Vaccination after recovery from COVID-19 affects nasal antibody levels

Introduction: Vaccines prevent severe disease, but to prevent viral transmission and lessen the risk of new variants emerging they need to also enhance mucosal protection. Intramuscular (IM) vaccines induce systemic antibody and appear to transiently reduce transmission, but their effect on nasal antibody in previously infected subjects has not been studied. Aim(s): To study durability of local and systemic antibody responses after COVID-19 in those subsequently vaccinated. Method(s): Nasal fluid and plasma were collected from 448 hospitalised COVID-19 cases during admission and convalescence via the ISARIC4C/PHOSP-COVID studies. IgA/G to wildtype SARS-CoV-2 S, NP and to receptor binding domain (RBD) of Delta and Omicron variants were measured by ELISA. Result(s): Nasal IgA/G anti-S/RBD responses appeared within 28 days and remained high for 1 year(figure 1). Plasma IgA/G responses to S also remained elevated at 1 year(P<0.001). 87% of those with complete data were vaccinated between 6-12 months after infection;when nasal and plasma anti-NP IgA/G waned, whilst anti-S/RBD responses to Delta and Omicron were maintained or increased. Conclusion(s): This is the first study to demonstrate that IM vaccination may boost nasal antibody 1 year after COVID19. This may explain why IM vaccination reduces transmission, adding to the evidence for booster vaccines in COVID-19 recoverees. (Figure Presented).

Cell-based high throughput screening to identify FDA/ EMA approved drugs that inhibit the endothelial pro-thrombotic switch during severe COVID19 infection

Background: A major complication of COVID19 is severe endothelial injury with micro-and macro-thrombotic disease in the lung and other organs. Several studies have identified high levels of inflammatory cytokines ( cytokine storm ), powerful activators of the endothelium, in plasma of severe COVID19 patients;indeed, COVID19 plasma was shown to activate endothelial cells (EC) in vitro. A consequence of EC activation is loss of anti-coagulant function, with release of pro-thrombotic Von Willebrand Factor (VWF). High levels of plasma VWF in severe COVID19 patients indicate systemic endothelial activation and increased risk of thrombosis. Aim(s): To identify drugs that decrease endothelial activation and VWF release, which may have a therapeutic impact in COVID19 patients. Method(s): We established an in vitro model of endothelial activation driven by 6 cytokines selected because of their high levels in COVID19 plasma. Cells were treated with the 6-cytokine cocktail for 24 hr;endothelial activation was confirmed by a panel of markers including ICAM1, measured by RT-qPCR and immunofluorescence (IF). Result(s): The treatment induced release of VWF and increased VWF-platelet string formation in a platelet flow-based assay. To identify drugs that blocked cytokine-induced VWF release, a high-throughput screening was carried out in human umbilical vein EC (HUVEC);VWF and ICAM1 expression were detected by IF;DAPI was used as nuclear stain. High content imaging screen of 3049 drugs from FDA/EMA-approved drug libraries identified drugs able to decrease VWF release following cytokine treatment. Top hits from several therapeutic classes including anti-inflammatory, anti-viral and hormones were taken forward for validation. Two hits were confirmed to inhibit cytokine-induced VWF release and VWF-platelet string formation. Selected findings were validated in lung microvascular EC. Conclusion(s): This study identified candidate drugs that reduce the enhanced VWF release caused by the cytokine storm typical of severe COVID19;these may be beneficial in the treatment of the pro-thrombotic risk in COVID19 patients.

Improving Access to Psychological Therapies (IAPT): the impact of service changes due to COVID-19 on people with learning disabilities

Purpose Primary care psychological interventions for people with common mental health problems in England are primarily delivered through Improving Access to Psychological Therapies (IAPT) services. People with learning disabilities within IAPT have poorer key clinical outcomes than people who do not identify as having a learning disability. During the global COVID-19 pandemic remote consultations have accounted for nearly 90% of all contacts in IAPT services;this paper aims to report the effects of these on outcomes for people with learning disabilities. Design/methodology/approach Publicly available national data from the COVID-affected period are compared to the most recent available comparison periods that are not during the COVID pandemic. Data are presented graphically. Findings People with learning disabilities differ little from those with no disabilities on several key process and outcome variables, although their clinical recovery is very much lower than those without disabilities. People with learning disabilities appear to have been affected by the changes in service delivery in a similar way to those without learning disabilities. Originality/value Despite the shift to predominantly remote therapy delivery, outcomes for people with learning disabilities have not been differentially affected compared to those who have no recorded disability. The potential to learn what has worked and not worked in the delivery of remote interventions for people with learning disabilities is highlighted.