We read with interest the highly impactful CLARITY IBD study that demonstrated a diminished serological response to SARS-CoV-2 in individuals with IBD receiving infliximab as compared with those receiving vedolizumab.¹ We assessed the prevalence of antibodies to SARS-CoV-2 in patients with IBD and evaluated whether serological response to SARS-CoV-2 wanes over time following infection.

Individuals with IBD from Calgary, Canada, were recruited from October 2020 to April 2021 and stratified into two cohorts: (1) serosurveillance (n=279) defined as those who were not previously diagnosed with COVID-19; and (2) COVID-19 recovered (n=45), defined as those with a molecular-confirmed diagnosis of SARS-CoV-2 infection via PCR.

Serum was analysed using the Abbott Architect SARS-CoV-2 IgG antibody to the nucleocapsid protein. A positive antibody test was defined as an index signal/cut-off ≥1.4. The assay has been validated with 95% sensitivity and >99% specificity 12 days following symptom onset and correlates to neutralising antibodies.²

We assessed the proportion, with 95% CIs, of individuals with IBD who mounted an antibody response among those undergoing serosurveillance and following infection with SARS-CoV-2. In those diagnosed with COVID-19, we calculated the days from diagnosis to serological testing and developed a logistic regression model that assessed the effect of time from COVID-19 diagnosis to serology testing (before vs after 90 days) on nucleocapsid positive versus negative antibody; adjusted for age, sex and anti-tumour necrosis factor (TNF) usage.

The baseline characteristics of the two cohorts are summarised in table 1. Among the serosurveillance cohort, 1.08% (95% CI 0.22 to 3.11) tested positive for nucleocapsid antibody (table 1, figure 1A). Among those who recovered from COVID-19, 53.3% (95% CI 37.9 to 68.3) had a positive nucleocapsid antibody (table 1). The proportion of patients who were nucleocapsid antibody positive was 80.8% (95% CI 60.6 to 93.4) at 0–90 days from diagnosis and 21.7% (95% CI 7.5 to 43.7) after 90 days. Tests performed within 90 days of their diagnosis were associated with nucleocapsid seropositivity (OR: 14.1; 95% CI 3.46 to 57.6) as compared with testing beyond 90 days of COVID-19 diagnosis. An interactive dashboard displaying these data can be found here: https://kaplan-gi.shinyapps.io/COVID_Serology/.

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Figure 1

The proportion of individuals with IBD who mounted an antibody response (A) Among those undergoing serosurveillance and (B) following infection with SARS-CoV-2. All clinical and serological data from this study are available open access on an online interactive dashboard: https://sc-epi.shinyapps.io/COVID_Serology/.

Table 1

Demographic and clinical characteristics of the serosurveillance and COVID-19 recovered individuals with IBD

Baseline characteristics	Serosurveillance cohort (n=279)*	COVID-19 recovered (n=45)
		Total COVID-19 recovered (n=45)*	Nucleocapsid positive (n=24)†	Nucleocapsid negative (n=21)†
Age, median (IQR)	48.1 (36.4–59.1)‡	43.1 (32.2–49.8)‡	44.2 (33.6–55.6)	37.9 (30.5–48.8)
Sex, n (%)
Female	156 (55.9)	27 (60.0)	17 (70.8)	10 (47.6)
Male	123 (44.1)	18 (40.0)	7 (29.2)	11 (52.4)
Disease, n (%)
Crohn’s Disease	226 (81.0)	29 (64.4)	17 (70.8)	12 (57.1)
Ulcerative Colitis	53 (19.0)	16 (35.6)	7 (29.2)	9 (42.9)
Anti-TNF§, n (%)	138 (49.5)	27 (60)	15 (62.5)	12 (57.1)
Ustekinumab, n (%)	89 (32.0)‡	4 (8.9)‡	3 (12.5)	1 (4.8)
Vedolizumab, n (%)	44 (16.1)	6 (13.3)	2 (8.3)	4 (19.1)
Tofacitinib, n (%)	2 (0.72)	1 (2.2)	1 (4.2)	0
Combination therapy¶, n (%)	54 (19.4)	7 (15.6)	3 (12.5)	4 (19.1)
Oral prednisone, n (%)	9 (3.2)	0	0	0
5-ASA alone or no IBD medications, n (%)	5 (1.8)‡	5 (11.1)‡	2 (8.3)	3 (14.3)
Nucleocapsid antibody, n (%)
Positive (≥1.4 S/C index)	3 (1.1)‡	23 (51.1)‡	NA	NA
Days from COVID-19 diagnosis to serology test, median (IQR)*	NA	85 (41.5–122)	51 (25–71)**	123 (93–209)**
COVID-19 severity, n (%)
Ambulatory	NA	44 (97.8)	23 (95.8)	21 (100)
Hospitalised		1 (2.2)	1 (4.2)	0

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Those previously diagnosed with COVID-19 are further stratified by positive versus negative nucleocapsid antibody test based on an S/C index of ≥1.4.

*Two individuals in the serosurveillance cohort were diagnosed with COVID-19 after their serosurveillance serology testing.

†Nucleocapsid positive or negative were based on their first serology test after COVID-19 diagnosis.

‡Significant p value comparing serosurveillance cohort to COVID-19 recovered cohort. Statistically significant at p<0.05; either defined by two-sample test of proportion (categorical variable) or Wilcoxon rank-sum test (continuous variable).

§Anti-TNF is one of golimumab, adalimumab or infliximab (originator or biosimilar).

¶Any combination of two or more of the following therapies: anti-TNF therapy, vedolizumab, ustekinumab, tofacitinib, azathioprine, 6-mercaptopurine or methotrexate.

**Significant p value comparing COVID-19 recovered nucleocapsid positive to nucleocapsid negative. Statistically significant at p<0.05; either defined by two-sample test of proportion (categorical variable) or Wilcoxon rank-sum test (continuous variable).

Anti-TNF, anti-tumour necrosis factor; NA, not applicable; S/C, signal/cut-off.

Seropositivity for SARS-CoV-2 nucleocapsid antibodies was found in 1% of individuals with IBD. In contrast, seropositivity in the general population in Calgary during the same time period was 1.8%, suggesting that patients with IBD were less exposed to SARS-CoV-2 or that serological response postinfection was not as robust as the general population.³

Our seropositivity was lower than prior IBD studies in the USA (3%)⁴ and the UK (4.3%).¹ The difference in seropositivity may be explained by the lower prevalence of COVID-19 in the general population in Canada; for example, 5.4% of patients with IBD had antibodies to SARS-CoV-2 in Milan as compared with only 0.4% in regions in Europe with lower rates of infection in their general populations.⁵

In our study, the primary factor associated with seropositivity was the interval from diagnosis to serology testing. Three-quarters were seropositive if tested within 2 months of diagnosis, whereas no one tested after 4 months was seropositive. Limitations include sample size required to compare across therapies and not testing for neutralising antibodies or immunological memory.⁶

Nonetheless, these data have important clinical implications for individuals with IBD. Serosurveillance studies in IBD may only be reliable for a 3-month window of testing. Moreover, 4 months following COVID-19 diagnosis, patients with IBD may continue to be susceptible to SARS-CoV-2. Our data highlight the importance of studying sustained antibody response over time in order to develop strategies to ensure durable protection and inform public health policy.