Self assessment overestimates historical COVID-19 disease relative to sensitive serological assays: cross sectional study in UK key workers

Objective

To measure the association between self-reported signs and symptoms and SARS-CoV-2 seropositivity.

Design

Cross-sectional study of three key worker groups.

Setting

Six acute NHS hospitals and two Police and Fire and Rescue sites in England.

Participants

Individuals were recruited from three streams: (A) Police and Fire and Rescue services (n = 1147), (B) healthcare workers (n = 1546) and (C) healthcare workers with previously positive virus detection (n = 154).

Main outcome measures

Detection of anti-SARS-CoV-2 antibodies in plasma.

Results

943 of the 2847 participants (33%) reported belief they had had COVID-19, having experienced compatible symptoms (including 152 from Stream C). Among individuals reporting COVID-19 compatible symptoms, 466 (49%) were seronegative on both Nucleoprotein (Roche) and Spike-protein (EUROIMMUN) antibody assays. However, among the 268 individuals with prior positive SARS-CoV-2 tests, of whom 96% reported symptoms with onset a median of 63 days (IQR 52 – 75 days) prior to venesection, Roche and EUROIMMUN assays had 96.6% (95% CI 93.7% – 98.2%) and 93.3% (95% CI 89.6% – 95.7%) sensitivity respectively. Symptomatic but seronegative individuals had significantly earlier symptom onset dates than the symptomatic seropositive individuals, shorter illness duration and a much lower anosmia reporting frequency.

Conclusions

Self-reported belief of COVID-19 was common among our frontline worker cohort. About half of these individuals were seronegative, despite a high sensitivity of serology in this cohort, at least in individuals with previous positive PCR results. This is compatible with non-COVID-19 respiratory disease during the COVID-19 outbreak having been commonly mistaken for COVID-19 within the key worker cohort studied.

What is already known on this topic

Screening for SARS-CoV-2 antibodies is under way in some key worker groups; however, how this adds to self-reported COVID-19 illness is unclear. There are limited studies that investigate the association between self-reported belief of COVID-19 illness and seropositivity.

What this study adds

About one third of a large cohort of key frontline workers believed they had had COVID-19 infection. In around half of these there was no serological evidence of infection. Individuals who believed they had previous infection, but were seronegative, differed systematically from the seropositive individuals: disordered sense of taste and smell was less common, illness duration was shorter, and reported onset of illness commonly predated the main COVID-19 epidemic in the UK.

Although some individuals with previous COVID-19 may be seronegative, among symptomatic individuals who had PCR-confirmed SARS-CoV-2 within our cohort, sensitivity of the two immunoassays used (Roche Elecsys ® and EUROIMMUN) exceeded 90%. Together, these data indicate that many key workers may falsely believe, based on symptomatic illness experienced during 2020, that they have had COVID-19. Further research investigating the relationship between antibody detection and protection from future infection, with and without a history of COVID-19 disease, will help define the role serological testing can play in clinical practice.