Humoral Immune Response to Messenger RNA COVID-19 Vaccines Among Patients With Inflammatory Bowel Disease.

Early indicators suggest that highly effective messenger RNA (mRNA) vaccinations (BNT 162b2 [Pfizer-BioNTech] and mRNA-1273 [NIH-Moderna]) are beginning to curb the coronavirus disease 2019 (COVID-19) pandemic that has already taken the lives of 3 million individuals worldwide. However, questions about vaccine effectiveness remain for individuals with inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, who are frequently treated with immune suppression. An early study among transplant recipients indicated low humoral immune response after an initial vaccination, in contrast to the robust response observed in healthy individuals in phase III clinical trials. Similarly, a recent study in IBD patients suggested that treatment with infliximab is associated with an attenuated level of anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike after a single dose of mRNA vaccine.

However, the more clinically relevant question relates to seroprotection after completing the approved 2-part vaccination series. In a follow-up study of 658 transplant recipients, antispike antibody was detected in 54% of participants at a median of 29 days after the second vaccine dose. Preliminary results suggest that IBD patients may fare better. In a single-center US study all patients (n = 26) who completed 2-dose vaccine schedules had detectible antibody. Additionally, in a multicenter UK study, 85% (17/20) of infliximab-treated patients and 86% (6/7) of vedolizumab-treated patients seroconverted after the second vaccine dose.

Despite this early reassuring data, larger studies evaluating COVID-19 vaccine effectiveness in IBD patients are urgently needed to guide optimal approaches to the COVID-19 vaccination. We assessed serologic response after completion of the 2-part mRNA vaccination series in a geographically diverse US IBD population.

Methods

The Partnership to Report Effectiveness of Vaccination in populations Excluded from iNitial Trials of COVID (PREVENT-COVID) is a prospective, observational, cohort study of patients with IBD who have received any COVID-19 vaccine granted Emergency Use Authorization in the United States. Eligibility criteria were a diagnosis of IBD, receipt of 1 or more doses of any COVID-19 vaccine within the prior 90 days, age 16 years or older, US residence, access to the internet and ability to complete surveys in English, and willingness to remain in study for 18 months. Participants were recruited through education, social media, and other outreach efforts in collaboration with the Crohn’s & Colitis Foundation and by referral at selected clinical sites (Appendix 1) and will be followed through internet surveys for up to 18 months to ascertain outcomes of COVID-19 infection and safety events.

We performed quantitative measurement of antireceptor binding domain IgG antibodies specific to SARS-CoV-2 at approximately 8 weeks after completing the vaccination series using the LabCorp Cov2Quant IgG assay. Results of 1.0 μg/mL or greater suggest vaccination and/or prior infection with SARS-CoV-2. We also performed qualitative assessment of nucleocapsid in a subset of participants as an indicator of past infection.

This analysis included all participants who completed their 2-part vaccination series and underwent laboratory testing before May 14, 2021. Participants who reported prior COVID-19 infection and/or had positive nucleocapsid antibody indicating prior native infection were excluded. We performed descriptive statistics to characterize the study population and antibody response, including subgroup analyses stratified by age, vaccine type, and reported medication use at the time of initial immunization. We used box and whisker plots to display mean, median, and interquartile ranges of antibody values overall and across subgroups. The study protocol was approved by the Institutional Review Board at the University of North Carolina at Chapel Hill.

Results

The study population included 317 participants (mean age, 50.9 years; 75% women). Antibody testing was obtained at a median of 64 days (interquartile range, 59–73) after the second vaccination. Additional demographic characteristics and medication use are shown in Table 1 .

Table 1

Demographics, Treatment Characteristics, and Humoral Immune Response to COVID-19 Immunization Among Patients With IBD Enrolled in the PREVENT-COVID Study

	Overall Population (N = 317)		Anti-TNF Monotherapy (n = 108)		Anti-TNF Combination Therapy (n = 24)		6MP/AZA/MTX Alone (n = 20)		5ASA, Sulfasalazine, Budesonide, or No Medication (n = 65)		Vedolizumab Monotherapy (n = 46)		Ustekinumab Monotherapy (n = 39)
Median time from second vaccine dose to antibody test, days (interquartile range)	64.0	(59.0–72.5)	65.0	(61.0–72.0)	67.5	(61.5–75.5)	69.0	(63.0–75.5)	64.0	(59.0–72.0)	61.0	(55.0–70.0)	63.0	(56.0–71.0)
Mean age, y (SD)	50.9	(16.7)	48.0	(16.5)	43.9	(16.0)	56.5	(18.9)	57.2	(15.4)	53.3	(16.7)	48.0	(16.1)
Female	238	(75)	79	(73)	19	(79)	15	(75)	52	(80)	33	(72)	30	(77)
Type of vaccine at first dose
Pfizer	173	(55)	57	(53)	11	(46)	14	(70)	33	(51)	26	(57)	22	(56)
Moderna	144	(45)	51	(47)	13	(54)	6	(30)	32	(49)	20	(43)	17	(44)
Race
White	301	(95)	102	(94)	23	(96)	19	(95)	63	(97)	43	(93)	37	(95)
Black/African American	1	(0)	1	(1)	0	(0)	0	(0)	0	(0)	0	(0)	0	(0)
Asian	5	(2)	3	(3)	0	(0)	0	(0)	1	(2)	1	(2)	0	(0)
Native Hawaiian/Pacific	1	(0)	0	(0)	0	(0)	0	(0)	0	(0)	0	(0)	1	(3)
More than 1 race	4	(1)	1	(1)	1	(4)	0	(0)	0	(0)	1	(2)	1	(3)
Other	5	(2)	1	(1)	0	(0)	1	(5)	1	(2)	1	(2)	0	(0)
Hispanic
Yes	9	(3)	1	(1)	1	(4)	1	(5)	1	(2)	1	(2)	3	(8)
No	308	(97)	107	(99)	23	(96)	19	(95)	64	(98)	45	(98)	36	(92)
Region
Northeast	80	(25)	32	(30)	6	(25)	4	(20)	16	(25)	12	(26)	8	(21)
South	108	(34)	39	(36)	6	(25)	8	(40)	19	(29)	13	(28)	18	(46)
Midwest	76	(24)	22	(20)	7	(29)	4	(20)	16	(25)	16	(35)	8	(21)
West	53	(17)	15	(14)	5	(21)	4	(20)	14	(22)	5	(11)	5	(13)
Mean antispike antibody level (SD)	28.6	(47.5)	15.1	(18.4)	11.5	(9.4)	24.0	(25.2)	44.2	(79.0)	45.2	(51.0)	34.6	(47.2)
Median antispike antibody level (interquartile range)	17.0	(7.8–30.0	10.0	(4.6–18.0	8.5	(5.6–18.0	15.5	(7.0–30.0	24.0	(14.0–42.0	30.0	(20.0–40.0	22.0	(10.0–35.0
Proportion with detectible antispike antibody	300	(95)	101	(94)	21	(88)	19	(95)	61	(94)	46	(100)	38	(97)

Values are n (%) unless otherwise defined. 5ASA, 5-aminosalicylic acid; 6MP, 6-mercaptopurine; AZA, azathioprine; MTX, methotrexate; TNF, tumor necrosis factor.

Overall, 300 of 317 participants (95% confidence interval [CI], 92–97) had detectable antibodies. The distribution of antibody response across medication classes and other patient characteristics are shown in Table 1. Participants receiving systemic corticosteroids appeared to have somewhat diminished antibody response, although formal hypothesis testing was not done in this exploratory analysis. Of 13 patients taking corticosteroids, the proportion with detectible antibodies was 85% (95% CI, 58–96) versus 95% (95% CI, 92–97) among nonsteroid users (mean antibody level, 22 μg/mL vs 29 μg/mL) among nonusers (Supplementary Table 1). Antibody response was generally similar across age group, vaccine type, and use of other classes of IBD medications (Supplementary Figure 1). Of the 10 participants with positive nucleocapsid antibody indicative of prior infection who were excluded from the above analyses, all had detectable antispike antibodies (mean, 70 μg/mL; median, 32 μg/mL).

Supplementary Table 1

Humoral Immune Response to COVID-19 Immunization, Stratified by Corticosteroid Use, Among Patients With IBD Enrolled in the PREVENT-COVID Study

	Corticosteroids (n = 13)	No corticosteroids (n = 304)
Positive antispike antibody, % (95% CI)	84.6 (57.8–95.7)	95.1 (92.0–97.0)
Mean antispike antibody level (SD)	21.6 (24.8)	28.9 (48.3)
Median antispike antibody level (interquartile range)	14.0 (3.7–26.0)	17.5 (7.8–30.5)

Supplementary Figure 1

Antispike antibody levels among IBD patients enrolled in the PREVENT-COVID study. Box and whisker plots illustrating mean (X), median, interquartile range, overall range of antispike antibody levels (μg/mL), and the proportion of participants with detectible antibody stratified by (A) age group, (B) type of vaccination, (C) IBD medication use (all participants), and (D) medication use among patients not taking corticosteroids.

Discussion

In this study of the humoral response to 2 doses of mRNA SARS-CoV-2 vaccine in a geographically diverse cohort of over 300 patients with IBD, most had detectable antibody responses after the second dose. Overall, these results reinforce the findings of 2 small reports (<30 participants each) indicating positive humoral immune response with complete vaccination. , Taken together, these emerging data provide reassurance that most medications for IBD do not markedly reduce the response to COVID-19 immunization and support recent consensus recommendations to vaccinate all patients with IBD regardless of immune-modifying therapies. Our finding of somewhat attenuated humoral immune response in patients receiving corticosteroids requires further prospective evaluation and may ultimately warrant special consideration regarding timing of vaccination efforts, utility of antibody testing after vaccination, and/or the possible need for booster vaccination beyond the standard 2-dose series.

Study limitations include a convenience sample that lacks racial and ethnic diversity and under-represents men and the reliance of self-report in our direct-to-patient cohort. We did not conduct formal hypothesis testing in this exploratory analysis. Additionally, no threshold has been established for protective immunity in the quantitative antibody testing.

Although many questions remain and ongoing research efforts will help to further optimize immunization strategies for patients with IBD, these findings provide reassurance that most patients mount detectable humoral immune response to mRNA vaccinations and support current recommendations to vaccinate patients regardless of immunosuppressive treatment.