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

ABSTRACT

OBJECTIVEDetermine indications and clinical utility of SARS-CoV-2 serology testing in adults and children. DESIGNProspective evaluation of initial three weeks of a daily Monday to Friday pilot SARS-CoV-2 serology service for patients. SETTINGEarly post "first-wave" SARS-CoV-2 transmission period at single centre London teaching hospital that provides care to the local community, as well as regional and national referral pathways for specialist services. PARTICIPANTS110 (72 adults, 38 children, age range 0-83 years, 52.7% female (n=58)). INTERVENTIONSPatient serum from vetted referrals tested on CE marked and internally validated lateral flow immunoassay (LFIA) (SureScreen Diagnostics) detecting antibodies to SARS-CoV-2 spike proteins, with result and clinical interpretation provided to the direct care team. MAIN OUTCOME MEASURESPerformance characteristics, source and nature of referrals, feasibility and clinical utility of the service, particularly the benefit for clinical decision-making. RESULTSThe LFIA was deemed suitable for clinical advice and decision making following evaluation with 310 serum samples from SARS-CoV-2 PCR positive patients and 300 pre-pandemic samples, giving a sensitivity and specificity of 96.1% and 99.3% respectively. For the pilot, 115 referrals were received leading to 113 tests performed on 108 participants (sample not available for two participants); paediatrics (n=35), medicine (n=69), surgery (n=2) and general practice (n=2). 43.4% participants (n=49) had detectable antibodies to SARS-CoV-2. There were three main indications for serology; new acute presentations potentially triggered by recent COVID-19 infection e.g. PIMS-TS (n=26) and pulmonary embolism (n=5), potential missed diagnoses in context of a recent compatible illness (n=40), and making infection control and immunosuppression treatment decisions in persistently SARS-CoV-2 RNA PCR positive individuals (n=6). CONCLUSIONSThis study shows acceptable performance characteristics, feasibility and clinical utility of a SARS-CoV-2 serology service using a rapid, inexpensive and portable assay for adults and children presenting with a range of clinical indications. Results correlated closely with a confirmatory in-house ELISA. The study showed the benefit of introducing a serology service where there is a reasonable pre-test probability, and the result can be linked with clinical advice or intervention. Experience thus far is that the volume of requests from hospital referral routes are manageable within existing clinical and laboratory services; however, the demand from community referrals has not yet been assessed. Given recent evidence for a rapid decline in antibodies, particularly following mild infection, there is likely a limited window of opportunity to realise the benefit of serology testing for individuals infected during the "first-wave" before they potentially fall below a measurable threshold. Rapidly expanding availability of serology services for NHS patients will also help understand the long-term implications of serostatus and prior infection in different patient groups, particularly before emergence of any "second-wave" outbreak or introduction of a vaccination programme. SUMMARY BOXO_ST_ABSWHAT IS ALREADY KNOWN ON THIS TOPICC_ST_ABSThe mechanisms and utility of providing a SARS-CoV-2 (COVID-19) serology service is under evaluation. There are different technologies detecting antibodies against different SARS-CoV-2 proteins. Antibodies are known to appear from about 10 days after symptom onset but it is unclear how long they persist. WHAT THIS STUDY ADDSA SARS-CoV-2 serology service using a validated lateral flow immunoassay measuring antibodies against spike protein can be rapidly introduced with clinical benefit demonstrated for a broad range of individuals. Indications include missed diagnoses where COVID-19 infection has been suspected but SARS-COV-2 RNA tests were either negative or not performed, conditions potentially triggered by COVID-19 such as pulmonary embolism, and predicting infectivity or immunity in patients with persistently detectable SARS-CoV-2 RNA. Testing is quick, simple to perform and inexpensive, however emerging evidence that antibodies fall rapidly particularly in mild disease, and the observed breadth of emerging indications highlight the urgent need for targeted testing with clinical interpretation provided on a case-by-case basis.