ABSTRACT
The targeted screening and sequencing approaches for COVID-19 surveillance need to be adjusted to fit the evolving surveillance objectives which necessarily change over time. We present the development of variant screening assays that can be applied to new targets in a timely manner and enable multiplexing of targets for efficient implementation in the laboratory. By targeting the HV69/70 deletion for Alpha, K417N for Beta, K417T for Gamma, and HV69/70 deletion plus K417N for sub-variants BA.1, BA.3, BA.4, and BA.5 of Omicron, we achieved simultaneous detection and differentiation of Alpha, Beta, Gamma, and Omicron in a single assay. Targeting both T478K and P681R mutations enabled specific detection of the Delta variant. The multiplex assays used in combination, targeting K417N and T478K, specifically detected the Omicron sub-variant BA.2. The limits of detection for the five variants of concern were 4-16 copies of the viral RNA per reaction. Both assays achieved 100% clinical sensitivity and 100% specificity. Analyses of 377 clinical samples and 24 wastewater samples revealed the Delta variant in 100 clinical samples (nasopharyngeal and throat swab) collected in November 2021. Omicron BA.1 was detected in 79 nasopharyngeal swab samples collected in January 2022. Alpha, Beta, and Gamma variants were detected in 24 wastewater samples collected in May-June 2021 from two major cities of Alberta (Canada), and the results were consistent with the clinical cases of multiple variants reported in the community. © 2023 The Authors. Published by American Chemical Society.
ABSTRACT
Background The rapid development and distribution of SARS-CoV-2 vaccines has raised concerns surrounding vaccine safety in immunocompromised populations, such as those with inflammatory bowel disease (IBD). Purpose We described adverse events (AEs) following SARS-CoV-2 vaccination in those with IBD and determined relationships between AEs to post-vaccination antibody titres. Method Individuals with IBD from a prospective cohort in Calgary, Canada (n=670) who received a 1st, 2nd, 3rd, and/or 4th dose of a SARS-CoV-2 vaccine (Pfizer-BioNTech, Moderna, and/or AstraZeneca) were interviewed via telephone for AEs using the Adverse Events Following Immunization form. Subsequently, we assessed injection site reaction as a specific AE outcome. Multivariable logistic regression models were used to assess the association between anti-SARS-CoV-2 spike protein antibody (anti-S) levels within 1–12 weeks of vaccination and injection site reaction following 1st, 2nd, and 3rd dose vaccination. Models were adjusted for age, sex, IBD type, IBD medications, vaccine type, and prior COVID-19 infection. Additionally, we evaluated the risk of flare of IBD within 30 days of vaccination via chart review. Result(s) Table 1 describes AEs in individuals with IBD following 1st dose (n=331), 2nd dose (n=331), 3rd dose (n=195), and 4th dose (n=100) of a SARS-CoV-2 vaccine. AEs were reported in 83.3% of participants after 1st dose, 79.1% after 2nd dose, 77.4% after 3rd dose, and 67.0% after 4th dose. Injection site reaction (pain, redness, etc.) was the most common AE (50.8% of AEs), with fatigue and malaise (18.1%), headache and migraine (8.6%), musculoskeletal discomfort (8.2%), and fever and chills (6.5%) also commonly reported. Multivariable logistic regression determined no associations between anti-S concentration and injection site reaction for all doses. Age above 65 years was associated with decreased injection site reaction following 1st and 3rd doses, while female sex and mRNA vaccine type were associated with increased injection site reaction following 1st and 2nd doses. Prior COVID-19 infection, IBD type, and medication class were not associated with injection site reaction with any dose. Only one participant was diagnosed with a severe AE requiring hospitalization: Immune thrombocytopenic purpura (ITP) following 2nd dose of a Pfizer vaccination. No cases of IBD flare occurred within 30 days of vaccination. Image Conclusion(s) AEs following SARS-CoV-2 vaccination are generally mild and become less common with each consecutive dose. Antibody levels following each dose of the vaccine were not associated with injection site reactions. Females, those under 65 years of age, and those administered mRNA vaccines were more likely to experience an injection site reaction. Prior COVID-19 infection, IBD type, and IBD medication class did not predict injection site reactions. Vaccination was not associated with IBD flare within 30 days of vaccination. Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding;Helmsley Disclosure of Interest A. Markovinovic: None Declared, M. Herauf: None Declared, J. Quan: None Declared, L. Hracs: None Declared, J. Windsor: None Declared, N. Sharifi: None Declared, S. Coward: None Declared, L. Caplan: None Declared, J. Gorospe: None Declared, C. Ma Grant / Research support from: Ferring, Pfizer, , Consultant of: AbbVie, Alimentiv, Amgen, Ferring, Pfizer, Takeda, , Speakers bureau of: AbbVie, Alimentiv, Amgen, Ferring, Pfizer, Takeda, R. Panaccione Grant / Research support from: AbbVie, Ferring, Janssen, Pfizer, Takeda, Consultant of: Abbott, AbbVie, Alimentiv, Amgen, Arena, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Genentech, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, Mylan, Oppilan Pharma, Pandion Therapeutics, Pandion Pharma, Pfizer, Progenity, Pro agonist, Roche, Sandoz, Satisfai Health, Schering-Plough, Shire, Sublimity Therapeutics, Takeda, Theravance, UCB, Speakers bureau of: AbbVie, Arena, Celgene, Eli Lilly, Ferring, Gilead Sciences, Janssen, Merck, Pfizer, Roche, Sandoz, Shire, Takeda, R. Ingram: None Declared, J. Kanji: None Declared, G. Tipples: None Declared, J. Holodinsky: None Declared, C. Berstein Grant / Research support from: AbbVie, Amgen, Janssen, Pfizer, Takeda, Speakers bureau of: AbbVie, Janssen, Pfizer, Takeda, D. Mahoney: None Declared, S. Bernatsky: None Declared, E. Benchimol: None Declared, G. Kaplan Grant / Research support from: Ferring, Speakers bureau of: AbbVie, Janssen, Pfizer
ABSTRACT
Background: The immune response of SARS-CoV-2 vaccines is uncertain in those with Inflammatory Bowel Disease (IBD) due to a diverse array of immune-modifying therapies that vary in the mechanism of immunosuppression. Aim: We aimed to quantify the serological response to SARS-CoV-2 vaccines in those with IBD and determine antibody levels across varying therapeutic options. Methods: Individuals with IBD who received a first and/or second dose of a COVID-19 vaccine (Pfizer-BioNTech, Moderna, and/or AstraZeneca) were assessed for serological response (1–8 weeks after first dose;1–8 weeks after second dose, 8–18 weeks after second dose, 18+ weeks after second dose) using the SARS-CoV-2 IgG II Quant assay to the receptor-binding domain of the SARS-CoV-2 spike protein. The cohort was stratified based on age, sex, vaccine received, IBD type, IBD therapeutic, and prior confirmed diagnosis of COVID-19. The primary outcome was seroconversion defined as IgG levels of ³50 AU/mL. Secondarily, we evaluated the geometric mean titer (GMT) with 95% confidence intervals (CI). Results: Table 1 describes the characteristics of individuals with IBD (n=466) with serological data following the first dose (n=247) and/or second dose (n=413) of a COVID-19 vaccine. After 1–8 weeks following first dose of the vaccine, 81.4% seroconverted, with the lowest first-dose conversion rates in patients taking anti- TNF monotherapy (80.3%), anti-TNF combination therapy (51.5%), and corticosteroids (50.0%) (Table 1). Overall, 98.4% of the cohort seroconverted within 1–8 weeks of the second dose. Over time, seropositive rates decreased with 95.8% seroconversion within 8– 18 weeks of the second dose and 90.5% after 18 weeks. Seroconversion after second dose was consistently high across all medication classes (range: 94.6%–100.0%), except for oral corticosteroids (62.5%). GMT levels significantly increased (p<0.0001) from first dose (1825 AU/mL [95% CI: 981, 2668 AU/mL]) to second dose at 1–8 week (9059 AU/mL [7698, 10420 AU/mL]) but fell significantly (p<0.0001) to 3649 AU/mL (95% CI: 2562, 4736 AU/ mL) 8–18 weeks from second dose and 2527 AU/mL (95% CI: 883, 4172 AU/mL) 18+ weeks after second dose (Table 1, Figure 1). GMT levels 1–8 weeks after second dose were higher in those with prior COVID-19 (16,770 AU/mL), but lower in those receiving anti- TNF combination therapy (4231 AU/mL) and oral corticosteroids (5996 AU/mL) (Table 1). Conclusion: Seroconversion rates following full-regimen vaccination are high in patients with inflammatory bowel disease across all medication classes except for anti-TNF combination therapy and oral corticosteroids. Antibody titres and seroconversion rates tend to decrease after eight weeks post-full vaccination, which is consistent across medication classes. (Table Presented) Table 1. Patient and vaccine characteristics, seroconversion rates, and geometric mean titres by prior PCR-confirmed COVID-19 status for each medication class. (Figure Presented) Figure 1. Log-transformed anti-SARS-CoV-2 spike antibody concentration per vaccine category. Black points represent GMTs while narrow black bars represent bounds of 95% CI associated with each GMT. Solid blue line represents threshold for positive seroconversion [ln (50 AU/mL)].
ABSTRACT
Background: The immune response to a two-dose regimen of SARS-CoV-2 vaccination in those with Inflammatory Bowel Disease (IBD) has been consistently high in emerging research. Serological responses following a third dose have yet to be established. Aim: We aimed to quantify the serological response to a third dose of SARS-CoV-2 vaccines in those with IBD and compare to responses after a two-dose regimen. Methods: Individuals with IBD who have received at least two doses of a COVID-19 vaccine were assessed for serological response using the SARS-CoV-2 IgG II Quant assay to the receptor-binding domain of the SARSCoV- 2 spike protein at least eight weeks after second dose and then after third dose. The primary outcome was seroconversion defined as IgG levels of ≥50 AU/mL. Secondarily, we evaluated the geometric mean titer (GMT) with 95% confidence intervals (CI). Outcomes were stratified by prior COVID-19 history. A Wilcoxon rank sum test was used to compare antibody titres following 3rd dose vaccination and titres following 2nd dose vaccination. For patients with both post-2nd and post-3rd vaccination serology, the difference in antibody titres between doses was determined and the mean difference was tested using one-sample Student's t-tests. Results: Table 1 describes the characteristics of individuals with IBD (n = 271) with serological data following the corresponding dose for those with 2nd dose vaccination (n = 175) compared to those with a 3rd dose of vaccine (n = 96). Seroconversion following 3rd dose vaccination occurred for all individuals (100.0%), compared to a 94.4% seroconversion rate at least eight weeks following 2nd dose vaccination (range: 8 to 35 weeks post-2nd dose). GMT for the post-3rd dose cohort (16424 AU/mL [13437, 19411 AU/mL]) was significantly higher (p<0.0001) than the post-2nd dose cohort (3261 AU/mL [2356, 4165 AU/mL] (Table 1, Figure 1b). Individual titres as a function of time following 2nd dose vaccination are seen in Figure 1a for both 3rd dose and 2nd dose cohorts. For individuals with serology following both 2nd dose and 3rd dose vaccination (n = 82), seroconversion rates increased from 97.6% to 100.0% after the 3rd dose. GMT following post-3rd dose vaccination also increased with a mean difference in antibody titres between post-3rd dose and post-2nd dose vaccination of 11384 AU/mL (8541, 14228 AU/mL, p < 0.0001). This difference was significant for both individuals with prior COVID-19 history (11682 AU/mL [95% CI: 8618, 14746 AU/mL, p<0.0001]) and individuals without (8194 AU/mL [95% CI: 988, 15400 AU/mL]). Conclusion: Seroconversion rates and antibody response following third dose vaccination are substantially increased as compared to second dose in patients with IBD. Third dose vaccination can counter the decrease in antibody concentration over time following a two-dose regimen. (Table Presented) Table 1. Patient characteristics, vaccine type, seroconversion rates, and geometric mean titres by prior COVID-19 status for post-3rd dose and post-2nd dose cohorts
ABSTRACT
BACKGROUND: The immune response of SARS-CoV-2 vaccines is uncertain in those with Inflammatory Bowel Disease (IBD) due to a diverse array of immune-modifying therapies that vary in the mechanism of immunosuppression. AIM: We aimed to quantify the serological response to SARS-CoV-2 vaccines in those with IBD and determine antibody levels across varying therapeutic options. METHODS: Individuals with IBD who received first and/or second dose of a COVID- 19 vaccine (Pfizer-BioNTech, Moderna, and/or AstraZeneca) were assessed for serological response (2-4 weeks after first dose;2-8 weeks after second dose and 8-18 weeks after second dose) using the SARS-CoV-2 IgG II Quant assay to the spike protein of SARS-CoV-2. The cohort was stratified based on age, sex, vaccine received, IBD type, IBD therapeutic, and prior confirmed diagnosis of COVID-19. The primary outcome was seroconversion defined as IgG levels of ≥50 AU/mL. Secondarily, we evaluated the geometric mean titer (GMT) with 95% confidence intervals (CI). RESULTS: Table 1 describes the characteristics of individuals with IBD (n=464) with serological data following the first dose (n=266) and/or second dose (n=303) of a COVID-19 vaccine. After the first dose of the vaccine, 81.6% seroconverted, with the lowest first-dose conversion rates in patients taking anti-TNF monotherapy (79.7%), anti-TNF combination therapy (52.9%), and corticosteroids (50.0%) (Table 1). Overall, 98.4% of the cohort seroconverted within 2-8 weeks of the second dose, with 94.6% seropositive within 8-18 weeks of the second dose. Seroconversion after second dose was consistently high across all medication classes (range: 94.6%-100.0%), except for oral corticosteroids (62.5%). GMT levels significantly increased (p<0.0001) from first dose (1679 AU/mL) to second dose at 2-8 week (7943 AU/mL) but fell significantly (<0.0001) to 3565 AU/mL 8-18 weeks from second dose (Table 1, Figure 1). GMT levels 2-8 weeks after second dose were higher in those with prior COVID-19 (12,729 AU/mL), but lower in those receiving anti-TNF combination therapy (4231 AU/mL) and oral corticosteroids (5996 AU/mL) (Table 1). CONCLUSION: Seroconversion rates following fullregimen vaccination are high in patients with inflammatory bowel disease across all medication classes except for anti-TNF combination therapy and oral corticosteroids. Antibody titres and seroconversion rates tend to decrease after 8 weeks postfull vaccination, which is consistent across medication classes.