This is how the antigen test and PCR differ

The antigen test detects SARS-CoV-2 proteins, the PCR its genetic information. In principle, both the sensitivity and the specificity of the antigen tests are lower than in the case of PCR. These are the main reasons:

  • During the PCR process, the nucleic acid sought is multiplied (amplified) many times, so that even low initial quantities ultimately lead to a really positive detection. Only a few virus copies are sufficient for this. No multiplication takes place during the antigen test; the amount of virus material in the starting material must be above a certain threshold for the test to be positive.
  • For this reason, possible weaknesses in sampling (smear depth, smear time) have a stronger effect on the antigen test than on the PCR.
  • The bond between antibody and antigen in the test system is also generally prone to cross-reactions: the antibodies prepared in the test sometimes bind unspecifically to similar antigens that are not specific for SARS-CoV-2. This increases the false positive rate compared to PCR.

 

The sample material is in common

Both test methods detect the pathogen directly and require a deep throat swab for this. In both cases, this swab material must also be transferred from the swab into an inactivation solution, from which we then carry out the following examination. The requirements of the Infection Protection Act and occupational health and safety measures must be complied with in all work steps for PCR and antigen detection.

 

How safe are negative results in comparison?

The viral load in the case of a SARS-CoV-2 infection runs like a bell curve over the period of several weeks: At the beginning there are few viruses in the respiratory tract, then the amount increases, reaches a maximum, gradually decreases again until it finally falls below the detection limit. So there are two points in time at which the corona virus load is measurable but low: At the beginning and at the end of the infection.

When we measure a sample in the laboratory, we usually don't know at what stage of the possible infection the smear was taken. A low-positive PCR result (CT value> 30) can therefore reflect the beginning or the end of the infection. An internal investigation in the Bioscientia Lab Ingelheim showed that the examined antigen tests showed samples with a Ct value of 30 and higher as negative. We report PCR samples up to a Ct value of 39 as positive because without further data on the patient it is not clear whether the low viral load indicates the beginning or end of the infection. So if it is important to always detect a weak viral load, we recommend SARS-CoV-2 detection with PCR.

In a recently published study at the Institute for Virology at the Berlin Charité, 7 different rapid antigen tests were compared. Despite the preliminary nature of the results, it is first recommended to confirm positive rapid test results with the PCR. Secondly, it was pointed out that because of their limited sensitivity, rapid antigen tests can be used as a snapshot of infectivity, but not for the reliable exclusion of an infection in asymptomatic persons ("Given the limitations of sensitivity, the results of AgPOCT should be understood as a momentary assessment of infectiousness rather than a diagnosis with power to exclude infection.").

A current RKI graphic shows very clearly how informative the antigen tests and the spread of the virus are related to a population group. In short: the higher the infection rate in a group of people tested, the lower the negative predictive value, i.e. the probability that a negative test result will be correct.


Conclusion

  • For patients with Covid symptoms, the rapid antigen test is a viable alternative to PCR when time is of the essence.
  • In a special laboratory, antigen tests hardly offer a time advantage because the time-consuming manual sample preparation is largely identical to the PCR.
  • In order to safely rule out SARS-CoV-2 infection in all stages of infection in asymptomatic people, PCR remains the gold standard. Because the risk of overlooking a real infection in the early stages is greater with all antigen tests.