POST-VACCINATION SYMPTOMS AFTER A THIRD DOSE OF SARS-COV-2 MRNA VACCINATION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE

Background:Symptoms after SARS-CoV-2 primary vaccination among patients with inflammatory bowel disease (IBD) are generally similar to the general population,although symptoms after the second dose are more frequent and severe than after the first dose.Postvaccination symptoms after a 3rd mRNA vaccine dose in the predominantly immune-compromised IBD population is unknown.Methods:Adults with IBD participating in the prospective Coronavirus Risk Associations and Longitudinal Evaluation in IBD (CORALE-IBD) vaccine registry who received a 3rd mRNA vaccine dose were asked to complete a detailed symptom survey 1 week after vaccination.Symptoms were assessed across 11 organ systems,and graded as mild,moderate,or severe,or requiring hospitalization.“Severe+” referred to those with severe symptoms or who required hospitalization.We stratified by age (<or> 50 years) given prior distinct symptom profiles after dose 2 (D2).We also evaluated whether severe+ symptoms after D2 predicted severe+ symptoms after dose 3 (D3).Results:We included 524 participants (70% female, mean age 45 years) who received a 3rd mRNA vaccine through October 11, 2021.Most had Crohn's disease (71%), and 89% were on biologic therapies.Most (58%) had received primary vaccination with BNT562b2,and only 3.5% reported prior COVID infection at the time of initial vaccination.Overall, 97% of subjects received a 3rd dose with the same mRNA vaccine as in their initial series with the remainder receiving the other mRNA vaccine type.No participants received a 3rd dose with the Ad26.CoV.2 (J&J) vaccine. Overall, 41% reported symptoms after a 3rd dose,with symptoms generally more frequent and severe among those <55 years (Table).The most frequent postvaccination symptom was injection site pain (39%).Common systemic symptoms included fatigue/malaise (34%),headache (23%),and muscle, bone or joint symptoms (13%).These were all less frequent after D3 than after D2 (Figure).Gastrointestinal symptoms were reported by 8.8%, which was slightly more frequent than after D2 (7.8%).Among those with postvaccination symptoms, the proportion with severe symptoms after D3 was lower than D2 for fatigue/ malaise, headache, dizziness and lightheadedness, fever/chills, and rheumatologic symptoms, but was slightly higher than D2 for gastrointestinal symptoms.Severe+ symptoms were seen in 17% after D2 and in 14% after D3. Of those with severe+ symptoms after D2, 34% had severe+ symptoms after D3.In contrast, about 22% had severe+ symptoms after D3 but did not report severe+ symptoms after D2.Conclusion:The frequency and severity of symptoms after a 3rd mRNA vaccine dose are generally similar or lower than those after a second dose.Furthermore, prior severe+ symptoms after D2 do not necessarily predict severe+ symptoms after D3. Further evaluation of postvaccination gastrointestinal symptoms in this population is warranted. (Figure Presented) (Table Presented)

PATIENTS WITH INFLAMMATORY BOWEL DISEASE HAVE IMPAIRED HUMORAL BUT PRESERVED CELLULAR RESPONSES TO SARS-COV-2 MRNA VACCINATION

Background: Vaccine-induced protection against SARS-CoV-2 infection is predominantly mediated by humoral immunity;protection against disease progression is primarily determined by cellular immunity. Patients with inflammatory bowel disease (IBD) have high rates of post-vaccination anti-Spike IgG [IgG(S)] seroconversion, but postvaccination immune responses relative to non-IBD controls have not been well described. We aimed to assess post-vaccination humoral (antibody) and cellular (T-cell) responses in IBD relative to healthcare worker (HCW) controls. Methods: We evaluated IBD patients enrolled in a US registry referred from 26 centers at 2, 8, and 16 weeks after completing 2 doses of SARSCoV- 2 mRNA vaccination and compared results to non-IBD non-immunosuppressed HCW participating in a parallel study. We analyzed plasma antibodies to the receptor binding domain of the viral spike protein using the SARS-CoV-2 IgG-II assay (Abbott Labs, Abbott Park, IL);IgG(S) > 50 AU/mL was defined as positive. Those with prior COVID were excluded. We also performed T-cell clonal analysis by T-cell receptor (TCR) immunosequencing at 8 weeks (Adaptive Biotechnologies, Seattle, WA). The breadth (number of unique sequences to a given protein) and depth (relative abundance of all the unique sequences to a given protein) of the T-cell clonal response were quantified using reference datasets. Analyses were adjusted for age, sex and vaccine type. Results: Overall, 1805 subjects were included (IBD n=1074 (65% Crohn's disease, 35% ulcerative colitis);HCW n=731). Age and sex were similar between both cohorts;Hispanic ethnicity and Asian race were less common among IBD than HCW (Table). Vaccine type included BNT162b2 (Pfizer) (75% of IBD, 98% of HCW) and the remainder mRNA-1274 (Moderna). IBD treatments included anti- TNF (46%), other biologics (33%), other immune suppressing therapy (9%), and no immune suppression (12%). Postvaccination antibody levels were lower among IBD than HCW both before and after adjusting for vaccine type (p<0.0001 each timepoint;Figure). After further restricting the IBD cohort to those on no immune-suppressive therapies, antibodies remained lower in IBD vs HCW at 2w (p=0.008) and 8w (p<0.0001), but not 16w (p=0.07). Among 321 subjects with available whole cell samples at 8 weeks (IBD n=163, HCW =158), Spikespecific TCR responses were similar between IBD and HCW for both clonal breadth and depth in both unadjusted and adjusted analyses;sub-analyses of those on biologics yielded similar results. Conclusion: Patients with IBD have dampened humoral responses, but similar cellular responses, after SARS-CoV-2 mRNA vaccination relative to HCW. These findings suggest a potentially greater risk of infection, but not of disease progression, among those with IBD, and should be considered to help guide booster dosing strategies for the IBD population. (Figure Presented) (Figure Presented) Figure: Post-vaccination immune responses: (A) Antibody responses are lower in IBD relative to non-IBD healthcare workers at 2, 8, and 16 weeks (p<0.0001 at each timepoint). In contrast, post-vaccination Spike-specific T-cell receptor clonal breadth (B1) and clonal depth (B2) at 8 weeks are similar in IBD compared to healthcare workers.

The Gut Microbiome Of Covid-19 Recovered Patients Returns To Uninfected Status In A Minority-Dominated United States Cohort

Introduction: Intestinal Microbiota Influences Both Susceptibility And Severity Of Bacterial And Viral-Induced Pathogenicity, Including Respiratory Diseases. In This Study, We Investigated The Relationship Between Intestinal Microbiota And Sars-Cov-2-Mediated Pathogenicity In The United States, Majority African American Cohort. Hypothesis: Intestinal Microbiota Is Modulated By Sars-Cov-2 Infection And Is Related To Symptom Severity And Recovery From The Disease. Methods: We Conducted A Single-Institution Study, Prospectively Collecting Fecal Samples From 50 Sars-Cov-2 Infected Patients Within 3 Days Of Icu Admission And 9 Sars-Cov-2 Recovered Patients Upon Testing Negative For The Virus. Feces Of 34 Uninfected Subjects At The Hospital With Unrelated Respiratory Medical Conditions Were Used As Controls. Total Fecal Rna/Dna Was Extracted And Microbiota Composition Was Determined Using 16s Rrna Gene Sequencing Of The V1-V3 Region. The 16s Rdna Sequencing Reads Were Processed Using Dada2 To Generate Amplicon Sequence Variants (Asv). Rt-Pcr On Fecal Rna Using Two Sets Of Validated Primer/Probes Was Performed To Establish The Presence Or Absence Of Sars-Cov-2 Viral Rna. Results: The Fecal Microbial Composition Was Found To Be Significantly Different Between Sars-Cov-2 Patients And Controls (Permanova Fdr-P=0.004), Independent Of Treatments Such As Antibiotic Exposure. Peptoniphilus, Corynebacterium And Campylobacter Were Identified As The Three Most Significantly Enriched Genera In Covid Patients Compared To Controls. Actively Infected Patients Were Also Found To Have A Different Gut Microbiota Than Recovered Patients (Permanova Fdr-P=0.003), And The Most Enriched Genera In The Covid-19 Patients Was Campylobacter, With Agathobacter Being Enriched In The Recovered Patients. No Difference In Microbial Community Structure Between Recovered Patients And Uninfected Controls Was Observed (Permanova Fdr-P=0.93), With Phocea Being The Top Genus Associated With Patients Who Recovered From Covid-19. Furthermore, No Difference In Alpha Diversity Between The Three Groups Was Noticed. More Importantly, 24 Of The 50 Covid-19 Patients (48%) Tested Positive Via Rt-Qpcr For Fecal Sars-Cov-2 Rna. A Significant Difference In Gut Microbial Composition Between Sars-Cov-2 Positive And Negative Samples Was Observed, With Klebsiella And Agathobacter Being Enriched In The Positive Cohort And Phocea In The Negative Cohort. No Significant Associations Between Microbiome Composition And Disease Severity Or Proton Pump Inhibitor Treatment Were Found. Conclusion: The Intestinal Microbiota Is Sensitive To The Presence Of Sars-Cov-2, With Increased Relative Abundance Of Genera (Campylobacter, Klebsiella) Associated With Gi Disease. Further Studies Are Needed To Investigate The Functional Impact Of Deleterious Bacterial Genera In Sars-Cov-2 On Gi Health.

Gastrointestinal symptoms in patients with inflammatory bowel disease after SARS-CoV-2 mRNA vaccination

Introduction: In the SARS-CoV2 mRNA vaccine trials, post-vaccination gastrointestinal (GI) symptoms were reported in 10-20% of participants. These symptoms could be perceived as inflammatory bowel disease (IBD) flare which could lead to patient anxiety, and unnecessary tests or treatment. We aimed to assess GI symptoms after SARS-CoV2 mRNA vaccination in patients with IBD relative to non-IBD healthcare workers (HCW). Methods: We assessed GI symptoms in adults with IBD and HCW at baseline and after each dose of a SARS-CoV-2 mRNA vaccine. We analyzed patient-reported IBD-specific disease activity (PRO2) after each dose (stool frequency (SF) and rectal bleeding for ulcerative colitis (UC), SF and abdominal pain for Crohn's disease (CD)). We also compared the frequency, severity, and duration of postvaccination GI symptoms in IBD patients compared to HCW. Severity was defined by impact on daily activities (mild, did not interfere;moderate, some interference;severe, prevented routine activity;extreme, required hospitalization). Severe and extreme were combined and designated as severe+. Duration was classified as<2 days, 2-7 days, or>7 days. Results: Post-vaccination GI symptoms were assessed after dose 1 (D1) (1391 IBD, 933 HCW) and dose 2 (D2) (1271 IBD, 884 HCW) (Table). About 60% of IBD and>99% of HCW received the BNT162b vaccine (Pfizer);the remainder received mRNA-1273 (Moderna). New GI symptoms after D1 were more frequent among IBD than HCW (6.0% vs 2.9%, p=0.001) but not after D2 (12.1% vs 12.7%, p=NS). Relative to HCW, IBD patients reported more diarrhea (3.8% vs. 1% (p<0.001) after D1 and 7.5% vs 4.2% (p=0.003) after D2) and abdominal pain (2.2% vs. 0.4% (p=0.001) after D1 and 6.2% vs 3% (p=0.002) after D2). Severe1 symptoms were noted in 1.5% IBD and 0.3% HCW (p=NS) after D1 and in 3.3% IBD and 0.1% HCW (p<0.001) after D2 (Figure 1). Longer GI symptom duration was more common in IBD than HCW after D1 (2.1% vs 0.5%, p=0.002) and D2 (5.4% vs. 2.1%, p<0.001). Among 423 CD and 300 UC patients with PRO2 data, 71%, 68%, and 65% of CD and 86%, 86%, and 83% of UC were in clinical remission at baseline, after D1, and after D2, respectively. Conclusion: The frequency of GI symptoms in IBD was greater than HCW after D1, but similar after D2. More severe and longer duration of GI symptoms were noted in a small number of IBD patients. Reassuringly, the mRNA vaccines do not seem to increase the risk of a disease flare in the vast majority of IBD patients.

Enrollment rate of African Americans in a colon cancer screening trial at a historically black college and university is similar to other patient populations

Introduction: Clinical trials often have low enrollment of minorities, particularly African-Americans (AAs), which may limit the generalizability of research findings. Previously identified barriers to AAs recruitment include historical abuses leading to mistrust, communication issues with providers, socio-economic factors, and a lack of access to clinical trials. In a Historically Black College and University (HBCU) serving a primarily AA population at a large safe-net hospital, we evaluated the enrollment of eligible AA patients for a colorectal cancer (CRC) screening clinical trial. This was compared to the enrollment rates across other study sites. Methods: A large, prospective, multi-centered clinical trial to validate a blood-based test for early detection of CRC (PREEMPT-CRC) was initiated at a HBCU, where 84% of patients are AAs. To maximize study recruitment, culturally sensitive methods were employed including racially congruent recruitment staff as well as synchronized timing of consent/study procedures with preendoscopy COVID testing/clinic visits. Detailed information for all eligible subjects was recorded. Demographic and socio-economic data including census information for enrolled and not enrolled subjects were compared. The enrollment rate (defined as enrolled/eligible patients) over the first 6 weeks at the HBCU and that of the other study sites providing screening logs was analyzed. Results: The enrollment rate at the HBCU was 55% (44 out of 80 eligible patients;95% CI 43.5- 66.2%), compared to 49.8% (258 out of 518 eligible patients;95% CI 45.4- 54.2%) at the other 26 study sites. While age and gender of enrolled patients at the HBCU were comparable to other sites, the main difference was race: at the HBCU the study participants were 79.5% AAs and 9.1% whites, while at the other sites the participants were 11.5% AAs and 82.8% whites (p< 0.001). At the HBCU, the demographic characteristics and socio-demographic data including income, marital status insurance status/type, and census tract median household income of the 44 enrolled and 36 notenrolled subjects were similar (Table 1). Conclusion: Contrary to conventional belief that AAs do not want to be involved in clinical trials, we find their enrollment is similar to a predominant white study population when offered the opportunity in a culturally sensitive setting. Future trials should consider including HBCU sites in order to attain adequate AA enrollment to improve the generalizability of research findings. (Table Presented).

Statins and mortality risk in hospitalized community acquired pneumonia patients

Rationale: Statins, anti-hypertensives, Proton pump inhibitors (PPIs) and H2 receptor antagonist (H2RAs) are amongst the most commonly prescribed medications for adults over the age of 50 (Kantor et al, 2015). PPI use was recently reported to have worse clinical outcomes during the COVID-19 pandemic (Lee et al, 2020). Before COVID-19, PPI use was associated with an increased risk of community acquired pneumonia (CAP) (Hertzig et al, 2009;Othman et al, 2016;Zirk-Sadowski et al, 2018). In this study, we examined the mortality risk associated with these four medications in hospitalized CAP patients not due to novel SARS-CoV-2 infection. Methods: We analyzed de-identified patient data from a research database of 6 hospitals in an integrated tertiary university healthcare system from January 1 to December 31, 2019. ICD-10 codes for CAP at the time of hospital admission were used to identify patients. A list of 17 variables relevant to outcome of CAP including demographic, comorbid conditions and medications of interests were extracted. Statistical analysis included Wilcoxon rank-sum tests, chi-squared tests, and multivariable logistic regression models were used to assess the mortality risk of all the factors. Results: Of 1223 patients admitted with CAP, the overall mortality rate was 19.9% (243/1223), baseline characteristics are shown in Table 1. There were 613 (50%) patients on PPIs, 551 (45%) on anti-hypertensives, 276 (23%) on H2RAs, and 271 (22%) on statins. PPI users had a mortality rate of 26.3% (161/613) vs 13.4% (82/610) in non-PPI users (p < 0.001). In multivariate analysis, PPI use without statins was not associated with increased mortality OR = 1.10 (0.76 to 1.60), while statin use without PPI was associated significant lower mortality: OR = 0.28 (0.13 to 0.59). This benefit was eliminated when statins and PPI were used together (OR = 0.86;95% CI of 0.53 to 1.39). Variables associated with increased mortality risk in the logistic regression model are: each decade of age (OR = 1.16;95% CI of 1.08 to 1.25), congestive heart failure OR = 2.09 (1.48 to 2.95), cancer (OR = 1.69;95% CI of 1.23 to 2.34), cardiovascular disease (OR = 2.18;95% CI of 1.27 to 3.75), and stroke (OR = 1.48;95% CI of 1.01 to 2.16). Conclusions: Statin use was associated with reduced mortality in patients with CAP, but the benefit was no longer present when combined with PPIs. The etiology for the increased mortality warrants further investigation.

Proton pump inhibitor use is associated with increased mortality in african american COVID-19 patients

Rationale Coronavirus disease 2019 (COVID-19) has disproportionally affected African Americans (AA), with underlying medical conditions and socioeconomic determinants of health believed to be major contributors (Price-Haywood et al, 2020). The use of proton pump inhibitors (PPIs) was recently found to be associated with increased risk and worse outcomes of SARS-CoV-2 infection (Almario et al, 2020;Luxenberger et al, 2020;Lee et al, 2020). Methods We performed a retrospective cohort analysis of patients hospitalized for SARS-CoV-2 in an integrated health system of six hospitals between March 15 and August 15, 2020. To determine predictive factors of mortality, a set of 17 covariates were selected on the basis of clinical relevance to COVID-19 outcomes. The indications for medication use were evaluated in a subset of research patients. Results In 694 hospitalized COVID-19 patients (median age = 58 yr, 46% men, 65% AA), an overall mortality rate was 17.4% (121/694). Logistic regression analysis identified age (aOR=1.66 per decade, p<0.001), race other than AA or white (aOR=3.03, p=0.002), cancer (aOR=2.22, p=0.008), diabetes (aOR=1.95, p=0.003), anti-HTN (aOR=0.46, p=0.001) and PPI use (aOR=2.72, p<0.001) as predictors of mortality. There was no significant mortality difference observed with the use of H2 receptor antagonists. Moreover, PPI use was associated with higher mortality risk in AA (aOR=4.16, 95% CI = 2.28 to 7.59) than in non-AA patients (aOR=1.62, 95% CI = 0.82, 3.19, p=0.04 for interaction) (see Figure 1). The prevalence of PPI use in African Americans (32.6%147/451) and non-AA patients (32.9%, 80/243) were comparable. No other associations were found to differ between the two groups. Indications for PPI use in 31 of 87 research participants were: erosive esophagitis / recent hemorrhage (13%), non-erosive GERD symptoms (45%) and NSAID prophylaxis (42%). Conclusion PPIs are frequently used medications with a growing list of complications. Their use is associated with significant mortality risk in AA COVID-19 patients, and should be reassessed during the pandemic. This risk was not seen in patients who received H2 receptor antagonists. The gastrointestinal tract is a potential site of SARSCoV- 2 entry and replication and this association warrants further study.

Evaluation of the MP Rapid 2019-NCOV IgM/IgG combo POCT test vs. an established platform-based method.

BACKGROUND: Accurate and rapid testing for SARS-COV-2 antibodies could improve the diagnosis and management of COVID-19. In this study, we aim to evaluate the diagnostic accuracy of a commercially available point-of-care lateral flow kit independently and in comparison to an established platform-based system. METHOD: Samples from 144 PCR-confirmed COVID-19 cases and 130 pre-pandemic negative controls were tested in parallel by MP Rapid 2019-NCOV IgM/IgG Combo test and Roche Elecsys. Comparison of results based on serum and capillary blood testing was undertaken. RESULTS: Sensitivity at day 15 onwards was 100% for both methods. Between days 1 and 7 post admission, the IgM/IgG Combo test and Roche Elecsys shown sensitivity of 74% (95%CI: 62%-85%) vs. 67% (95% CI: 55%-79%, P = 0.3947). Combo test specificities were 100% for IgG, 98.5% for IgM vs. Roche Elecsys specificity of 100%. Concordance analysis showed 98.5% agreement to the Roche Elecsys method (Cohen's Kappa 0.96 95% CI [0.92-0.99]). Capillary blood results showed complete agreement with serum samples using the Combo test. CONCLUSION: In comparison to Roche Elecsys, our data show that the MP Rapid 2019-NCOV IgM/IgG Combo test provides a high-confidence assay system for the detection of previous exposure to SARS-COV-2 infection with advantage of affording near-patient testing.