Enhanced surveillance of COVID-19 in Scotland: population-based seroprevalence surveillance for SARS-CoV-2 during the first wave of the epidemic

This work was funded by the Scottish Government.Objectives: The impact of the COVID-19 pandemic in Scotland has been amongst the most severe in Europe. Serological surveillance is critical to determine the overall extent of infection across populations and to inform the public health response. This study aimed to estimate the proportion of people who have antibodies to SARS-CoV-2 ('seroprevalence') in the general population of Scotland and to see if this changes over time. Study Design/Methods: Between International Organization for Standardization (ISO) week 17 (i.e. week commencing 20th April) and ISO week 25 (week commencing 15 June), 4751 residual blood samples were obtained from regional biochemistry laboratories in six participating regional health authority areas covering approximately 75% of the Scottish population. Samples were tested for the presence of anti-SARS-CoV-2 IgG antibodies using the LIAISON®SARS-CoV-2 S1/S2 IgG assay (DiaSorin, Italy). Seroprevalence rates were adjusted for the sensitivity and specificity of the assay using Bayesian methods. Results: The combined adjusted seroprevalence across the study period was 4.3% (95% confidence interval: 4.2%-4.5%). The proportion varied each week between 1.9% and 6.8% with no difference in antibody positivity by age, sex or geographical area. Conclusions: At the end of the first wave of the COVID-19 pandemic, only a small fraction of the Scottish population had antibodies to SARS-CoV-2. Control of COVID-19 requires the ability to detect asymptomatic and mild infections that would otherwise remain undetected through existing surveillance systems. This is important to determine the true number of infections within the general population which, in turn, can help to understand transmission, inform control measures and provide a denominator for the estimation of severity measures such as the proportion of infected people who have been hospitalised and/or have died.PostprintPeer reviewe

Comparison of SARS-CoV-2 serological assays for use in epidemiological surveillance in Scotland

Background: Sero-surveillance of SARS-CoV-2 is crucial to monitoring levels of population exposure and informing public health responses, but may be influenced by variability in performance between available assays. Methods: Five commercial immunoassays and a neutralising activity assay were used to detect antibodies to SARS-CoV-2 in routine primary care and paediatric samples collected during the first wave of the pandemic in NHS Lothian, Scotland as part of ongoing surveillance efforts. For each assay, sensitivity and specificity was calculated relative to consensus results (majority of immunoassays positive = overall positive) and neutralising activity. Quantitative correlation was performed between serological and neutralising titres. Results: Seroprevalence ranged from 3.4–7.3 % in primary care patients and 3–5.9 % in paediatric patients according to different immunoassays. Neutralising activity was detectable in 2.8 % and 1.3 % respectively. Relative assay performance changed depending on comparison to immunoassay consensus versus neutralising activity and qualititative versus quantitative agreement. Cross-reactivity with endemic seasonal coronaviruses was confirmed by neutralising assay in false positives for one immunoassay. Presence of false positives for another assay was found specifically in paediatric but not adult samples. Conclusions: Five serological assays show variable accuracy when applied to the general population, impacting seroprevalence estimates. Assay performance may also vary in detection of protective neutralising antibody levels. These aspects should be considered in assay selection and interpretation in epidemiological studies

Longitudinal variation in SARS-CoV-2 antibody levels and emergence of viral variants:a serological analysis

BACKGROUND: Serological assays are being used to monitor antibody responses in individuals who had SARS-CoV-2 infection and those who received a COVID-19 vaccine. We aimed to determine whether such assays can predict neutralising antibody titres as antibody levels wane and viral variants emerge. METHODS: We measured antibody levels in serum samples from a cohort of 112 participants with SARS-CoV-2 infection using ten high-throughput serological tests and functional neutralisation assays. Serum samples were taken at baseline and at up to four subsequent visits. We assessed the effects of time and spike protein sequence variation on the performance and predictive value of the various assays. We did correlation analyses for individual timepoints using non-parametric Spearman correlation, and differences between timepoints were determined by use of a two-tailed Wilcoxon matched-pairs signed rank test. FINDINGS: Neutralising antibody titres decreased over the first few months post-infection but stabilised thereafter, at about 30% of the level observed shortly after infection. Serological assays commonly used to measure antibodies against SARS-CoV-2 displayed a range of sensitivities that declined to varying extents over time. Quantitative measurements generated by serological assays based on the spike protein were better at predicting neutralising antibody titres than those based on nucleocapsid, but performance was variable, and manufacturer positivity thresholds were not able to predict the presence or absence of detectable neutralising activity. Although we observed some deterioration in correlation between serological measurements and functional neutralisation activity, some assays maintained an ability to predict neutralising titres, even against variants of concern. INTERPRETATION: The ability of high-throughput serological assays to predict neutralising antibody titres is likely to be crucial for evaluation of immunity at the population scale. These data can facilitate the selection of the most suitable assays as surrogates of functional neutralising activity and suggest that such measurements might be useful in clinical practice. FUNDING: US National Institutes of Health and National Health Service Research Scotland BioResource

Tick-borne diseases under the radar in the North Sea Region

The impact of tick-borne diseases caused by pathogens such as Anaplasma phagocytophilum, Neoehrlichia mikur-ensis, Borrelia miyamotoi, Rickettsia helvetica and Babesia species on public health is largely unknown. Data on the prevalence of these pathogens in Ixodes ricinus ticks from seven countries within the North Sea Region in Europe as well as the types and availability of diagnostic tests and the main clinical features of their corresponding diseases is reported and discussed. Raised awareness is needed to discover cases of these under-recognized types of tick-borne disease, which should provide valuable insights into these diseases and their clinical significance.Funding Agencies|European Union through the European Regional Development Fund; Interreg North Sea Region Program 2014-2020 as a part of the NorthTick project [38-2-7-19]</p