SEROLOGICAL TESTING OF BLOOD DONORS TO CHARACTERISE THE IMPACT OF COVID-19 IN MELBOURNE, AUSTRALIA, 2020 (preprint)

Rapidly identifying and isolating people with acute SARS-CoV-2 infection has been a core strategy to contain COVID-19 in Australia, but a proportion of infections go undetected. We estimated SARS-CoV-2 specific antibody prevalence (seroprevalence) among blood donors in metropolitan Melbourne following a COVID-19 outbreak in the city between June and September 2020. The aim was to determine the extent of infection spread and whether seroprevalence varied demographically in proportion to reported cases of infection. The design involved stratified sampling of residual specimens from blood donors (aged 20-69 years) in three postcode groups defined by low (<3 cases/1,000 population), medium (3{-}{-}-7 cases/1,000 population) and high (>7 cases/1,000 population) COVID-19 incidence based on case notification data. All specimens were tested using the Wantai SARS-CoV-2 total antibody assay. Seroprevalence was estimated with adjustment for test sensitivity and specificity for the Melbourne metropolitan blood donor and residential populations, using multilevel regression and poststratification. Overall, 4,799 specimens were collected between 23 November and 17 December 2020. Seroprevalence for blood donors was 0.87% (90% credible interval: 0.25-1.49%). The highest estimates, of 1.13% (0.25-2.15%) and 1.11% (0.28-1.95%), respectively, were observed among donors living in the lowest socioeconomic areas (Quintiles 1 and 2) and lowest at 0.69% (0.14-1.39%) among donors living in the highest socioeconomic areas (Quintile 5). When extrapolated to the Melbourne residential population, overall seroprevalence was 0.90% (0.26-1.51%), with estimates by demography groups similar to those for the blood donors. The results suggest a lack of extensive community transmission and good COVID-19 case ascertainment based on routine testing during Victorias second epidemic wave. Residual blood donor samples provide a practical epidemiological tool for estimating seroprevalence and information on population patterns of infection, against which the effectiveness of ongoing responses to the pandemic can be assessed.

SARS-CoV-2 neutralizing antibodies; longevity, breadth, and evasion by emerging viral variants (preprint)

The SARS-CoV-2 antibody neutralization response and its evasion by emerging viral variants are unknown. Antibody immunoreactivity against SARS-CoV-2 antigens and Spike variants, inhibition of Spike-driven virus-cell fusion, and infectious SARS-CoV-2 neutralization were characterized in 807 serial samples from 233 RT-PCR-confirmed COVID-19 individuals with detailed demographics and followed up to seven months. A broad and sustained polyantigenic immunoreactivity against SARS-CoV-2 Spike, Membrane, and Nucleocapsid proteins, along with high viral neutralization were associated with COVID-19 severity. A subgroup of high responders maintained high neutralizing responses over time, representing ideal convalescent plasma therapy donors. Antibodies generated against SARS-CoV-2 during the first COVID-19 wave had reduced immunoreactivity and neutralization potency to emerging Spike variants. Accurate monitoring of SARS-CoV-2 antibody responses would be essential for selection of optimal plasma donors and vaccine monitoring and design.

SARS Coronavirus-2 microneutralisation and commercial serological assays correlated closely for some but not all enzyme immunoassays (preprint)

BackgroundSerological testing for SARS-CoV-2 specific antibodies provides important research and diagnostic information relating to COVID-19 prevalence, incidence, and host immune response. A greater understanding of the relationship between functionally neutralising antibodies detected using microneutralisation assays and binding antibodies detected using scalable enzyme immunoassays (EIA) is needed in order to address protective immunity post-infection or vaccination, and assess EIA suitability as a surrogate test for screening of convalescent plasma donors. We assessed whether neutralising antibody titres correlated with signal cut-off ratios in five commercially available EIAs, and one in-house assay based on expressed spike protein targets. MethodsSera from individuals recovered from patients or convalescent plasma donors who reported laboratory-confirmed SARS-CoV-2 infection (n=200), and negative control sera collected prior to the COVID-19 pandemic (n=100) were assessed in parallel. Performance was assessed by calculating EIA sensitivity and specificity with reference to microneutralisation. ResultsNeutralising antibodies were detected in 166 (83%) samples. Compared with this, the most sensitive EIAs were the Cobas Elecsys Anti-SARS-CoV-2 (98%) and Vitros Immunodiagnostic Anti-SARS-CoV-2 (100%), which detect total antibody targeting the N and S1 antigens, respectively. The assay with the best quantitative relationship with microneutralisation was the Euroimmun IgG. ConclusionsThese results suggest the marker used (total Ab vs IgG vs IgA), and the target antigen are important determinants of assay performance. The strong correlation between microneutralisation and some commercially available assays demonstrate their potential for clinical and research use in assessing protection following infection or vaccination, and use as a surrogate test to assess donor suitability for convalescent plasma donation.