A point-of-care lateral flow assay for neutralising antibodies against SARS-CoV-2

As vaccines against SARS-CoV-2 are now being rolled out, a better understanding of immunity to the virus; whether through infection, or passive or active immunisation, and the durability of this protection is required. This will benefit from the ability to measure SARS-CoV-2 immunity, ideally with rapid turnaround and without the need for laboratory-based testing. Current rapid point-of-care (POC) tests measure antibodies (Ab) against the SARS-CoV-2 virus, however, these tests provide no information on whether the antibodies can neutralise virus infectivity and are potentially protective, especially against newly emerging variants of the virus. Neutralising Antibodies (NAb) are emerging as a strong correlate of protection, but most current NAb assays require many hours or days, samples of venous blood, and access to laboratory facilities, which is especially problematic in resource-limited settings. We have developed a lateral flow POC test that can measure levels of RBD-ACE2 neutralising antibodies from whole blood, with a result that can be determined by eye (semi-quantitative) or on a small instrument (quantitative), and results show high correlation with microneutralisation assays. This assay also provides a measure of total anti-RBD antibody, thereby providing evidence of exposure to SARS-CoV-2, regardless of whether NAb are present in the sample. By testing samples from immunised macaques, we demonstrate that this test is equally applicable for use with animal samples, and we show that this assay is readily adaptable to test for immunity to newly emerging SARS-CoV-2 variants. Accordingly, the COVID-19 NAb-test test described here can provide a rapid readout of immunity to SARS-CoV-2 at the point of care.

Understanding how Victoria, Australia gained control of its second COVID-19 wave

Victoria has been Australias hardest hit state by the COVID-19 pandemic, but was successful in reversing its second wave of infections through aggressive policy interventions. The clear reversal in the epidemic trajectory combined with information on the timing and geographical scope of policy interventions offers the opportunity to estimate the relative contribution of each change. We developed a compartmental model of the COVID-19 epidemic in Victoria that incorporated age and geographical structure, and calibrated it to data on case notifications, deaths and health service needs according to the administrative divisions of Victorias healthcare, termed clusters. We achieved a good fit to epidemiological indicators, at both the state level and for individual clusters, through a combination of time-varying processes that included changes to case detection rates, population mobility, school closures, seasonal forcing, physical distancing and use of face coverings. Estimates of the risk of hospitalisation and death among persons with disease that were needed to achieve this close fit were markedly higher than international estimates, likely reflecting the concentration of the epidemic in groups at particular risk of adverse outcomes, such as residential facilities. Otherwise, most fitted parameters were consistent with the existing literature on COVID-19 epidemiology and outcomes. We estimated a significant effect for each of the calibrated time-varying processes on reducing the risk of transmission per contact, with broad estimates of the reduction in transmission risk attributable to seasonal forcing (27.8%, 95% credible interval [95%CI] 9.26-44.7% for mid-summer compared to mid-winter), but narrower estimates for the individual-level effect of physical distancing of 12.5% (95%CI 5.69-27.9%) and of face coverings of 39.1% (95%CI 31.3-45.8%). That the multi-factorial public health interventions and mobility restrictions led to the dramatic reversal in the epidemic trajectory is supported by our model results, with the mandatory face coverings likely to have been particularly important.

Distinct systems serology features in children, elderly and COVID patients

SARS-CoV-2, the pandemic coronavirus that causes COVID-19, has infected millions worldwide, causing unparalleled social and economic disruptions. COVID-19 results in higher pathogenicity and mortality in the elderly compared to children. Examining baseline SARS-CoV-2 cross-reactive coronavirus immunological responses, induced by circulating human coronaviruses, is critical to understand such divergent clinical outcomes. The cross-reactivity of coronavirus antibody responses of healthy children (n=89), adults (n=98), elderly (n=57), and COVID-19 patients (n=19) were analysed by systems serology. While moderate levels of cross-reactive SARS-CoV-2 IgG, IgM, and IgA were detected in healthy individuals, we identified serological signatures associated with SARS-CoV-2 antigen-specific Fc{gamma} receptor binding, which accurately distinguished COVID-19 patients from healthy individuals and suggested that SARS-CoV-2 induces qualitative changes to antibody Fc upon infection, enhancing Fc{gamma} receptor engagement. Vastly different serological signatures were observed between healthy children and elderly, with markedly higher cross-reactive SARS-CoV-2 IgA and IgG observed in elderly, whereas children displayed elevated SARS-CoV-2 IgM, including receptor binding domain-specific IgM with higher avidity. These results suggest that less-experienced humoral immunity associated with higher IgM, as observed in children, may have the potential to induce more potent antibodies upon SARS-CoV-2 infection. These key insights will inform COVID-19 vaccination strategies, improved serological diagnostics and therapeutics.