Prevalence of antibody positivity to SARS-CoV-2 following the first peak of infection in England: Serial cross-sectional studies of 365,000 adults

Abstract

Background: The time-concentrated nature of the first wave of the COVID-19 epidemic in England in March and April 2020 provides a natural experiment to measure changes in antibody positivity at the population level before onset of the second wave and initiation of the vaccination programme.

Methods: Three cross-sectional national surveys with non-overlapping random samples of the population in England undertaken between late June and September 2020 (REACT-2 study). 365,104 adults completed questionnaires and self-administered lateral flow immunoassay (LFIA) tests for IgG against SARS-CoV-2.

Findings: Overall, 17,576 people had detectable antibodies, a prevalence of 4.9% (95% confidence intervals 4.9, 5.0) when adjusted for test characteristics and weighted to the adult population of England. The prevalence declined from 6.0% (5.8, 6.1), to 4.8% (4.7, 5.0) and 4.4% (4.3, 4.5), over the three rounds of the study a difference of -26.5% (-29.0, -23.8). The highest prevalence and smallest overall decline in positivity was in the youngest age group (18-24 years) at -14.9% (-21.6, -8.1), and lowest prevalence and largest decline in the oldest group (>74 years) at -39.0% (-50.8, -27.2). The decline from June to September 2020 was largest in those who did not report a history of COVID-19 at -64.0% (-75.6, -52.3), compared to -22.3% (-27.0, -17.7) in those with SARS-CoV-2 infection confirmed on PCR.

Interpretation: A large proportion of the population remained susceptible to SARS-CoV-2 infection in England based on naturally acquired immunity from the first wave. Widespread vaccination is needed to confer immunity and control the epidemic at population level.

Funding: This work was funded by the Department of Health and Social Care in England.

Fig. 1

Prevalence of antibody positivity to SARS-CoV-2 using LFIA test, by round of study (95% confidence intervals) by sex, age group, ethnicity, employment, history of COVID-19, symptom severity. Legend: Dates: Round 1 (20 June – 13 July 2020), Round 2 (31 July–13 August 2020), Round 3 (15–28 September 2020). Bars show antibody positivity by round of study for each category of covariate with 95% confidence intervals indicated in the error bars. NB: y axis scale is different for each row. All estimates of prevalence (95% confidence intervals) are adjusted for imperfect test sensitivity and specificity, and re-weighted to account for sample design and for variation in response rate (age, sex, ethnicity, region and deprivation) to be representative of the England population (18+). Full data shown in Supplementary Table S3.

Fig. 2

Epidemic curve reconstructed from reported date of onset from 11,908 IgG antibody positive people who reported symptoms, by round of study¹. Legend: Seven-day rolling average of number of infections (by day of onset) in 11,908 participants testing positive for antibodies and who reported a date of onset for symptoms of COVID19, shown separately for each round. 3,759 symptomatic cases were recorded in round 1 (from 99,908 tested); 3,363 were recorded in round 2 (from 105,829 tested); and 4,786 were recorded in round 3 (from 159,367 tested). ¹ See Table 1 for dates of rounds.

Fig. 3

Association of LFIA result with virus micro-neutralisation titre in 49 healthcare workers with RT-PCR-confirmed SARS-CoV-2 infection. Legend: Virus micro-neutralisation titre, log scale y-axis, by LFIA results, x-axis, in 49 healthcare workers with RT-PCR confirmed SARS-CoV-2 infection. Serum samples were assayed by live virus neutralisation assay and tested by Fortress LFIA. The median for those with a negative test (n=9) was less than 10 (lower limit of detection denoted by dotted line), and for those with a positive test (n=40) it was 1:40. Mann-Whitney test z-score =3.68, two-sided P= 0.00024. LFIA (lateral flow immunoassay).