Update on influenza epidemiology and vaccines

COVID-19 pandemic mitigation measures, including travel restrictions, effectively limited global circulation of influenza viruses for much of 2020 and 2021. Travel bans and quarantine requirements were lifted on 1 November 2021 enabling recirculation of influenza. In Victoria, follow up of early influenza cases detected Dec-Feb revealed a history of travel or contact with a recent traveller. Cases were few during the Omicron epidemic in January-February. However, in late March, there was a sharp increase in cases, which in Victoria was associated with an outbreak in university residential colleges. Genomic sequencing supported a likely point-source outbreak that spread throughout the state and to other jurisdictions. In the Northern Territory and New South Wales circulation of A(H1N1)pdm09 preceded circulation of A(H3N2) and was associated with a high rate of paediatric hospitalisations. Both the A(H1N1)pdm09 and A(H3N2) viruses that circulated were well matched to the vaccine, but the early onset of the epidemic meant that many cases were infected prior to availability of vaccines in April. Nationally, circulation declined sharply in June-July coincident with another COVID-19 wave. Circulation of influenza may continue to be disrupted by SARS-CoV-2 epidemics until it establishes a seasonal pattern, which may impact seasonal influenza preparedness. Copyright © 2021

ASSESSING VACCINE EFFECTIVENESS in the REAL WORLD

The test-negative design has been used to estimate influenza vaccine effectiveness (VE) for many years and has more recently been employed for the estimation of COVID-19 VE. In these studies, patients meeting a pre-specified clinical case definition are tested for the disease of interest. Vaccine coverage is compared between those testing positive versus those testing negative to estimate VE. The key advantage of the test-negative design is cost-it can easily be incorporated into surveillance systems or applied to health management data if diagnostic and vaccination records are available. The design has been extensively validated for influenza but its adoption for COVID-19 has not always been accompanied by an assessment of its suitability to the data available. Blind application of the design may not overcome serious validity issues, especially when using administrative data. First, the test negative design reduces selection bias associated with differential health care-seeking behavior by vaccination status when patients are recruited based on clinical criteria thereby confirming they would have presented for testing when ill irrespective of vaccination. In studies where patients are tested for reasons other than symptoms, vaccine coverage in the test-negatives may not be representative of the source population. Second, the test-negative design should reduce outcome misclassification, because all participants are tested for the disease of interest. However, in the context of low prevalence or the use of less sensitive and less specific rapid antigen tests, the probability of misclassifying a case may increase. Third, test negative studies may be vulnerable to exposure misclassification, particularly when vaccination records must be linked to testing or case management records. Finally, test-negative studies cannot overcome the bias associated with confounding if relevant variables are unmeasured. For example, in a tiered vaccination framework, which prioritizes high-risk groups, information about vaccination eligibility is required for appropriate adjustment. The extent to which these biases might distort VE estimates will be explored using causal graphs and simulations. Rapid dissemination of COVID-19 VE estimates has been vital for ongoing pandemic management, but the speed with which estimates can be made should not come at the expense of validity.

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.

Constructing an ethical framework for priority allocation of pandemic vaccines.

BACKGROUND: Allocation of scarce resources during a pandemic extends to the allocation of vaccines when they eventually become available. We describe a framework for priority vaccine allocation that employed a cross-disciplinary approach, guided by ethical considerations and informed by local risk assessment. METHODS: Published and grey literature was reviewed, and augmented by consultation with key informants, to collate past experience, existing guidelines and emerging strategies for pandemic vaccine deployment. Identified ethical issues and decision-making processes were also included. Concurrently, simulation modelling studies estimated the likely impacts of alternative vaccine allocation approaches. Assembled evidence was presented to a workshop of national experts in pandemic preparedness, vaccine strategy, implementation and ethics. All of this evidence was then used to generate a proposed ethical framework for vaccine priorities best suited to the Australian context. FINDINGS: Published and emerging guidance for priority pandemic vaccine distribution differed widely with respect to strategic objectives, specification of target groups, and explicit discussion of ethical considerations and decision-making processes. Flexibility in response was universally emphasised, informed by real-time assessment of the pandemic impact level, and identification of disproportionately affected groups. Model outputs aided identification of vaccine approaches most likely to achieve overarching goals in pandemics of varying transmissibility and severity. Pandemic response aims deemed most relevant for an Australian framework were: creating and maintaining trust, promoting equity, and reducing harmful outcomes. INTERPRETATION: Defining clear and ethically-defendable objectives for pandemic response in context aids development of flexible and adaptive decision support frameworks and facilitates clear communication and engagement activities.