The relationship between antigen concentration and the performance of diagnostic tests for SARS-CoV-2 on different specimen types


In a recent study published on medRxiv* server, a team of researchers investigated how antigen concentration and viral load in different sample types affected the performance of rapid diagnostic tests (RDTs) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 ).

Study: Antigen Concentration, Viral Load, and Test Performance for SARS-CoV-2 in Multiple Specimen Types. Image Credit: ilze kalve/Shutterstock

Background

Understanding antigen concentration and viral load dynamics in different specimen types can inform RDT performance across infection stages and coronavirus disease 2019 (COVID-19) use scenarios. These two variables, the concentration of nucleocapsid (N) antigen and viral loads vary between different types of samples and between individuals. Additionally, relative viral loads vary by SARS-CoV-2 variant and vaccination status.

Reverse transcriptase-polymerase chain reaction (RT-PCR) remains the gold standard for detection of SARS-CoV-2 in nasopharyngeal swab (NPS) specimens, regardless of specimen source for the index test. Antigen concentration in the sampled oral or nasal cavity and viral copies in NPS samples limited the comparison of the performance of TDR versus RT-PCR. Yet, the performance of RDTs was compared to that of RT-PCR during the early phases of the COVID-19 pandemic for regulatory purposes.

About the study

In the present study, researchers presented the results of baseline antigen concentration measurements on samples collected for a study conducted in Porto Velho, Brazil, in 2021 to determine correlations between antigen concentration and load. viral on the performance of RDTs.

The study included 214 contacts aged 12 and older and with different vaccination status, with recent exposures to confirmed cases of COVID-19. They measured antigen concentration in NPS, anterior nostril (ANS) swabs and saliva samples. Subsequently, they performed RT-PCR on the NPS and saliva samples. Likewise, they performed two RDTs on SNA samples and one on saliva samples.

Study results

The NPS antigen concentration corresponded to the NPS viral load and the saliva antigen concentration measured in the saliva samples was correlated to the cycle threshold (CJ) SalivaDirect test values. However, antigen concentrations in ANS and saliva samples did not correlate with viral load measured in NPS samples from the same study participants. The results confirmed higher antigen concentrations in symptomatic cases compared to asymptomatic and oligosymptomatic cases in all three specimen types. The overall lower antigen levels observed in saliva in this study suggest that currently used RATs are not sensitive enough to take advantage of this opportunity for early detection of SARS-CoV-2 infection.

The study population covered symptomatic, asymptomatic and oligosymptomatic cases. Likewise, the study samples had low viral loads and low antigen concentrations. Larger datasets of paired measurements of viral load and antigen concentration in different specimen types, variants, and different study populations may improve the ability to predict the performance of antigen detection tests in different scenarios and use cases.

This study showed that discrepant results are possible if the source of the sample for the RDT is different from the sample used to measure viral load by RT-PCR. Within a sample type, antigen concentration and antigen-based detection test performance can be related to viral load. Discordant results between RT-PCR on NPS samples and RDTs performed on ANS could therefore be attributable to antigen concentration values. These results also elucidate observed performance differences for SARS-CoV-2 assays on different specimen types.

conclusion

The current study has shown the value of understanding the underlying dynamics of antigen concentration and its relationship to viral load in different sample types to inform and predict the performance of RDTs in parameters, variants of the SARS-CoV-2 and use cases.

Saliva samples have lower antigen concentrations, so tests using saliva samples require greater analytical sensitivity to achieve clinical sensitivity comparable to nasal samples. The dynamics of antigens in different specimen types seen in SARS-CoV-2 disease progression support the use of RDTs in nasal specimens. In summary, the analytical detection limit of RDTs could help predict the performance of RDTs in populations for which the antigen concentration is known.

*Important Notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be considered conclusive, guide clinical practice/health-related behaviors, or treated as established information.

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