Detection of neutralising antibodies to SARS-CoV-2 to determine population exposure in Scottish blood donors between March and May 2020
Craig P Thompson, Nicholas E Grayson , Robert S Paton , Jai S Bolton , José Lourenço , Bridget S Penman5, Lian N Lee, Valerie Odon , Juthathip Mongkolsapaya , Senthil Chinnakannan , Wanwisa Dejnirattisai , Matthew Edmans, Alex Fyfe , Carol Imlach , Kreepa Kooblall , Nicholas Lim , Chang Liu , César López-Camacho , Carol McInally , Anna L McNaughton, Narayan Ramamurthy , Jeremy Ratcliff , Piyada Supasa , Oliver Sampson , Beibei Wang , Alexander J Mentzer, Marc Turner, Malcolm G Semple, Kenneth Baillie , ISARIC4C Investigators, Heli Harvala , Gavin R Screaton, Nigel Temperton, Paul Klenerman , Lisa M Jarvis, Sunetra Gupta, Peter Simmonds
Background The progression and geographical distribution of SARS coronavirus 2 (SARS-CoV-2) infection in the UK and elsewhere is unknown because typically only symptomatic individuals are diagnosed. We performed a serological study of blood donors in Scotland between the 17th of March and the 18th of May to detect neutralising antibodies to SARS-CoV-2 as a marker of past infection and epidemic progression.
Aim To determine if sera from blood bank donors can be used to track the emergence and progression of the SARS-CoV-2 epidemic.
Methods A pseudotyped SARS-CoV-2 virus microneutralisation assay was used to detect neutralising antibodies to SARS-CoV-2. The study group comprised samples from 3,500 blood donors collected in Scotland between the 17th of March and 19th of May, 2020. Controls were collected from 100 donors in Scotland during 2019.
Results All samples collected on the 17th March, 2020 (n=500) were negative in the pseudotyped SARS-CoV-2 virus microneutralisation assay. Neutralising antibodies were detected in 6/500 donors from the 23th-26th of March. The number of samples containing neutralising antibodies did not significantly rise after the 5th-6th April until the end of the study on the 18th of May. We find that infections are concentrated in certain postcodes indicating that outbreaks of infection are extremely localised. In contrast, other areas remain comparatively untouched by the epidemic.
Conclusion These data indicate that sero-surveys of blood banks can serve as a useful tool for tracking the emergence and progression of an epidemic like the current SARS-CoV-2 outbreak.
SARS coronavirus 2 (SARS-CoV-2) emerged in late 2019 in Hubei province China as a cause of respiratory disease occasionally leading to acute respiratory distress syndrome and death (COVID-19) (1,2). On the 11th of March, the WHO declared the SARS-CoV-2 outbreak a pandemic. As of July 2020, roughly 10 million confirmed cases of COVID-19 have occurred resulting in 500,000 deaths (3). Increasing age, male gender, smoking and comorbidities such as cardiac disease, hypertension and diabetes have been identified as risk factors for severe infections (4,5).
Symptomatic individuals typically exhibit fever, cough and shortness of breath 2-14 days after infection (6). However, an unknown proportion of individuals experience no symptoms (7–9). Antibody responses in both symptomatic and asymptomatic individuals are detectable in the blood 14 to 28 days after infection (10,11). Subsequently antibody levels drop and can become undetectable by some antibody assays in the early convalescent phase (10,12,13)
In this study, we follow blood donors as a means of estimating population exposure from the start of the pandemic in March through to mid-May when PCR-detected cases in the UK had plateaued (14,15). Samples from donors in an age range of 18-75 years collected across Scotland were assayed for neutralising antibody to SARS-CoV-2 using a pseudotyped SARS-CoV-2 virus microneutralisation (pMN) assay used previously for SARS-CoV and Ebola virus seroepidemiology purposes (16–18). The sensitivity of the neutralisation assay was confirmed using an enzyme-immunosorbant (ELISA) assay detecting antibodies to spike protein. The detection frequency of neutralising antibodies in blood donors and a discussion of its applicability for estimating population level exposure are presented.
1. Patient Research for Public Health
2. Diagnostic and Host Response