Clinical utility of targeted SARS-CoV-2 serology testing to aid the diagnosis and management of suspected missed, late or post-COVID-19 infection syndromes: Results from a pilot service implemented during the first pandemic wave

Abstract

During the first wave of the global COVID-19 pandemic the clinical utility and indications for SARS-CoV-2 serological testing were not clearly defined. The urgency to deploy serological assays required rapid evaluation of their performance characteristics. We undertook an internal validation of a CE marked lateral flow immunoassay (LFIA) (SureScreen Diagnostics) using serum from SARS-CoV-2 RNA positive individuals and pre-pandemic samples. This was followed by the delivery of a same-day named patient SARS-CoV-2 serology service using LFIA on vetted referrals at central London teaching hospital with clinical interpretation of result provided to the direct care team. Assay performance, source and nature of referrals, feasibility and clinical utility of the service, particularly benefit in clinical decision-making, were recorded. Sensitivity and specificity of LFIA were 96.1% and 99.3% respectively. 113 tests were performed on 108 participants during three-week pilot. 44% participants (n = 48) had detectable antibodies. Three main indications were identified for serological testing; new acute presentations potentially triggered by recent COVID-19 e.g. pulmonary embolism (n = 5), potential missed diagnoses in context of a recent COVID-19 compatible illness (n = 40), and making infection control or immunosuppression management decisions in persistently SARS-CoV-2 RNA PCR positive individuals (n = 6). We demonstrate acceptable performance characteristics, feasibility and clinical utility of using a LFIA that detects anti-spike antibodies to deliver SARS-CoV-2 serology service in adults and children. Greatest benefit was seen where there is reasonable pre-test probability and results can be linked with clinical advice or intervention. Experience from this pilot can help inform practicalities and benefits of rapidly implementing new tests such as LFIAs into clinical service as the pandemic evolves.

Fig 1. Comparative assessment of 168 serum samples from SARS-CoV-2-infected individuals by ELISA and lateral flow immunoassay.

168 serum samples from individuals with confirmed SARS-CoV-2 infection were tested for the presence of antibody by ELISA to the full spike (S), receptor binding domain (RBD) and nucleocapsid (N), and by SureScreen lateral flow immunoassay. Detection of IgG is shown in the top panel, and IgM in the bottom panel. Samples are arranged according to days post onset of symptoms, ranging from 14 to 40 days. Results are displayed as a heatmap, with white indicating a negative result, and gradations of orange indicating the magnitude of response detected.

Fig 2

a: Testing of samples that were pre-pandemic from patients with other infectious diseases and known confounders to estimate specificity of the SureScreen lateral flow immunoassay. b: Sensitivity estimates of SureScreen lateral flow immunoassay using serum samples obtained from SARS-CoV-2 PCR positive patients at greater than 14 and 20 days post reported onset of symptoms. POS = post onset of symptoms.

Fig 3. Referral characteristics and RNA results of individuals having SARS-CoV-2 serology testing performed during the pilot.