological evidence in Europe, Israel, America and Australasia on smoking and COVID-19

Table 1 Main results for endpoint: Tested positive for coronavirus disease 2019

Selection of estimates1		Statistic2	Ever vs never	Current vs non-current	Current vs never	Former vs never	Closest to current	Closest to never
Population = general3
Best-adjusted	All	EE (95%CI)	1.04 (0.79-1.37)	0.76 (0.56-1.02)	0.87 (0.52-1.47)	1.09 (0.94-1.28)	0.78 (0.57-1.06)	0.89 (0.73-1.09)
		n	5	7	5	5	7	7
	C	EE (95%CI)	1.10 (0.70-1.72)	0.93 (0.43-2.01)	0.96 (0.42-2.17)	1.10 (0.86-1.40)	0.96 (0.42-2.17)	1.10 (0.70-1.72)
		n	3	3	3	3	3	3
	U	EE (95%CI)	0.71 (0.63-0.80)	0.56 (0.43-0.75)	0.45 (0.36-0.55)	0.92 (0.80-1.05)	0.56 (0.42-0.75)	0.65 (0.55-0.77)
		n	1	3	1	1	3	3
All estimates	U	EE (95%CI)	1.04 (0.83-1.29)	0.79 (0.51-1.22)	0.90 (0.46-1.78)	1.13 (0.97-1.31)	0.80 (0.53-1.22)	0.89 (0.74-1.08)
		n	5	7	5	5	7	7
Population = tested for COVID-194
Best-adjusted	All	EE (95%CI)	0.71 (0.60-0.84)	0.61 (0.52-0.71)	0.52 (0.43-0.64)	0.97 (0.86-1.09)	0.55 (0.47-0.65)	0.70 (0.63-0.77)
		n	10	13	8	8	17	17
	C	EE (95%CI)	0.77 (0.56-1.05)	0.60 (0.45-0.79)	0.53 (0.34-0.83)	0.90 (0.76-1.08)	0.58 (0.43-0.80)	0.77 (0.64-0.92)
		n	4	5	4	4	5	5
	U	EE (95%CI)	0.67 (0.52-0.86)	0.62 (0.51-0.75)	0.49 (0.42-0.58)	1.04 (0.85-1.28)	0.55 (0.45-0.67)	0.67 (0.58-0.78)
		n	6	8	4	4	11	11
All estimates	U	EE (95%CI)	0.72 (0.62-0.85)	0.61 (0.50-0.73)	0.53 (0.46-0.61)	0.97 (0.87-1.09)	0.55 (0.46-0.66)	0.71 (0.64-0.79)
		n	10	12	8	8	17	17

¹Best-adjusted = estimates for a study selected in preference order of adjustment (C = comorbidities, D = demographics only, U = unadjusted, P = includes post-coronavirus disease responses).

²EE: Effect estimate from random-effects meta-analysis.

³For population = general, the results are from six studies, one providing sex-specific estimates. Four provided odds ratio (OR)s, one hazard ratios and one relative risk (RR)s and ORs.

⁴For population = tested, the results are from 15 studies, two providing sex-specific estimates, with 13 providing only ORs and two RRs, one of these also providing ORs. COVID-19: Coronavirus disease 2019; CI: Confidence interval.

Table 2 Main results for endpoint: Hospitalized with coronavirus disease 2019

Selection of estimates1		Statistic2	Ever vs never	Current vs non-current	Current vs never	Former vs never	Closest to current	Closest to ever
Population = positive for COVID-193
Best-adjusted	All	EE (95%CI)	1.34 (1.13-1.60)	1.00 (0.86-1.16)	1.05 (0.84-1.32)	1.31 (0.93-1.85)	1.31 (1.12-1.54)	1.38 (1.17-1.63)
		n	19	13	11	11	22	22
	C	EE (95%CI)	1.00 (0.76-1.32)	0.90 (0.76-1.07)	0.82 (0.52-1.30)	0.87 (0.67-1.12)	0.96 (0.79-1.18)	0.93 (0.80-1.08)
		n	6	6	4	4	8	8
	U	EE (95%CI)	1.53 (1.14-2.06)	1.03 (0.75-1.41)	1.13 (0.81-1.59)	1.77 (1.04-3.04)	1.44 (1.03-2.01)	1.71 (1.24-2.36)
		n	10	6	6	6	11	11
All estimates	U	EE (95%CI)	1.64 (1.41-1.91)	0.97 (0.71-1.32)	1.20 (1.01-1.42)	1.75 (1.35-2.27)	1.47 (1.21-1.77)	1.72 (1.46-2.02)
		n	18	13	11	11	21	21

¹Best-adjusted = estimates for a study selected in preference order of adjustment (C = comorbidities, D = demographics only, U = unadjusted, P = includes post-COVID responses).

²EE = effect estimate from random-effects meta-analysis.

³The results are from 21 studies, one study providing sex-specific estimates. Nineteen studies provide odds ratio (OR)s, one relative risk (RR)s and hazard ratios, and one ORs and RRs. COVID-19: Coronavirus disease 2019; CI: Confidence interval.

Table 3 Main results for endpoint: Admitted to intensive care unit

Selection of estimates1		Statistic2	Ever vs never	Current vs non-current	Current vs never	Former vs never	Closest to current	Closest to ever
Population = positive for COVID-193
Best-adjusted	All	EE (95%CI)	1.57 (1.14-2.17)	0.87 (0.67-1.12)	0.94 (0.60-1.48)	1.55 (1.00-2.42)	1.13 (0.82-1.54)	1.40 (1.09-1.80)
		n	7	6	5	5	8	8
	C	EE (95%CI)	1.68 (1.15-2.46)	0.85 (0.77-0.94)	0.61 (0.11-3.36)	1.58 (0.97-2.57)	1.14 (0.54-2.41)	1.30 (0.74-2.31)
		n	2	2	1	1	3	3
	U	EE (95%CI)	1.42 (0.94-2.14)	0.94 (0.57-1.57)	0.98 (0.60-1.60)	1.55 (0.91-2.65)	0.98 (0.60-1.60)	1.42(0.94-2.14)
		n	4	4	4	4	4	4
All estimates	U	EE (95%CI)	1.52 (1.04-2.22)	1.03 (0.56-1.88)	0.92 (0.60-1.43)	1.68 (1.05-2.68)	1.11 (0.62-2.00)	1.61 (1.13-2.29)
		n	5	6	5	5	6	6
Population = hospitalized with COVID-194
Best-adjusted	All	EE (95%CI)	1.10 (0.99-1.22)	0.90 (0.72-1.12)	0.88 (0.72-1.08)	1.21 (0.99-1.47)	1.02 (0.87-1.21)	1.11 (0.98-1.25)
		n	9	9	6	6	14	14
	C	EE (95%CI)	1.01 (0.88-1.16)	0.80 (0.61-1.04)	0.81 (0.61-1.07)	1.07 (0.92-1.24)	0.81 (0.61-1.07)	1.01 (0.88-1.16)
		n	1	1	1	1	1	1
	U	EE (95%CI)	1.22 (1.04-1.43)	1.09 (0.93-1.27)	0.96 (0.70-1.31)	1.30 (1.00-1.70)	1.16 (1.05-1.28)	1.19 (1.08-1.30)
		n	8	7	5	5	12	12
All estimates	U	EE (95%CI)	1.20 (1.09-1.32)	1.00 (0.87-1.13)	0.89 (0.74-1.06)	1.28 (1.10-1.48)	1.05 (0.95-1.17)	1.14 (1.04-1.24)
		n	9	9	6	6	14	14

¹Best-adjusted = estimates for a study selected in preference order of adjustment (C = comorbidities, U = unadjusted, P = includes post coronavirus disease responses).

²EE = effect estimate from random-effects meta-analysis.

³For population = positive, the results are from eight studies. Six provided odds ratio (OR)s and two relative risk (RR)s;

⁴For population = hospitalized, the results are from 14 studies. Twelve provided ORs and two RRs. COVID-19: Coronavirus disease 2019; CI: Confidence interval.

Table 4 Main results for endpoint: Mechanically ventilated

Selection of estimates1		Statistic2	Ever vs never	Current vs non-current	Current vs never	Former vs never	Closest to current	Closest to ever
Population = hospitalized for COVID-193
Best-adjusted	All	EE (95%CI)	1.05 (0.88-1.25)	1.11 (0.72-1.71)	1.12 (0.60-2.09)	1.16 (0.87-1.55)	1.08 (0.86-1.36)	1.11 (0.92-1.35)
		n	12	8	5	5	15	15
	C	EE (95%CI)	1.04 (0.79-1.36)	1.94 (0.40-9.49)	2.77 (0.28-27.2)	2.43 (0.32-18.5)	0.99 (0.77-1.29)	1.04 (0.79-1.36)
		n	7	2	2	2	7	7
	U	EE (95%CI)	1.06 (0.94-1.21)	1.12 (0.60-2.09)	0.76 (0.59-0.98)	1.10 (0.96-1.27)	1.16 (0.80-1.67)	1.24 (0.99-1.54)
		n	5	5	3	3	7	7
All estimates	U	EE (95%CI)	1.07 (0.92-1.26)	1.10 (0.80-1.51)	1.09 (0.60-1.95)	1.12 (0.98-1.28)	1.12 (0.98-1.38)	1.17 (1.00-1.37)
		n	10	8	5	5	13	13

¹Best-adjusted = estimates for a study selected in preference order of adjustment (C = comorbidities, D = demographics only, U = unadjusted, P = includes post-coronavirus disease responses).

²EE = effect estimate from random-effects meta-analysis.

³Fourteen studies provided results, one providing estimates for two age groups. Thirteen studies provided odds ratios and one relative risks. COVID-19: Coronavirus disease 2019; CI: Confidence interval.

Table 5 Results for endpoint: Severe coronavirus disease 2019¹

Selection of estimates2			Statistic3	Ever vs never	Current vs non-current	Current vs never	Former vs never	Closest to current	Closest to ever
Population = positive4
Best-adjusted	All		EE (95%CI)	1.39 (1.07-1.80)	1.04 (0.91-1.20)	1.27 (0.82-1.95)	1.20 (0.62-2.32)	1.10 (0.97-1.25)	1.10 (0.97-1.25)
			n	7	5	4	4	8	8
	C		EE (95%CI)	-	1.02 (0.88-1.18)	-	-	1.02 (0.88-1.18)	1.02 (0.88-1.18)
			n	0	1	0	0	1	1
	U		EE (95%CI)	1.30 (0.94-1.79)	1.26 (0.82-1.93)	1.27 (0.82-1.95)	1.20 (0.62-2.32)	1.35 (0.95-1.92)	1.30 (0.94-1.79)
			n	5	4	4	4	5	5
All estimates	U		EE (95%CI)	1.63 (1.27-2.10)	1.17 (1.09-1.25)	1.27 (0.82-1.95)	1.20 (0.62-2.32)	1.48 (1.13-1.94)	1.45 (1.12-1.86)
			n	7	5	4	4	8	8
Population = hospitalized5
Best-adjusted		All	EE (95%CI)	1.15 (0.87-1.51)	1.05 (0.93-1.18)	0.74 (0.49-1.12)	1.07 (0.87-1.32)	1.08 (0.94-1.25)	1.09 (0.98-1.22)
			n	7	5	2	2	10	10
		C	EE (95%CI)	1.35 (0.66-2.75)	0.76 (0.50-1.15)	0.77 (0.51-1.17)	1.06 (0.86-1.31)	1.23 (0.46-3.27)	1.35 (0.66-2.75)
			n	2	1	1	1	2	2
		U	EE (95%CI)	1.38 (1.04-1.83)	1.12 (1.04-1.21)	0.29 (0.03-2.64)	1.25 (0.56-2.76)	1.17 (0.99-1.37)	1.14 (1.06-1.23)
			n	4	3	1	1	6	6
All estimates		U	EE (95%CI)	1.40 (1.20-1.63)	1.14 (1.04-1.24)	0.89 (0.54-1.46)	1.48 (1.23-1.80)	1.17 (1.08-1.27)	1.21 (1.12-1.29)
			n	6	5	2	2	9	9

¹In most studies the endpoint was severe coronavirus disease 2019 (COVID-19) as defined by the author, but it was admitted to ICU or died in two studies, pneumonia in one, increased oxygen required in one and COVID-19 progressed in one.

²Best-adjusted = estimates for a study selected in preference order of adjustment (C = comorbidities, U = unadjusted, P = includes post-COVID responses).

³EE = effect estimate from random-effects meta-analysis.

⁴For population = positive, the results are from five studies, one study providing four estimates by age and sex. All estimates are odds ratio (OR)s.

⁵For population = hospitalized, the results are from 10 studies, nine providing ORs and one relative risks and hazard ratios. COVID-19: Coronavirus disease 2019; CI: Confidence interval.

Table 6 Main results for endpoint: Died

Selection of estimates1		Statistic2	Ever vs never	Current vs non-current	Current vs never	Former vs never	Closest to current	Closest to ever
Population = hospitalized with COVID-193
Best-adjusted	All	EE (95%CI)	1.42 (1.19-1.70)	0.99 (0.89-1.10)	1.12 (0.98-1.29)	1.61 (1.34-1.92)	1.27 (1.08-1.49)	1.42 (1.22-1.65)
		n	18	10	10	10	25	25
	C	EE (95%CI)	1.07 (0.82-1.38)	0.64 (0.12-3.35)	1.02 (0.70-1.49)	1.15 (1.02-1.29)	1.09 (0.84-1.40)	1.12 (0.91-1.39)
		n	8	2	3	3	10	10
	U	EE (95%CI)	1.78 (1.40-2.26)	0.95 (0.77-1.16)	1.18 (0.91-1.52)	1.92 (1.48-2.50)	1.52 (1.22-1.91)	1.79 (1.47-2.19)
		n	9	6	6	6	13	13
All estimates	U	EE (95%CI)	1.59 (1.37-1.83)	1.00 (0.88-1.13)	1.12 (0.97-1.29)	1.80 (1.48-2.17)	1.33 (1.18-1.51)	1.58 (1.39-1.78)
		n	15	10	9	9	20	20
Population = with COVID-194
Best-adjusted	All	EE (95%CI)	1.41 (0.93-2.14)	0.96 (0.92-1.01)	0.98 (0.72-1.32)	1.61 (0.79-3.29)	1.08 (0.82-1.42)	1.34 (0.96-1.86)
		n	7	6	5	5	8	8
	C	EE (95%CI)	0.99 (0.87-1.13)	0.96 (0.92-1.01)	0.85 (0.67-1.07)	1.04 (0.91-1.19)	0.96 (0.92-1.01)	0.97 (0.93-1.02)
		n	3	4	3	3	4	4
	U	EE (95%CI)	2.07 (1.12-3.82)	0.93 (0.60-1.46)	1.49 (0.94-2.36)	2.70 (1.11-6.58)	1.59 (1.40-1.80)	2.07 (1.12-3.82)
		n	3	2	2	2	3	3
All estimates	U	EE (95%CI)	2.04 (1.39-3.02)	1.06 (0.39-2.90)	1.07 (0.72-1.58)	2.58 (1.31-5.07)	1.52 (0.89-2.60)	2.22 (1.51-3.27)
		n	5	5	4	4	6	6

¹Best-adjusted = estimates for a study selected in preference order of adjustment [C = comorbidities, D = demographics only, U = unadjusted, P = includes post-coronavirus disease (COVID) responses.

²EE = effect estimate from random-effects meta-analysis.

³For population = hospitalized, the results are from twenty four studies, one providing age-specific estimates. Seventeen provided only odds ratio (OR)s, two only hazard ratio (HR)s, two only relative risk (RR)s, and three RRs and HRs, one of these also providing ORs.

⁴For population = with COVID-19, the results are from eight studies, six providing ORs, one RRs and one HRs and RRs. COVID-19: Coronavirus disease 2019; CI: Confidence interval.

Table 7 Results for endpoint: Worsened or died¹

Selection of estimates2	Statistic3	Ever vs never	Current vs non-current	Current vs never	Former vs never	Closest to current	Closest to ever
Unadjusted4	EE (95%CI)	1.34 (1.00-1.79)	1.31 (1.06-1.62)	1.21 (0.35-4.17)	2.01 (0.67-6.09)	1.27 (1.15-1.39)	1.36 (1.15-1.62)
	n	5	5	3	3	9	9

¹Seven studies considered death among those admitted to the intensive care unit (ICU), and one of these and one other considered death among those mechanically ventilated. One considered admission to ICU or death among those hospitalized with severe coronavirus disease 2019.

²All estimates were unadjusted.

³EE = effect estimate from random-effects meta-analysis.

⁴The data are from nine studies, five reporting odds ratio (OR)s, two relative risk (RR)s and two RRs and hazard ratios, one of these also reporting ORs. CI: Confidence interval.

Table 8 Variations in best-adjusted effect estimates by level of adjustment, effect estimate type, location and study size

Factor/level	Endpoint	CP	H	IC	MV	S	M
	Population	T	CP	H	H	H	H
	Estimates	17	22	14	15	10	25
Estimates for closest to current smoking
Adjustment	U	0.55 (0.45-0.67)	1.44 (1.03-2.01)	1.16 (1.05-1.28)	1.16 (0.80-1.67)	1.17 (0.99-1.37)	1.52 (1.22-1.91)
	D	0.23 (0.09-0.59)	1.52 (1.18-1.95)	0.73 (0.56-0.96)	0.85 (0.67-1.07)	1.02 (0.89-1.16)	1.01 (0.87-1.17)
	C	0.58 (0.43-0.80)	0.96 (0.79-1.18)	0.81 (0.61-1.07)	0.99 (0.77-1.29)	1.23 (0.46-3.27)	1.09 (0.84-1.40)
	PC	-	-	-	-	0.71 (0.41-1.23)	-
	P	NS	< 0.05	< 0.001	NS	NS	< 0.05
Estimate type	OR	0.54 (0.46-0.63)	1.26 (0.97-1.64)	1.07 (0.87-1.32)	1.13 (0.88-1.44)	1.09 (0.93-1.27)	1.35 (1.07-1.70)
	RR	0.64 (0.31-1.34)	1.25 (1.20-1.31)	0.90 (0.71-1.15)	0.73 (0.56-0.95)	-	1.11 (0.87-1.40)
	HR	-	1.10 (0.97-1.24)	-	-	1.02 (0.64-1.63)	1.15 (0.89-1.50)
	P	NS	NS	NS	< 0.05	NS	NS
Location	United States	0.45 (0.37-0.54)	1.27 (1.11-1.46)	1.00 (0.81-1.22)	1.02 (0.83-1.26)	1.06 (0.72-1.56)	1.21 (0.95-1.53)
	Other	0.64 (0.55-0.73)	1.11 (0.48-2.57)	1.08 (0.79-1.49)	1.05 (0.65-1.71)	1.10 (1.02-1.17)	1.34 (1.07-1.69)
	P	< 0.01	NS	NS	NS	NS	NS
Study size	< 500	-	0.99 (0.58-1.69)	1.25 (0.91-1.71)	1.35 (1.02-1.80)	1.02 (0.65-1.59)	1.29 (0.97-1.72)
	500-	0.40 (0.27-0.61)	1.42 (1.17-1.72)	1.07 (0.69-1.65)	0.92 (0.34-2.46)	1.62 (1.14-2.29)	1.57 (1.20-2.05)
	5000-	0.51 (0.39-0.66)	1.43 (0.97-2.10)	0.64 (0.29-1.42)	0.83 (0.70-0.98)	0.81 (0.56-1.19)	1.03 (0.83-1.28)
	50,000+	0.67 (0.51-0.87)	1.00 (0.85-1.18)	0.97 (0.72-1.31)	0.98 (0.61-1.59)	1.09 (0.99-1.19)	0.94 (0.82-1.07)
	P	NS	< 0.05	NS	< 0.05	NS	< 0.01
Estimates for closest to ever smoking
Adjustment	U	0.67 (0.58-0.78)	1.71 (1.24-2.36)	1.19 (1.08-1.30)	1.24 (0.99-1.54)	1.14 (1.06-1.23)	1.79 (1.47-2.19)
	D	0.23 (0.09-0.59)	1.41 (1.04-1.92)	0.73 (0.56-0.96)	0.85 (0.67-1.07)	1.02 (0.89-1.16)	1.11 (0.81-1.53)
	C	0.77 (0.64-0.92)	0.93 (0.80-1.08)	1.01 (0.88-1.16)	1.04 (0.79-1.36)	1.35 (0.66-2.75)	1.12 (0.91-1.39)
	PC	-	-	-	-	0.71 (0.41-1.23)	-
	P	< 0.05	< 0.001	< 0.01	NS	NS	< 0.01
Estimate type	OR	0.67 (0.59-0.76)	1.39 (1.08-1.79)	1.16 (0.99-1.37)	1.14 (0.91-1.42)	1.10 (0.98-1.24)	1.53 (1.19-1.96)
	RR	0.87 (0.59-1.27)	1.25 (1.20-1.31)	1.01 (0.89-1.15)	1.02 (0.88-1.18)	-	1.16 (1.05-1.29)
	HR	-	1.03 (0.95-1.11)	-	-	1.02 (0.64-1.63)	1.28 (1.14-1.44)
	P	NS	< 0.001	NS	NS	NS	NS
Location	United States	0.65 (0.50-0.84)	1.38 (1.14-1.67)	1.10 (0.99-1.23)	1.08 (0.90-1.30)	1.15 (0.87-1.51)	1.43 (1.11-1.84)
	Other	0.74 (0.66-0.82)	1.31 (0.64-2.71)	1.08 (0.79-1.49)	1.05 (0.65-1.71)	1.10 (1.02-1.17)	1.43 (1.19-1.73)
	P	NS	NS	NS	NS	NS	NS
Study size	< 500	-	1.21 (0.84-1.75)	1.25 (0.93-1.69)	1.29 (0.95-1.76)	1.06 (0.74-1.52)	1.36 (1.05-1.75)
	500-	0.55 (0.37-0.80)	1.32 (0.99-1.76)	1.04 (0.92-1.18)	1.24 (0.77-2.00)	1.62 (1.14-2.29)	1.70 (1.34-2.16)
	5000-	0.64 (0.50-0.81)	1.71 (1.18-2.49)	1.48 (1.10-2.00)	0.83 (0.70-0.98)	1.00 (0.83-1.22)	1.27 (0.96-1.68)
	50000+	0.81 (0.73-0.89)	0.97 (0.88-1.07)	0.97 (0.73-1.28)	1.10 (0.79-1.52)	1.09 (0.99-1.19)	0.94 (0.82-1.07)
	P	< 0.05	< 0.01	NS	< 0.05	NS	< 0.001

The table shows effect estimates with 95% confidence interval. Variation between levels of a factor is coded as P < 0.001, P < 0.01, P < 0.05 or NS (P ≥ 0.05). C: Adjusted for comorbidities; CP: Coronavirus disease 2019 positive; D: Adjusted for demographics only; H: Hospitalized; HR: Hazard ratio; IC: Intensive care; M: Mortality; MV: Mechanical ventilation; OR: Odds ratio; PC: Adjusted for variables including post-coronavirus disease 2019 responses; RR: Relative risk; S: Severe coronavirus disease 2019; T: Tested for coronavirus disease 2019; U: Unadjusted.

Table 9 Summary of results from meta-analyses¹

Endpoint	Population	Smoking index = closest to current smoking			Smoking index = closest to ever smoking
		Best estimate2	Comorbidity adjusted3	Unadjusted4	Best estimate2	Comorbidity adjusted3	Unadjusted4
Positive	General	0.78 (0.57-1.06)5	0.96 (0.42-2.17)	0.56 (0.42-0.75)5	0.89 (0.73-1.09)	1.10 (0.70-1.72)	0.65 (0.55-0.77)
Positive	Tested	0.55 (0.47-0.65)	0.58 (0.43-0.80)	0.55 (0.45-0.67)	0.70 (0.63-0.77)	0.77 (0.64-0.92)	0.67 (0.58-0.78)
Hospitalized	Positive	1.31 (1.12-1.54)	0.96 (0.79-1.18)	1.44 (1.03-2.01)	1.38 (1.17-1.63)	0.93 (0.80-1.08)	1.71 (1.24-2.36)
ICU admission	Positive	1.13 (0.82-1.54)	1.14 (0.54-2.41)	0.98 (0.60-1.60)	1.40 (1.09-1.80)5	1.30 (0.74-2.31)	1.42 (0.94-2.14)
ICU admission	Hospitalized	1.02 (0.87-1.21)	0.81 (0.61-1.07)	1.16 (1.05-1.28)	1.11 (0.98-1.25)	1.01 (0.88-1.16)	1.19 (1.08-1.30)
Mechanically ventilated	Hospitalized	1.08 (0.86-1.36)	0.99 (0.77-1.29)5	1.16 (0.80-1.67)	1.11 (0.92-1.35)	1.04 (0.79-1.36)5	1.24 (0.99-1.54)
Severe	Positive	1.10 (0.97-1.25)5	1.02 (0.88-1.18)	1.35 (0.95-1.92)	1.10 (0.97-1.25)5	1.02 (0.88-1.18)	1.30 (0.94-1.79)
Severe	Hospitalized	1.08 (0.94-1.25)	1.23 (0.46-3.27)	1.17 (0.99-1.37)	1.09 (0.98-1.22)	1.35 (0.66-2.75)	1.14 (1.06-1.23)
Died	Positive	1.08 (0.82-1.42)	0.96 (0.92-1.01)	1.59 (1.40-1.80)	1.34 (0.96-1.86)	0.97 (0.93-1.02)	2.07 (1.12-3.82)
Died	Hospitalized	1.27 (1.08-1.49)5	1.09 (0.84-1.40)	1.52 (1.22-1.91)	1.42 (1.22-1.65)	1.12 (0.91-1.39)	1.79 (1.47-2.19)

¹See also Tables 1 to 6 for further details. Data shown are random-effects estimates with 95% confidence interval.

²Best estimates based on, respectively, 7, 17, 22, 8, 14, 15, 8, 10, 8 and 25 effect estimates (total 134).

³Comorbidity adjusted estimates based on, respectively, 3, 5, 8, 3, 1, 7, 1, 2, 4 and 10 (total 44).

⁴Unadjusted estimates based on, respectively, 3, 11, 11, 4, 12, 7, 5, 6, 3 and 13 (total 75). The unadjusted results shown are based only on those included in the best estimates;

⁵Significant publication bias (P < 0.05). ICU: Intensive care unit.