ABSTRACT
Background: COVID-19 associated gut microbiome dysbiosis has been strongly linked to more severe disease and has most recently been shown to persist long after symptomatic recovery. While studies have correlated the depletion of gut commensals, like Faecalibacterium and Bifidobacterium, to disease severity, little is known about specific microbes that may be protective against disease, especially in the context of vaccination against SARS-CoV-2. We aimed to characterize changes in the gut microbiota following COVID-19 vaccination and associate them with antibody titers against SARS-CoV-2. Methods: We obtained paired stool samples from a cohort of 8 patients, the first sample taken within 10 days before the beginning of their COVID-19 mRNA vaccine series and the second taken within 10 days after their second vaccine. 16s rRNA gene sequencing and principal coordinate analysis were performed. In parallel, blood samples were also collected at 1, 3, 6, and 12 months to enumerate serum IgG antibody titers. Patients were stratified into 2 groups—medium and high—based on IgG titers following vaccination, wherein the `high' response group maintained significantly higher titers beyond 6 months follow-up. We used linear discriminant analysis effect size (LefSe) to estimate which microbes significantly differed at baseline between the 2 response groups. Results: The gut microbiome composition differed before and after vaccination for all patients, with medium responders showing significant differences by both Bray-Curtis dissimilarity (p = 0.04, pairwise PERMANOVA) and unweighted UniFrac (p = 0.03, pairwise PERMANOVA) beta diversity metrics (Figure 1), while differences within high responders were non-significant. The most abundant families present before vaccination in all subjects included Lachnospiraceae, Bacteroidaceae, Ruminococcaceae, and Enterobacteriaceae. Following vaccination, a stark contraction in the relative abundance of the family Bacteroidaceae occurred in all subjects, and in the majority of cases was accompanied by a concomitant increase in the abundance of Lachnospiraceae. The relative abundances of Ruminococcaceae, Bifidobacteriaceae, and Streptococcaceae were also increased in the majority of post-vaccination samples. Post-vaccination samples were also increased in community evenness and community richness for both response groups. LefSe analysis indicated that the orders Bifidobacteriales and Lactobacillales were significantly associated with high responders (Figure 2). Conclusion: Altogether, these findings demonstrate an association between the gut microbiota and COVID-19 immunity and highlight a potential link between specific taxa and the strength of humoral responses following vaccination. (Figure Presented) (Figure Presented)
ABSTRACT
Background: Several SARS-CoV-2 vaccines are highly effective in preventing most infections, serious disease, hospitalization, and death from COVID-19 in the general population, but data regarding their use and efficacy in patients with inflammatory bowel disease (IBD) are limited. In this study we assessed the use patterns and efficacy of SARS-CoV-2 vaccines in patients with IBD. Methods: We established a multicenter matched case-control cohort of patients with IBD [Crohn's disease (CD), ulcerative colitis (UC)] and COVID-19 between February 2020 and December 2020 for the Surveillance of COVID-19 Impact on Long- Term Outcomes in IBD (SCOUT IBD) study. Cases were defined by the presence of COVID- 19-related symptoms and confirmatory SARS-CoV-2 PCR or IgG testing and non-COVID controls were defined as absence of symptoms and both a negative PCR and IgG in 2020. Cases were matched 1:1 to controls based on age, sex and IBD type. Data were collected on vaccine administration in 2021 and incidence of interval COVID-19 (defined as above) between January and September 2021. Results: The total cohort included 502 patients with IBD [UC (n=222, 44%), CD (n=278, 55%), IBD-undefined (n=2, 1%)] of whom 251 had a history of COVID-19 in 2020. The overall vaccination rate was 61% (n=306) with 189 (62%) patients receiving Pfizer-BioNTech, 101 (33%) Moderna, and 12 (4%) Johnson & Johnson. Vaccinated patients were more likely to be older (P=0.02), female (P=0.07), have a co-morbidity (cardiovascular, respiratory, renal) (P=0.04), or currently be on a biologic (P=0.01), and less likely to have had prior COVID-19 (P<0.001) than patients who did not get vaccinated (Table 1). The overall incidence of interval COVID-19 was 1.6% (N=8), with an infection rate of 0.3% (1/311) in vaccinated patients vs. 3.7% (7/184) in unvaccinated patients (P<0.01). Of infections occurring in unvaccinated patients, 1/7 (14.2%) was severe and required hospitalization requiring ICU admission, and the breakthrough infection in the vaccinated patient was mild and self-limited. COVID-19 reinfection occurred in one patient (0.4%) with prior COVID-19 who was unvaccinated. Under multivariable logistic regression, COVID-19 vaccination (aOR 0.05, 95% CI 0.01-0.41) and prior COVID-19 infection (OR 0.07, 95% CI 0.01-0.63) were highly protective against interval COVID-19. Conclusion: COVID-19 vaccines are effective in patients with IBD and markedly reduce the incidence of COVID-19. Prior COVID-19 is also protective against subsequent infection, although re-infections may occur at a very low rate. These results reaffirm the importance of COVID-19 vaccination in patients with IBD.(Table Presented)(Table Presented)
ABSTRACT
Background: Inflammatory bowel disease (IBD) and IBD-related biologic therapies are not associated with worse outcomes of Coronavirus Disease 2019 (COVID-19), however, data are lacking regarding the long-term impact of COVID-19 and its inflammatory sequelae on the disease course of IBD. We aimed to investigate the long-term outcomes of patients with IBD and COVID-19. Methods: We performed a multicenter matched case-control study of patients with IBD [Crohn's disease (CD), ulcerative colitis (UC)] and COVID-19 between February 2020 and December 2020 at 5 large health systems. Cases were defined by the presence of COVID-19-related symptoms and confirmatory SARS-CoV-2 PCR or IgG testing. Non-COVID controls were defined as absence of symptoms and both a negative PCR and IgG during the study entry period. Cases were matched 1:1 to controls based on age, sex and IBD type. The primary composite outcome was IBD-related hospitalization or surgery, and outcomes were sub-stratified by COVID-19 severity. Results: We identified 251 cases with IBD [UC (n=111, 44%), CD (n=139, 55%)] and confirmed COVID-19, matched with 251 non-COVID-19 IBD controls, with a median follow-up of 394 days. COVID-19 patients had higher rates of prior IBD-related hospitalizations (36% vs. 27%;P=0.03), corticosteroid use (75% vs. 65%;P=0.06), and biologic exposure (73% vs. 64%;P=0.04) than controls. There were no differences in UC extent or CD phenotype between groups. In COVID-19 positive patients, the most common symptoms were fever (61%), cough (48%), fatigue (30%) and diarrhea (28%). Severe COVID-19 (defined as hospitalization, ICU requirement or mechanical ventilation) occurred in 16% (n=39) of cases. The primary composite outcome of IBD-related hospitalization or surgery occurred in 12% (n=38) of cases vs. 15% (n=29) of controls (P=0.24;Table 1). When further stratified by COVID-19 severity, the incidence of the primary composite outcome was highest in patients with severe COVID-19, followed by controls and non-severe COVID-19 (Figure 1). Under multivariate Cox regression, severe COVID-19 remained a predictor of worse IBD outcomes (aHR 2.09, 95% CI 0.91-4.86) whereas non-severe COVID-19 was associated with decreased risk (aHR 0.52, 95% CI 0.28- 0.99). Prior IBD-related hospitalization or surgery (aHR 3.10, 95% CI 1.70-6.57) and current steroid use (aHR 2.17, 95% CI 0.95-4.94) were also predictive of worse IBD outcomes. Conclusion: In this matched case-control study, a history of any COVID-19 infection did not appear to exacerbate the course of IBD, however, severe COVID-19 was associated with worse IBD outcomes. These data suggest that the inflammatory sequelae of COVID-19 may adversely impact the subsequent disease course of IBD. Further studies are required to confirm these associations, which underscore the importance of COVID-19 mitigation measures.(Table Presented) (Figure Presented)