Evaluation of antibody levels for COVID-19 patients who attended a laboratory in Buenos Aires city

At the end of 2019 the first cases of SARS-CoV-2-associated pneumonia were reported in China. Consequently, the World Health Organization (WHO) named it COVID-19 and in January 2020, it declared the international health emergency due to the worldwide rapid spread of the infection. The first cases in Argentina were detected in early March 2020. Molecular tests like RT PCR and LAMP were immediately used. Serological tests for antibody detection were approved a few months later;however, these are still not the preferred diagnostic method for the disease. In our laboratory, the latter began to be used during the first wave of COVID-19. With the results obtained in that moment, an observational retrospective study in a cohort of patients who came voluntarily to test for SARS-CoV-2 IgG antibodies and whose results were positive was performed. The notification rate to the Argentine Integrated System for Health Information (SISA for its acronym in Spanish) was calculated and antibody levels were evaluated, clustering them according to the following facts: if the event had been notified to the SISA and if they had a previous RT PCR/LAMP result, the symptoms experienced by these patients and the time elapsed between RT PCR/LAMP and antibody test results. It was not possible to demonstrate differences between patients with detectable and undetectable RT PCR/LAMP, neither with the type of declared symptoms nor with respect to the days elapsed post-infection. However, it was found that there was a significant difference between notified and non-notified patients, and a high rate of non-notified patients with positive antibodies. Therefore, antibodies level might be considered as a surrogate marker of SARS-CoV-2 contact when a diagnosis through molecular methods is not available.

Consumer decisions toward halal purchase before and during COVID-19 pandemic: a grey relational analysis approach

Purpose: The main objective of this research is to investigate the factors that influence consumer purchase decisions for halal products before and during the COVID-19 pandemic, based on the Engel-Kollat-Blackwell (EKB) theory. Design/methodology/approach: The research was conducted as a survey. The influencing factors were determined based on the grey relational analysis (GRA) approach. Findings: The findings indicate before the COVID-19 pandemic, consumers mainly purchased halal products based on four key factors: purchasing experience, certification label, Internet searches and past consumption experience. However, during the pandemic, the ranking and factors have changed to six indicators, which are past consumption experience, purchasing experience, certification labels, standardized specifications, Internet searches and halal certification labels. Research limitations/implications: The study was limited by the sample size and geographical area. Nevertheless, the findings could be further explored by expanding related theories toward understand human decisions based on spiritual beliefs. Practical implications: The findings of this study have important implications for research, practice and society. Understanding the factors influencing halal purchase decisions before and during the pandemic can help businesses, policymakers and halal certification bodies to better cater to consumers' needs and preferences and ensure the continued growth and development of the halal industry. Originality/value: This study evaluates halal purchasing decisions between periods of certainty and uncertainty by using the GRA. Changes in halal consumption and purchase decisions in response to COVID-19 pandemic have become an emerging topic of discovery. The study addresses the gap in the literature regarding changes in consumer decision pattern. © 2023, Emerald Publishing Limited.

Neutralising antibody potency against SARS-CoV-2 wild-type and Omicron BA.1 and BA.4/5 variants in infliximab and vedolizumab treated patients with Inflammatory Bowel Disease after three doses of COVID-19 vaccine: A prospective multicentre cohort study

Background: Anti-tumour necrosis factor drugs such as infliximab are associated with attenuated antibody responses after COVID-19 vaccination It is unknown how infliximab impacts vaccine-induced serological responses against highly transmissible Omicron variants, which possess the ability to evade host immunity and are now the dominating variants causing current waves of infection Methods: In this prospective, multicentre, observational cohort study we investigated neutralising antibody responses against SARS-CoV-2 wild-type and Omicron BA.1 and BA.4/5 variants after three doses of COVID-19 vaccination in 1288 patients with IBD without prior COVID-19 infection, who were established on either infliximab (n=871) or vedolizumab (n=417). Cox proportional hazards models were constructed to investigate the risk of breakthrough infection in relation to neutralising antibody titres Results: Following three doses of COVID-19 vaccine, neutralising titre NT50 (half-inhibitory neutralising titre) was significantly diminished in patients treated with infliximab as compared to patients treated with vedolizumab, against wild-type, BA.1 and BA.4/5 variants (Fig 1). Patients with Crohn's disease showed lower antibody NT50 compared to patients with ulcerative colitis against wild-type strain and BA.4/5 (Fig 2). Older age and thiopurine were independently associated with lower NT50 against wild-type strain and BA.4/5 (Fig 2). Non-white ethnicity was associated with higher NT50 compared to white ethnicity against wild-type strain, BA.1 and BA.4/5 (Fig 2). Breakthrough infection was significantly more frequent in patients treated with infliximab compared to patients treated with vedolizumab (Fig 3). Cox proportional hazards models of time to breakthrough infection after the third dose showed infliximab treatment to be associated with a higher hazard risk (HR) of 1.71 (95% CI [1.08 to 2.71], p=0.022) compared to vedolizumab (Fig 4). Higher neutralising antibody titres against BA.4/5 were associated with a lower hazard risk and a longer time to breakthrough infection (HR 0.87 [0.79 to 0.95] p=0.0028) (Fig 4) Conclusion(s): Following a third COVID-19 vaccine dose, patients established on infliximab treatment have significantly lower neutralising titres against SARS-CoV-2, which were especially low against Omicron variants. Increased breakthrough infection in infliximab recipients was associated with lower neutralising antibody titres against BA.4/5. These data underline the importance of continued COVID-19 vaccination programs, including second-generation bivalent vaccines, especially in patient subgroups where vaccine immunogenicity and efficacy may be reduced.

COVID-19 vaccine-induced neutralising antibody responses against SARS-CoV-2 Omicron BA.4/5 are diminished in patients with inflammatory bowel disease on anti-TNF or JAK-inhibitor therapy

Background: Patients with Inflammatory bowel disease (IBD) receiving anti-TNF or JAK-inhibitor therapy have attenuated responses to COVID-19 vaccination. We aimed to determine how IBD treatments affect neutralising antibody responses against the currently dominant Omicron BA.4/5 variants. Method(s): We prospectively recruited 329 adults (68 healthy controls (HC) and 261 IBD) who had received three doses of COVID-19 vaccine at nine UK centres. The IBD population was established (>12 weeks therapy) on either thiopurine (n=60), infliximab (IFX) (n=43), thiopurine and IFX combination (n=46), ustekinumab (n=43), vedolizumab (n=46) or tofacitinib (n=23). Pseudoneutralisation assays were performed and the half maximal inhibitory concentration (NT50) of participant sera was calculated. The primary outcome was anti-SARSCoV-2 neutralising response against wild-type (WT) virus and the BA.4/5 variant after the second and third doses of anti-SARS-CoV-2 vaccine, stratified by immunosuppressive therapy, adjusting for prior infection, ethnicity, vaccine type and age. Result(s): Heterologous (two doses adenovirus vaccine, third dose mRNA vaccine) and homologous (three doses mRNA vaccine) vaccination strategies significantly increased neutralising titres against both WT SARS-CoV-2 virus and the BA.4/5 variants in HCs and IBD (fig 1). Antibody titres against BA.4/5 were significantly lower than antibodies against WT virus in both groups (Geometric Mean Ratio (GMR) [95% CI], 0.11 [0.09, 0.15], P<0.0001 in healthy participants;GMR 0.07 [0.06, 0.08], P<0.0001 in IBD patients). Multivariable models showed that neutralising antibodies against BA.4/5 after three doses of vaccine were significantly lower in IBD patients on IFX (GMR 0.44 [0.20, 0.97], P=0.042), IFX and thiopurine combination (GMR 0.34 [0.15, 0.77], P=0.0098) or tofacitinib (GMR 0.37 [0.15, 0.92], P=0.032), but not in patients on thiopurine monotherapy, ustekinumab or vedolizumab. Breakthrough infection was associated with lower neutralising antibodies against WT and BA.4/5 (P<0.05). Conclusion(s): A third dose of COVID-19 vaccine based on the WT spike glycoprotein boosts neutralising antibody titres in patients with IBD. However, responses are lower against the currently dominant variant BA.4/5, particularly in patients taking anti-TNF or JAK-inhibitor therapy. Breakthrough infections are associated with lower neutralising antibodies and immunosuppressed IBD patients may receive additional benefit from bivalent vaccine boosters which target Omicron variants. .

Soft skills in academic procrastination in postgraduate students, COVID-19

Objective: the research was aimed at verifying the incidence of soft skills in academic procrastination. Method(s): the study was causal correlational, with a sample of 352 graduate stu-dents, who were evaluated with the CPA Academic Procrastination questionnaire and the Soft Skills questionnaire, which were submitted online in Google Forms, with prior informed consent. Result(s): The results evidenced an inverse association between soft skills and academic procrastination;furthermore, a low but significant incidence (-,369**) was found between the variables under study. Conclusion(s): A low but significant inverse incidence of the antecedent variable on the consequent variable was found.Copyright © 2022, Venezuelan Society of Pharmacology and Clinical and Therapeutic Pharmacology. All rights reserved.

Activation of immune receptor RIG-I protects human differentiated epithelial cells of the upper respiratory tract from SARS-CoV-2

SARS-CoV-2 virus has evolved non structural proteins (NSLs) to avoid recogniton by innate immune receptors such as RIG-I which induces an antiviral type I IFN response. A proper type I IFN response is essential for an effective defense against SARS-CoV-2. The aim of this project is the evaluation of the effect of a prophylactic activation of RIG-I by a specific synthetic RNA ligand (5-triphosphate RNA, 3pRNA) to an antiviral state in cells that protects against SARSCoV- 2. We analysed the effect of activation of RIG-I by 3pRNA on SARS-CoV-2 infection in primary upper airway cells. Primary nasal epithelial cells (PNEC) and primary bronchial cells (NHBEC) were cultivated in air-liquid interface and differentiated to cilia bearing epithelial cells. Viral replication was analyzed by plaque assay and qPCR. Furthermore, interferon-stimulated genes and ACE2/TMPRSS2 were determined on the transcriptional level and IP-10 protein was quantified in supernatants by ELISA. Only PNEC in a fully differentiated state could be infected with SARS-CoV-2, while undifferentiated cells were not susceptible to infection with this virus. Upon stimulation with 3pRNA at 6h prior to infection, PNEC produced more than 10.000 pg/ml IP-10. Infection with SARS-CoV-2 significantly decreased the average of 3pRNA-induced IP-10 production. 3pRNA pretreatment of PNEC significantly reduced SARS-CoV-2 replication at 48 h by up to 99,7 % as evaluated by plaque assay and up to 90 % as measured by qPCR. These results demonstrate for the first time that RIG-I activation protects primary fully differentiated epithelial cells against SARS-CoV-2 replication. Our results support the concept that RIG-I-mediated prophylaxis is a promising strategy to mitigate SARS-CoV-2 infection.

COVID-19 VACCINE-INDUCED ANTIBODY RESPONSES ARE IMPAIRED IN IBD PATIENTS TREATED WITH INFLIXIMAB, USTEKINUMAB OR TOFACITINIB, BUT NOT THIOPURINES OR VEDOLIZUMAB

Background : Robust COVID-19 vaccine-induced antibody (Ab) responses are important for protective anti-viral immunity. Data are urgently needed to determine whether vaccineinduced immunity is impacted by commonly used immunosuppressive drug regimens in IBD. Methods: We prospectively recruited 447 adults (90 healthy controls and 357 IBD) at nine UK centres. The IBD study population was established (>12 weeks therapy) on either thiopurine monotherapy (n=78), infliximab (IFX) monotherapy (n=61), thiopurine & IFX combination therapy (n=70), ustekinumab (uste) monotherapy (n=56), vedolizumab (vedo) monotherapy (n=62) or tofacitinib (tofa) monotherapy (n=30). Participants had two doses of either ChAdOx1 nCoV-19, BNT162b2 or mRNA1273 vaccines. The primary outcome was anti-SARS-CoV-2 spike (S1 RBD) Ab concentrations, measured using the Elecsys anti- SARS-CoV-2 spike (S) Ab assay, 53-92 days after second vaccine dose, in participants without prior infection, adjusted by age & vaccine type. Secondary outcomes included proportions failing to generate protective Ab responses (defined cut-off anti-S concentration 15 U/ml, which correlated with 20% viral neutralization). Results: Geometric mean S Ab concentrations (figure 1) were lower in patients treated with IFX (153U/ml;p<0.0001), IFX and thiopurine combination (109U/mL;p<0.0001), tofa (430U/ml;p<0.0001) and uste (561U/ml;p=0.013) compared to controls (1596U/ml). No differences in S Ab concentrations were found between controls and thiopurine monotherapy-treated patients (1020U/ml;p=0.62), nor between controls and vedo-treated patients (944U/ml;p=0.69). In multivariable modelling (figure 2), lower S Ab concentrations were independently associated with IFX (FC 0.10 [95% CI 0.07-0.14], p<0.0001), tofa (0.36 [95% CI 0.19-0.69], p=0.002) and uste (0.56 [95% CI 0.31-1.00], p=0.049), but not with thiopurine (0.77 [95% CI 0.54-1.11], p=0.17) or vedo (1.01 [95% CI 0.61-1.68], p=0.96). mRNA vaccines (3.67 [95% CI 2.72-4.96], p<0.0001) and older age (0.82 [95% CI 0.73-0.91], p=0.0003) were independently associated with higher & lower S Ab concentrations respectively. Protective Ab responses were generated by all thiopurine monotherapy, vedo, tofa and healthy control participants, but not by 11% of patients on IFX monotherapy, 13% on thiopurine & IFX combination therapy and 4% on uste. Conclusions : COVID-19 vaccine-induced Ab responses are significantly reduced in patients treated with IFX, or tofa, and to a lesser extent with uste. No significant reduction was seen in vedo or thiopurine monotherapy-treated patients. Our data suggest that 3rd primary or booster vaccine doses for IBD patients might be tailored to an individual's immunosuppressive treatment. (Figure Presented) (Figure Presented)

THE IMPACT OF COVID-19 ON YOUNGSTERS

COVID-19 is caused by the coronavirus, and is transferable from one person to another through contact. The virus which usually affects the respiratory functions of a person, was first identified in China. The impact created by this pandemic is very severe. The COVID-19 disease and the related measures taken by the governments, like the lockdown, have created a significant impact on young people which need to be analysed and understood. The lockdown days brought about a number of changes in the normal life of the youth. The purpose of this research is to identify the impact of COVID-19 on college students in Kerala. Various studies on the subject have concluded that COVID-19 has affected the students’ family relationships, their use of the social media, their social behaviour, their skill development and academic activities. This study shows that COVID-19 led to a more positive family relationship than a negative one, although arguments and clashes of opinion in the family occurred more frequently. The use of the social media considerably increased during the pandemic. Students spent time on social media more for leisure than for academic purposes. Another important area of understanding relates to the beginning of negative behavioural changes in them. The study found that students became lazier, lethargic and sleepy during the lockdown. Their seriousness towards academic activities took a downward turn. On a positive note, it was found that COVID-19 and the lockdown made positive changes in the skill development of the youth. Cooking and gardening were two areas in which the youth improved their skills. The study concludes by asserting that COVID-19 and the lockdown made significant changes in the minds of the young people. © 2022 by Nova Science Publishers, Inc.

All-cause versus cause-specific excess deaths for estimating influenza-associated mortality in Denmark, Spain, and the United States.

BACKGROUND: Seasonal influenza-associated excess mortality estimates can be timely and provide useful information on the severity of an epidemic. This methodology can be leveraged during an emergency response or pandemic. METHOD: For Denmark, Spain, and the United States, we estimated age-stratified excess mortality for (i) all-cause, (ii) respiratory and circulatory, (iii) circulatory, (iv) respiratory, and (v) pneumonia, and influenza causes of death for the 2015/2016 and 2016/2017 influenza seasons. We quantified differences between the countries and seasonal excess mortality estimates and the death categories. We used a time-series linear regression model accounting for time and seasonal trends using mortality data from 2010 through 2017. RESULTS: The respective periods of weekly excess mortality for all-cause and cause-specific deaths were similar in their chronological patterns. Seasonal all-cause excess mortality rates for the 2015/2016 and 2016/2017 influenza seasons were 4.7 (3.3-6.1) and 14.3 (13.0-15.6) per 100,000 population, for the United States; 20.3 (15.8-25.0) and 24.0 (19.3-28.7) per 100,000 population for Denmark; and 22.9 (18.9-26.9) and 52.9 (49.1-56.8) per 100,000 population for Spain. Seasonal respiratory and circulatory excess mortality estimates were two to three times lower than the all-cause estimates. DISCUSSION: We observed fewer influenza-associated deaths when we examined cause-specific death categories compared with all-cause deaths and observed the same trends in peaks in deaths with all death causes. Because all-cause deaths are more available, these models can be used to monitor virus activity in near real time. This approach may contribute to the development of timely mortality monitoring systems during public health emergencies.

PREPARE-IBD: Physician responses to disease flares and patient adaptation in relation to events in inflammatory bowel disease during the COVID-19 pandemic: A multicentre cohort analysis

Background: The COVID-19 pandemic continues to pose complex problems across Europe and the world, with rising numbers of infections and the ongoing need for drastic public health interventions. This is difficult for patients with immune-mediated disorders like Inflammatory Bowel Disease (IBD), where immunosuppressive medications may affect susceptibility to serious infection. It was particularly challenging for physicians and patients during the first wave of the pandemic, when it was unclear whether anti-inflammatory flare treatment should be adapted to reduce infection risk, whilst trying to ensure symptomatic control and avoid admission to overwhelmed hospitals. Despite the development of various IBD / COVID-19 databases, the treatment adaptations and outcomes of patients experiencing IBD flares during the COVID-19 pandemic remain undefined. We aimed to compare IBD management and outcomes between pandemic and prepandemic cohorts. Methods: An observational cohort study was performed, comprising patients who contacted IBD teams for a symptom flare between March - June, 2020 in, 60 National Health Service trusts in the United Kingdom. Data were compared to a pre-pandemic cohort after propensity- matching for age and disease severity. Statistical analyses were performed using R (version, 4.1.0, Vienna, Austria). Results: In total, 3728 patients in the pandemic (n=1864) and pre-pandemic (n=1864) cohorts were included. The principal findings were reduced systemic corticosteroid prescription during the pandemic in both Crohn's disease (prednisolone: pandemic, 199/752, 26.5% vs, 263/708, 37.1%;p<0.001) and ulcerative colitis (UC) (prednisolone: pandemic, 372/1112, 33.5% vs, 470/1156, 40.7%, p<0.001), with increases in poorly bioavailable oral corticosteroids in Crohn's (pandemic, 117/752, 15.6% vs, 48/708, 6.8%;p<0.001) and UC (pandemic, 131/1112, 11.8% vs, 60/1156, 5.2%;p<0.001). Ustekinumab (Crohn's and UC) and vedolizumab (UC) treatment also significantly increased during the pandemic. Three-month steroid-free remission was similar in both Crohn's (pandemic, 175/616, 28.4% vs, 195/608, 32.1%;p=0.17) and UC (pandemic, 312/858, 36.4% vs, 404/1006, 40.2%;p=0.095). The, 65 patients experiencing a flare and COVID-19 were more likely to have moderate-to-severely active disease at three months compared to those with a flare alone. Conclusion: Despite several treatment adaptations during the pandemic, steroid-free outcomes were comparable to pre-pandemic levels, though patients with a flare and COVID-19 experienced worse outcomes. These findings have implications for IBD management during future waves or pandemics.

Antibody decay, T cell immunity and breakthrough infections following SARS-CoV-2 vaccination in infliximab- and vedolizumab-treated patients

Background: Antibody responses following SARS-CoV-2 infection or a single-dose of SARS-CoV-2 vaccine are impaired in patients with inflammatory bowel disease treated with anti-TNF compared to those treated with vedolizumab, a gut-selective anti-integrin α4β7 monoclonal antibody. Here we sought to determine if patients treated with infliximab have attenuated serological and T cell responses and an increased risk of breakthrough COVID-19 infection following primary SARS-CoV-2 vaccination. Methods: Anti-spike (S) receptor binding domain (RBD) antibody concentration in 2306 infliximab-treated patients were compared to a cohort of 1045 vedolizumab-treated patients. Our primary outcome was anti-S RBD antibodies 2 to 10 weeks after a second dose of the BNT162b2 or ChAdOx1 nCoV-19 vaccines. Secondary outcomes were anti-spike T cell responses, durability of vaccine responses and risk of breakthrough infections following two doses of vaccine. Results: Anti-S RBD antibody concentrations were lower in patients treated with infliximab than in those treated with vedolizumab, following a second dose of BNT162b2 (567.3 U/mL [6.1] vs 4601.1 U/ mL [5.3], p <0.0001) and ChAdOx1 nCoV-19 (183.9 U/mL [5.0] vs 789.4 U/mL [3.5], p <0.0001) vaccines (Fig. 1). Vaccination with the BNT162b2 vaccine compared to the ChAdOx1 nCoV-19 was independently associated with a 3.7-fold [95% CI 3.30 - 4.13] higher anti-S RBD antibody concentration (p < 0.0001) (Fig. 2). There were no significant differences in the magnitude of anti-spike T cell responses observed in infliximab- compared with vedolizumabtreated patients after one or two doses of either vaccine. Antibody half-life was shorter in infliximab- than vedolizumabtreated patients following two-doses of BNT162b2 (4.0 weeks [95% CI 3.8 - 4.1] vs 7.2 weeks [95% CI 6.8 - 7.6]) and ChAdOx1 nCoV- 19 (5.3 weeks [95% CI 5.1 - 5.5] vs 9.3 weeks [95% CI 8.5 - 10.2], p value < 0.0001). Breakthrough SARS-CoV-2 infections were more frequent (5.8% (202/3467) vs 3.9% (66/1691), p = 0.0032) and the time to breakthrough shorter in patients treated with infliximab than vedolizumab (p = 0.0023) (Fig. 3). Higher anti-S RBD antibody concentrations following a second dose of SARS-CoV-2 vaccine protected against breakthrough SARS-CoV-2 infection: overall, for every 10-fold rise in anti-S RBD antibody level we observed a 0.8-fold reduction in odds of breakthrough infection ([95% CI 0.70 - 0.99], p = 0.035). Conclusion: Infliximab was associated with attenuated, less durable vaccine induced anti-S RBD antibody responses and a 50% increase in breakthrough SARS-CoV-2 infection. Further follow-up is required to assess whether third primary doses can mitigate the effects of infliximab on anti-S RBD antibody responses.

COVID-19 vaccine-induced antibody responses are impaired in Inflammatory Bowel Disease patients treated with infliximab, ustekinumab or tofacitinib, but not thiopurines or vedolizumab

Background: Robust COVID-19 vaccine-induced antibody (Ab) responses are important for protective anti-viral immunity. Data are urgently needed to determine whether vaccine-induced immunity is impacted by commonly used immunosuppressive drug regimens in IBD. Methods: We prospectively recruited 447 adults (90 healthy controls and 357 IBD) at nine UK centres. The IBD study population was established (>12 weeks therapy) on either thiopurine monotherapy (n=78), infliximab (IFX) monotherapy (n=61), thiopurine & IFX combination therapy (n=70), ustekinumab (uste) monotherapy (n=56), vedolizumab (vedo) monotherapy (n=62) or tofacitinib (tofa) monotherapy (n=30). Participants had two doses of either ChAdOx1 nCoV-19, BNT162b2 or mRNA1273 vaccines. The primary outcome was anti-SARS-CoV-2 spike (S1 RBD) Ab concentrations, measured using the Elecsys anti- SARS-CoV-2 spike (S) Ab assay, 53-92 days after second vaccine dose, in participants without prior infection, adjusted by age & vaccine type. Secondary outcomes included proportions failing to generate protective Ab responses (defined cut-off anti-S concentration 15 U/mL, which correlated with 20% viral neutralization). Results: Geometric mean S Ab concentrations (figure 1) were lower in patients treated with IFX (153U/mL;p<0.0001), IFX and thiopurine combination (109U/mL;p<0.0001), tofa (430U/mL;p<0.0001) and uste (561U/mL;p=0.013) compared to controls (1596U/ml). No differences in S Ab concentrations were found between controls and thiopurine monotherapy- treated patients (1020U/mL;p=0.62), nor between controls and vedo-treated patients (944 U/mL;p=0.69). In multivariable modelling (figure 2), lower S Ab concentrations were independently associated with IFX (FC 0.10 [95% CI 0.07-0.14], p<0.0001), tofa (0.36 [95% CI 0.19-0.69], p=0.002) and uste (0.56 [95% CI 0.31-1.00], p=0.049), but not with thiopurine (0.77 [95% CI 0.54-1.11], p=0.17) or vedo (1.01 [95% CI 0.61-1.68], p=0.96). mRNA vaccines (3.67 [95% CI 2.72- 4.96], p<0.0001) and older age (0.82 [95% CI 0.73-0.91], p=0.0003) were independently associated with higher & lower S Ab concentrations respectively. Protective Ab responses were generated by all thiopurine monotherapy, vedo, tofa and healthy control participants, but not by 11% of patients on IFX monotherapy, 13% on thiopurine & IFX combination therapy and 4% on uste. Conclusion: COVID-19 vaccine-induced Ab responses are significantly reduced in patients treated with IFX, or tofa, and to a lesser extent with uste. No significant reduction was seen in vedo or thiopurine monotherapy-treated patients. Our data suggest that 3rd primary or booster vaccine doses for IBD patients might be tailored to an individual's immunosuppressive treatment.

DISEASE ACTIVITY IS ASSOCIATED WITH COVID-19 OUTCOMES IN IBD PATIENTS WITH EFFECT MODIFICATION BY AGE

Background: Surveillance Epidemiology of Coronavirus Under Research Exclusion for Inflammatory Bowel Disease (SECURE-IBD) is an international database that monitors COVID-19 outcomes in IBD patients. We examined the influence of IBD disease activity on COVID-19 severity, while accounting for confounders and exploring the modifying effect of age. Methods: This was a retrospective analysis of all cases reported to SECURE-IBD with complete Physician Global Assessment (PGA) of IBD activity and age data (N=3028). PGA was categorized as remission/mild (reference) vs moderate vs severe. Outcomes used as surrogates of severe SARS-CoV2 infection were hospitalization and a composite of ICU/ ventilation/death. We compared cohort characteristics across PGA categories using the Chisquare and Kruskal-Wallis test. Using logistic regression, we determined the unadjusted association between disease activity and COVID-19 outcomes, overall and by age decade. Multivariable logistic regression models included PGA, age, sex, IBD type, comorbidities (0, 1, ≥2) and systemic corticosteroids (CS) a priori and additional confounders if they changed the estimate by ≥10% (we tested BMI, race, and medications). Risk estimates were expressed as crude and adjusted odds ratios (OR) with 95% CI. We also built models stratified by age (≤50 vs >50 years). Results: Race, IBD type, BMI and current medications (CS, anti-TNF, thiopurine monotherapy, aminosalicylates, ustekinumab and tofacitinib) differed across PGA categories (p<0.05). COVID-19 was more severe in patients with more active IBD: hospitalization rates 19% (remission/mild), 26% (moderate) and 45% (severe);ICU/ventilation/death rates 5% (remission/ mild), 6% (moderate) and 12% (severe) (p<0.05 for both outcomes). In unadjusted analyses, higher PGA was associated with an increased risk of hospitalization (moderate: OR 1.52, 95% CI 1.21-1.92;severe: OR 3.57, 95% CI 2.56-4.98) and ICU/ventilation/death (moderate: OR 1.40, 95% CI 0.94-2.10;severe: OR 2.72, 95% CI 1.63-4.55). Figure 1 illustrates the OR for hospitalization and ICU/ventilation/death for severe PGA vs remission/ mild by decade;effect sizes are greatest in patients ≤50 years. In multivariable analyses, PGA remained significantly associated with hospitalization, but not ICU/ventilation/death (effect lost after adjusting for CS) (Table 1). However, in analyses stratified by age, PGA remained significantly associated with both hospitalization and ICU/ventilation/death, even after adjusting for medications, in patients ≤50 but not >50 years (Table 1).Conclusions: The association between IBD activity and severe COVID-19 varied with age. The association was stronger in younger patients and, after adjusting for the confounding effect of medications, particularly CS, disease activity was significantly associated with severe outcomes only in younger (≤50 years) patients.(Figure Presented)Odds Ratios for A) hospitalization and B) ICU/ventilation/death for severe PGA vs remission/mild by decade (Table Presented)Adjusted Odds Ratios for Hospitalization and ICU/ventilation/death by Disease Activity, Overall and Stratified by Age

Thrombotic events in COVID-19 are associated with a lower use of prophylactic anticoagulation before hospitalizationand followed by decreases in platelet reactivity

Background : Coronavirus disease of 2019 (COVID-19) is associated with a prothrombotic state and high incidence of thrombotic events (TE). Platelet hyperreactivity has been reported in COVID-19 patients and might contribute to TE development. Aims : To study platelet reactivity in hospitalized COVID-19 patients and to determine a possible association with the clinical outcomes thrombosis and all-cause mortality. Methods : 79 hospitalized COVID-19 patients were enrolled in this retrospective cohort study and provided blood samples in which platelet reactivity in response to stimulation with ADP and TRAP-6 was determined using flow cytometry. Clinical outcomes included thrombotic events, and all-cause mortality. Results : The incidence of TE in this study was 28% and all-cause mortality 16%. Patients that developed a TE were younger than patients that did not (median age of 55 versus 70 years;adjusted odds ratio (AOR), 0.96 per 1 year of age [95% CI, 0.92-1.00];P = 0.042). Furthermore, patients using preexisting thromboprophylaxis were less likely to develop a TE than patients that were not (18% versus 54%;adjusted odds ratio, 0.18 [95% CI, 0.04-0.82];P = 0.026). Conversely, having asthma strongly increased the risk on TE development (adjusted odds ratio, 6.4 [95% CI, 1.17-35.4];P = 0.032). No significant differences in baseline P-selectin expression or platelet reactivity were observed between the COVID-19 positive patients ( n = 79) and COVID-19 negative hospitalized control patients ( n = 24), nor between COVID-19 survivors or non-survivors. However, patients showed decreased platelet reactivity in response TRAP-6 following TE development compared to patients without TE. Conclusions : We observed an association between the use of preexisting thromboprophylaxis and a decreased risk of TE during COVID-19. This suggests that these therapies are beneficial for coping with COVID-19 associated hypercoagulability. This highlights the importance of patient therapy adherence. We observed lowered platelet reactivity after the development of TE, which might be attributed to platelet desensitization during thromboinflammation.

Assessment of Lockdown Effectiveness in the Wake of COVID-19 in India Using the Auto Regressive Integrated Moving Average Model

Background The novel coronavirus disease (COVID-19) has been recognized as a global threat, and several studies are being conducted using various mathematical models to predict the probable evolution of this epidemic, which are subject to potential bias. In this study, we aimed to assess and compare the impact of lockdown among the Punjab, Delhi, and Gujarat states of India using the Auto Regressive Integrated Moving Average (ARIMA) model by comparing forecasted COVID-19 data with real-time data. Methods We analyzed the COVID-19 data of Indian states from the index case until May 17, 2020. Auto Regressive Integrated Moving Average (1,1,3) (0,0,0) model was used to forecast the possible cumulative cases until May 17, from data up to May 3, and compared with real-time data. Recovery rate, case-fatality rate, and test per millions of states were collated. Results The trend of cumulative cases in Punjab was moving downward below the forecasted lower confidence limit (R-2 = 0.9799), whereas the cumulative case trend of Delhi was moving along the forecasted upper confidence limit with the forecasted data until May 3 (R-2 = 0.9971) and the trend of cumulative cases was below the forecasted upper confidence limit (R-2 = 0.9992) in Gujarat. Conclusions In Gujarat and Delhi, the lockdown was not effective in controlling the rise in COVID-19 cases even after the 56th day of lockdown, whereas the Punjab state succeeded in preventing havoc of COVID-19. In lieu of lockdown, using facemasks and improving ventilation in closed workspace settings, crowded spaces, and close-contact settings are more pragmatic than keeping away from others in India.