ABSTRACT
Background IBD patients on immune-modulatory therapies are considered high-risk for SARS-CoV-2 infection. Direct comparisons of serological responses to SARS-CoV-2 infection in IBD patients across different continents and medications are lacking. We performed SARS-CoV-2 sero-surveillance of IBD patients prior to vaccination at seven large tertiary centres in Asia, Europe, and North America. Methods Clinical data and sera were collected from, 2,213 IBD patients receiving routine care at institutions in Belgium, Canada, Hong Kong, India, Japan, the United Kingdom, and the United States between, 26 May, 2020 and, 24 September, 2021 (Table, 1). Sera were taken prior to vaccination. Clinical data were collected through patient questionnaires and medical records. Antibody reactivity to the SARS-CoV-2 spike protein was assessed using the Roche SARS-CoV-2 anti-spike total antibody and/or Siemens Healthineers COV2T anti-spike total antibody assays, which showed, 99.4% concordance. Univariate analysis was performed to evaluate association between individual variables and sero-status. Results The pre-vaccination seroprevalence of antibodies to SARS-CoV-2 in IBD patient varied widely according to location from, 0% in Hong Kong to, 57.9% in New Delhi, India (p<0.001). Rates in Europe and North America were similar (range, 3.57%-8.94%). Overall, SARS-CoV-2 seroprevalence appears to be equal to or less than local populations (Table, 2). Seroprevalence rates were associated with IBD type (7.8% CD, 12.4% UC, 15% IBD-U, p<0.001), smoking status (p<0.001), and history of COVID diagnosis (p<0.001) or COVID hospitalization (p=0.001), and any IMM (p<0.001). (Table, 3). Whilst there were no significant differences in seroprevalence between patients receiving infliximab (IFX), vedolizumab (VDZ), and ustekinumab (UST), antibody levels were attenuated in patients on IFX monotherapy and combination therapy (both p=0.002) and VDZ (p=0.02), compared with no medications (Figure 1). Conclusion We confirm in diverse poulations that exposure to biologics or immunomodulators, type of disease, and smoking status are associated with seroprevalence and antibody levels. We show for the first time the dominant influence of geographical location on sero-status in these patients. These observations should be considered as we look towards post-vaccination data to help stratify patients for clinical guidelines on SARS-CoV-2 vaccination.
ABSTRACT
Background: IBD patients on immune-modulatory therapies are considered high-risk for SARS-CoV-2 infection. Direct comparisons of serological responses to SARS-CoV-2 infection in IBD patients across different continents and medications are lacking. We performed SARSCoV- 2 sero-surveillance of IBD patients prior to vaccination at seven large tertiary centres in Asia, Europe, and North America. Methods: Clinical data and sera were collected from 2,241 IBD patients receiving routine care at institutions in Belgium, Canada, Hong Kong, India, Japan, United Kingdom, and the United States between May 2020 and September 2021 (Table 1). Sera were taken prior to vaccination. Clinical data were collected from patient questionnaires and medical records. Antibody reactivity to the SARS-CoV-2 spike protein was assessed using the Roche SARS-CoV-2 anti-spike total antibody and/or Siemens Healthineers COV2T anti-spike total antibody assays, which showed 99.4% concordance. We performed univariate analysis to evaluate association between variables and sero-status. Results: The pre-vaccination seroprevalence of antibodies to SARS-CoV-2 in IBD patient varied widely according to location from 0% in Hong Kong, China, to 57.9% in New Delhi, India. Rates in Europe and North America were similar (range 3.6%-8.9%). Overall, SARSCoV- 2 seroprevalence appears to be equal to or less than local populations (Table 1). Seroprevalence rates were associated with IBD type (Crohn's disease 7.8%, ulcerative colitis 12.4%, IBD-unclassified 15.0%, p<0.001), smoking status (p<0.001), and history of COVID diagnosis (p<0.001) or COVID hospitalization (p=0.001), and any immunomodulator (IMM) (p<0.001) (Table 1). Infection as indicated by seropositivity in the absence of known COVID infection occurred in 7.3% of patients. Whilst there were no significant differences in seroprevalence between patients receiving anti-tumor necrosis factor (anti-TNF) medications, vedolizumab (VDZ), and ustekinumab (UST), antibody levels were attenuated in patients on anti-TNF monotherapy (p=0.002), anti-TNF + IMM combination therapy (p=0.002), and VDZ (p=0.02), compared with no medications (Figure 1). Conclusion: We confirm in diverse populations that exposure to anti-TNFs, vedolizumab and immunomodulators, type of disease, and smoking status are associated with seroprevalence and antibody levels. We show for the first time the dominant influence of geographical location on sero-status in these patients. These observations should be considered as we look towards post-vaccination data to help stratify patients for clinical guidelines on SARS-CoV-2 vaccination. (Table Presented) Table 1. Seroprevalence of total anti-SARS-CoV-2 spike antibodies in IBD patients by ICARUS centre with non-IBD controls noted for New Delhi, India, and publicly reported local seroprevalence and by selected patient characteristics.(Figure Presented) Figure 1. Antibody levels by medication group.
ABSTRACT
Introduction: Gut dysbiosis is associated with immune dysfunction and severity in COVID- 191-2. This study aimed to determine targeting dysbiosis as a therapy and its effect on antibody formation, gut dysbiosis and immune profile in patients with COVID-19. Material & Methods: In an open-label study, 25 consecutive hospitalized patients with COVID- 19 received a novel microbiome immunity formula (SIM01) for 28 days;30 patients who did not receive the intervention acted as controls. We collected fecal and blood samples at baseline and week 5 and followed subjects from admission up to five weeks. We performed multi-omics analysis using data from peripheral blood mononuclear cell (PBMC) transcriptome, fecal metagenomic sequencing and fecal metabolomic profiling (Figure 1A). Results: Significantly more COVID-19 patients on SIM01 developed anti-SARS-CoV-2 IgG than the control group at 2 weeks (Figure 1B). Patients on SIM01 (but not controls) showed a significant reduction of plasma levels of interleukin (IL)-6, macrophage colony-stimulating factor (M-CSF), tumour necrosis factor (TNF-a), IL-1RA (Figure 1C) and downregulated COVID-19 related signalling pathway in PBMC at Week 5. Fecal samples of subjects on SIM01 were enriched in commensal bacteria and reduced in opportunistic pathogens at week 4 and 5. Elevated plasma acetic acid in SIM01 group showed a negative correlation with SARS-CoV-2 viral load in nasopharyngeal samples (Figure 2A). Increased relative abundance of Bifidobacteria adolescentis and Coprococcus comes in fecal samples in SIM01 group positively correlated with plasma acetic acid levels (Figure 2B). Conclusion: We showed for the first time a novel microbiome formula SIM01 was effective in hastening antibody formation against SARS-CoV-2, reduced pro-inflammatory immune markers and restored gut dysbiosis in hospitalised COVID-19 patients. References: 1. Zuo T, Zhang F, Lui GCY, et al. Alterations in gut microbiota of patients with COVID-19 during time of hospitalization. Gastroenterology 2020;159:944-955 e8. 2. Yeoh YK, Zuo T, Lui GC, et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID- 19. Gut 2021;70:698-706. (Figure Presented) (Figure Presented)
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Introduction In the United States (US), race and ethnicity impact outcomes of chronic diseases including inflammatory bowel disease (IBD). The aim of this study was to evaluate racial and ethnic disparities in the coronavirus disease 2019 (COVID-19) outcomes among IBD patients and to assess the degree to which observed disparities may be attributed to non-IBD comorbidities. Methods Using data from the Surveillance of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD), an international, collaborative registry of IBD patients with confirmed COVID-19, we used multivariable logistic regression to evaluate associations between race and ethnicity and COVID-19 outcomes. These included hospitalization and severe COVID-19 defined as a composite of intensive care unit stay, mechanical ventilation and/or death. Results We analyzed 988 US cases (96 [9.7%] Hispanic;141 [14.3%] non-Hispanic Black;680 [68.8%] non-Hispanic White). Bivariate analyses of outcomes are reported in the Table. Compared to non-Hispanic White patients, Hispanic patients had higher odds of hospitalization [adjusted odds ratio (aOR) 2.01, 95% CI 1.07 to 3.79] but not severe COVID-19 (2.75, 95% CI 0.93 to 8.10). Compared to non-Hispanic White patients, non-Hispanic Black patients had higher odds of hospitalizations (aOR 2.47, 95% CI 1.48 to 4.11) and severe COVID-19 (2.50, 95% CI 1.01 to 6.20) after adjusting for age, sex, and IBD activity (Figure). Upon adjusting for comorbidities, the odds of hospitalization and severe COVID-19 remained unchanged in Hispanic individuals compared to non-White Hispanic individuals (aOR 2.14, 95% CI 1.09 to 4.18 for hospitalizations and 2.69, 95% CI 0.77 to 9.38 for severe COVID-19), but decreased in Black individuals compared to non-White Hispanic individuals (aOR 2.21, 95% CI 1.30 to 3.76 for hospitalization and 2.13, 95% CI 0.81 to 5.59 for severe COVID-19). Conclusions The odds of adverse COVID-19 outcomes are higher in Hispanic and non-Hispanic Black, compared with non-Hispanic White individuals with IBD, accounted for partially by underlying comorbidities. (Table presented) COVID-19 Outcomes for United States cases reported to SECURE-IBD, overall and stratified by race/ethnicity (Figure presented) Odds ratios of A) hospitalization due to COVID-19 and B) severe COVID-19 outcomes (ICU stay, mechanical ventilation or death) among Hispanic vs. non-Hispanic White individuals and among non-Hispanic Black vs. non-Hispanic White individuals
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Introduction: Growing evidence indicates that gut microbiota plays an important role in COVID-191-5. We previously reported that patients with COVID-19 had altered faecal microbiomes characterised by enrichment of opportunistic pathogens and depletion of beneficial commensals1,2. Our results showed that gut dysbiosis correlated with the severity of COVID- 19 and persisted even after clearance of SARS-CoV-2 in respiratory samples and resolution of respiratory symptoms1,2. Although probiotics has been advocated in the management of COVID-196, whether targeting dysbiosis will improve outcomes of COVID-19 is largely unknown. Aims & Methods: The aim was to assess the effects of a novel microbiome formula (SIM01) as an adjuvant therapy on immunological responses and changes in gut microbiota of hospitalised COVID-19 patients. Methods: This was an open-label, proof-of-concept study. Consecutive COVID-19 patients admitted to an infectious disease referral centre in Hong Kong were given a novel formula of Bifidobacteria strains, galactooligosaccharides, xylooligosaccharide, and resistant dextrin (SIM01). The latter was derived from metagenomic databases of COVID-19 patients and healthy population. COVID-19 patients who were admitted under another independent infectious disease team during the similar period without receiving the SIM01 formula acted as controls. All patients received standard treatments for COVID-19 according to the hospital protocol. We assessed antibody response, proinflammatory markers and faecal microbiota profile from admission up to Week 5. Results: Twenty-five consecutive patients received SIM01 for 28 days;30 patients without receiving the formula acted as controls. Significantly more patients receiving SIM01 than the control group developed antibody (88% vs. 63.3%;p =0.037) by Day 16. One (4%) patient in the SIM01 group and 8 (26.7%) in the control group did not develop positive IgG antibody upon discharge. At Week 5, plasma levels of interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), macrophage colony-stimulating factor (M-CSF), tumour necrosis factor (TNF-α), and IL-1RA dropped significantly in the SIM01 group but not in the control group. Metagenomic analysis showed that the bacterial species of the SIM01 formula were found in greater abundance, leading to enrichment of commensal bacteria and suppression of opportunistic pathogens in COVID-19 patients by Week 4 and Week 5. Conclusion: The use of a novel microbiome formula SIM01 hastened antibody formation against SARS-CoV-2, reduced pro-inflammatory immune markers and restored gut dysbiosis in hospitalised COVID-19 patients.
ABSTRACT
Background Evidence regarding the use of proton-pump inhibitors (PPIs) in COVID-19 patients remains elusive. We examined the impact of PPI use on clinical outcomes of COVID-19 patients in a territory-wide cohort. Methods We performed a retrospective cohort study using data from an electronic healthcare database managed by the Hospital Authority, Hong Kong. COVID-19 patients diagnosed virologically between 23 January 2020 and 1 January 2021 in Hong Kong were identified. The primary endpoint was a composite of intensive care unit admission, use of invasive mechanical ventilation, and/or death. PPI user was identified by PPI use within 12 months before the diagnosis of COVID-19. In subgroup analysis, current PPI users were defined as patients who used PPIs within 1 month before the diagnosis of COVID-19;past PPI users were defined as patients who used PPIs 1 to 12 months before COVID-19 diagnosis. We performed sensitivity analysis after excluding patients with short-term new NSAID use within 1 month before COVID-19 diagnosis to minimize reverse causation bias. Results We identified 8,675 COVID-19 patients (mean age 46 years, 49% male, 97.6% of all the reported cases in Hong Kong);579 (6.7%) patients had used PPI. PPI users were older, more likely to have comorbidities, concomitant medications and unfavorable laboratory parameters than non-users. Of 8,675 COVID-19 patients, 500 (5.8%) developed the primary endpoint. After propensity score (PS) balancing for patients' demographics, comorbidities, laboratory parameters, and use of medications, PPI use was not associated with the development of primary endpoint in PS weighting (weighted hazard ratio [HR] 1.11, 95% confidence interval [CI] 0.83-1.47, P=0.482) (IDDF2021-ABS- 0122 Figure 1. Cumulative incidence of primary endpoint (a composite endpoint of intensive care unit [ICU] admission, use of invasive mechanical ventilation [IMV], and death) in COVID-19 patients who were and were not proton- pump inhibitor (PPI) users after propensity score (PS) weighting in a single multiple imputation data set.), and PS matching analysis (weighted HR 0.81, 95%CI 0.57-1.14, P=0.228) (IDDF2021-ABS-0122 Figure 2. Cumulative incidence of primary endpoint (a composite endpoint of intensive care unit [ICU] admission, use of invasive mechanical ventilation [IMV], and death) in COVID-19 patients who were and were not proton-pump inhibitor (PPI) users after propensity score (PS) matching in a single multiple imputation data set). Consistent non-association was observed after multivariable adjustment (adjusted HR 0.84, 95%CI 0.66- 1.07, P=0.151), in subgroups of current and past PPI users, and in sensitivity analysis after excluding short-term new NSAID users. Conclusions PPI use is not associated with adverse clinical outcomes in COVID-19 patients. The result remains robust after PS weighting, PS matching, multivariable adjustment, and subgroup analyses.