Diagnosis value of SARS-CoV-2 antigen/antibody combined testing using rapid diagnostic tests at hospital admission

Abstract

The implementation of rapid diagnostic tests (RDTs) may enhance the efficiency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing, as RDTs are widely accessible and easy to use. The aim of this study was to evaluate the performance of a diagnosis strategy based on a combination of antigen and immunoglobulin M (IgM) or immunoglobulin G (IgG) serological RDTs. Plasma and nasopharyngeal samples were collected between 14 March and 11 April 2020 at hospital admission from 45 patients with reverse transcription polymerase chain reaction (RT-PCR) confirmed COVID-19 and 20 negative controls. SARS-CoV-2 antigen (Ag) was assessed in nasopharyngeal swabs using the Coris Respi-Strip. For IgM/IgG detection, SureScreen Diagnostics and Szybio Biotech RDTs were used in addition to laboratory assays (Abbott Alinity i SARS-CoV-2 IgG and Theradiag COVID-19 IgM enzyme-linked immunosorbent assay). Using the Ag RDT, 13 out of 45 (29.0%) specimens tested positive, the sensitivity was 87.0% for cycle threshold (C_t ) values ≤25% and 0% for C_t values greater than 25. IgG detection was associated with high C_t values and the amount of time after the onset of symptoms. The profile of isolated IgM on RDTs was more frequently observed during the first and second week after the onset of symptoms. The combination of Ag and IgM/IgG RDTs enabled the detection of up to 84.0% of COVID-19 confirmed cases at hospital admission. Antigen and antibody-based RDTs showed suboptimal performances when used alone. However when used in combination, they are able to identify most COVID-19 patients admitted in an emergency department.

Keywords: SARS-CoV-2 antibody; SARS-CoV-2 antigen; coronavirus disease-19 (COVID-19); diagnosis; rapid diagnostic tests.

Figure 1

Coris coronavirus disease 2019 (COVID‐19) Ag Respi‐Strip results according to reverse transcription polymerase chain reaction (RT‐PCR) cyclic threshold (C _t) values. C _t values recorded by RT‐PCR methods Allple 2019‐nCoV Assay Seegene. The boxes represent interquartile ranges with the horizontal line indicating the median C _t value and the whiskers showing minimal and maximal C _t values. The p value (two‐tailed) was calculated using the Mann–Whitney U test, and compares the median of C _t values in samples with positive antigenic diagnosis tests versus negative results. Patients tested positive for Coris COVID‐19 antigen had lower C _t values

Figure 2

Anti‐SARS‐CoV‐2 immunoglobulin M (IgM) detection using rapid serological diagnosis tests and ELISA according to RT‐PCR C _t values. C _t values recorded by RT‐PCR methods Allplex 2019‐nCoV Assay Seegene. The boxes represent interquartile ranges with the horizontal line indicating the median C _t value and the whiskers showing minimal and maximal C _t values. The p value (two‐tailed) was calculated using the Mann–Whitney U test, and compares the median of C _t values in samples with positive IgM serological diagnosis tests versus negative results. Patients tested positive for anti‐SARS‐CoV‐2 IgM had higher C _t values regardless of the test used. C _t, cyclic threshold; ELISA, enzyme‐linked immunosorbent assay; RT‐PCR, reverse transciption polymease chain reaction; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2

Figure 3

Anti‐SARS‐CoV‐2 immunoglobulin G (IgG) detection using rapid serological diagnosis tests and chemoluminescence immunoassay according to RT‐PCR C _t values. C _t values recorded by RT‐PCR methods Allplex 2019‐nCoV Assay Seegene. The boxes represent interquartile ranges with the horizontal line indicating the median C _t value and the whiskers showing minimal and maximal C _t values. The p value (two‐tailed) was calculated using the Mann–Whitney U test, and compares the median of C _t values in samples with positive IgG serological diagnosis tests versus negative results. Patients tested positive for anti‐SARS‐CoV‐2 IgG had higher C _t values regardless of the test used. C _t, cycle threshold; RT‐PCR, reverse transcription polymerase chain reaction; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2

Figure 4

Performances of diagnostic strategies combining antigen and serological rapid diagnostic tests (RDTs) at hospital admission in patients with COVID‐19 confirmed by RT‐PCR. The diagnostic test results correspond to the proportion of patients with COVID‐19 detected by RDTs. The p value (two‐tailed) was calculated using the Exact binomial's test and compares the performances of a combination of antigen and serological RDTs versus antigen and serological RDTs use alone. COVID‐19, coronavirus disease 2019; RT‐PCR, reverse transcription polymerase chain reaction

Figure 5

Variation over time in biological markers for COVID‐19 diagnosis. High viral load (RT‐PCR) C _t value less than 25 and antigen detection in nasopharyngeal specimens characterize the first week after the onset of symptoms when the risk of SARS‐CoV‐2 transmission is at its maximum. The second week of COVID‐19 infection is the period when the absence of detectable Ag and IgM/IgG is the most probable. The eclipse phase of antigen/IgM/IgG combined RDTs is most likely observable during this time period. A low level or the absence of SARS‐CoV‐2 RNA alongside IgG and IgM detection is observed two weeks after the onset of symptoms in most patients. COVID‐19, coronavirus disease 2019; C _t, cycle threshold; IgG, immunoglobulin G; IgM, immunoglobulin M; RT‐PCR, reverse transcription polymerase chain reaction; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2