To the Editors,

Coronavirus disease 2019 (COVID-19), an infectious disease caused by coronavirus SARS-CoV-2, has rapidly spread to a global pandemic. For patients with inflammatory bowel disease (IBD), significant concern arises from the widespread use of immunosuppressive therapies,1 yet preliminary data do not indicate a worse clinical course.2,3 However, limited data are available concerning the risk of acquiring COVID-19.

We conducted a retrospective cohort study among adult IBD patients followed in our center in Lombardy, aimed at defining prevalence and risk factors for acquiring the infection.

All patients were individually contacted by phone between March and April 2020. Because during the study period virologic testing was available only for inpatients or health care workers besides laboratory confirmed diagnosis, we also included probable cases according to WHO reccomendations (ie, occurrence of an acute respiratory illness AND residence in a high-prevalence area or contact with a COVID-19 case). To ensure validity of the diagnosis of probable cases, one of the following additional criteria was also required: previous influenza vaccination or close contact with a COVID-19 case.

Patients provided verbal informed consent for the inclusion in the study.

Among 704 included patients (suppl Fig 1 and suppl Table 1), 53 (7.5%) were diagnosed with COVID-19, and 9 (1.2%) had a laboratory-proven diagnosis. Demographic and clinical characteristics are listed in Table 1. At logistic regression, only severely active IBD (odds ratio [OR], 12.6; 95% CI, 1.7–92.4; P = 0.01) was significantly associated with COVID-19 (suppl Table 2). Diarrhea was the presenting symptom in 26 (49%) patients, and significantly more cases reported diarrhea compared with non-COVID-19 patients (OR, 29; P < 0.0001), independently from disease activity at multiple regression analysis (suppl Table 2).

TABLE 1.

Demographic and Clinical Characteristics of COVID-19 IBD Patients Compared with Non COVID-19 IBD Patients

IBD Patients With COVID-19 (n=53) IBD Patients Without COVID-19 (n=651)P
Age(years)50 (42–62)53 (41–65)P = ns
Females26 (49)275 (42.2)P = ns
Type of IBD
Crohn’s disease20 (37.7)275 (42.2)P = ns
Ulcerative colitis33 (62.3)376 (57.7)
CD extension
Ileal10 (50)95 (34.5)P = 0.02
Colonic2 (10)69 (25)
Ileocolonic8 (40)111 (40.4)
Upper disease5 (25)21 (7.6)
Perianal disease0 (0)33 (12)
UC extension
Proctitis11 (33)72 (19.1P = 0.004
Left-sided colitis15 (46)106 (28.2)
Extensive colitis7 (21)198 (52.7)
Flu vaccination23 (43.4)320 (49.1)P = ns
Active cigarette smoking8 (15.1)110 (16.9)P = ns
Therapy for IBD
None4 (7.5)59 (9)P = ns
Aminosalicylates30 (56.6)365 (56.1)
Immunosuppressants (thiopurines /methotrexate)8 (15.1)97 (14.9)
High dose systemic corticosteroids 2 (3.7)9 (1.4)
Anti-TNF8 (15.1)87 (13.4)
Vedolizumab1 (1.9)25 (3.8)
Ustekinumab1 (1.9)15 (2.3)
Investigational drugs (within a clinical trial)0 (0)1 (0.1)
Disease Activity
Inactive44 (83)554 (85)P = 0.01
Mild5 (9.5)72 (11)
Moderate 2 (3.8)23 (3.5)
Severe2 (3.8)2 (0.3)
Comorbidities
Systemic hypertension9 (16.9)148 (22.7)P = ns
Cardiac disease5 (9.4)31 (4.8)
COPD 2 (3.8)25 (3.8)
Diabetes mellitus0 (0)31 (4.8)
Chronic kidney disease3 (5.7)14 (2.1)
Any comorbidity18 (33.9)277 (42.5)P = ns
BMI23.5 (21–27)24.1 (21.6–26.6)P = ns
IBD Patients With COVID-19 (n=53) IBD Patients Without COVID-19 (n=651)P
Age(years)50 (42–62)53 (41–65)P = ns
Females26 (49)275 (42.2)P = ns
Type of IBD
Crohn’s disease20 (37.7)275 (42.2)P = ns
Ulcerative colitis33 (62.3)376 (57.7)
CD extension
Ileal10 (50)95 (34.5)P = 0.02
Colonic2 (10)69 (25)
Ileocolonic8 (40)111 (40.4)
Upper disease5 (25)21 (7.6)
Perianal disease0 (0)33 (12)
UC extension
Proctitis11 (33)72 (19.1P = 0.004
Left-sided colitis15 (46)106 (28.2)
Extensive colitis7 (21)198 (52.7)
Flu vaccination23 (43.4)320 (49.1)P = ns
Active cigarette smoking8 (15.1)110 (16.9)P = ns
Therapy for IBD
None4 (7.5)59 (9)P = ns
Aminosalicylates30 (56.6)365 (56.1)
Immunosuppressants (thiopurines /methotrexate)8 (15.1)97 (14.9)
High dose systemic corticosteroids 2 (3.7)9 (1.4)
Anti-TNF8 (15.1)87 (13.4)
Vedolizumab1 (1.9)25 (3.8)
Ustekinumab1 (1.9)15 (2.3)
Investigational drugs (within a clinical trial)0 (0)1 (0.1)
Disease Activity
Inactive44 (83)554 (85)P = 0.01
Mild5 (9.5)72 (11)
Moderate 2 (3.8)23 (3.5)
Severe2 (3.8)2 (0.3)
Comorbidities
Systemic hypertension9 (16.9)148 (22.7)P = ns
Cardiac disease5 (9.4)31 (4.8)
COPD 2 (3.8)25 (3.8)
Diabetes mellitus0 (0)31 (4.8)
Chronic kidney disease3 (5.7)14 (2.1)
Any comorbidity18 (33.9)277 (42.5)P = ns
BMI23.5 (21–27)24.1 (21.6–26.6)P = ns

Data are reported as absolute frequencies (%) and medians (IQR). Abbreviations: CD, Crohn’s disease; UC, ulcerative colitis; COPD, chronic obstructive pulmonary disease; BMI, body mass index.

TABLE 1.

Demographic and Clinical Characteristics of COVID-19 IBD Patients Compared with Non COVID-19 IBD Patients

IBD Patients With COVID-19 (n=53) IBD Patients Without COVID-19 (n=651)P
Age(years)50 (42–62)53 (41–65)P = ns
Females26 (49)275 (42.2)P = ns
Type of IBD
Crohn’s disease20 (37.7)275 (42.2)P = ns
Ulcerative colitis33 (62.3)376 (57.7)
CD extension
Ileal10 (50)95 (34.5)P = 0.02
Colonic2 (10)69 (25)
Ileocolonic8 (40)111 (40.4)
Upper disease5 (25)21 (7.6)
Perianal disease0 (0)33 (12)
UC extension
Proctitis11 (33)72 (19.1P = 0.004
Left-sided colitis15 (46)106 (28.2)
Extensive colitis7 (21)198 (52.7)
Flu vaccination23 (43.4)320 (49.1)P = ns
Active cigarette smoking8 (15.1)110 (16.9)P = ns
Therapy for IBD
None4 (7.5)59 (9)P = ns
Aminosalicylates30 (56.6)365 (56.1)
Immunosuppressants (thiopurines /methotrexate)8 (15.1)97 (14.9)
High dose systemic corticosteroids 2 (3.7)9 (1.4)
Anti-TNF8 (15.1)87 (13.4)
Vedolizumab1 (1.9)25 (3.8)
Ustekinumab1 (1.9)15 (2.3)
Investigational drugs (within a clinical trial)0 (0)1 (0.1)
Disease Activity
Inactive44 (83)554 (85)P = 0.01
Mild5 (9.5)72 (11)
Moderate 2 (3.8)23 (3.5)
Severe2 (3.8)2 (0.3)
Comorbidities
Systemic hypertension9 (16.9)148 (22.7)P = ns
Cardiac disease5 (9.4)31 (4.8)
COPD 2 (3.8)25 (3.8)
Diabetes mellitus0 (0)31 (4.8)
Chronic kidney disease3 (5.7)14 (2.1)
Any comorbidity18 (33.9)277 (42.5)P = ns
BMI23.5 (21–27)24.1 (21.6–26.6)P = ns
IBD Patients With COVID-19 (n=53) IBD Patients Without COVID-19 (n=651)P
Age(years)50 (42–62)53 (41–65)P = ns
Females26 (49)275 (42.2)P = ns
Type of IBD
Crohn’s disease20 (37.7)275 (42.2)P = ns
Ulcerative colitis33 (62.3)376 (57.7)
CD extension
Ileal10 (50)95 (34.5)P = 0.02
Colonic2 (10)69 (25)
Ileocolonic8 (40)111 (40.4)
Upper disease5 (25)21 (7.6)
Perianal disease0 (0)33 (12)
UC extension
Proctitis11 (33)72 (19.1P = 0.004
Left-sided colitis15 (46)106 (28.2)
Extensive colitis7 (21)198 (52.7)
Flu vaccination23 (43.4)320 (49.1)P = ns
Active cigarette smoking8 (15.1)110 (16.9)P = ns
Therapy for IBD
None4 (7.5)59 (9)P = ns
Aminosalicylates30 (56.6)365 (56.1)
Immunosuppressants (thiopurines /methotrexate)8 (15.1)97 (14.9)
High dose systemic corticosteroids 2 (3.7)9 (1.4)
Anti-TNF8 (15.1)87 (13.4)
Vedolizumab1 (1.9)25 (3.8)
Ustekinumab1 (1.9)15 (2.3)
Investigational drugs (within a clinical trial)0 (0)1 (0.1)
Disease Activity
Inactive44 (83)554 (85)P = 0.01
Mild5 (9.5)72 (11)
Moderate 2 (3.8)23 (3.5)
Severe2 (3.8)2 (0.3)
Comorbidities
Systemic hypertension9 (16.9)148 (22.7)P = ns
Cardiac disease5 (9.4)31 (4.8)
COPD 2 (3.8)25 (3.8)
Diabetes mellitus0 (0)31 (4.8)
Chronic kidney disease3 (5.7)14 (2.1)
Any comorbidity18 (33.9)277 (42.5)P = ns
BMI23.5 (21–27)24.1 (21.6–26.6)P = ns

Data are reported as absolute frequencies (%) and medians (IQR). Abbreviations: CD, Crohn’s disease; UC, ulcerative colitis; COPD, chronic obstructive pulmonary disease; BMI, body mass index.

As of May 11, 2020, 81,507 laboratory-confirmed cases have been reported in Lombardy, with a cumulative incidence rate of 0.81%; in our cohort, this was roughly similar (1.2%). Yet given the inability to test outpatients with milder symptoms, a 10-fold higher period prevalence has been hypothesized based on mortality and assumptive case-fatality rate,4 again not dissimilar from our data.

Severely active IBD was associated with COVID-19, though this has to be considered with caution because severe flare leading to hospitalization was actually a reason for testing. No other association with any disease aspect, including immunosuppressive therapies, was found.

Accordingly, maintaining effective treatment to avoid severe flares of IBD could reduce the risk of COVID-19.

Moreover, this diarrhea-predominant picture of COVID-19 in IBD has to be taken into specific consideration to avoid erroneous attribution of newly developed symptoms and incorrect management.5

Author Contribution: CV, SM, and MED planned and designed the study. LP, LC, MB, MM, and AER performed the data extraction and interviewing of patients. CV and SM analyzed the data. SM performed the statistical analyses. CV drafted the manuscript. SM, LC, MED, and LP provided critical review of the manuscript. PI provided major intellectual revision. The data underlying this article will be shared upon reasonable request to the corresponding author.

Conflicts of Interest: PI, CV, SM, LP, LC, MF, MB, and MM are members of the European Reference Network on Hepatological Rare Diseases (ERN RARE LIVER).

REFERENCES

1.

D’amico
F
,
Danese
S
,
Peyrin-Biroulet
L
;
ECCO COVID taskforce
.
Inflammatory bowel disease management during the COVID-19 outbreak: a survey from the European Crohn’s and Colitis Organization (ECCO)
.
Gastroenterology.
2020
;
S0016-5085(20)30578-3
. doi: 10.1053/j.gastro.2020.04.059.

2.

Bezzio
C
,
Saibeni
S
,
Variola
A
, et al. ;
Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD)
.
Outcomes of COVID-19 in 79 patients with IBD in Italy: an IG-IBD study
.
Gut.
2020
;
69
:
1213
1217
.

3.

Brenner
EJ
,
Ungaro
RC
,
Gearry
RB
, et al.
Corticosteroids, but not TNF antagonists, are associated with adverse COVID-19 outcomes in patients with inflammatory bowel diseases: results from an international registry
.
Gastroenterology.
2020
. doi: 10.1053/j.gastro.2020.05.032.

4.

Signorelli
C
,
Scognamiglio
T
,
Odone
A
.
COVID-19 in Italy: impact of containment measures and prevalence estimates of infection in the general population
.
Acta Biomed.
2020
;
91
:
175
179
.

5.

Parigi
TL
,
Bonifacio
C
,
Danese
S
.
Is it Crohn’s disease?
Gastroenterology.
2020
;
S0016-5085(20)30587-4
. doi: 10.1053/j.gastro.2020.04.066.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://dbpia.nl.go.kr/pages/standard-publication-reuse-rights)