Core protocol for the adaptive Platform Trial In COVID-19 Vaccine priming and BOOsting (PICOBOO).

BACKGROUND: The need for coronavirus 2019 (COVID-19) vaccination in different age groups and populations is a subject of great uncertainty and an ongoing global debate. Critical knowledge gaps regarding COVID-19 vaccination include the duration of protection offered by different priming and booster vaccination regimens in different populations, including homologous or heterologous schedules; how vaccination impacts key elements of the immune system; how this is modified by prior or subsequent exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and future variants; and how immune responses correlate with protection against infection and disease, including antibodies and effector and T cell central memory. METHODS: The Platform Trial In COVID-19 priming and BOOsting (PICOBOO) is a multi-site, multi-arm, Bayesian, adaptive, randomised controlled platform trial. PICOBOO will expeditiously generate and translate high-quality evidence of the immunogenicity, reactogenicity and cross-protection of different COVID-19 priming and booster vaccination strategies against SARS-CoV-2 and its variants/subvariants, specific to the Australian context. While the platform is designed to be vaccine agnostic, participants will be randomised to one of three vaccines at trial commencement, including Pfizer's Comirnaty, Moderna's Spikevax or Novavax's Nuvaxovid COVID-19 vaccine. The protocol structure specifying PICOBOO is modular and hierarchical. Here, we describe the Core Protocol, which outlines the trial processes applicable to all study participants included in the platform trial. DISCUSSION: PICOBOO is the first adaptive platform trial evaluating different COVID-19 priming and booster vaccination strategies in Australia, and one of the few established internationally, that is designed to generate high-quality evidence to inform immunisation practice and policy. The modular, hierarchical protocol structure is intended to standardise outcomes, endpoints, data collection and other study processes for nested substudies included in the trial platform and to minimise duplication. It is anticipated that this flexible trial structure will enable investigators to respond with agility to new research questions as they arise, such as the utility of new vaccines (such as bivalent, or SARS-CoV-2 variant-specific vaccines) as they become available for use. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ACTRN12622000238774. Registered on 10 February 2022.

Immunocompromised children and young people are at no increased risk of severe COVID-19.

OBJECTIVES: We aimed to prospectively describe the incidence and clinical spectrum of SARS-CoV-2 infection in immunocompromised paediatric patients in the UK. METHODS: From March 2020 to 2021 weekly questionnaires were sent to immunocompromised paediatric patients or their parents. Information, including symptom presentation and SARS-CoV-2 PCR test results, was collected from 1527 participants from 46 hospitals. Cross-sectional serology was investigated in February and March 2021. RESULTS: Until the end of September 2020, no cases were reported. From September 28th 2020 to March 2021 a total of 38 PCR-detected SARS-CoV-2 infections were reported. Of these, four children were admitted to hospital but none had acute severe COVID-19. Increasing age in association with immunodeficiency increased reporting of SARS-CoV-2 infection. Worsening of fever, cough, and sore throat were associated with participants reporting SARS-CoV-2 infection. Serology data included 452 unvaccinated participants. In those reporting prior positive SARS-CoV-2 PCR, there were detectable antibodies in 9 of 18 (50%). In those with no prior report of infection, antibodies were detected in 32 of 434 (7•4%). CONCLUSIONS: This study shows SARS-CoV-2 infections have occurred in immunocompromised children and young people with no increased risk of severe disease. No children died.

Symptoms of COVID-19 and anxiety levels inadult patients receiving b-and ts-DMARDS using anonline reporting system

Background/AimsThe coronavirus disease-2019 (COVID-19) caused by the severe acuterespiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible forover 120, 000 UK deaths. Those with chronic inflammatory conditionsor receiving immunosuppressive medications are at higher risk ofCOVID-19 than the general population. As a result, rheumatologypatients taking b- or ts-DMARDs were advised to shield. We plannedto observe COVID-19 related symptoms and anxiety levels reported byrheumatology patients during the pandemic.MethodsFrom April 2020, 1, 004 rheumatology patients from an advancedtherapy database were invited to participate in the adultImmunoCOVID study to collect daily symptoms (fever, cough, shortness of breath (SOB), sore throat, blocked nose, red-eye, headache, fatigue, joint pain, muscle pain, chills, nausea, diarrhoeaand vomiting, loss of senses) and anxiety level using an online portal.Loss of senses were not recorded until week 7 as these were notofficially recognized at the pandemic onset.Results153 patients (rheumatoid arthritis, n = 75, psoriatic arthritis, n = 28, Axial spondyloarthropathy, n = 24, systemic lupus erythematosus, n = 2 and other connective tissue diseases, n = 24) consented andparticipated. By week 25, 142 patients remained. Among those, 36.57% (6.09%) (average (SD)) reported no symptoms over the 25week period. The main symptoms reported were joint pain(mean=47.94%) followed by fatigue (27.17%). Few patients reportedfever (0.94%), cough (8.34%), SOB (4.53%), or loss of senses (1.11%)with more symptoms reported during the first 8 weeks (April/May 2020)and another increase in September/October 2020. The anxiety score(pragmatic 10-point scale) mean (SD) was 5.60 (0.34) and remainedelevated throughout the study though higher when lockdown began.ConclusionDuring the first peak of SARS-CoV-2, the number of patients reportingCOVID-19 symptoms appeared high and was associated with highlevels of anxiety. As only a small number have been swab-tested, thismay suggest that larger numbers of untested individuals have hadCOVID-19 with mild symptoms. Features of inflammatory rheumaticillnesses may mimic COVID-19 symptoms and create diagnosticdifficulty (joint pain and fatigue) whilst anxiety may lead to overreporting of symptoms in the absence of infection. The key symptomsof fever, cough and SOB were less common and may be most reliable.