Incident New Onset Diabetes after Covid-19 Infection: A National Multicenter Cohort

Background: It is known that survivors of acute SARS-CoV-2 infection can experience a complex disease known as post-acute sequelae of COVID-19 (PASC). The clinical manifestations of acute COVID-19 have been well characterized however less is known about the risk of new onset diabetes mellitus (DM) in the post-acute phase of COVID-19. Method(s): An adult cohort with confirmed COVID-19 (by diagnosis or positive test) and without COVID-19 was sampled from a large national health research network between January 1st, 2020 and July 8th, 2022. We investigated the outcomes of a new diagnosis of DM (type I or II) occurring after COVID-19 through 12 months after infection. Risk estimates [incidence, relative risk (RR), attributable risk] were used to describe the probability of incident post-COVID diabetes. Hazard ratios and 95% confidence intervals were used to describe risk factors associated with new diabetes. Result(s): The 3-month probability of new diabetes was 2.48/1,000 among COVID+ and the relative risk (RR) of new diabetes was highest at 12 months [8.94 (8.54, 9.36)]. Vitamin D deficiency [HR: 1.52 (95% CI: 1.42, 1.63)] was associated with increased risk of T2DM and having vitamin D deficiency with either obesity (BMI > 30 kg/m2) or kidney dysfunction (GFR < 60) was associated with more than five times increased risk of T1DM. Conclusion(s): We observed a large proportion of excess diabetes starting at 3 months post COVID infection. Traditional risk factors for diabetes, omicron variant, and vitamin D deficiency are associated with increased risk of new diabetes outcome. PASC care should involve identification and management of diabetes. (Figure Presented).

Molnupavir in Previously Uninfected Nonhospitalized Persons with Covid-19

Background: Clinical benefit of Molnupiravir (MPV) in COVID-19 infected subpopulations is unclear. Method(s): We used a matched cohort design emulating a target trial to analyze the VA COVID-19 Shared Resource database to determine the association of MPV with hospitalization or death within 30 days compared with untreated controls in previously uninfected non-hospitalized persons. Incidence of hospitalization/ death and absolute risk difference (ARD) with 95% confidence intervals were calculated for the treated and untreated groups. Result(s): Among 1,459 matched pairs, the incidence of hospitalization/death was not different among MPV treated vs. untreated controls (48 vs. 44 cases;ARD [95% CI] 0.27 [-0.94,1.49]). No benefit was observed among those >60 or <60 years old (ARD 0.27 [-1.25,1.79] vs. -0.29 [-1.22,1.80]), those with specific comorbidities, or by vaccination status. A significant benefit was observed in asymptomatic but not in symptomatic persons (ARD -2.80 [-4.74,-0.87] vs. 1.12 [-0.31,2.55]). Kaplan-Meier curves did not show a significant reduction in proportion of persons who were hospitalized or died among those treated with MPV compared with untreated controls (logrank P=0.7). Conclusion(s): MPV was not associated with a significant reduction in hospitalization or death within 30 days of COVID-19 diagnosis overall. A subgroup of patients presenting without symptoms experienced a benefit.

Clinical efficacy and safety of ivermectin (400 mug/kg, single dose) in patients with severe COVID-19: a randomized clinical trial

Purpose: To evaluate the clinical efficacy of including Ivermectin (single dose on day 1 of 400 mug/kg PO) in the standard of care in hospitalized adults with severe COVID-19. Method(s): Double-blinded, parallel, placebo-controlled, single-center, randomized clinical trial. Seventy-five patients were randomly assigned (1:1) to receive standard of care plus ivermectin or placebo and were followed up for 21 days. Primary outcome measure was admission to ICU and secondary outcomes were the requirement of intensive mechanical ventilation (IMV) and in-hospital death. Intention-to-treat analyses, estimated risk differences (RD), and Hazard ratios (HR) with Cox regression were performed. Result(s): Enrollment stopped due to the lack of eligible patients. Thirty-seven patients were assigned to intervention and 38 to placebo. Patients in the ivermectin group were 54.5 years on average, 62.2% were male. Comorbidities were more prevalent in the control group (78.9% vs. 56.8%). There was no difference in the 21-day risk of admission to the ICU between ivermectin (21.6%) and placebo (15.8%) (RD= 5.8%;95%CI: -11.8%-23.5%);neither in the risk of requirement of IMV (18.9% vs 13.2%), mortality (5.4% vs 10.5%) or in adverse events (32.4% vs. 28.9%). Discussion(s): Ivermectin showed no significant benefit in reducing the requirement of ICU, IMV, or mortality for severe COVID-19 patients.Copyright © 2022 Asociacion Colombiana de Infectologia. All rights reserved.

Efficacy and safety of arbidol in the treatment of novel coronavirus pneumonia: a systematic review based on current and previous antiviral therapy.

Objective: To systematically evaluate the efficacy and safety of arbidol in the treatment of novel coronavirus pneumonia (COVID-19). Method(s): Randomized controlled trials (RCTs), cohort studies, and case-control studies on the efficacy and safety of arbidol for COVID-19, influenza, andother respiratory virus infections were collected by searching related database at home and abroad and network platform for preprint of Health Science Papers (medRxiv) (up to April 25, 2020). Quality of the enrolled studies was evaluated by bias risk assessment tool of Cochrane collaboration network and Newcastle-Ottawa Scale (NOS). Meta-analysis and descriptive analysis of relevant outcome indicators were performed using RevMan 5.3 software. Result(s): A total of 15 studies were enrolled in the study, including 7 cohort studies with high-quality and 8 RCTs, 6 of which were with low bias risk and the other 2 of which were with medium bias risk. Among these studies, 8 were on arbidol treatment for COVID-19, including 5 retrospective cohort studies, 2 prospective cohort studies, and 1 RCT, and involving 809 patients (479 patients in the arbidol group and 330 in the control group);7 were RCTs on arbidol treatment for influenza or other respiratory virus infections, involving 1 471 patients (745 patients in the arbidol group and 726 in the control group).In these studies, patients were treated with arbidol (0.15-1.2 g daily for 5-21 d) in the arbidol group while with the other antiviral agents or without any antiviral drug in the control group. Meta analysis on the efficacy and safety of arbidol in treatment for COVID-19 showed that the novel coronavirus (2019-nCoV) nucleic acid negative conversion rate in the arbidol group was significantly higher than that in the control group [71.7% (109/152) vs. 58.8% (94/160), relative risk (RR)=1.30, 95% confidence interval (CI): 1.01-1.67, P=0.04];the difference of time taken for 2019-nCoV nucleic acid negative conversion between the 2 groups was not statistically significant (standardized mean difference=-0.17, 95%CI: -0.72-0.38, P=0.55);the difference of disease improvement rate shown by chest CT on day 7 after treatment between the 2 groups was not statistically significant [46.2% (30/65) vs. 50.7% (36/71), RR=0.88, 95%CI: 0.39-1.98, P=0.76];and the difference of incidence of adverse reactions between the 2 groups was not statistically significant [16.9% (39/231) vs. 19.2% (47/245), risk difference (RD)=-0.03, 95%CI: -0.10-0.04, P=0.44]. Meta analysis on the safety of arbidol in treatment for influenza and other respiratory virus infections showed that the incidence of adverse reactions in the arbidol group was significantly lower than that in the control group [5.9% (44/745) vs. 11.3% (82/726), RR=0.52, 95%CI: 0.37-0.74, P<0.01]. Conclusion(s): Arbidol could effectively increase the 2019-nCoV nucleic acid negative conversion rate and it might be safe to treat COVID-19 using arbidol.Copyright © 2020 by the Chinese Medical Association.

Higher versus lower dose corticosteroids for moderate to severe COVID-19: a systematic review, dose response and network meta-analysis

Background: Corticosteroids are standard of care for moderate-to-severe COVID-19. However, the optimal dosing is unclear. Our objective was to compare higher dose corticosteroids to lower dose corticosteroids in patients with moderate-to-severe COVID-19. Method(s): We searched for randomized trials of adult patients with moderate-to-severe COVID-19 that compared corticosteroids versus placebo, standard care or that compared alternative doses of corticosteroids. We performed both a frequentist network and dose-response meta-analysis. We assessed risk of bias using a modified version of the Cochrane RoB 2.0 and used GRADE to assess the certainty of evidence. Result(s): We included 21 randomized trials with 9,640 patients. Our dose response analysis found that higher dose corticosteroids probably reduce mortality compared to lower dose (risk difference 13 fewer deaths per 1000 (95% CI 22.6 to 3.92 fewer);moderate certainty), may decrease the need of mechanical ventilation dose (risk difference 10 fewer per 1000 (95% CI 20.5 to 4.8 fewer) and probably decreases risk of infections (16.7 fewer infections per 1000 (95% CI 25 to 5.4 fewer);moderate certainty). Our network meta-analysis found that high dose corticosteroids probably reduce the duration of mechanical ventilation as compared to low dose (6.9 fewer days (95% CI 8.5 to 5.2 fewer);moderate certainty). The results of our network and dose response analysis were consistent. Conclusion(s): High dose corticosteroids is more effective than than low dose in reducing mortality.

Comorbidities Associated with Increased Risk of Death in Ckd Patients with Covid-19

Introduction: The COVID-19 pandemic has increased the burden on patients living with kidney disease. The higher lethality in this population is associated with an increase in 7 to 18-fold mortality compared to patients with chronic kidney disease who were not infected with the virus. This increased toll on patients with kidney disease urges that further studies be performed to understand the extent of the vulnerability of this population. Method(s): Retrospective cohort study. Patients with previous diagnoses of chronic kidney disease ( CKD) hospitalized with acute respiratory failure with a confirmed COVID-19 diagnosis from January to June 2021 were included. Anonymized data was obtained from the DATASUS public database. Missing data were excluded. Collected data included patients' demographics, clinical characteristics, and outcomes. Patients were stratified on the presence of other comorbidities. P-values < 0.05 were considered significant. Statistical analysis was performed using Microsoft Excel, SPSS IBM e Epi Info 7. Result(s): A total of 18,877 patients were included in the analysis. The majority (59,3 %) were male, and the mean age was 64,5 +/-15,4 years. The most common symptoms or signs in this population were dyspnea (72,5 %) followed by cough (60,9%) and low peripheral O2 saturation(71,0%). Regarding the comorbidities associated with chronic kidney disease, the most prevalent were Cardiovascular disease (55,9%), Diabetes mellitus (42,7%), and Obesity (11%). The presence of each individual comorbidity associated with CKD was noted to increase the risk of death for these patients (Table 1). [Formula presented] 95% C.I.:95 % Confidence Interval Conclusion(s): Cardiovascular disease, diabetes mellitus, and obesity associated with chronic kidney disease significantly increase the risk of poor outcomes in patients hospitalized with acute respiratory failure due to COVID-19. This increased risk should be considered when managing these patients. Furthermore, the interactions between the types of comorbidities must also be worthy of attention due to their risk differences. The simple quantification of the number of comorbidities of each patient or the presence or absence should be replaced and individualized on a patient-by-patient basis. No conflict of interestCopyright © 2023

A municipality-level analysis of excess mortality in Italy in the period January-April 2020.

BACKGROUND: the first confirmed cases of COVID-19 in WHO European Region was reported at the end of January 2020 and, from that moment, the epidemic has been speeding up and rapidly spreading across Europe. The health, social, and economic consequences of the pandemic are difficult to evaluate, since there are many scientific uncertainties and unknowns. OBJECTIVES: the main focus of this paper is on statistical methods for profiling municipalities by excess mortality, directly or indirectly caused by COVID-19. METHODS: the use of excess mortality for all causes has been advocated as a measure of impact less vulnerable to biases. In this paper, observed mortality for all causes at municipality level in Italy in the period January-April 2020 was compared to the mortality observed in the corresponding period in the previous 5 years (2015-2019). Mortality data were made available by the Ministry of Internal Affairs Italian National Resident Population Demographic Archive and the Italian National Institute of Statistics (Istat). For each municipality, the posterior predictive distribution under a hierarchical null model was obtained. From the posterior predictive distribution, we obtained excess death counts, attributable community rates and q-values. Full Bayesian models implemented via MCMC simulations were used. RESULTS: absolute number of excess deaths highlights the burden paid by major cities to the pandemic. The Attributable Community Rate provides a detailed picture of the spread of the pandemic among the municipalities of Lombardy, Piedmont, and Emilia-Romagna Regions. Using Q-values, it is clearly recognizable evidence of an excess of mortality from late February to April 2020 in a very geographically scattered number of municipalities. A trade-off between false discoveries and false non-discoveries shows the different values of public health actions. CONCLUSIONS: despite the variety of approaches to calculate excess mortality, this study provides an original methodological approach to profile municipalities with excess deaths accounting for spatial and temporal uncertainty.

Population-level impact of beliefs and attitudes on vaccine decision-making in South Africa: results from the COVID-19 Vaccine Survey (2021/2022).

OBJECTIVES: In addition to being home to more than seven million HIV-infected individuals, South Africa also has a high burden of COVID-19 and related comorbidities worldwide. We aimed to identify the most influential "beliefs" and "attitudes" on vaccine decision-making behavior. STUDY DESIGN: This study used panel data from cross-sectional surveys. METHODS: We used the data from Black South Africans who participated in the "COVID-19 Vaccine Surveys" (November 2021 and February/March 2022) in South Africa. Besides standard risk factor analysis, such as multivariable logistic regression models, we also used the modified version of population attributable risk percent and estimated the population-level impacts of beliefs and attitudes on vaccine decision-making behavior using the methodology in multifactorial setting. RESULTS: A total of 1399 people (57% men and 43% women) who participated in both surveys were analyzed. Of these, 336 (24%) reported being vaccinated in survey 2. Overall low perceived risk, concerns around efficacy, and safety were identified as the most influential factors and associated with 52%-72% (<40 years) and 34%-55% (40+ years) of the unvaccinated individuals. CONCLUSION: Our findings highlighted the most influential beliefs and attitudes on vaccine decision-making and their population-level impacts, which are likely to have significant public health implications exclusively for this population.

Quantifying impact of obesity on cardiometabolic comorbidities and public health implications: Insights from South Africa.

INTRODUCTION: South Africa has the highest obesity and hypertension rates in the African region. In this cross-sectional study, we aimed to quantify the correlates and burden of obesity and their impacts on cardiometabolic conditions. METHODS: The study population was 80,270 men(41 %) and women(59 %) who participated in South African national surveys (2008-to-2017). Weighted-logistic regression models and the population attributable risk (PAR %) were used after accounting for the correlation structure of the risk factors in a multifactorial setting. RESULTS: Overall, 63 % of the women and 28 % of the men were either overweight or obese. Parity was identified as the most influential factor and exclusively associated with 62 % of the obesity in women; being married/cohabiting had the highest impact on obesity in men and associated with 37 % of the obesity. Overall, 69 % of them had comorbidities including hypertension, diabetes and heart disease. More than 40 % of the comorbidities were attributed to overweight/obesity. CONCLUSION: Developing culturally appropriate prevention programs are urgently needed to raise awareness of obesity, hypertension and their impacts on severe cardiometabolic diseases. This approach would also significantly reduce COVID-19 related poor health outcomes and premature deaths.

Covid-19 Vaccine Protection against Mortality in Patients with Oxygen: A Multicontinental Study

INTRODUCTION: The COVID-19 vaccines have effectiveness above 90% for avoiding hospitalization. However, 5% of vaccinated patients require hospitalization with a mortality ratio between 15% to 24%, similar to the one reported for unvaccinated hospitalized patients. These vaccinated patients belong to the most sensitive groups with a high comorbidity burden. The similarity in the mortality ratio between vaccinated and unvaccinated patients has been used to make claims against the vaccine's efficacy. A thoughtful analysis, taking into account the comorbidities of each group, on how vaccination protects patients with moderate or severe illness, is missing. METHOD(S): We perform a multi-continental retrospective cohort study in 111 hospitals in Spain and 37 in Argentina. We included hospitalized patients who received oxygen therapy older than 18 years with COVID-19. To assess the relation between COVID-19 vaccine status and death, we performed a logistic regression adjusting by confounders. Also, as a sensitivity analysis, we perform a propensityscore matching. Additionally, we studied the Population Attributable Risk (PAR). RESULT(S): Between January 2020 and May 2022, we included 21,479 patients, 717 (3 3%) were vaccinated. Hospitalized vaccinated patients with oxygen therapy had a higher proportion of comorbidities. The overall mortality in vaccinated patients was 20 9%, and 19 5% in unvaccinated patients. The crude Odds Ratio was 1 07 (IC95% 0 89-1 29;p=0 41), while the adjusted was 0 73 (IC95% 0 56-0 95;p=0 02) in the complete case analysis (6,352 patients) and 0 77 (CI 95% 0 54-0 97;p=0 02) in the complete dataset after multiple imputations. These observations were robust to the sensitivity analysis. The adjusted PAR reduction was 4 3% (95%CI 1%-5%). Therefore, as the death proportion in unvaccinated patients was 19 6% (95%CI 19%-20 1%), if they were vaccinated the expected death proportion would have been 15 3% (95%CI 12 9%-18%;p< 0 01). CONCLUSION(S): Even with the high protection of the COVID-19 vaccine, patients with a high burden of comorbidities will be hospitalized in future pandemic waves. In this study, we observed that the COVID-19 vaccines significantly reduce the probability of death even when lung inflammation has already been initiated, with moderate or severe COVID-19 disease.

Effect of intravenous pulses of methylprednisolone 250 mg versus dexamethasone 6 mg in hospitalized adults with severe COVID-19 pneumonia: an open-label randomized trial

Background. Pulse glucocorticoid therapy is used in COVID-19 infection. We evaluated the effectiveness of methylprednisolone 250 mg/d for 3 days vs. dexamethasone 6 mg/ d for 10 days in patients with severe but not critical COVID-19 pneumonia. Methods. A multicentre, randomized, open-label, controlled trial was conducted between February 2021 and August 2021 at 4 hospitals in Spain and included 128 hospitalized adults with confirmed COVID-19 pneumonia needing oxygen therapy but not critically ill. Patients were randomly assigned in a 1:1 ratio to receive dexamethasone 6 once daily for 10 days or methylprednisolone 250 mg once daily for 3 days. The primary outcome was 28-day mortality. Results. Of the 128 randomized patients, 125 were analysed (mean age 60 +/- 17 years;82 males [66%]). Mortality at 28 days was 4.8% in the 250 mg methylprednisolone group vs. 4.8 % in the 6 mg dexamethasone group (absolute risk difference, 0.1% [95% CI, -8.8 to 9.1%];P=0.98). The post-hoc added composite outcome of mortality at 90 days or intubation was 15.9% in the 250 mg methylprednisolone group vs. 15% in the 6 mg dexamethasone group (absolute risk difference, -0.9% [95% CI, -13.8 to 12.3%];P=0.83). Hyperglycaemia was more frequent in the methylprednisolone group, at 27.0 vs. 8.1 % (absolute risk difference, -18.9% [95% CI, -31.8 to - 5.6%];P=0.007). Conclusion. Among severe but not critical patients with COVID-19, 250 mg/d for 3 days of methylprednisolone compared with 6 mg/d for 10 days of dexamethasone did not result in a decrease in mortality or intubation.

Clinical and Virologic Outcomes with Early Adintrevimab (ADI) Monoclonal Antibody Therapy in Mild and Moderate COVID-19

Background. Peak SARS-CoV-2 viral replication occurs in the upper respiratory tract in presymptomatic and early symptomatic phases. Administration of a monoclonal antibody may be most beneficial in the early time period immediately after symptom onset. Here we describe the effect of early therapy on efficacy in patients receiving ADI. Methods. High risk patients with mild or moderate COVID-19 were enrolled in the ADI treatment study (STAMP), with primary endpoint of COVID-19 related hospitalization or all-cause death through Day 29 in patients with disease due to confirmed or suspected SARS-CoV-2 variants other than Omicron. Patients were randomized 1:1 to receive ADI or placebo administered by a single intramuscular (IM) injection. For this subgroup analysis, patients that had received therapy within 3 days of symptom onset were evaluated. Results. In the overall population, the study met the primary endpoint demonstrating 66% relative risk reduction of COVID-19 hospitalization or all cause death in 336 patients. Among 261 patients receiving therapy within 3 days of symptom onset (n=133 ADI, n=128 placebo), ADI was associated with a statistically significant reduction in the risk of COVID-19-related hospitalization or all-cause death through Day 29 compared with placebo (4 [3%] vs. 15 [11.7%], standardized risk difference -8%, 95% CI: -14.11, -1.86, p=0.0106), demonstrating a 72% standardized relative risk reduction in favor of ADI. When given as early therapy, ADI provided a greater reduction in viral load from baseline to Day 5 compared with placebo as assessed by saliva samples, with an adjusted least-squares mean difference of -0.97 log10 copies/mL (95% CI: -1.540, -0.391;p=0.0011). No study drug related SAEs, including deaths, and no hypersensitivity reactions were reported. Conclusion. Early therapy with a single dose of ADI 300 mg IM provided a 72% reduction in the risk of COVID-19 related hospitalization and all-cause death compared to placebo in high-risk ambulatory patients with mild to moderate COVID-19. Therapy within the first 3 days also led to a greater reduction in viral load compared to placebo and favorable outcomes in patients who are at high risk for progression of disease.

Clinical Features and Predisposing Factors Influencing the Outcome of COVID-19 in First and Second Wave at Nanded, Maharashtra- A Retrospective Study

Introduction: It is crucial to determine possible factors associated with exacerbation of the disease due to the alarming global spread, morbidity and mortality associated with Coronavirus Disease-2019 (COVID-19). It is important to determine the co-morbidities associated with this disease which will help in better treatment of patients in time and to make amendments to management policy. Aim: To compare the clinical features, and predisposing factors (socio-demographic factors and co-morbidities) influencing the outcome in COVID-19 infected patients admitted in a tertiary care centre in the first and second wave of COVID-19 pandemic. Materials and Methods: The retrospective study was conducted at the Department of Microbiology, Dr. Shankarrao Chavan Government Medical College, Nanded, Maharashtra, India. The data was collected from the electronic resource which was maintained by the institute Integrated Disease Surveillance Program (IDSP) health record reporting database for the duration of June 2020 to August 2021. This data included patient’s demographic details (age, sex, address, contact number), other details (history of close contacts, international travel) clinical history, different types of symptoms (ICMR patient category), co-morbidities, number of patients requiring ICU admission, type of sample, the outcome in terms of death and discharge, cause of death. The analysis was done for the complete data and then for two separate durations of the first and second wave which were compared later with Chi-square test (Bivariate analysis). Results: A total of 8841 patients were involved and the majority of patients in the study were between the age group of 30-75 years, there was a predominance of males in first and second waves with 6514 (73.7%) and 5795 (58.6%) respectively. The paediatric patients had a mortality rate of 100% (n=7) found in the second wave. Fever (39%) and dyspnea (22%) were found as the commonest presentation in both waves. Gastrointestinal manifestations were observed relatively more in the second wave. The serious patients on ventilator were found to have (>91%) the highest mortality. It appeared that the highest attributable risk to severity and mortality (eight to ten times increased) was due to hypertension, diabetes and other co-morbidities. Pregnancy did not predisposed to be as a risk factor. Conclusion: Prompt management and preventive care are needed for patients with co-morbidities to avoid the exacerbation of COVID-19 as well as drug cross interactions.

DISEASE ACTIVITY-GUIDED TAPERING of BIOLOGICS in PATIENTS with INFLAMMATORY ARTHRITIS: A RANDOMISED, OPEN-LABEL, EQUIVALENCE TRIAL

Background: Traditionally, biologics are maintained lifelong at standard dose in patients with infammatory arthritis (IA) when sustained low disease activity (LDA) is reached. However, evidence of possible tapering is emerging but data on the optimal approach is lacking. Objectives: The primary outcomes at 18 months follow-up are: Superiority: The proportion of patients reduced to ≤50% of their baseline biologic dose. Equivalence: Disease activity (rheumatoid arthritis [RA] and psoriatic arthritis [PsA]: Disease Activity Score28-C-Reactive Protein [DAS28-CRP] and axial spondyloarthritis [axSpA]: Ankylosing Spondylitis Disease Activity Score [ASDAS]). Methods: The BIODOPT trial was a randomised, open-label, equivalence trial (EudraCT 2017-001970-41). Eligible patients were adults with RA, PsA, or axSpA in LDA on stable biologic doses during ≥12 months. The randomisation ratio was 2:1 (tapering:continuation) stratifed by diagnosis, centre, and repeated biologic failures. In the tapering group, the biologic dosing interval was prolonged by 25% every four months until fare or discontinuation. The continuation group was kept on their baseline biologic dosing interval;however, a small increase was allowed (as usual practise) if requested by the patient. The sample size calculation was based on a pre-defned equivalence margin of ±0.5 disease activity points (<half of the minimal important difference in DAS28-CRP [>1.2] or ASDAS [>1.1]) yielding a power of 87% for 180 enrolled patients. All analyses were based on the intention-to-treat population. Continuous outcomes were analysed with repeated-measures linear mixed-effects models with group, diagnosis, centre, repeated biologic failures, time point, and the interaction between group and time as fxed factors and the baseline value of the relevant variable as a covariate. Categorical outcomes were analysed using logistic regression with missing data imputed as trial failures. Results: Between May, 2018, and March, 2020, 142 patients were enrolled of which 95 were randomised to tapering and 47 to continuation;inclusion was closed in April 2020 due to national implications of the coronavirus pandemic. At 18 months, signifcantly more patients in the tapering group (35 patients [(37%]) achieved a signifcant reduction in their biologic dose (≥50%) compared to the continuation group (one patient [2%]), absolute risk difference (RD) 35%, 95%CI: 24% to 45%, p<0.0001, Table 1. Furthermore, disease activity at 18 months was within the equivalence margins of ±0.5, mean difference between groups 0.08, 95%CI:-0.12 to 0.29;Table 1 and Figure 1. Flares were more frequent in the tapering group (39 [41%] vs 10 [21%], RD 0.20, 95%CI: 0.04 to 0.35, p=0.011) but managed with rescue therapy (e.g. biologic dose escalation or glucocorticoids) as only one patient (1%) in the tapering group and three patients (6%) in the continuation group lost therapeutic response and were switched to another biological agent. Conclusion: Across IA conditions, a signifcant reduction of biologic dose is possible with disease activity-guided tapering while maintaining a similar disease activity state compared to continuation of biologic as usual care.

COVID-19 VACCINE IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS

INTRODUCTION Patients with inflammatory bowel disease (IBD) may be more susceptible to certain infections including COVID-19. There are concerns regarding the safety and efficacy of the current available COVID-19 vaccines among IBD patients. The aim of this study is to perform a systematic review regarding the willingness of IBD patients to receive these types of vaccines, assess the reported adverse events and the efficacy of the vaccine among IBD patients. METHODS Medline, Embase, Scopus, Web of Science, and Cochrane databases were reviewed since inception till November 11th, 2021, by two independent reviewers. Relevant conference s were manually reviewed to identify additional studies. Studies that reported the willingness or rate of COVID vaccination, the adverse events, and/or efficacy of the COVID vaccine among IBD patients were included. Efficacy was defined as the ability of a vaccine to produce detectable antibodies. Meta-analysis was performed using a bivariate random-effects model. RESULTS 2049 studies were identified through database search and additional 10 conference s were extracted. 24 studies, with the majority (79%) from North America or Europe were included. Four studies reported the rate of adverse events of vaccines ranging from 39% to 74% after the first and second doses of vaccine, respectively. Pooled estimates of nine studies showed that only 59% of IBD patients (95% confidence interval (CI):39%-79%) were willing or had already received a vaccine. Pooled estimates of six studies showed the vaccine was 96% (95% CI: 92%-99%) effective in creating seroconversion in IBD patients. Three studies reported the incidence of break-through infection following COVID vaccination;The pooled estimates showed no statistically significant difference between the risk ratio of IBD patients versus healthy control (Risk difference:0.02 (95%CI: -0.02, 0.06), P-value:0.3). Mean values of antibody level were statistically significantly lower in IBD patients receiving immunosuppression compared with those who were not on immunosuppression (Standardized mean difference: -0.38 (95% CI: -0.58, -0.18), P-value:0.002). CONCLUSION COVID vaccines are protective against preventing COVID-19 infection in IBD patients. However, patients on immunosuppression may have reduced response and could benefit from a booster dose. More importantly, there should be more efforts in encouraging IBD patients towards vaccination. Additionally, is scarce data and further studies are required to assess the global effect of the COVID vaccine in IBD patients, particularly in underdeveloped countries. (Figure Presented)

Randomised trial of synthetic osmotic cervical dilator versus dinoprostone for labour induction

Background: Induction of labor is a commonly performed obstetric intervention. Vaginal prostaglandin E2 (dinoprostone) is the recommended first choice agent in the UK. Mechanical methods of induction are slower to achieve cervical ripening but have a lower risk of adverse effects. Objective: To compare the efficacy, maternal and neonatal safety, and maternal satisfaction of a synthetic osmotic cervical dilator (Dilapan-S) with vaginal prostaglandin E2 (dinoprostone) in cervical ripening for induction of labour. Design: Open-label, multicentre, superiority, randomised controlled trial in four UK National Health Service maternity units. Participants: Eligible participants were women ≥ 16 years of age undergoing induction of labour for a singleton pregnancy, ≥ 37 weeks' gestation with vertex presentation and intact membranes. The trial did not reach its planned sample size of 860 due to restrictions on research during the Covid-19 pandemic. Interventions: Women were randomly assigned to receive Dilapan-S or dinoprostone using a telephone randomisation system minimised by hospital, parity, BMI and maternal age. The induction agent was replaced as required until the cervix was assessed as favourable for labour. Main outcome measures: The primary outcome was failure to achieve vaginal delivery (i.e. caesarean delivery). Secondary outcome measures included maternal and neonatal adverse events. Analysis was by intention-to- treat, adjusting for design variables where possible. Results: Between 19 December 2017 and 26 January 2021, 674 women were enrolled: 337 were randomly assigned to Dilapan-S and 337 to dinoprostone (n = 337). The primary outcome was missing for two women in the dinoprostone group. Failure to achieve vaginal delivery (caesarean section) occurred in 126 women (37.4%) allocated to Dilapan-S, and 115 (34.3%) women allocated to dinoprostone (adjusted risk difference 0.02, 95% confidence interval -0.05 to 0.10). There were similar maternal and neonatal adverse events between the groups. Conclusions: Women undergoing induction of labour with Dilapan-S have similar rates of caesarean section and maternal and neonatal adverse events compared to dinoprostone.

Lowered COVID-19 mRNA vaccine antibody response in MS patientstreated with B-cell depleting and S1P-receptor-targeting therapies compared to controls: interim analysis

Objective: Assess the SARS-CoV2 Spike antibody response in multiple sclerosis (MS) patients on high efficacy immunotherapies. Background: There is limited knowledge about SARS-CoV2 mRNA vaccine response in MS patients on immunotherapy. Design/Methods: Patients with MS, aged 18-65, on fingolimod, siponimod, ofatumumab, or ocrelizumab for at least 3 months prior to first mRNA SARS-CoV2 vaccine (Pfizer or Moderna) were offered enrollment. A cohort of healthy controls who received the mRNA vaccines were also enrolled. Blood samples for the SARS-CoV2 Spike antibody (Anti-SARS-CoV2 S, RocheElecsys) were collected 2-3 months after the second mRNA vaccine. The proportion who seroconverted (antibody>0.4 U/ml), and SARS-CoV2 Spike antibody levels were assessed. Results: A total of 39 MS patients (6 fingolimod, 33 ocrelizumab) and 31 controls were included in this interim analysis. 33%(13/39) of MS patients seroconverted, compared to 100%(31/31) in the control group, with an estimated risk difference of -0.67,(95% confidence interval: -0.81, -0.52;Fisher's exact test, p=9.0∗10-10 ). There was no difference in seroconversion rates between MS patients who received the Pfizer (34%, 10/29) versus the Moderna vaccine (30%, 3/10) (95% confidence interval -0.38, 0.29;Fisher's exact test=1). Seroconversion was found in 100% (31/31) of controls, 66.7% (4/6) of fingolimod-treated patients, and 27.3% (9/33) of ocrelizumab-treated patients (three group comparison, Fisher's exact test p-value =2.7∗10 -10). The median Spike antibody level was <0.4 U/ml in MS patients, and 1,663 U/ml in controls (Wilcoxon rank sum test, p-value= 1.0∗10-12 ). The median Spike antibody level in the ocrelizumab group was <0.4 U/ml, 3.45 U/ml in the fingolimod group, and 1,663 U/ml in the control group (Kruskal Wallis test, p-value=5.9∗10-12 ). Total IgG correlated with Spike antibody levels in the ocrelizumab-treated group only (Spearman correlation, p=0.025). Conclusions: MS patients on ocrelizumab and fingolimod have significantly lower rates of seroconversion, and lower median Spike antibody levels in response to the mRNA SARS-CoV2 vaccines compared to controls.

INTRAMUSCULAR SOTROVIMAB IS NONINFERIOR to INTRAVENOUS SOTROVIMAB for COVID-19

Background: Sotrovimab is a pan-sarbecovirus neutralizing monoclonal antibody shown to be safe and effective for the treatment of early COVID-19 in high-risk patients and retains activity against variants of concern, including delta and omicron. To facilitate wider access to sotrovimab, it was formulated to allow for either intramuscular (IM) or intravenous (IV) administration. Methods: COMET-TAIL (NCT04913675) is a Phase III, randomized, multicenter, open-label, noninferiority (NI) study of IM vs IV sotrovimab for the treatment of mild/moderate COVID-19 in participants ≥12 years of age at high risk of disease progression. Participants were randomized to receive sotrovimab by single 500 mg IV infusion or IM injection (500 mg or 250 mg). The primary objective was to evaluate the efficacy of 500 mg IM vs 500 mg IV sotrovimab in preventing hospitalization for >24 hours for acute management of illness due to any cause or death. The 250 mg IM arm discontinued early due to a greater number of hospitalizations seen in that arm. A 3.5% NI margin on the risk difference scale was prespecified. Results: COMET-TAIL enrollment occurred from Jun-Aug 2021, coinciding with a surge in the SARS-CoV-2 delta variant in southern USA. The majority (∼85%) of participants were Hispanic or Latino and ∼25% were ≥65 years of age. In the 500 mg IM sotrovimab arm, 10/376 (2.7%) participants compared with 5/378 (1.3%) in the sotrovimab 500 mg IV arm met progression criteria for the primary endpoint (adjusted risk difference: 1.07% [95% CI:-1.25%, 3.39%]), meeting the NI margin of 3.5%. The overall rate of adverse events and injection/infusion-related reactions was low and similar between the 500 mg treatment arms. Most injection-site reactions were mild (grade 1), occurred shortly after dosing, and were limited in duration. Disease-related events (DREs) were balanced between the 500 mg IV and 500 mg IM arms. The most frequent DREs were COVID-19 pneumonia and pneumonia. There was a low percentage of participants (∼1%) with serious adverse events across all treatment arms, and none were considered related to treatment. Two participants (1 with BMI 69 mg/kg2 and an 82-year-old man) in the 500 mg IM arm died due to progression of COVID-19;no deaths occurred in the 500 mg IV arm. Conclusion: In the COMET-TAIL trial, sotrovimab given by 500 mg IM injection was found to be noninferior to IV infusion and was well tolerated. The option of IM administration will expand the potential for outpatient treatment with sotrovimab.

Myocarditis and/or pericarditis risk after mRNA COVID-19 vaccination: A Canadian head to head comparison of BNT162b2 and mRNA-1273 vaccines.

BACKGROUND: Canadian and international data suggest the risk of myocarditis and/or pericarditis is elevated during the week after mRNA COVID-19 vaccination, particularly in younger age groups, in males, and after second doses. OBJECTIVES: This article examines whether there is a product-specific difference in the risk for myocarditis and/or pericarditis between the two mRNA vaccines administered in Canada: BNT162b2 (Pfizer-BioNTech Comirnaty) and mRNA-1273 (Moderna Spikevax). MATERIALS AND METHODS: Reporting rates of myocarditis and/or pericarditis were calculated from reports received by the Canadian Adverse Events Following Immunization Surveillance System from December 2020-March 2022. Excess cases and attributable incidence among individuals aged 18-39 were estimated for each vaccine in comparison with background rates from 2015 to 2019. Head-to-head comparisons used Poisson regression, conditioned on week of vaccine administration, to estimate rate ratios for the week after mRNA-1273 vaccination versus the week after BNT162b2, by age and sex as well as overall. Analyses were restricted to May 30-March 13, 2021, when heightened media awareness was unlikely to have affected reporting rates for the two products differentially. RESULTS: In 18-29 year-old males who received a second dose of mRNA COVID-19 vaccine, attributable risk of myocarditis and/or pericarditis was found to be 5.69 (95% CI: 4.07 - 7.95; p < 0.001) times higher among mRNA-1273 recipients (n = 106) as compared to BNT162b2 recipients (n = 33). In the same group, Poisson regression modelling estimated that the risk of myocarditis and/or pericarditis was 4.72 (p-value = <0.001) times higher after mRNA-1723 compared to BNT162b2 vaccination. CONCLUSIONS: The risk of myocarditis and/or pericarditis is higher after mRNA-1723 vaccination than BNT162b2 vaccination in those aged 18-39 years, especially in males aged 18-29 years, where the risk is several times higher.