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.

Longitudinal evaluation of laboratory-based serological assays for SARS-CoV-2 antibody detection.

Serological assays for SARS-CoV-2 infection are now widely available for use in diagnostic laboratories. Limited data are available on the performance characteristics in different settings, and at time periods remote from the initial infection. Validation of the Abbott (Architect SARS-CoV-2 IgG), DiaSorin (Liaison SARS-CoV-2 S1/S2 IgG) and Roche (Cobas Elecsys Anti-SARS-CoV-2) assays was undertaken utilising 217 serum samples from 131 participants up to 7 months following COVID-19 infection. The Abbott and DiaSorin assays were implemented into routine laboratory workflow, with outcomes reported for 2764 clinical specimens. Sensitivity and specificity were concordant with the range reported by the manufacturers for all assays. Sensitivity across the convalescent period was highest for the Roche at 95.2-100% (95% CI 81.0-100%), then the DiaSorin at 88.1-100% (95% CI 76.0-100%), followed by the Abbott 68.2-100% (95% CI 53.4-100%). Sensitivity of the Abbott assay fell from approximately 5 months; on this assay paired serum samples for 45 participants showed a significant drop in the signal-to-cut-off ratio and 10 sero-reversion events. When used in clinical practice, all samples testing positive by both DiaSorin and Abbott assays were confirmed as true positive results. In this low prevalence setting, despite high laboratory specificity, the positive predictive value of a single positive assay was low. Comprehensive validation of serological assays is necessary to determine the optimal assay for each diagnostic setting. In this low prevalence setting we found implementation of two assays with different antibody targets maximised sensitivity and specificity, with confirmatory testing necessary for any sample which was positive in only one assay.

Symptoms and laboratory manifestations of mild COVID-19 in a repatriated cruise ship cohort.

Much of our current understanding about novel coronavirus disease 2019 (COVID-19) comes from hospitalised patients. However, the spectrum of mild and subclinical disease has implications for population-level screening and control. Forty-nine participants were recruited from a group of 99 adults repatriated from a cruise ship with a high incidence of COVID-19. Respiratory and rectal swabs were tested by polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sera were tested for anti-SARS-CoV-2 antibodies by enzyme-linked immunosorbent assay (ELISA) and microneutralisation assay. Symptoms, viral shedding and antibody response were examined. Forty-five participants (92%) were considered cases based on either positive PCR or positive ELISA for immunoglobulin G. Forty-two percent of cases were asymptomatic. Only 15% of symptomatic cases reported fever. Serial respiratory and rectal swabs were positive for 10% and 5% of participants respectively about 3 weeks after median symptom onset. Cycle threshold values were high (range 31-45). Attempts to isolate live virus were unsuccessful. The presence of symptoms was not associated with demographics, comorbidities or antibody response. In closed settings, incidence of COVID-19 could be almost double that suggested by symptom-based screening. Serology may be useful in diagnosis of mild disease and in aiding public health investigations.