SARS-CoV-2 antigen rapid detection tests: test performance during the COVID-19 pandemic and the impact of COVID-19 vaccination

Abstract

Background: SARS-CoV-2 antigen rapid detection tests (RDTs) emerged as point-of-care diagnostics alongside reverse transcription polymerase chain reaction (RT-qPCR) as reference.

Methods: In a prospective performance assessment from 12 November 2020 to 30 June 2023 at a single centre tertiary care hospital, the sensitivity and specificity (primary endpoints) of RDTs from three manufacturers (NADAL®, Panbio™, MEDsan®) were compared to RT-qPCR as reference standard among patients, accompanying persons and staff aged ≥ six month in large-scale, clinical screening use. Regression models were used to assess influencing factors on RDT performance (secondary endpoints).

Findings: Among 78,798 paired RDT/RT-qPCR results analysed, overall RDT sensitivity was 34.5% (695/2016; 95% CI 32.4-36.6%), specificity 99.6% (76,503/76,782; 95% CI 99.6-99.7%). Over the pandemic course, sensitivity decreased in line with a lower rate of individuals showing typical COVID-19 symptoms. The lasso regression model showed that a higher viral load and typical COVID-19 symptoms were directly significantly correlated with the likelihood of a positive RDT result in SARS-CoV-2 infection, whereas age, sex, vaccination status, and the Omicron VOC were not.

Interpretation: The decline in RDT sensitivity throughout the pandemic can primarily be attributed to the reduced prevalence of symptomatic infections among vaccinated individuals and individuals infected with Omicron VOC. RDTs remain valuable for detecting SARS-CoV-2 in symptomatic individuals and offer potential for detecting other respiratory pathogens in the post-pandemic era, underscoring their importance in infection control efforts.

Funding: German Federal Ministry of Education and Research (BMBF), Free State of Bavaria, Bavarian State Ministry of Health and Care.

Keywords: COVID-19 symptoms; COVID-19 vaccination; SARS-CoV-2 rapid antigen detection test; Test performance; Viral load; Virus variants of concern.

Fig. 1

Schematic overview of data acquisition. HIS: hospital information system. RDT: Antigen rapid detection test. RT-qPCR: Quantitative reverse transcription-polymerase chain reaction. VOC: SARS-CoV-2 virus variant of concern.

Fig. 2

Enrolment of SARS-CoV-2 antigen rapid detection tests (RDTs), VOC: virus variant of concern, RDT: Antigen Rapid Detection Test, RT-qPCR: Quantitative reverse transcription-polymerase chain reaction.

Fig. 3

Characterisation of the study population. a) Age characterisation in categories of five years stratified by sex in reference to the German population (n = 78,798). b) COVID-19 vaccination status stratified by SARS-CoV-2 VOC among RT-qPCR positive samples (n = 2016). c) Viral load depending on days since symptom onset (n = 356). d) Distribution of viral load stratified by symptoms in absolute numbers among RT-qPCR positive samples (n = 2016). e) COVID-19 symptom status stratified by SARS-CoV-2 VOC among RT-qPCR positive samples (n = 2016). f) COVID-19 symptom status stratified by vaccination status among RT-qPCR positive samples (n = 2016). RDT: Antigen Rapid Detection Test. NA: no information available. Data source: Bayerisches Landesamt für Statistik, Robert Koch-Institut.^,

Fig. 4

RDT sensitivity, SARS-CoV-2 viral load, and Odds Ratios of RDT performance influencing factors. a) RDT sensitivity overall and by RDT performance influencing factors (n = 2016). b) Viral load overall and by RDT performance influencing factors (n = 2016; Mann-Whitney-U tests). c) Odds Ratio of the several RDT performance influencing factors (n = 1472; linear regression models: full model including all influencing factors selected by the lasso step, single models for each influencing factor (viral load, symptoms, Omicron VOC, vaccination status), models including relevant combinations of influencing factors (viral load and symptoms, vaccination status and viral load, vaccination status and symptoms)). In the case of whiskers in the figures, these represent the respective 95% confidence intervals. RDT: Antigen Rapid Detection Test, VOC: virus variant of concern.