key: cord-0736975-9deqh42t
authors: Beverland, Andrew; Keogan, Mary; Connell, Jeff; De Gascun, Cillian; Igoe, Derval
title: Longitudinal Serological Analysis following National Seroprevalence Study to Investigate COVID-19 Infection in People Living in Ireland
date: 2021-06-30
journal: J Infect Dis
DOI: 10.1093/infdis/jiab346
sha: c5ab73939be22e232d1fe19369d9fb76e7f7f51f
doc_id: 736975
cord_uid: 9deqh42t

nan

A c c e p t e d M a n u s c r i p t 2 | P a g e To the editor-We read with interest the article by Muecksch et al [1] reporting differences in SARS-CoV-2 serological assays during longitudinal surveillance, and calling for extended follow up. The authors reported declining antibody titres and sensitivity over time using the Abbott Architect SARS-COV-2 IgG anti-Nucleocapsid (N) assay, with an initial sensitivity >95%, decreasing to 71% approximately 3 months after diagnosis. Conversely, they reported that the sensitivity of the Roche Elecsys® anti-SARS-CoV-2 (N) assay was maintained, with increasing antibody titers demonstrated.

Similarly, two anti-Spike (S) assays studied, Siemens SARS-CoV-2 IgG/IgM & DiaSorin LIAISON® SARS-CoV-2 S1/S2 IgG, maintained their sensitivity and titres over the same period. Twenty-two of 33 participants (67%) with detectable anti-SARS -CoV-2 serology, identified in July 2020 (visit 1) in a national Irish seroprevalence study [2] , consented to participate. Serology was repeated at 3 months (visit 2, October 2020) & 6 months (visit 3, January 2021). Participants were encouraged to seek testing if they developed new symptoms or became a close contact and completed a questionnaire before each visit, inquiring about symptoms, exposures, and diagnostic tests in relation to SARS-CoV-2.

The median age of participants was 41.5 years (range 15-66), comprising 15 females and 7 males, with none requiring hospitalization. Prior to visit 1, most reported symptoms in April 2020; however, A c c e p t e d M a n u s c r i p t 3 | P a g e due to limited capacity and restricted testing criteria at that time, only 5 of 20 symptomatic participants had a SARS-CoV-2 RNA test performed, confirming their diagnosis. Two remaining participants reported no symptoms, close contacts, or prior tests. At 3 months, 11 participants (50%) reported ongoing symptoms, with fatigue being the most common (n=6), followed by myalgia and dyspnea (n=4 for each); by 6 months, only 7 (32%) reported ongoing symptoms, with fatigue remaining the most common. By 6 months, no participants reported vaccination or reinfection, with 14 negative SARS-CoV-2 RNA results, following 8 close contacts, 6 hospital screening tests, and one febrile episode. A c c e p t e d M a n u s c r i p t 4 | P a g e Interestingly one participant who reported 2 close contacts between visits 2 and 3, had a 2.5-fold increase in their Roche anti-(N) assay along with a 1.7-fold increase in their Roche anti-(S) result over the same period, suggesting boosting following exposure: however, they reported no new symptoms and had 2 negative SARS-CoV-2 PCR tests.

Our data, together with those described by Muecksh et al, provide vital information on assay performance, essential when selecting appropriate assays and interpreting results. Longitudinal assay evaluation, following initial assessment of sensitivity and specificity is necessary when temporally remote evidence of infection is sought, and here has shown divergence between 2 anti-(N) assays. Due to the significant under detection from as early as 3 months, the Abbott anti-(N) assay is unsuitable for seroprevalence studies. This is particularly relevant with investigators now seeking anti-(N) assays to differentiate natural infection from vaccine response, with anti-(S) assays alone, being insufficient [3] .

Potential conflicts of interest. The authors report no conflicts of interest.

Financial support. This work was supported by the Heath Service Executive (HSE) Ireland.

A c c e p t e d M a n u s c r i p t M a n u s c r i p t 6 | P a g e A c c e p t e d M a n u s c r i p t

Longitudinal Serological Analysis and Neutralizing Antibody Levels in Coronavirus Disease 2019 Convalescent Patients

Preliminary report of the results of the Study to Investigate COVID-19 Infection in People Living in Ireland (SCOPI): A national seroprevalence study

Identification of natural SARS-CoV-2 infection in seroprevalence studies among vaccinated populations. medRxiv : the preprint server for health sciences