ABSTRACT
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.
ABSTRACT
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. .
ABSTRACT
Prior literature suggests that computer science education (CSE) was less affected by the pandemic than other disciplines. However, it is unclear how the pandemic affected the quality and quantity of students' studying in CSE. We measure the impact of the pandemic on the amount and spacing of students' studying in a large introductory computer science course. Spacing is defined as the distribution of studying over multiple sessions, which is shown to improve long-term learning. Using multiple regression models, we analyzed the total number of students' interactions with the eBook and the number of days they used it, as a proxy for studying amount and spacing, respectively. We compared two sequential winter semesters of the course, one during (Winter 2021) and one prior to the pandemic (Winter 2020). After controlling for possible confounders, the results show that students had 1,345.87 fewer eBook interactions and distributed their studying on 2.36 fewer days during the pandemic when compared to the previous semester prior to the pandemic. We also compared four semesters prior to the pandemic (Fall and Winter of 2018 and 2019) to two semesters during the pandemic (Fall 2020 and Winter 2021). We found, on average, students had 3,376.30 fewer interactions with the eBook and studied the eBook on 16.35 fewer days during the pandemic. Contrary to prior studies, our results indicate that the pandemic negatively affected the amount and spacing of studying in an introductory computer science course, which may have a negative impact on their education. © 2022 ACM.
ABSTRACT
Background: We have little knowledge about public opinion on death and dying in the UK. Previous studies have focused on specific groups e.g. older people or those with life limiting conditions. This paper presents deliberative discussion groups as a novel methodology for investigating the topic which proved adaptable to online data collection following Covid-19 restrictions. Aim: To engage the UK public in discussion about death and dying. Method: Deliberative discussion groups of different topics over four sessions with a range of members of the public. Participants were provided with information resources prior to each meeting as a spur to thought and differing perspectives. Five individual interviews were also undertaken with participants who were unable to attend groups. A thematic approach to analysis was used. Results: Seven discussion groups and five individual interviews involving 41 participants (men n=9/women n=32, age range 30-81yrs). Discussion: We identified three key areas of methodological learning: 1) Recruitment to online groups allowed wider geographical reach and opened contact with sections of the population that would not otherwise have been available e.g. those usually at work. However, the constraints of Covid-19 reduced our ability to recruit by making direct contact with some groups, such as ethnic minorities and younger age groups. 2) Deliberative discussions were an effective way to build rapport among participants and encourage detailed consideration of key topics. Feedback from participants was overwhelmingly positive. 3) Moving to online data collection proved to be feasible, with scheduling made easier, more convenient and cost effective. There were some technical issues, but participants generally considered it to be a convenient way to participate. The online format worked best with smaller groups and shorter sessions, and also without presentation of interactive resources during the discussion.
ABSTRACT
Since the emergence of COVID-19, caused by the SARS-CoV-2 virus at the end of 2019, there has been an explosion of vaccine development. By 24 September 2020, a staggering number of vaccines (more than 200) had started preclinical development, of which 43 had entered clinical trials, including some approaches that have not previously been licensed for human vaccines. Vaccines have been widely considered as part of the exit strategy to enable the return to previous patterns of working, schooling and socializing. Importantly, to effectively control the COVID-19 pandemic, production needs to be scaled-up from a small number of preclinical doses to enough filled vials to immunize the world's population, which requires close engagement with manufacturers and regulators. It will require a global effort to control the virus, necessitating equitable access for all countries to effective vaccines. This review explores the immune responses required to protect against SARS-CoV-2 and the potential for vaccine-induced immunopathology. We describe the profile of the different platforms and the advantages and disadvantages of each approach. The review also addresses the critical steps between promising preclinical leads and manufacturing at scale. The issues faced during this pandemic and the platforms being developed to address it will be invaluable for future outbreak control. Nine months after the outbreak began we are at a point where preclinical and early clinical data are being generated for the vaccines; an overview of this important area will help our understanding of the next phases.