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IntroductionFew data exist regarding the immunogenicity of third dose of BNT162b2 relative to second dose in patients with inflammatory bowel disease (IBD) on different immunosuppressive therapies. We investigated the immunogenicity of BNT162b2 vaccine booster dose in patients with IBD on infliximab combination therapy. MethodsThis is prospective single center observational study conducted between January 1st, 2022 until February 28th, 2022. Patients were recruited at the time of attendance at the infusion center. Eligibility criteria included patients with confirmed diagnosis of IBD who are receiving infliximab with azathioprine or 6-mercaptopurine and have received two or three-dose of BNT162b2 vaccine. Patients were excluded if they were infected or had symptoms of SARS-CoV-2 previously since the start of the pandemic or received other vaccines than the BNT162b2. Our primary outcome was the concentrations of SARS-CoV-2 antibodies Immunoglobulin G (IgG) and neutralizing antibodies 40-45 weeks from the first dose of BNT162b2 in patients with IBD receiving infliximab combination therapy. Medians with interquartile range (IQR) were calculated. Results162 patients with IBD and receiving infliximab combination therapy were recruited and the number of patients in each group was 81. Median (IQR) SARS-CoV-2 IgG levels were significantly lower after the second dose [125 BAU/mL (43, 192)] compared to patients who received the third booster dose [207 BAU/mL (181, 234)] (p = 0.003). Neutralizing antibody levels were also lower after the second dose [80 BAU/mL (21, 95)] compared to patients who received the third booster dose [96 BAU/mL (93, 99)] (p = <0.001). The percentage of patients who achieved positive SARS-CoV-2 IgG levels in the third (booster) dose group was higher (96.3%) than those in second dose group (90%)(p = 0.026). Percentage of patients who received third (booster) dose and achieved positive SARS-CoV-2-neutralizing antibody level was 100%, whereas it was lower (88.9%) in patients who received second dose only (p=0.009). ConclusionMost patients with IBD on infliximab combination therapy had positive SARS-CoV-2 IgG and neutralizing antibody concentrations 40-45 weeks post BNT162b2 vaccination. However, SARS-CoV-2 IgG and neutralizing antibody concentrations were lower in patients who received 2 doses only compared to patients who received a third dose.
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IntroductionSARS-CoV-2 vaccination has been effective in protecting against severe COVID-19 infections and related mortality. It is recommended for all individuals including patients with inflammatory bowel disease (IBD). However, safety data is lacking in this group of patients. Therefore, we aim to evaluate the short- and long-term vaccine related adverse events (AEs) in patients with IBD. MethodThis is a prospective, observational cohort study investigating short- and long-term AEs related to BNT162b2 vaccine in patients with IBD (study group) after first and second dose compared to healthy participants (study group). Patients were recruited at the time of attendance to clinic or infusion rooms. Short term (<3 weeks) localized and systemic AEs were assessed via questionnaire. Follow-up phone-based survey was made to collect data on long term (up to 24 weeks) AEs. ResultsA total of 408 patients answered the questionnaires, 204 patients in each group, the study and control group. No serious adverse events were reported in either the study nor the control group after the first or the second dose. Participants in the control group reported more frequent pain at the injection site than those in the study group after the first dose (58 (57%) vs 38 (37%) respectively, P-value= 0.005). After the second dose, tiredness was reported more frequently in the control group [49 (48%)] compared to the study group [25 (24%), (P-value<0.001)]. At 20-24 weeks post vaccination, 386 out of 408 (94.6%) patients were willing to participate in the follow-up phone based questionnaire (196 (96.1%) in the study group vs 190 (93.1%) in the control group). In both groups, none of the patients reported local, systemic or severe adverse events (0 out of 386) at week 20-244 post second dose. ConclusionThe BNT162b2 vaccine is safe in patients with IBD. No severe or long-term adverse events were reported in our study. The frequency of local and systemic adverse events after the second dose was generally higher among healthy participants compared to patients with IBD. Further studies including a larger cohort with longer follow-up duration are needed to assess for possible rare adverse events.
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IntroductionImmunogenicity of SARS-CoV-2 vaccines in patients with inflammatory bowel disease (IBD) on biologics are not well studied. The goal of this study is to measure serological response to BNT162b2 and ChAdOx1 nCoV-19 vaccines in patients with IBD receiving different biologic therapies. MethodWe performed a multi-center prospective study between August 1st, 2021, and September 15th, 2021. We measured seropositivity of SARS-CoV2 antibodies, SARS-CoV-2 IgG and neutralizing antibody concentrations, in patients with IBD receiving biologic therapies between 4-10 weeks after second dose or 3-6 weeks after first dose of vaccination with BNT162b2 or ChAdOx1 nCoV-19 vaccines. ResultsThere were 126 patients enrolled (mean age, 31 years; 60% male; 71% Crohns disease, 29% ulcerative colitis). 92 patients were vaccinated with BNT162b2 vaccine (73%) and 34 patients with ChAdOx1 nCoV-19 vaccine (27%). The proportion of patients who achieved positive anti-SARS-CoV-2 IgG antibody levels after receiving 2 doses of the vaccine in patients treated with infliximab and adalimumab were 44 out of 59 patients (74.5%) and 13 out of 16 patients (81.2%), respectively. Whereas the proportion of patients who achieved positive anti-SARS-CoV-2 IgG antibody levels after receiving two doses of the vaccine in patients treated with ustekinumab and vedolizumab were 100% and 92.8%, respectively. In patients receiving infliximab and adalimumab, the proportion of patients who had positive anti-SARS-CoV-2 neutralizing antibody levels after two-dose vaccination was 40 out of 59 patients (67.7%) and 14 out 16 patients (87.5%), respectively. Whereas the proportions of patients who had positive anti-SARS-CoV-2 neutralizing antibody levels were 12 out of 13 patients (92.3%) and 13 out of 14 patients (92.8%) in patients receiving ustekinumab and vedolizumab. ConclusionThe majority of patients with IBD on infliximab, adalimumab, and vedolizumab seroconverted after two doses of SARS-CoV-2 vaccination. All patients on ustekinumab seroconverted after two doses of SARS-CoV-2 vaccine. BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 are both likely to be effective after two doses in patients with IBD on biologics. A follow up larger studies are needed to evaluate if decay of antibodies occurs over time.
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BackgroundThe emergence of new COVID-19 variants of concern coupled with a global inequity in vaccine access and distribution, prompted many public health authorities to circumvent the vaccine shortages by altering vaccination protocols and prioritizing high-risk individuals. Those with previous COVID-19 infection may have not been prioritized due to existing humoral immunity. ObjectiveWe aim to study the association between previous COVID-19 infection and antibody levels after COVID-19 vaccination. MethodsA serological analysis to measure SARS-CoV-2 IgG, IgA and neutralizing antibodies was performed on individuals who received one or two doses of either BNT162b2 or ChAdOx1 vaccines in Kuwait. Generalized linear regression models adjusted for individual characteristics and comorbidities were fitted to study the average levels of IgG and neutralizing antibodies in vaccinated individuals based who had previous COVID-19 infection compared to those who had not. ResultsA total of 1025 individuals were recruited. The mean levels of IgG, IgA and neutralizing antibodies were higher in vaccinated subjects with previous COVID-19 infection when compared with those vaccinated without previous COVID-19 infection. Regression analysis showed a steeper slope of decline for IgG in vaccinated individuals without previous COVID-19 infection in comparison with vaccinated individuals with previous COVID-19 infection. ConclusionPrevious COVID-19 infection appears to elicit robust and sustained levels of SARS-CoV-2 antibodies in vaccinated individuals. Given the inconsistent supply of COVID-19 vaccines in many countries due to the global inequity, our results point towards wider vaccination plans to especially cover individuals without previous COVID-19 infection.
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The emergence of effective vaccines for COVID-19 has been welcomed by the world with great optimism. Given their increased susceptibility to COVID-19, the question arises whether individuals with type-2 diabetes mellitus (T2DM) and other metabolic conditions can respond effectively to the mRNA-based vaccine. We aimed to evaluate the levels of anti-SARS-CoV-2 IgG and neutralizing antibodies in people with T2DM and/or other metabolic risk factors (hypertension and obesity) compared to those without. This study included 262 people that took two doses of BNT162b2 (Pfizer-BioNTech) mRNA vaccine. Both T2DM and non-diabetic individuals had a robust response to vaccination as demonstrated by their high antibody titers. However, both SARS-CoV-2 IgG and neutralizing antibodies titers were lower in people with T2DM. Their levels were 154{+/-}49.1 vs. 138{+/-}59.4BAU/mL for IgG and 87.1{+/-}11.6 vs. 79.7{+/-}19.5% for neutralizing antibodies in individuals without diabetes compared to those with T2DM, respectively. In a multiple linear regression adjusted for individual characteristics, comorbidities, previous COVID-19 infection and duration since second vaccine dose, diabetics had 13.86 BAU/ml (95%CI: -27.08 to -0.64BAU/ml, p=0.041) less IgG antibodies and 4.42% (95%CI: -8.53 to -0.32%, p=0.036) less neutralizing antibodies than non-diabetics. Hypertension and obesity did not show significant changes in antibody titers. Taken together, both type-2 diabetic and non-diabetic individuals elicited strong immune responses to SARS-CoV-2 BNT162b2 mRNA vaccine; nonetheless, lower levels were seen in people with diabetes. Continuous monitoring of the antibody levels might be a good indicator to guide personalized needs for further booster shots to maintain adaptive immunity.
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COVID-19 is challenging healthcare preparedness, world economies, and livelihoods. The infection and death rates associated with this pandemic are strikingly variable in different countries. To elucidate this discrepancy, we analyzed 2431 early spread SARS-CoV-2 sequences from GISAID. We estimated continental-wise admixture proportions, assessed haplotype block estimation, and tested for the presence or absence of strains recombination. Herein, we identified 1010 unique missense mutations and seven different SARS-CoV-2 clusters. In samples from Asia, a small haplotype block was identified; whereas, samples from Europe and North America harbored large and different haplotype blocks with nonsynonymous variants. Variant frequency and linkage disequilibrium varied among continents, especially in North America. Recombination between different strains was only observed in North American and European sequences. Additionally, we structurally modeled the two most common mutations D614G and P314L which suggested that these linked mutations may enhance viral entry and stability. Overall, we propose that COVID-19 virulence may be more severe in Europe and North America due to coinfection with different SARS-CoV-2 strains leading to genomic recombination which might be challenging for current treatment regimens and vaccine development. Furthermore, our study provides a possible explanation for the more severe second wave of COVID-19 that many countries are currently experiencing presented as higher rates of infection and death.
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ObjectivesTo investigate the role of ethnicity in COVID-19 outcome disparities in a cohort in Kuwait. MethodsThis is a retrospective analysis of 405 individuals infected with SARS-CoV-2 in Kuwait. Outcomes such as symptoms severity and mortality were considered. Multivariate logistic regression models were used to report the odds ratios (OR) for ICU admission and dying from COVID-19. ResultsThe cohort included 290 Arabs and 115 South Asians. South Asians recorded significantly higher COVID-19 death rates compared to Arabs (33% vs. 7.6%, P value<0.001). When compared to Arabs, South Asians also had higher odds of being admitted to the ICU (OR = 6.28, 95% CI: 3.34 - 11.80, p < 0.001). South Asian patients showed 7.62 (95% CI: 3.62 - 16.02, p < 0.001) times the odds of dying from COVID-19. ConclusionCOVID-19 patients with South Asians ethnicity are more likely to have worse prognosis and outcome when compared to patients with Arab ethnicity. This suggest a possible role for ethnicity in COVID-19 outcome disparities and this role is likely to be multifactorial.
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BackgroundCOVID-19 has a highly variable clinical presentation, ranging from asymptomatic to severe respiratory symptoms and death. Diabetes seems to be one of the main comorbidities contributing to a worse COVID-19 outcome. ObjectiveIn here we analyze the clinical characteristics and outcomes of diabetic COVID-19 patients Kuwait. MethodsIn this single-center, retrospective study of 417 consecutive COVID-19 patients, we analyze and compare disease severity, outcome, associated complications, and clinical laboratory findings between diabetic and non-diabetic COVID-19 patients. ResultsCOVID-19 patients with diabetes had more ICU admission than non-diabetic COVID-19 patients (20.1% vs. 16.8%, p<0.001). Diabetic COVID-19 patients also recorded higher mortality in comparison to non-diabetic COVID-19 patients (16.7% vs. 12.1%, p<0.001). Diabetic COVID-19 patients had significantly higher prevalence of comorbidities, such as hypertension. Laboratory investigations also highlighted notably higher levels of C-reactive protein in diabetic COVID019 patients and lower estimated glomerular filtration rate. They also showed a higher incidence of complications. logistic regression analysis showed that every 1 mmol/L increase in fasting blood glucose in COVID-19 patients is associated with 1.52 (95% CI: 1.34 - 1.72, p<0.001) times the odds of dying from COVID-19. ConclusionDiabetes is a major contributor to worsening outcomes in COVID-19 patients. Understanding the pathophysiology underlining these findings could provide insight into better management and improved outcome of such cases. Highlights of the StudyO_LIA significantly higher proportion of COVID-19 patients with diabetes mellitus required admission to the ICU. C_LIO_LIHigher fasting blood glucose was associated with higher risk of COVID-19 associated mortality. C_LIO_LICOVID-19 patients with diabetes mellitus had significantly higher incidence of complications including sepsis, ARDS, cardiac failure and renal failure. C_LI
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This is a retrospective single-center study of 417 consecutive patients with coronavirus disease 2019 (COVID-19) admitted to Jaber Al-Ahmad Hospital in Kuwait between February 24, 2020 and May 24, 2020. In total, 39.3% of patients were asymptomatic, 41% were symptomatic with mild/moderate symptoms, 5.3% were admitted to the intensive care unit (ICU) and recovered, and 14.4% died. The mean age of death cases was 54.20 years ({+/-} 11.09). Comorbidities were more prevalent in patients who died compared with others. Key findings include abnormal levels of markers assicated with infection, inflammation, abnormal blood clotting, heart problems and kidney problems in patients with severe form of the disease and poor putcome. We report a rapidly deteriorating estimated glomerular filtration rate (eGFR) in deaths during ICU stay with kidney injury complications reported in 65% of deaths (p < 0.05). Our dynamic profiling of eGFR in ICU highlights the potential role of renal markers in forecasting disease outcome that could perhaps identify patients at risk of poor outcome.
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BackgroundMany countries have succeeded in curbing the outbreak of COVID-19 by employing strict public health control measures. However, little is known about the effectiveness of such control measures in curbing the outbreak in developing countries. In this study, we seek to assess the impact of various outbreak control measures in Kuwait to gain more insight into the outbreak progression and the associated healthcare burden. MethodsWe use a SEIR mathematical model to simulate the epidemic outbreak of COVID-19 in Kuwait with additional testing and hospitalization compartments. We use a NBD observational framework for confirmed case and death counts. We forecast model trajectories and assess the effectiveness of public health interventions by using maximum likelihood to estimate both the basic and effective reproduction numbers. ResultsOur results indicate that the early strict control measures had the effect of delaying the intensity of the outbreak but were unsuccessful in reducing the effective reproduction number below 1. Forecasted model trajectories suggest a need to expand the healthcare system capacity to cope with the associated epidemic burden of such ineffectiveness. ConclusionStrict public health interventions may not always lead to the same desired outcomes, particularly when population and demographic factors are not accounted for as in the case in some developing countries. Real-time dynamic modeling can provide an early assessment of the impact of such control measures as well as a forecasting tool to support outbreak surveillance and the associated healthcare expansion planning. SUMMARY BOXO_ST_ABSWhat is already known on the subject?C_ST_ABSEvidence is accumulating about the positive impact of various strict public health interventions on the transmission of COVID-19 in the developed world. Currently, however, many developing countries are still struggling to control and suppress the initial wave of the outbreak. In particular, less attention is given to assessing the impact of taking similar strict control measures. What does this study add?Our modeling study provides the first evidence showing how the imposition of strict public health measures has not led to a reduction in COVID-19 transmission in Kuwait. It highlights the importance of performing systematic epidemiological and public health investigations of the population factors which may limit the effectiveness of standard public health interventions in developing countries. It also emphasizes the utility of adopting dynamic modeling approaches for intervention assessment and healthcare capacity re-adjustment at the earliest stages of the outbreak.
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The severity of the new COVID-19 pandemic caused by the SARS-CoV-2 virus is strikingly variable in different global populations. SARS-CoV-2 uses ACE2 as a cell receptor, TMPRSS2 protease, and FURIN peptidase to invade human cells. Here, we investigated 1,378 whole-exome sequences of individuals from the Middle Eastern populations (Kuwait, Qatar, and Iran) to explore natural variations in the ACE2, TMPRSS2, and FURIN genes. We identified two activating variants (K26R and N720D) in the ACE2 gene that are more common in Europeans than in the Middle Eastern, East Asian, and African populations. We postulate that K26R can activate ACE2 and facilitate binding to S-protein RBD while N720D enhances TMPRSS2 cutting and, ultimately, viral entry. We also detected deleterious variants in FURIN that are frequent in the Middle Eastern but not in the European populations. This study highlights specific genetic variations in the ACE2 and FURIN genes that may explain SARS-CoV-2 clinical disparity. We showed structural evidence of the functionality of these activating variants that increase the SARS-CoV-2 aggressiveness. Finally, our data illustrate a significant correlation between ACE2 variants identified in people from Middle Eastern origins that can be further explored to explain the variation in COVID-19 infection and mortality rates globally.
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In planning a model-based phylogenic study for highly related ethnic data, the SNP marker number is an important factor to determine for relationship inferences. Genotype frequency data, utilizing a sub sampling method, from 63 Pan Asian ethnic groups was used for determining the minimum SNP number required to establish such relationships. Bootstrap random sub-samplings were done from 5.6K PASNPi SNP data. DA distance was calculated and neighbour-joining trees were drawn with every re-sampling data set. Consensus trees were made with the same 100 sub-samples and bootstrap proportions were calculated. The tree consistency to the one obtained from the whole marker set, improved with increasing marker numbers. The bootstrap proportions became reliable when more than 7,000 SNPs were used at a time. Within highly related ethnic groups, the minimum SNPs number for a robust neighbor-joining tree inference was about 7,000 for a 95% bootstrap support.
