Analytical performances of the COVISTIX and Panbio antigen rapid tests for SARS-CoV-2 detection in an unselected population (all commers)

TLDR: In this paper, the authors evaluated the performance and validity of the COVISTIX™ rapid antigen test, for the detection of SARS-CoV-2 in an unselected population and compare it to Panbio™ Rapid Antigen Test and RT-PCR.

Abstract: Importance A steady increase in acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases worldwide is causing some regions of the world to withstand a third or even fourth wave of contagion. Swift detection of SARS-CoV-2 infection is paramount for the containment of cases, prevention of sustained contagion; and most importantly, for the reduction of mortality. Objective To evaluate the performance and validity of the COVISTIX™ rapid antigen test, for the detection of SARS-CoV-2 in an unselected population and compare it to Panbio™ rapid antigen test and RT-PCR. Design This is comparative effectiveness study; samples were collected at two point-of-care facilities in Mexico City between May and August 2021. Participants Recruited individuals were probable COVID-19 cases, either symptomatic or asymptomatic persons that were at risk of infection due to close contact to SARS-CoV-2 positive cases. Diagnostic intervention RT-PCR was used as gold standard for detection of SARS-CoV-2 in nasal and nasopharyngeal swabs, study subjects were tested in parallel either with the COVISTIX™ or with Panbio™ rapid antigen test. Main outcome Diagnostic performance of the COVISTIX™ assay is adequate in all commers since its accuracy parameters were not affected in samples collected after 7 days of symptom onset, and it detected almost 65% of samples with a Ct-value between 30 and 34. Results For the population tested with COVISTIX™ (n=783), specificity and sensitivity of the was 96.0% (CI95% 94.0-98.0) and 81% (CI95% 76.0-85.0), as for the Panbio™ (n=2202) population, was 99.0% (CI95%: 0.99-1.00) and 62% (CI%: 58.0-64.0%), respectively. Conclusions and relevance The COVISTIX™ rapid antigen test shows a high performance in all comers, thus, this test is also adequate for testing patients who have passed the peak of viral shedding or for asymptomatic patients.

Figures

Table 3. COVISTIXTM and PanbioTM results compared to RT- PCR (N = 783 and 2202 respectively) depending on the Ct-value.

Table 2. Results of PanbioTM SARS-CoV-2 antigen rapid test in swabs from 2202 individuals (all comers) compared to RT-PCR.

Table 1. Results of COVI-STIXTM SARS-CoV-2 antigen rapid test in swabs from 783 individuals (all commers) compared to RT-PCR.

Table 4. Overall performance of the COVISTIXTM rapid antigen test in symptomatic and asymptomatic individuals.

Full text

1
Analytical performances of the COVISTIX
TM
and Panbio
TM
antigen rapid tests for
SARS-CoV-2 detection in an unselected population (all commers).
Francisco Garcia-Cardenas
1
, Alba Franco
1
, Ricardo Cortés
1
, Jenny Bertin
2
, Rafael
Valdéz
2
, Fernando Peñaloza
1
, Emmanuel Frias-Jimenez
1
, Alberto Cedro-Tanda
1
, Alfredo
Mendoza-Vargas
1
, Juan Pablo Reyes-Grajeda
1
, Alfredo Hidalgo-Miranda
1
*, Luis A.
Herrera
1, 3
*
1
Instituto Nacional de Medicina Genómica, Mexico City, Mexico
2
Centro Citibanamex COVID, Mexico City, Mexico
3
Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología-
Instituto de Investigaciones Biomédicas, UNAM, Mexico City, Mexico.
*Corresponding authors:
Luis A. Herrera, Instituto Nacional de Medicina Genómica, Periférico Sur 4809, Arenal
Tepepan, C.P. 14610, Tlalpan, CDMX, México; e-mail: lherrera@inmegen.gob.mx
Alfredo Hidalgo, Instituto Nacional de Medicina Genómica, Periférico Sur 4809, Arenal
Tepepan, C.P. 14610, Tlalpan, CDMX, México; e-mail: ahidalgo@inmegen.gob.mx
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint
The copyright holder for thisthis version posted September 14, 2021. ; https://doi.org/10.1101/2021.09.10.21263410doi: medRxiv preprint
NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

2
Abstract
Importance: A steady increase in acute respiratory syndrome coronavirus 2 (SARS-CoV-
2) cases worldwide is causing some regions of the world to withstand a third or even
fourth wave of contagion. Swift detection of SARS-CoV-2 infection is paramount for the
containment of cases, prevention of sustained contagion; and most importantly, for the
reduction of mortality. Objective: To evaluate the performance and validity of the
COVISTIX
TM
rapid antigen test, for the detection of SARS-CoV-2 in an unselected
population and compare it to Panbio
TM
rapid antigen test and RT-PCR. Design: This is
comparative effectiveness study; samples were collected at two point-of-care facilities in
Mexico City between May and August 2021. Participants: Recruited individuals were
probable COVID-19 cases, either symptomatic or asymptomatic persons that were at risk
of infection due to close contact to SARS-CoV-2 positive cases. Diagnostic
intervention: RT-PCR was used as gold standard for detection of SARS-CoV-2 in nasal
and nasopharyngeal swabs, study subjects were tested in parallel either with the
COVISTIX
TM
or with Panbio
TM
rapid antigen test. Main outcome: Diagnostic performance
of the COVISTIX
TM
assay is adequate in all commers since its accuracy parameters were
not affected in samples collected after 7 days of symptom onset, and it detected almost
65% of samples with a Ct-value between 30 and 34. Results: For the population tested
with COVISTIX
TM
(n=783), specificity and sensitivity of the was 96.0% (CI95% 94.0-98.0)
and 81% (CI95% 76.0-85.0), as for the Panbio
TM
(n=2202) population, was 99.0%
(CI95%: 0.99-1.00) and 62% (CI%: 58.0-64.0%), respectively. Conclusions and
relevance: The COVISTIX
TM
rapid antigen test shows a high performance in all comers,
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint
The copyright holder for thisthis version posted September 14, 2021. ; https://doi.org/10.1101/2021.09.10.21263410doi: medRxiv preprint

3
thus, this test is also adequate for testing patients who have passed the peak of viral
shedding or for asymptomatic patients.
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint
The copyright holder for thisthis version posted September 14, 2021. ; https://doi.org/10.1101/2021.09.10.21263410doi: medRxiv preprint

4
Introduction
The Coronavirus Disease 2019 (COVID-19) pandemic has exerted unprecedented
effects on healthcare and economic systems globally. A steady increase in acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) cases worldwide is causing some
regions of the world to withstand a third or even fourth wave of contagion. (1,2) Swift
detection of SARS-CoV-2 infection is paramount for the containment of cases, prevention
of sustained contagion to return to economic and education activities; and most
importantly, for the reduction of mortality. (3,4)
Reverse transcription polymerase chain reaction (RT-PCR) is considered the gold
standard method for detecting SARS-CoV-2 infection due to its high sensitivity and
specificity (5,6). However, implementing RT-PCR testing in massive screening
campaigns requires specialized protective equipment, qualified personnel, and sample
transportation to a centralized laboratory, which has proven to be challenging, particularly
in resource-limited settings (2,7). As a result of these limitations, several rapid tests based
on SARS-CoV-2 antigen detection by immunochromatography have been introduced,
offering improved access to testing due to faster result availability, simple use at point-of-
care, and low costs. Rapid antigen tests represent an appealing alternative for large-scale
testing of the general population (8,9).
As an essential part of the public health response to the COVID-19 pandemic, Mexico
City’s government implemented a surveillance strategy intended to detect active cases
among the general population, which was initially based on RT-PCR. In November 2020,
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint
The copyright holder for thisthis version posted September 14, 2021. ; https://doi.org/10.1101/2021.09.10.21263410doi: medRxiv preprint

5
rapid antigen tests were also included in the strategy. According to data reported by
Mexico City’s Digital Agency of Public Innovation (ADIP), almost 1 million antigen tests
have been performed by the beginning of February 2021(10).
Although rapid technological advances in automated portable assays have allowed
testing to be performed outside laboratory ambiences, these technologies have not
shown a similar sensitivity compared to the efficient but highly consuming molecular
assays performed in laboratory settings, increasing the risk of false negative results
(11,12). Two inherent characteristics should be considered when considering which test
to use; sensitivity and specificity which provide information on the accuracy of the test to
measure the absence or presence of the disease. Nonetheless, the adequacy of a test in
a certain population is elucidated by the positive predictive value and negative predictive
value. These last measures vary depending on the true prevalence of the disease in a
population as they evaluate the probability that a person with a positive or negative test
result truly has or does not have the disease respectively. Thus, parameters such as the
likelihood ratio, which is not influenced by the prevalence, should be taken into
consideration in this pandemic since prevalence fluctuates across populations and over
time (9).
The World Health Organization (WHO) recognizes that although antigen tests have
proven lower sensitivity than molecular tests, they provide rapid and less resource-
consuming means of detection of SARS-CoV-2 in individuals who have high viral loads;
therefore, have higher risk of disease transmission (13). Currently, Mexico´s Institute of
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.(which was not certified by peer review)preprint
The copyright holder for thisthis version posted September 14, 2021. ; https://doi.org/10.1101/2021.09.10.21263410doi: medRxiv preprint

Frequently asked questions

Q1. What contributions have the authors mentioned in the paper "Analytical performances of the covistixtm and panbiotm antigen rapid tests for sars-cov-2 detection in an unselected population (all commers)" ?

It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 

Q2. What is the Ct-value for the COVISTIXTM rapid antigen test?

Ct-value is considered a surrogate parameter for viral load, the lower the Ct-value the higher the expected viral load, therefore the authors evaluated the performance of the COVISTIXTM rapid antigen test based on the RT-PCR Ct-value. 

Q3. How many subjects were tested for SARS-CoV-2?

A total of 783 subjects were included to evaluate the COVISTIXTM assay, 254 of which had a positive RT-PCR test (prevalence 32.4%). 

Q4. What is the main reason for the increase in cases of SARS?

A steady increase in acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases worldwide is causing some regions of the world to withstand a third or even fourth wave of contagion. 

Q5. How many people have been tested for SARS-CoV-2?

Samples from seven-hundred eighty-three individuals were collected at the Citibanamex COVID temporal unit and at INMEGEN, Mexico City between May 1st and August 16th, 2021; nasal and nasopharyngeal swabs were obtained and tested with the COVISTIXTM rapid antigen test according to manufacturer’s indications, as well as with RT-PCR. 

Q6. What are the characteristics of a rapid antigen test?

Two inherent characteristics should be considered when considering which test to use; sensitivity and specificity which provide information on the accuracy of the test to measure the absence or presence of the disease. 

Q7. What is the sensitivity of the COVISTIXTM rapid antigen test?

The algorithm implemented for testing with the COVISTIXTM rapid antigen test was to assess first a nasal swab, if negative, a second test was performed with a nasopharyngeal swab sample, if negative, the subject was considered as negative for SARS-CoV-2. 

Q8. What was the first strategy for detecting active cases?

As an essential part of the public health response to the COVID-19 pandemic, Mexico City’s government implemented a surveillance strategy intended to detect active cases among the general population, which was initially based on RT-PCR. 

Q9. What is the sensitivity of the panbio COVID-19 Ag rapid test device?

The sensitivity of this test has been directly correlated to the magnitude of viral load in nasopharyngeal region, which might exhibit inconsistencies in these populations due to the behavior of SARS-CoV-2 load in the upper respiratory tract owing to the viral load peak timing is uncertain in asymptomatic patients (16,17). 

Q10. What are the advantages of rapid antigen testing?

As a result of these limitations, several rapid tests based on SARS-CoV-2 antigen detection by immunochromatography have been introduced, offering improved access to testing due to faster result availability, simple use at point-ofcare, and low costs. 

Q11. What is the main reason for the need for a more sensitive antigen test?

the need for an economic yet precise testing strategy and a more sensitive antigen test that can rapidly detect lower viral loads at the very beginning of the disease or after 8 days after the start of the symptoms has emerged. 

Q12. How long does it take to get a positive result?

Another limitation of this test is that it shows major sensitivity within the first 5-7 days after symptom onset depending on the viral load in the specimen used for evaluation; notwithstanding those patients with COVID-19 can remain positive for 2-3 weeks after the commencement of symptoms (11,18). 

Q13. What was the sensitivity of the COVISTIXTM rapid antigen test?

Overall specificity and sensitivity of the COVISTIXTM rapid antigen test was 96% (CI95%: 94-98) and 81% (CI95%: 76-85), respectively. 

Q14. What is the sensitivity of the COVISTIXTM assay?

These results indicate that the COVISTIXTM assay is effective to detect not only highly infectious individuals but also those potentially carrying low viral loads. 

Q15. What are the different strategies for mitigating SARS-CoV-2?

Different strategies for mitigating contagion using antigen rapid device test have been proposed such as the use only in symptomatic patients within 5-7 days after symptom onset due that the viral load is at its peak.