An interesting article by Murad and others in the Journal of Clinical Microbiology assessed both methods.

Clinical lab testing plays a central role in the management of this ongoing pandemic caused by SARS-CoV-2.  

At its most basic level, it is important to be able to reliably detect those who are acutely infected with the virus in order to provide care.  

Detection of viral RNA by means of the PCR based assay has proved to be a robust strategy.  

By targeting the multiple regions of the viral genome, a high level of specificity for SARS-CoV-2 can be attained.  

Furthermore, it is estimated that many PCR based assays can detect as few as 1800 copies per ml of the virus, making this the current gold standard for testing.  All alternative SARS-CoV-2 diagnostic tools are compared to the PCR.  

However, as impressive as PCR assays are, they have limitations such as:

  1. From a technical perspective, PCR relies on multiple amplifications of nucleic acid targets.  
  2. This requires trained personnel and instruments that are primarily found only in centralised clinical laboratories.  
  3. Implementation of SARS-CoV-2 PCR diagnostic aids in point of care settings has been challenging and almost unfeasible for home based testing.  

The clinical nature of SARS-CoV-2 infection also imposes additional restrictions.  

PCR can most effectively diagnose patients that have been infected by SARS-CoV-2 when they are actively shedding the virus or viral components.  

This estimated 7 to 10 day window of opportunity usually begins two days before patients become symptomatic and extends for a highly variable time afterwards.  

In the estimated 20-40% of patients that have few or no symptoms, optimising the timing of PCR testing to fall within this interval of viral shedding is very difficult.  

However, anti SARS-CoV-2 antibody tests were developed to address these temporal limitations.  

By assaying for host immune response antibodies to the virus, these antibodies would be expected to last weeks to months.  

The diagnosis of SARS-CoV-2 infection can then be made retrospectively.  

However, in comparison to PCR assays, serological test platforms have more variables that need to be addressed in their development including:

  1. Selection of target viral antigens.
  2. Development of monoclonal reagents.
  3. Implementation of the detection technologies.  

As a result, there has been greater performance variability across different anti SARS-CoV-2 antibody tests than there has been seen with the SARS-CoV-2 PCR platform. 

The researchers presented a retrospective study on the effectiveness of both PCR and serological testing platforms to diagnose SARS-CoV-2 infection. 

To limit possible confounding variation due to different testing platforms, the study population was limited to those patients that were tested in house at UCLA clinical laboratories.

The researchers’ goal was to highlight the real world experience, the strengths and shortcomings of PCR and those of serological testing in diagnosing SARS-CoV-2 infection. 

The researchers reviewed specimens for SARS-CoV-2 PCR and anti SARS-CoV-2 antibody tests collected by trained UCLA healthcare practitioners within the UCLA campus as well as inpatient wards before August 11th 2020 and processed within
24 hours at UCLA laboratories. 

The first analysis was designed to elucidate appropriate time intervals between individual PCR and serology tests by leveraging the fact that individual patients often have multiple PCR tests over time. 

The second analysis was to measure the association and agreement. 

The next analysis was to address whether the number of days between symptom onset and PCR testing was predictive of the quantitative results from PCR testing, all patients with a determinable symptom onset date and subsequent positive PCR test were extracted from the patient classes.

Finally, the quantitative relationship between symptoms and PCR test and days between symptoms and serology tests were compared.

Patients with SARS-CoV-2 can be diagnosed by PCR during the time of acute infection or later in their clinical course by detection of virus specific antibodies.  

Whilst in theory they are complimentary, both PCR and serological tests have practical shortcomings.  

This retrospective study was performed to further define these limitations in a clinical context and to determine how best to utilise these tests.  

Out of a total of 3075 patients who underwent both PCR and serology tests at UCLA during this study period, 2371, 89% had no positive test at all.  

72% had a positive PCR test and only negative serology test, 144, 5% had a positive serology test and only negative PCR test and 127, 4% had positive PCR and serology test.  

Approximately half of the patients with the discordant results i.e. PCR positive, serology negative or vice versa had mistimed tests in reference to the course of their disease.  

PCR positive patients who were asymptomatic or pregnant were less likely to generate a detectable humoral immune response to SARS-CoV-2.  

On a quantitative level, the logged number of days between symptom onset and PCR cycle threshold CT values were positively correlated.  

However, there was no apparent relationship between PCR, CT and serological AU/ml results.

The inference was that these participants either saw PCR testing after viral shedding would be expected to have ended PCR minus but seropositive, or sought serology tests before a detectable antibody response would be expected PCR positive but seronegative. 

Cycle threshold CT values for PCR tests were positively correlated with days since symptom onset, indicating that viral load decreased with increasing time.  However, no relationship was observed between CT values and antibody titres from serology tests.  

This is an interesting study which clearly confirms that both the PCR swab test and the antibody test have their limitations.  

The London General Practice as a leading London doctors’ clinic undertakes all types of private COVID testing and offers PCR swab tests for fit to fly, test for release at day five and Government day two and day eight mandatory COVID swab tests.  

It also is able to offer a rapid COVID test such as the lateral flow antigen test with results within the hour, same day COVID testing service in London and a same day PCR test. 

Swabs need to be collected prior to noon and a result is available same day early evening.  

It can also offer a rapid PCR swab test with results back within three to four hours.  

The antibody test which The London General Practice as the leading London doctors’ clinic offers is one which has been developed by Imperial College and is highly accurate, being specific to the spike protein of SARS-CoV-2, which is comparable to neutralising antibody activity.  

This test can be used effectively to help understand the level of antibody produced post COVID vaccination.

Dr Paul Ettlinger

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