Risk of Severe Covid-19 in Patients with Celiac Disease: A Population-Based Cohort Study

Figures & data

Figure 1 Flow chart of patients with celiac disease and their matched comparators.

Table 1 Baseline Characteristics of Study Cohort

Characteristics	Celiac Disease (n=40,963)	Matched Comparators (n=183,892)
Females, no. (%)	26,413 (64.5%)	119 438 (65.0%)
Males, no (%)	14,550 (35.5%)	64,454 (35.0%)
Age at index date
Mean (SD)	26.5 (21.8)	25.0 (20.9)
Median (IQR)	21.4 (6.5–43.7)	19.6 (6.1–41.2)
Range, min-max	0.0–92.4	0.0–92.6
Age categories, no. (%)
<18y	18,773 (45.8%)	88,147 (47.9%)
18y - <40y	10,247 (25.0%)	47,350 (25.7%)
40y - <60y	8065 (19.7%)	34,527 (18.8%)
≥60y	3878 (9.5%)	13,868 (7.5%)
Age at start of follow-up
Mean (SD)	42.8 (21.8)	41.0 (20.8)
Median (IQR)	36.6 (25.6–60.9)	34.8 (24.8–57.3)
Range, min-max	4.7–99.0	4.2–98.6
Categories, no. (%)
<18y	4490 (11.0%)	21,736 (11.8%)
18y - <40y	17,531 (42.8%)	81,888 (44.5%)
40y - <60y	8380 (20.5%)	38,918 (21.2%)
≥60y	10,562 (25.8%)	41,350 (22.5%)
Country of birth, no (%)
Nordic country	39,245 (95.8%)	168 842 (91.8%)
Other	1717 (4.2%)	15,045 (8.2%)
Missing	1 (0.0%)	5 (0.0%)
Level of education, no (%)
≤9 years	5459 (13.3%)	24,226 (13.2%)
10–12 years	9825 (24.0%)	43,456 (23.6%)
>12 years	7040 (17.2%)	29,370 (16.0%)
Missing	18,639 (45.5%)	86,840 (47.2%)
Level of education using highest level of education in parents when missing, no (%)
≤9 years	6443 (15.7%)	29,469 (16.0%)
10–12 years	17,707 (43.2%)	80,106 (43.6%)
>12 years	16,317 (39.8%)	72,295 (39.3%)
Missing	496 (1.2%)	2022 (1.1%)
Index year
1969–1989	2844 (6.9%)	11,846 (6.4%)
1990–1999	9938 (24.3%)	42,958 (23.4%)
2000–2009	16,925 (41.3%)	75,916 (41.3%)
2010–2016	11,256 (27.5%)	53,172 (28.9%)
Disease history ever before index date, no. (%)
Any cardiovascular disease	1867 (4.6%)	5305 (2.9%)
Diabetes	1902 (4.6%)	1914 (1.0%)
COPD	166 (0.4%)	551 (0.3%)
End-stage renal disease	49 (0.1%)	65 (0.0%)
Alcohol liver disease and alcohol use disorder	363 (0.9%)	1881 (1.0%)
Obesity/Dyslipidemia	578 (1.4%)	2500 (1.4%)
Obstructive sleep apnea	187 (0.5%)	797 (0.4%)
Cancer	684 (1.7%)	2116 (1.2%)
Psychiatric disease	2513 (6.1%)	8946 (4.9%)
Disease history ever before start of follow-up, no. (%)
Any cardiovascular disease	5466 (13.3%)	18,066 (9.8%)
Diabetes	3001 (7.3%)	5707 (3.1%)
COPD	584 (1.4%)	1862 (1.0%)
End-stage renal disease	202 (0.5%)	227 (0.1%)
Alcohol liver disease and alcohol use disorder	1226 (3.0%)	5486 (3.0%)
Obesity/Dyslipidemia	2617 (6.4%)	10,123 (5.5%)
Obstructive sleep apnea	797 (1.9%)	2792 (1.5%)
Cancer	2000 (4.9%)	6934 (3.8%)
Psychiatric disease	7979 (19.5%)	28,393 (15.4%)
Follow-up to hospital admission, months
Mean (SD)	5.9 (0.3)	5.9 (0.2)
Median (IQR)	6.0 (6.0–6.0)	6.0 (6.0–6.0)
Range, min-max	0.1–6.0	0.0–6.0

Abbreviation: COPD, chronic obstructive pulmonary disease.

Table 2 Risk of Covid-19 in Patients with Celiac Disease and Matched General Population Comparators from February 1 to July 31, 2020

Outcome	N Events (%)		Time at Risk (Years)		Incidence Rate (95% CI) per 1000 PY		HR* (95% CI)	HR** (95% CI)
	Celiac Disease	Comparators	Celiac Disease	Comparators	Celiac Disease	Comparators
Main outcomes
Hospital admission	58 (0.14%)	202 (0.11%)	20,254	90,995	2.9 (2.1–3.6)	2.2 (1.9–2.5)	1.08 (0.80–1.45)	1.10 (0.80–1.50)
Severe Covid-19	24 (0.06%)	78 (0.04%)	20,265	91,032	1.2 (0.7–1.7)	0.9 (0.7–1.0)	1.03 (0.65–1.63)	0.97 (0.59–1.59)
Secondary outcomes
Main outcomes combined	68 (0.17%)	230 (0.13%)	20,254	90,995	3.4 (2.6–4.2)	2.5 (2.2–2.9)	1.08 (0.82–1.42)	1.09 (0.82–1.46)
All-cause mortality	185 (0.45%)	597 (0.32%)	20,266	91,036	9.1 (7.8–10.4)	6.6 (6.0–7.1)	1.02 (0.86–1.21)	0.97 (0.81–1.15)
Any Covid-19	414 (1.01%)	1793 (0.98%)	20,193	90,731	20.5 (18.5–22.5)	19.8 (18.8–20.7)	1.01 (0.90–1.12)	1.00 (0.89–1.11)

Notes: *Conditioned on matching set (age, sex, county, and calendar period); **Conditioned on matching set and further adjusted for education, Nordic country of birth, and medical comorbidities at index date (cardiovascular disease, diabetes, COPD, end-stage renal disease, alcohol liver disease/alcohol use disorder, obesity/dyslipidemia, obstructive sleep apnea, cancer, psychiatric disease). (n celiac disease/n comparators = 40,963/183,892).

Table 3 Risk of Covid-19 (Hospital Admission) Overall and by Subgroups in Patients with Celiac Disease and Matched General Population Comparators from February 1 to July 31, 2020

Group	N (%)		N Events (%)		Incidence Rate (95% CI) per 1000 PY		HR* (95% CI)	HR** (95% CI)
	Celiac Disease	Comparators	Celiac Disease	Comparators	Celiac Disease	Comparators
Overall	40,963 (100%)	183 892 (100%)	58 (0.14%)	202 (0.11%)	2.9 (2.1–3.6)	2.2 (1.9–2.5)	1.08 (0.80–1.45)	1.10 (0.80–1.50)
Follow-up
0-<1m	40,963 (100%)	183 892 (100%)	0	1 (0.00%)	0.0 (0.0–0.0)	0.1 (0.0–0.2)	–	–
1-<2m	40,930 (99.9%)	183 786 (99.9%)	7 (0.02%)	30 (0.02%)	2.1 (0.5–3.6)	2.0 (1.3–2.7)	0.93 (0.40–2.16)	1.09 (0.38–3.14)
2-<3m	40,890 (99.8%)	183 664 (99.9%)	25 (0.06%)	75 (0.04%)	7.3 (4.5–10.2)	4.9 (3.8–6.0)	1.23 (0.78–1.95)	1.41 (0.85–2.33)
3-<4m	40,836 (99.7%)	183 471 (99.8%)	15 (0.04%)	61 (0.03%)	4.4 (2.2–6.6)	4.0 (3.0–5.0)	0.90 (0.51–1.59)	0.90 (0.49–1.65)
4-<5m	40,798 (99.6%)	183 332 (99.7%)	10 (0.02%)	32 (0.02%)	2.9 (1.1–4.8)	2.1 (1.4–2.8)	1.22 (0.60–2.50)	1.04 (0.45–2.41)
5-<6m	40,763 (99.5%)	183 209 (99.6%)	1 (0.00%)	3 (0.00%)	0.3 (0.0–0.9)	0.2 (0.0–0.4)	1.28 (0.13–12.78)	–
Sex
Females	26,413 (64.5%)	119 438 (65.0%)	35 (0.13%)	114 (0.10%)	2.7 (1.8–3.6)	1.9 (1.6–2.3)	1.17 (0.79–1.71)	1.09 (0.72–1.65)
Males	14,550 (35.5%)	64,454 (35.0%)	23 (0.16%)	88 (0.14%)	3.2 (1.9–4.5)	2.8 (2.2–3.3)	0.97 (0.61–1.54)	1.17 (0.71–1.95)
Age at index date
<18y	18,773 (45.8%)	88,147 (47.9%)	4 (0.02%)	20 (0.02%)	0.4 (0.0–0.9)	0.5 (0.3–0.7)	0.91 (0.31–2.67)	0.97 (0.27–3.42)
18y - <40y	10,247 (25.0%)	47,350 (25.7%)	11 (0.11%)	41 (0.09%)	2.2 (0.9–3.4)	1.7 (1.2–2.3)	1.17 (0.60–2.30)	1.32 (0.61–2.85)
40y - <60y	8065 (19.7%)	34,527 (18.8%)	18 (0.22%)	85 (0.25%)	4.5 (2.4–6.6)	5.0 (3.9–6.0)	0.83 (0.49–1.39)	0.88 (0.50–1.53)
≥60y	3878 (9.5%)	13,868 (7.5%)	25 (0.64%)	56 (0.40%)	13.2 (8.0–18.4)	8.3 (6.1–10.4)	1.37 (0.85–2.22)	1.25 (0.74–2.13)
Index year
1969–1989	2844 (6.9%)	11,846 (6.4%)	3 (0.11%)	17 (0.14%)	2.1 (0.0–4.6)	2.9 (1.5–4.3)	0.57 (0.16–1.99)	0.46 (0.12–1.69)
1990–1999	9938 (24.3%)	42,958 (23.4%)	21 (0.21%)	61 (0.14%)	4.3 (2.4–6.1)	2.9 (2.2–3.6)	1.36 (0.82–2.25)	1.37 (0.79–2.36)
2000–2009	16,925 (41.3%)	75,916 (41.3%)	26 (0.15%)	62 (0.08%)	3.1 (1.9–4.3)	1.7 (1.2–2.1)	1.53 (0.96–2.44)	1.50 (0.89–2.53)
2010–2017	11,256 (27.5%)	53,172 (28.9%)	8 (0.07%)	62 (0.12%)	1.4 (0.4–2.4)	2.4 (1.8–2.9)	0.50 (0.24–1.05)	0.47 (0.21–1.06)
Age at start of follow-up
<18y	4490 (11.0%)	21,736 (11.8%)	0	1 (0.00%)	0.0 (0.0–0.0)	0.1 (0.0–0.3)	–	–
18y - <40y	17,531 (42.8%)	81,888 (44.5%)	4 (0.02%)	26 (0.03%)	0.5 (0.0–0.9)	0.6 (0.4–0.9)	0.71 (0.25–2.03)	0.81 (0.28–2.38)
40y - <60y	8380 (20.5%)	38,918 (21.2%)	11 (0.13%)	47 (0.12%)	2.6 (1.1–4.2)	2.4 (1.7–3.1)	1.09 (0.56–2.10)	1.13 (0.56–2.28)
≥60y	10,562 (25.8%)	41,350 (22.5%)	43 (0.41%)	128 (0.31%)	8.3 (5.8–10.8)	6.3 (5.2–7.4)	1.15 (0.81–1.63)	1.18 (0.83–1.69)
Country of birth
Nordic	39,245 (95.8%)	168 842 (91.8%)	50 (0.13%)	155 (0.09%)	2.6 (1.9–3.3)	1.9 (1.6–2.1)	1.15 (0.83–1.59)	1.13 (0.80–1.59)
Other	1717 (4.2%)	15,045 (8.2%)	8 (0.47%)	47 (0.31%)	9.4 (2.9–16.0)	6.3 (4.5–8.1)	–	–
Level of education
≤9 years	6443 (15.7%)	29,469 (16.0%)	17 (0.26%)	59 (0.20%)	5.4 (2.8–7.9)	4.1 (3.0–5.1)	1.18 (0.58–2.40)	1.25 (0.55–2.86)
10–12 years	17,707 (43.2%)	80,106 (43.6%)	25 (0.14%)	77 (0.10%)	2.9 (1.7–4.0)	1.9 (1.5–2.4)	1.13 (0.65–1.96)	1.14 (0.61–2.13)
>12 years	16,317 (39.8%)	72,295 (39.3%)	13 (0.08%)	52 (0.07%)	1.6 (0.7–2.5)	1.5 (1.1–1.8)	0.98 (0.48–1.98)	0.90 (0.40–2.07)

Notes: *Conditioned on matching set (age, sex, county, and calendar period); **Conditioned on matching set and further adjusted for education, Nordic country of birth, and medical comorbidities at index date (cardiovascular disease, diabetes, COPD, end-stage renal disease, alcohol liver disease/alcohol use disorder, obesity/dyslipidemia, obstructive sleep apnea, cancer, psychiatric disease).

Figure 2 Kaplan–Meier failure curves of time from hospital admission for Covid-19 infection (A) and time from diagnosis of any Covid-19 infection (B) to all-cause mortality in patients with celiac disease and in general population comparators from February 1 to July 31, 2020.

Table 4 Risk of All-Cause Mortality in Individuals with Covid-19 and Celiac Disease and Matched General Population Comparators with Covid-19 from February 1 to July 31, 2020

Outcome	N Exposed (%)		N Death (%)			Incidence Rate (95% CI)			HR (95% CI)	Adjusted HR* (95% CI)
	Celiac Disease	Comparators	Celiac Disease		Comparators	Celiac Disease		Comparators
Inclusion Criterion
Hospital admission	58	202	11 (19.0%)		35 (17.3%)	0.9 (0.4–1.5)		0.9 (0.6–1.1)	1.11 (0.57–2.19)	0.96 (0.46–2.02)
Any Covid-19	414	1793	22 (5.3%)		74 (4.1%)	0.3 (0.2–0.4)		0.2 (0.2–0.3)	1.29 (0.80–2.07)	0.80 (0.48–1.31)

Notes: *Adjusted for age, sex, index year, education, Nordic country of birth, and medical comorbidities at index date [cardiovascular disease, diabetes, COPD, end-stage renal disease, alcohol liver disease/alcohol use disorder, obesity/dyslipidemia, obstructive sleep apnea, cancer, psychiatric disease]).