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Point-of-care serological assays for delayed SARS-CoV-2 case identification among health-care workers in the UK: a prospective multicentre cohort study.
Lancet Respir Med. 2020 09; 8(9):885-894.LR

Abstract

BACKGROUND

Health-care workers constitute a high-risk population for acquisition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Capacity for acute diagnosis via PCR testing was limited for individuals with mild to moderate SARS-CoV-2 infection in the early phase of the COVID-19 pandemic and a substantial proportion of health-care workers with suspected infection were not tested. We aimed to investigate the performance of point-of-care and laboratory serology assays and their utility in late case identification, and to estimate SARS-CoV-2 seroprevalence.

METHODS

We did a prospective multicentre cohort study between April 8 and June 12, 2020, in two phases. Symptomatic health-care workers with mild to moderate symptoms were eligible to participate 14 days after onset of COVID-19 symptoms, as per the Public Health England (PHE) case definition. Health-care workers were recruited to the asymptomatic cohort if they had not developed PHE-defined COVID-19 symptoms since Dec 1, 2019. In phase 1, two point-of-care lateral flow serological assays, the Onsite CTK Biotech COVID-19 split IgG/IgM Rapid Test (CTK Bitotech, Poway, CA, USA) and the Encode SARS-CoV-2 split IgM/IgG One Step Rapid Test Device (Zhuhai Encode Medical Engineering, Zhuhai, China), were evaluated for performance against a laboratory immunoassay (EDI Novel Coronavirus COVID-19 IgG ELISA kit [Epitope Diagnostics, San Diego, CA, USA]) in 300 samples from health-care workers and 100 pre-COVID-19 negative control samples. In phase 2 (n=6440), serosurveillance was done among 1299 (93·4%) of 1391 health-care workers reporting symptoms, and in a subset of asymptomatic health-care workers (405 [8·0%] of 5049).

FINDINGS

There was variation in test performance between the lateral flow serological assays; however, the Encode assay displayed reasonable IgG sensitivity (127 of 136; 93·4% [95% CI 87·8-96·9]) and specificity (99 of 100; 99·0% [94·6-100·0]) among PCR-proven cases and good agreement (282 of 300; 94·0% [91·3-96·7]) with the laboratory immunoassay. By contrast, the Onsite assay had reduced sensitivity (120 of 136; 88·2% [95% CI 81·6-93·1]) and specificity (94 of 100; 94·0% [87·4-97·8]) and agreement (254 of 300; 84·7% [80·6-88·7]). Five (7%) of 70 PCR-positive cases were negative across all assays. Late changes in lateral flow serological assay bands were recorded in 74 (9·3%) of 800 cassettes (35 [8·8%] of 400 Encode assays; 39 [9·8%] of 400 Onsite assays), but only seven (all Onsite assays) of these changes were concordant with the laboratory immunoassay. In phase 2, seroprevalence among the workforce was estimated to be 10·6% (95% CI 7·6-13·6) in asymptomatic health-care workers and 44·7% (42·0-47·4) in symptomatic health-care workers. Seroprevalence across the entire workforce was estimated at 18·0% (95% CI 17·0-18·9).

INTERPRETATION

Although a good positive predictive value was observed with both lateral flow serological assays and ELISA, this agreement only occurred if the pre-test probability was modified by a strict clinical case definition. Late development of lateral flow serological assay bands would preclude postal strategies and potentially home testing. Identification of false-negative results among health-care workers across all assays suggest caution in interpretation of IgG results at this stage; for now, testing is perhaps best delivered in a clinical setting, supported by government advice about physical distancing.

FUNDING

None.

Authors+Show Affiliations

Centre of Defence Pathology, Royal Centre for Defence Medicine, Queen Elizabeth Hospital Birmingham, Birmingham, UK; Chelsea and Westminster Hospital NHS Foundation Trust, London, UK. Electronic address: scott.pallett@nhs.net.Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.Chelsea and Westminster Hospital NHS Foundation Trust, London, UK; North West London Pathology, London, UK.Imperial College London, NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, London, UK.Department of Laboratory Medicine, Great Ormond Street Hospital for Children, London, UK.Department of Laboratory Medicine, Great Ormond Street Hospital for Children, London, UK.Department of Laboratory Medicine, Great Ormond Street Hospital for Children, London, UK.Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.North West London Pathology, London, UK.Chelsea and Westminster Hospital NHS Foundation Trust, London, UK; North West London Pathology, London, UK.Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.Chelsea and Westminster Hospital NHS Foundation Trust, London, UK; North West London Pathology, London, UK; Imperial College London, NIHR Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, London, UK.Chelsea and Westminster Hospital NHS Foundation Trust, London, UK.

Pub Type(s)

Clinical Trial
Journal Article
Multicenter Study

Language

eng

PubMed ID

32717210

Citation

Pallett, Scott J C., et al. "Point-of-care Serological Assays for Delayed SARS-CoV-2 Case Identification Among Health-care Workers in the UK: a Prospective Multicentre Cohort Study." The Lancet. Respiratory Medicine, vol. 8, no. 9, 2020, pp. 885-894.
Pallett SJC, Rayment M, Patel A, et al. Point-of-care serological assays for delayed SARS-CoV-2 case identification among health-care workers in the UK: a prospective multicentre cohort study. Lancet Respir Med. 2020;8(9):885-894.
Pallett, S. J. C., Rayment, M., Patel, A., Fitzgerald-Smith, S. A. M., Denny, S. J., Charani, E., Mai, A. L., Gilmour, K. C., Hatcher, J., Scott, C., Randell, P., Mughal, N., Jones, R., Moore, L. S. P., & Davies, G. W. (2020). Point-of-care serological assays for delayed SARS-CoV-2 case identification among health-care workers in the UK: a prospective multicentre cohort study. The Lancet. Respiratory Medicine, 8(9), 885-894. https://doi.org/10.1016/S2213-2600(20)30315-5
Pallett SJC, et al. Point-of-care Serological Assays for Delayed SARS-CoV-2 Case Identification Among Health-care Workers in the UK: a Prospective Multicentre Cohort Study. Lancet Respir Med. 2020;8(9):885-894. PubMed PMID: 32717210.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Point-of-care serological assays for delayed SARS-CoV-2 case identification among health-care workers in the UK: a prospective multicentre cohort study. AU - Pallett,Scott J C, AU - Rayment,Michael, AU - Patel,Aatish, AU - Fitzgerald-Smith,Sophia A M, AU - Denny,Sarah J, AU - Charani,Esmita, AU - Mai,Annabelle L, AU - Gilmour,Kimberly C, AU - Hatcher,James, AU - Scott,Christopher, AU - Randell,Paul, AU - Mughal,Nabeela, AU - Jones,Rachael, AU - Moore,Luke S P, AU - Davies,Gary W, Y1 - 2020/07/24/ PY - 2020/06/03/received PY - 2020/07/01/revised PY - 2020/07/02/accepted PY - 2020/7/28/pubmed PY - 2020/9/17/medline PY - 2020/7/28/entrez SP - 885 EP - 894 JF - The Lancet. Respiratory medicine JO - Lancet Respir Med VL - 8 IS - 9 N2 - BACKGROUND: Health-care workers constitute a high-risk population for acquisition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Capacity for acute diagnosis via PCR testing was limited for individuals with mild to moderate SARS-CoV-2 infection in the early phase of the COVID-19 pandemic and a substantial proportion of health-care workers with suspected infection were not tested. We aimed to investigate the performance of point-of-care and laboratory serology assays and their utility in late case identification, and to estimate SARS-CoV-2 seroprevalence. METHODS: We did a prospective multicentre cohort study between April 8 and June 12, 2020, in two phases. Symptomatic health-care workers with mild to moderate symptoms were eligible to participate 14 days after onset of COVID-19 symptoms, as per the Public Health England (PHE) case definition. Health-care workers were recruited to the asymptomatic cohort if they had not developed PHE-defined COVID-19 symptoms since Dec 1, 2019. In phase 1, two point-of-care lateral flow serological assays, the Onsite CTK Biotech COVID-19 split IgG/IgM Rapid Test (CTK Bitotech, Poway, CA, USA) and the Encode SARS-CoV-2 split IgM/IgG One Step Rapid Test Device (Zhuhai Encode Medical Engineering, Zhuhai, China), were evaluated for performance against a laboratory immunoassay (EDI Novel Coronavirus COVID-19 IgG ELISA kit [Epitope Diagnostics, San Diego, CA, USA]) in 300 samples from health-care workers and 100 pre-COVID-19 negative control samples. In phase 2 (n=6440), serosurveillance was done among 1299 (93·4%) of 1391 health-care workers reporting symptoms, and in a subset of asymptomatic health-care workers (405 [8·0%] of 5049). FINDINGS: There was variation in test performance between the lateral flow serological assays; however, the Encode assay displayed reasonable IgG sensitivity (127 of 136; 93·4% [95% CI 87·8-96·9]) and specificity (99 of 100; 99·0% [94·6-100·0]) among PCR-proven cases and good agreement (282 of 300; 94·0% [91·3-96·7]) with the laboratory immunoassay. By contrast, the Onsite assay had reduced sensitivity (120 of 136; 88·2% [95% CI 81·6-93·1]) and specificity (94 of 100; 94·0% [87·4-97·8]) and agreement (254 of 300; 84·7% [80·6-88·7]). Five (7%) of 70 PCR-positive cases were negative across all assays. Late changes in lateral flow serological assay bands were recorded in 74 (9·3%) of 800 cassettes (35 [8·8%] of 400 Encode assays; 39 [9·8%] of 400 Onsite assays), but only seven (all Onsite assays) of these changes were concordant with the laboratory immunoassay. In phase 2, seroprevalence among the workforce was estimated to be 10·6% (95% CI 7·6-13·6) in asymptomatic health-care workers and 44·7% (42·0-47·4) in symptomatic health-care workers. Seroprevalence across the entire workforce was estimated at 18·0% (95% CI 17·0-18·9). INTERPRETATION: Although a good positive predictive value was observed with both lateral flow serological assays and ELISA, this agreement only occurred if the pre-test probability was modified by a strict clinical case definition. Late development of lateral flow serological assay bands would preclude postal strategies and potentially home testing. Identification of false-negative results among health-care workers across all assays suggest caution in interpretation of IgG results at this stage; for now, testing is perhaps best delivered in a clinical setting, supported by government advice about physical distancing. FUNDING: None. SN - 2213-2619 UR - https://www.unboundmedicine.com/medline/citation/32717210/Point_of_care_serological_assays_for_delayed_SARS_CoV_2_case_identification_among_health_care_workers_in_the_UK:_a_prospective_multicentre_cohort_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2213-2600(20)30315-5 DB - PRIME DP - Unbound Medicine ER -