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

Abstract

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 to 75 days) prior to venesection, Roche and EUROIMMUN assays had 96.6% (95% CI 93.7% to 98.2%) and 93.3% (95% CI 89.6% to 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.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

The study was funded by Public Health England and supported by the NIHR Clinical Research Network (CRN) Portfolio.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was approved by NHS Research Ethics Committee (Health Research Authority, IRAS 284980) on 02/06/2020 and PHE Research Ethics and Governance Group (REGG, NR0198) on 21/05/2020.

All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

Yes

Data Availability

All data is stored securely on a secure PHE server. Data is available on reasonable request via PHE’s Office of Data Release (ODR).

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