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What are the different types of serological tests?

Text updated on 2020-04-30

There are several types of serological tests available to detect the presence of specific antibodies against the SARS-CoV-2 virus in the blood or their effectiveness against reinfection.

There are three types of serological tests that differ in terms of difficulty, sensitivity, and cost:

Rapid Diagnostic Test (RDT): duration 10-30 min.

It is generally a qualitative (positive or negative) side-flow test, small, and portable. These tests can use blood samples from a finger prick, saliva samples, or nasal swabs. TDRs are often similar to pregnancy tests in that the test shows the user coloured lines to indicate positive or negative results. For COVID-19, these tests most often look for the patient's antibodies (IgG and IgM) or for the viral antigen. These tests cannot quantify the amount of antibodies present in the patient's serum nor can they determine whether these antibodies are capable of preventing future infection.

Enzyme-linked immunosorbent assay (ELISA): duration 1 - 5 hours

This test can be qualitative or quantitative and is usually performed in a laboratory. These tests generally use samples of whole blood, or blood fractions from patients. The test is based on the use of a plate coated with a viral protein of interest, such as the "Spike" protein of the viral envelope. Patient samples are then incubated with the protein, and if the patient has antibodies to the viral protein, they bind together. The antibody-bound protein complex can then be detected by another 'antibody' that produces a coloured or fluorescent signal. In COVID-19, these tests most often detect the presence of antibodies produced by the patient (IgG and IgM). However, these tests cannot determine whether these antibodies are neutralizing, i.e., able to protect against future infection of the same virus.

Neutralization test: duration 3- 5 days

This test detects the presence of antibodies that can prevent viral infection in cells in the laboratory. Neutralization tests can tell researchers whether a patient has active and effective antibodies to the virus, even if they are asymptomatic or cured. These tests require samples of the patient's blood. Neutralization tests are based on cell culture, a laboratory method to allow the SARS-CoV-2 virus to multiply in cells. When the virus and cells are cultured with decreasing concentrations of the patient's antibodies, researchers can visualize and determine the dose of antibodies in the patient's blood that can block the virus from multiplying. These tests can determine whether the antibodies are capable of protecting against a future infection but cannot detect the presence of antibodies to viral proteins that are not involved in the infection process.

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Johns Hopkins University synthesis on serological tests developed mainly by the United States, China, South Korea, Singapore, Germany, and England.

Kinetics of antibody response: Using a recombinant viral nucleocapsid ELISA, a study examined the host humoral response to SARS-CoV-2, including IgA, IgM, and IgG responses. A total of 208 plasma samples were collected from 82 confirmed cases and 58 probable cases. The diagnostic value of IgM was evaluated in this cohort. The median duration of detection of IgM and IgA antibodies was 5 days, while IgG was detected over 14 days after symptom onset, with a positive rate of 85.4%, 92.7%, and 77.9% respectively.

Wu, F., Wang, A., Liu, M., Wang, Q., Chen, J., Xia, S., ... & Jiang, S. (2020). Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications.

One study measured the kinetics of IgM and IgG responses in 34 patients:

Xiao, Gao and Zhang. J Inf 2020. Profile of specific antibodies to SARS-CoV-2: The first report.

Immunological tests were also performed in 16 patients in Hong Kong using serum samples collected 14 days or more after the onset of symptoms. The following seropositivity rates were reported: 94% for anti-N IgG (n=15), 88% for anti-N IgM (n=14), 100% for anti-RBD IgG (n=16), and 94% for anti-RBD IgM (n=15). Levels of anti-SARS-CoV-2-N or anti-SARS-CoV-2-RBD IgG are correlated with viral neutralization titer.

To KK, Tsang OT, Leung WS, Tam AR, Wu TC, Lung DC, Yip CC, Cai JP, Chan JM, Chik TS, Lau DP, Choi CY, Chen LL, Chan WM, Chan KH, Ip JD, Ng AC, Poon RW, Luo CT, Cheng VC, Chan JF, Hung IF, Chen Z, Chen H, Yuen KY. Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. Lancet Infect Dis. 2020 Mar 23. pii: S1473-3099(20)30196-1.

One study characterized antibody responses in a cohort of 175 COVID-19 patients with mild symptoms. Elderly and middle-aged patients had significantly higher plasma NAb and binding antibody titers.<0,0001 et="" P="0,0003" respectivement="" e="" que="" ceux="" des="" jeunes="" patients.<="" p=""> Wu, F., Wang, A., Liu, M., Wang, Q., Chen, J., Xia, S., ... & Jiang, S. Neutralizing antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their implications.

Catalan-Dibene commented on a study showing the existence of virus-specific memory cells recognizing the SARS-CoV-2 S (spike) protein in infected patients.

Catalan-Dibene J. Human antibodies can neutralize SARS-CoV-2. Nat Rev Immunol. 2020 Apr 14.

Description of the high-quality Pasteur serological tests: Seroconversion and antibody neutralisation of the coronavirus occurred 5-14 days after the onset of symptoms, confirming previous studies.

Grzelak, L., Temmam, S., Planchais, C., Demeret, C., Huon, C., Guivel, F., ... van der Werf, S. (2020). SARS-CoV-2 serological analysis of COVID-19 hospitalized patients, pauci-symptomatic individuals and blood donors. medRxiv, 2020.2004.2021.20068858. doi:10.1101/2020.04.21.20068858.

Further reading

What do the abbreviations COVID, SARS, CoV, RNA, etc. mean?