RCPA advises against SARS-CoV-2 serology for the diagnosis of acute COVID-19 infection

In a new position statement released today, the Royal College of Pathologists of Australasia (RCPA) advises that serology testing has limited use in the diagnosis of COVID-19. If serology testing must be performed, the RCPA recommends that only laboratory-based assays are used due to their higher sensitivity and specificity and the current lack of a clinical or public health need for rapid point-of-care SARS-CoV-2 serology testing.

There are multiple TGA-licensed SARS-CoV-2 antibody assays available in Australia and New Zealand. Some of these assays are point-of-care tests while others are laboratory-based assays. In addition, some reference laboratories perform immunofluorescence and neutralising antibody assays.

Microbiologist and RCPA spokesperson, Dr Jim Newcombe, says that SARS-CoV-2 serology has low sensitivity in acute COVID-19 and is therefore not recommended for the diagnosis of acute infection.

“SARS-CoV-2 serology tests have a fundamental limitation; they rely on the detection of antibodies made by the patient in response to SARS-COV-2, they do not detect the virus. The sensitivity and specificity of laboratory-based serology assays used in Australia and New Zealand is high, however, the sensitivity is dependent on timing post-onset of COVID symptoms, with poor sensitivity at days 1-7 post-onset of symptoms (9-19%) and days 8-14 post-onset of symptoms (31-61%). After 14 days post-onset of symptoms, sensitivity is high (85-93%) but may decrease over time.

“A TGA Post Market Review of SARS-CoV-2 point-of-care antibody assays, performed by the Doherty Institute, found that manufacturers claimed higher sensitivity for their assays than that observed in Doherty Institute studies. Therefore, if serology testing must be performed, the RCPA recommends that only laboratory-based assays are used. Polymerase Chain Reaction (PCR) testing remains the gold-standard test for the diagnosis of acute COVID-19.”

SARS-CoV-2 antibody assays detect antibodies to either the spike protein (S) or nucleocapsid protein (N). S antibodies are detectable post-vaccination and post-natural infection while N antibodies are only detectable post-infection. After natural infection, serology cannot distinguish whether someone has or has not been vaccinated.

“There is currently no established antibody level that correlates with SARS-CoV-2 immunity, therefore, in line with PHLN recommendations, antibody levels should not be routinely reported and routine serology testing post-vaccination is not recommended. A negative antibody test also does not exclude prior infection, especially if a long period of time has elapsed between acute infection and serology testing.

“Laboratory interpretation of results is complex and requires comprehensive clinical notes, including the clinical query, vaccination status and timing of infection,” said Dr Newcombe.

For further information on the potential uses and limitations of SARS-CoV-2 serology testing, please read the RCPA’s full position statement on the website - https://www.rcpa.edu.au/getattachment/5fb8a015-8e4e-4472-8eb7-46268288a20f/COVID-19-Serology.aspx