Regular Inhaled Corticosteroids Use May Protect Against Severe COVID-19 Outcome in COPD

Figures & data

Table 1 Demographic Characteristics, Comorbidities, and Prescribed Medications of the Overall Cohorts of the Whole Population and COPD Patients on 1 Jan 2020, for Individuals ≥40 Years of Age Exposed and Non-Exposed to Prior Regular Treatment with Inhaled Corticosteroids (ICS), with Standardized Mean Differences (SMD) to Assess Differences for All Characteristics Between the Cohorts Before (Crude) and After ATT Weighting by Propensity Scores (Weighted)

	Whole Population (N = 5,243,479)				COPD Patients (N = 133,372)
	Non-Exposed*	Exposed**			Non-Exposed*	Exposed**
n (%)	5,056,902 (96.4%)	186,577 (3.6%)	SMD (Crude)	SMD (Weighted)	85,813 (64.3%)	47,559 (35.7%)	SMD (Crude)	SMD (Weighted)
Demographics
Age (mean ± SD)	60.8 (13.5)	66.1 (12.9)			72.7 (10.0)	73.4 (9.6)
Age categories (years)			0.419	0.219			0.075	0.008
40–49	1,282,612 (25.4%)	23,795 (12.8%)			1546 (1.8%)	662 (1.4%)
50–59	1,265,403 (25.0%)	35,980 (19.3%)			7374 (8.6%)	3502 (7.4%)
60–69	1,064,972 (21.1%)	44,788 (24.0%)			20,526 (23.9%)	10,629 (22.3%)
70–79	936,739 (18.5%)	52,789 (28.3%)			34,838 (40.6%)	20,270 (42.6%)
80–89	412,202 (8.2%)	24,568 (13.2%)			18,613 (21.7%)	10,816 (22.7%)
90+	94,974 (1.9%)	4657 (2.5%)			2916 (3.4%)	1680 (3.5%)
Gender = women	2,557,068 (50.6%)	114,079 (61.1%)	0.214	0.080	45,853 (53.4%)	28,437 (59.8%)	0.129	<0.001
Employment			0.389	0.192			0.075	0.005
Unemployed 40–64 years	413,324 (8.2%)	14,960 (8.0%)			7176 (8.4%)	3639 (7.7%)
Employed 40–64 years	2,679,672 (53.0%)	65,929 (35.3%)			10,101 (11.8%)	4716 (9.9%)
Employed ≥ 65 years	532,337 (10.5%)	22,594 (12.1%)			10,640 (12.4%)	5614 (11.8%)
Retired ≥ 65 years	1,428,055 (28.3%)	83,093 (44.5%)			57,892 (67.5%)	33,590 (70.6%)
Education			0.151	0.053			0.013	0.006
Primary	959,029 (19.3%)	44,999 (24.3%)			30,992 (36.6%)	17,303 (36.8%)
Secondary	2,201,763 (44.2%)	83,593 (45.2%)			39,167 (46.3%)	21,866 (46.6%)
Higher	1,816,319 (36.5%)	56,408 (30.5%)			14,465 (17.1%)	7796 (16.6%)
Comorbidities
Hypertension	723,351 (14.3%)	50,297 (27.0%)	0.317	0.084	38,932 (45.4%)	22,334 (47.0%)	0.032	0.001
Cardiovascular disease	1,096,906 (21.7%)	70,877 (38.0%)	0.362	0.102	52,708 (61.4%)	30,131 (63.4%)	0.040	0.003
Heart failure	124,714 (2.5%)	13,384 (7.2%)	0.221	0.061	13,329 (15.5%)	8255 (17.4%)	0.049	0.001
IHD	237585 (4.7%)	16,815 (9.0%)	0.171	0.029	16,528 (19.3%)	8832 (18.6%)	0.018	<0.001
Stroke	87,504 (1.7%)	4725 (2.5%)	0.056	0.032	4757 (5.5%)	2252 (4.7%)	0.037	0.002
Diabetes	290,310 (5.7%)	17,849 (9.6%)	0.144	0.017	14,429 (16.8%)	7411 (15.6%)	0.033	0.004
Respiratory disease	230,319 (4.6%)	81,305 (43.6%)	1.026	0.277	59,369 (69.2%)	39,095 (82.2%)	0.307	0.003
COPD ***	54,792 (1.1%)	36,982 (19.8%)	0.643	0.198	54,792 (63.9%)	36,982 (77.8%)	0.310	0.006
Asthma	57,686 (1.1%)	49,596 (26.6%)	0.792	0.239	6886 (8.0%)	11,266 (23.7%)	0.439	0.004
Respiratory failure	11,499 (0.2%)	4562 (2.4%)	0.194	0.091	3324 (3.9%)	3866 (8.1%)	0.180	0.007
Lung cancer	10,323 (0.2%)	1743 (0.9%)	0.097	0.010	2383 (2.8%)	1314 (2.8%)	0.001	0.002
Rheumatologic or immunological disease	228,940 (4.5%)	15,100 (8.1%)	0.147	0.022	11,259 (13.1%)	5948 (12.5%)	0.018	0.006
CKD	60896 (1.2%)	4103 (2.2%)	0.077	0.001	4808 (5.6%)	2223 (4.7%)	0.042	0.001
Kidney failure	85,588 (1.7%)	6103 (3.3%)	0.102	0.008	7019 (8.2%)	3399 (7.1%)	0.039	0.003
Prescribed medications
Oral corticosteroids	289,806 (5.7%)	54,109 (29.0%)	0.645	0.232	17,899 (20.9%)	19,724 (41.5%)	0.457	0.009
Biologics	618 (0.0%)	221 (0.1%)	0.042	0.024	11 (0.0%)	24 (0.1%)	0.021	0.006
Inhaled SABA	219279 (4.3%)	110,750 (59.4%)	1.463	0.299	26,885 (31.3%)	29,891 (62.9%)	0.666	0.002
Inhaled LABA	123119 (2.4%)	139,763 (74.9%)	2.228	0.294	27,281 (31.8%)	41,801 (87.9%)	1.395	0.001
Inhaled SAMA	6664 (0.1%)	7528 (4.0%)	0.276	0.162	2613 (3.0%)	4560 (9.6%)	0.271	0.001
Inhaled LAMA	66752 (1.3%)	50,416 (27.0%)	0.793	0.245	41,908 (48.8%)	35,551 (74.8%)	0.553	0.005
LTRA	15769 (0.3%)	24,334 (13.0%)	0.527	0.223	941 (1.1%)	3567 (7.5%)	0.32	0.010
Immunosuppressants	232,157 (4.6%)	36,636 (19.6%)	0.474	0.191	13,878 (16.2%)	14,267 (30.0%)	0.333	0.011
Statins	916,200 (18.1%)	51,190 (27.4%)	0.224	0.072	34,745 (40.5%)	18,493 (38.9%)	0.033	0.006
Other characteristics
Body mass index			0.129	0.085			0.044	0.006
Underweight	16,098 (0.3%)	2405 (1.3%)			2888 (3.4%)	1837 (3.9%)
Normal	179,854 (3.6%)	21,336 (11.4%)			17,831 (20.8%)	9970 (21.0%)
Overweight	275,816 (5.5%)	27,131 (14.5%)			18,411 (21.5%)	9941 (20.9%)
Obese	366,259 (7.2%)	32,455 (17.4%)			17,192 (20.0%)	10,100 (21.2%)
Missing	4,218,875 (83.4%)	103,250 (55.3%)			29,491 (34.4%)	15,711 (33.0%)
Smoking			0.357	0.142			0.207	0.014
Current	182,412 (3.6%)	17,169 (9.2%)			24,540 (28.6%)	10,274 (21.6%)
Former	211,152 (4.2%)	30,148 (16.2%)			24,539 (28.6%)	15,991 (33.6%)
Non-current	102,281 (2.0%)	3278 (1.8%)			1839 (2.1%)	994 (2.1%)
Never	346,797 (6.9%)	33,874 (18.2%)			8774 (10.2%)	5533 (11.6%)
Missing	4,214,260 (83.3%)	102,108 (54.7%)			26,121 (30.4%)	14,767 (31.0%)
FEV1 predicted^a							0.464	0.011
≥80	NA	NA			2443 (2.8%)	976 (2.1%)
50–79	NA	NA			8247 (9.6%)	4325 (9.1%)
30–49	NA	NA			2471 (2.9%)	2760 (5.8%)
<30	NA	NA			290 (0.3%)	749 (1.6%)
Missing	NA	NA			72,362 (84.3%)	38,749 (81.5%)

Notes: *Non-exposed = received less than 3 prescriptions of ICS in the year before index (1 Jan 2020). **Exposed = received at least three filled ICS prescriptions within the year before the index (1 Jan 2020). ***Narrow COPD definition only by ICD-10 code J44. ^aNA in the whole population as FEV₁ was considered a covariate more relevant for COPD patients.

Abbreviations: COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroids; ATT, average treatment for the treated; IHD, ischemic heart disease; CKD, chronic kidney disease; SABA, short-acting bronchodilator agonists; LABA, long-acting bronchodilator agonists; SAMA, short-acting muscarinic antagonists; LAMA, long-acting muscarinic antagonists; LTRA, leukotriene receptor antagonists; FEV₁ predicted, post-bronchodilator Forced Expiratory Volume in one second, percent of predicted; SD, standard deviation.

Table 2 Hazard Ratios with 95 Confidence Intervals Comparing the Risk of Various COVID-19 Outcomes Between Individuals ≥40 Years of Age with Prior Regular Exposure to ICS to Non-Exposed Individuals, Adjusted for Multiple Confounders by Propensity Score Weighting ATT* Weighting

Study Cohorts	Study Population (Whole/COPD Subpopulation)	COVID-19 Outcome	HR [95 CI]	p value
Overall cohort	Whole population	Onset	1.02 [0.99–1.05]	0.158
		Hospitalization	1.05 [0.99–1.11]	0.087
		ICU admission	1.07 [0.89–1.29]	0.454
		COVID-19 Death	1.10 [0.99–1.22]	0.091
	COPD patients	Onset	1.07 [1–1.16]	0.061
		Hospitalization	1.13 [1.02–1.26]	0.025
		ICU admission	0.9 [0.61–1.32]	0.577
		Death	1.1 [0.93–1.3]	0.258
COVID-19 diagnosed sub cohort	Whole population	Hospitalization	1.04 [0.98–1.11]	0.148
		ICU admission	1.05 [0.86–1.27]	0.646
		Death	1.05 [0.93–1.18]	0.439
	COPD patients	Hospitalization	1.08 [0.98–1.19]	0.119
		ICU admission	0.83 [0.58–1.21]	0.332
		Death	0.94 [0.8–1.11]	0.474
COVID-19 hospitalized sub cohort	Whole population	ICU admission	0.98 [0.8–1.19]	0.816
		Death	0.97 [0.84–1.11]	0.639
	COPD patients	ICU admission	0.74 [0.51–1.08]	0.117
		Death	0.82 [0.67–0.99]	0.045

Abbreviations: *ATT, average treatment effect for the treated; COVID-19, Coronavirus disease, 2019; ICD-10, International Classification of Diseases version 10, Swedish Edition (ICD-10); HR, hazard ratio.

Figure 1 Forest plot comparing the risk of various definitions of COVID-19 between persons with pre-index exposure to ICS to non-exposed persons. The figure summarizes Average treatment for the treated (ATT) adjusted hazard ratios with 95% CI.

Abbreviations: HR, hazard ratio; CI, confidence interval; ICU, intensive care unit; COPD, chronic obstructive pulmonary disease; COVID-19, Coronavirus disease.