Abstract Variants of SARS-CoV-2 may evade natural and vaccine induced immunity and monoclonal antibody immunotherapeutics. There is an urgent need to know how well antibodies, induced by healthy and Clinically Extremely Vulnerable (CEV) patients, will bind and thus help reduce transmission and severity of infection from variants of concern (VOC). This study determines the cross-reactive binding of serum antibodies obtained prior to and 28 days after a third vaccination in three cohorts; a health care worker cohort who received three doses of Pfizer-BioNtech (PPP), a cohort of CEV patients received two doses of the AstraZeneca-ChAdOx1-nCoV-19 (AAP) vaccine, followed by a third PFZ vaccine and a haemodialysis cohort that had a mixture of two AZ or PFZ vaccines followed by a PFZ booster. Six months post second vaccine there was evidence of antibody waning with 58.9% of individuals in the HD cohort seropositive against Wuhan, 34.4% Delta and 62.2% Omicron strains. For the AAP cohort, equivalent figures were 62.5%, 45.8% and 91.7% and the PPP cohort 92.2%, 90% and 91.1%. Post third dose vaccination there were universal increases in seropositivity and median optical density. For the HD cohort, 98.8% were seropositive to the Wuhan strain, 97.6% against Delta and 100% against Omicron strains. For the PPP and AAP cohorts, 100% were seropositive against all 3 strains. Lastly, we examined the WHO NIBSC 20/136 standard and there was no loss of antibody binding to either VOC. Similarly, a dilution series of Sotrovimab (GSK) found this therapeutic monoclonal antibody bound similarly to all VOC. Highlights IgG anti-SARS-CoV-2 Omicron spike glycoprotein antibody levels were high in 100% of health care workers (HCW), a general practice population considered clinically extremely vulnerable (CEV) and haemodialysis patients (HD) 4 weeks after a third SARS-CoV-2 vaccine dose (Pfizer-BioNtech-PFZ). For both Delta and Omicron variant spike glycoproteins these antibody levels were highest in the CEV cohort who had previously received two doses of AstraZeneca ChAdOx1 nCoV-19 vaccine (AAP), lower in HCW who had previously received two doses of PFZ (PPP) and lowest in HD who had a mix of vaccines for the first and second dose Prior to this third vaccine dose and 6 months post second vaccine dose there was evidence of significant waning of antibodies against VOC.
Clinicians with medical training work in an environment where randomised controlled trials (RCTs) overshadow other forms of medical evidence in informing clinical practice, policy and guidance. It is no surprise that clinical researchers tend towards RCTs, since they are considered the ‘gold standard’ of research, placed firmly at the top of traditional hierarchies of evidence. RCTs are grounded in a positivist paradigm, seeking to answer the question ‘does this intervention work?’ by generating and testing a hypothesis in order to propose or dispute a particular truth. This approach may work well for research about specific medical treatments or technologies, including drug treatments such as a new pain medication. However, it is limited when it comes to research that examines less well-circumscribed, complex interventions, such as pain management through a new clinic or play therapy. Furthermore, in the ‘real world’ of clinical practice, it is rarely possible to control the environment in which a healthcare intervention is delivered. In paediatrics, the nature of a child’s illness or ability to comply with medical treatments is multifactorial, depending on their medical condition and on other factors including their family dynamics, access to education, housing and mental health. Clinicians must take these into account when making skilled decisions about evidence-based medical …
ABSTRACT Genome sequencing is a powerful tool for identifying SARS-CoV-2 variant lineages, however there can be limitations due to sequence drop-out when used to identify specific key mutations. Recently, Thermo Fisher Scientific have developed genotyping assays to help bridge the gap between testing capacity and sequencing capability to generate real-time genotyping results based on specific variants. Over a 6-week period during the months of April and May 2021, we set out to assess the Thermo Fisher TaqMan Mutation Panel Genotyping Assay, initially for three mutations of concern and then an additional two mutations of concern, against SARS-CoV-2 positive clinical samples and the corresponding COG-UK sequencing data. We demonstrate that genotyping is a powerful in-depth technique for identifying specific mutations, an excellent complement to genome sequencing and has real clinical health value potential allowing laboratories to report and action variants of concern much quicker.
In rheumatoid arthritis (RA), the conventional therapies (first-line, second-line, third-line drugs) provide more or less effective symptomatic relief for a decade or so from the onset of the disease. However, the chronic inflammatory destructive processes involving connective tissue, cartilage and bone with their attendant disability progress relentlessly in majority of patients. Secondly, use of 'second-line' and 'third-line' drugs in RA are limited due to their side effects. Studies in animals and RA patients have confirmed that tumour necrosis factor-alpha (TNFalpha), an inflammatory cytokine, is of major importance in the rheumatoid disease process and thus, it might be an effective therapeutic target in RA. Animal model experiments and clinical trials were conducted with anti-TNFalpha monoclonal antibody (anti-TNFalpha MoAb) in RA recently. This anti-TNFalpha MoAb therapy was found to be both effective and safe which documented the coming-of-age of cytokine-based immunointervention in RA. Researchers are optimistic that modern medicine would certainly witness the application of this noble immunotherapy enabling to selectively target cytokines, e.g. TNFalpha, in RA as well as in other inflammatory autoimmune diseases in the near future.
Vaccination prevents severe morbidity and mortality from COVID-19 in the general population. The immunogenicity and efficacy of SARS-CoV-2 vaccines in patients with antibody deficiency is poorly understood.
Background There are many obstacles to contemporaneous record keeping following time-critical clinical events, which may lead to a delay in documentation. We postulated that such delays may create time for reflection that could influence the accuracy of recorded notes. Objective To observe whether a delay in documenting in patient notes and/or an opportunity to debrief affects the accuracy of note recording. Methodology University of Sheffield ethical approval was obtained. Final year Student doctors volunteered to participate in controlled simulated acute patient care scenarios. Standardised scenarios (anaphylaxis, cardiac arrest and sepsis) were chosen as appropriate to the level of learning. All scenarios took place in a formal simulation suite, set up as a general Hospital ward. Participants were split into three groups; each which followed a different approach to note keeping. Group 1 received no debrief/time for reflection and were required to make notes immediately after the critical event. Group 2 were debriefed immediately but recorded notes the following day. Group 3 were debriefed and made notes immediately following the event. Note keeping was limited to 10 minutes, with access to simulated patient records, in quiet environment without interruption. Scenarios were videoed, and the documented notes were subsequently scored for accuracy against the recorded events. This allowed for rating of each student’s performance to address any counfounding that could occur from using different groups with potentially different skills. Results Note keeping accuracy rates for Groups 1, 2 and 3 were 0.57, 0.63 and 0.69 respectively. Conclusion There is increased accuracy in patient note recording when the medical professional has the opportunity to immediately debrief and write up notes.