Evaluation of the IgG antibody response to SARS CoV-2 infection and performance of a lateral flow immunoassay: cross-sectional and longitudinal analysis over 11 months

Abstract

To evaluate the dynamics and longevity of the humoral immune response to SARS-CoV-2 infection and assess the performance of professional use of the UK-RTC AbC-19 Rapid Test lateral flow immunoassay (LFIA) for the target condition of SARS-CoV-2 spike protein IgG antibodies.

Design

Nationwide serological study.

Setting

Northern Ireland, UK, May 2020–February 2021.

Participants

Plasma samples were collected from a diverse cohort of individuals from the general public (n=279), Northern Ireland healthcare workers (n=195), pre-pandemic blood donations and research studies (n=223) and through a convalescent plasma programme (n=183). Plasma donors (n=101) were followed with sequential samples over 11 months post-symptom onset.

Main outcome measures

SARS-CoV-2 antibody levels in plasma samples using Roche Elecsys Anti-SARS-CoV-2 IgG/IgA/IgM, Abbott SARS-CoV-2 IgG and EuroImmun IgG SARS-CoV-2 ELISA immunoassays over time. UK-RTC AbC-19 LFIA sensitivity and specificity, estimated using a three-reference standard system to establish a characterised panel of 330 positive and 488 negative SARS-CoV-2 IgG samples.

Results

We detected persistence of SARS-CoV-2 IgG antibodies for up to 10 months post-infection, across a minimum of two laboratory immunoassays. On the known positive cohort, the UK-RTC AbC-19 LFIA showed a sensitivity of 97.58% (95.28% to 98.95%) and on known negatives, showed specificity of 99.59% (98.53 % to 99.95%).

Conclusions

Through comprehensive analysis of a cohort of pre-pandemic and pandemic individuals, we show detectable levels of IgG antibodies, lasting over 46 weeks when assessed by EuroImmun ELISA, providing insight to antibody levels at later time points post-infection. We show good laboratory validation performance metrics for the AbC-19 rapid test for SARS-CoV-2 spike protein IgG antibody detection in a laboratory-based setting.

SciScore for 10.1101/2020.09.29.20201509: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Institutional Review Board Statement	Consent: All participants provided informed consent with no adverse events. IRB: Pre-pandemic samples (prior to June 2019, n=136) were obtained from Ulster University ethics committee approved studies with ongoing consent and from NIBTS (n= 200, more than 3 years old).
Randomization	not detected.
Blinding	not detected.
Power Analysis	not detected.
Sex as a biological variable	not detected.

Table 2: Resources

Antibodies
Sentences	Resources
To enrich the cohort for samples potentially positive for SARS-CoV-2 IgG antibody, further participants were invited if they had previously tested PCR positive or had the distinctive symptom of loss of taste and smell.	SARS-CoV-2 IgG suggeste…

SciScore for 10.1101/2020.09.29.20201509: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Institutional Review Board Statement	Consent: All participants provided informed consent with no adverse events. IRB: Pre-pandemic samples (prior to June 2019, n=136) were obtained from Ulster University ethics committee approved studies with ongoing consent and from NIBTS (n= 200, more than 3 years old).
Randomization	not detected.
Blinding	not detected.
Power Analysis	not detected.
Sex as a biological variable	not detected.

Table 2: Resources

Antibodies
Sentences	Resources
To enrich the cohort for samples potentially positive for SARS-CoV-2 IgG antibody, further participants were invited if they had previously tested PCR positive or had the distinctive symptom of loss of taste and smell.	SARS-CoV-2 IgG suggested: None
Software and Algorithms
Sentences	Resources
AbC-19 LFIA performance analyses were performed using MedCalc online (MedCalc Software, Ostend, Belgium).	MedCalc suggested: (MedCalc, RRID:SCR_015044)
All plots were generated via ggplot2 or custom functions using base R(12).	ggplot2 suggested: (ggplot2, RRID:SCR_014601)

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

The PHE analyses for each of these tests used previous infection (RT-PCR positive status) as a reference standard, the limitations of which are discussed above. In the use of characterised ‘known positive’ and ‘known negative’ cohorts, one limitation of this study is its potential for spectrum bias, whereby our positive-by-two reference system may artificially raise the threshold for positive sample inclusion, possibly resulting in the overestimation of the sensitivity of any test evaluated (27). However, similar issues have been raised when using previous RT-PCR result or definitive COVID-19 symptoms as inclusion criteria given these will likely skew a cohort towards more severe disease (5). Importantly, our mixed origin of samples forming the cohort provides a positive cohort for assessing assay sensitivity that includes individuals from the general public, healthcare workers and from convalescent plasma programmes. Our analysis of specificity on only pre-pandemic individuals (n=223) shows similar specificity (99.55%) to the larger mixed ‘known negative cohort’ (n=488, sensitivity 99.59%). In the absence of a clear gold standard test, our system relies on no single test (each with their individual shortcomings) and instead takes an average of three. Our assessment of the UK RTC AbC-19 LFIA using our characterised cohorts of known SARS-CoV-2 antibody positive and antibody negative plasma, in a laboratory setting shows good performance metrics for its ability to detect SARS-C...

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

Results from rtransparent:

Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
No protocol registration statement was detected.

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