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SARS-CoV-2 Infection Elicits Robust Neutralizing Antibody Titres In Most Individuals

Prof Leo Poon and Prof Malik Peiris published in Nature Communications the results of their study on neutralizing antibody titres in SARS-CoV-2, concluding that the infection elicits robust neutralizing antibody titres in most individuals.

They proceeded by testing 293 sera from an observational cohort of 195 reverse transcription polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 infections collected from 0 to 209 days after onset of symptoms.

Introduction:

Many studies have reported antibody responses in COVID-19 patients using ELISA or other binding assays, but there are fewer reports using virus neutralization tests. Patients with COVID-19 infection develop detectable SARS-CoV-2 neutralizing antibody responses with some having detectable antibody at the end of the 1st week of illness, and almost all having neutralizing antibody after 4 weeks of illness. The magnitude of the antibody responses and the proportion of patients developing antibody responses have varied. Severely ill patients are reported to have higher peak neutralizing antibody titers.

The methods used for detecting neutralizing antibody has also varied. These include the use of pseudoparticle neutralization (ppNT), microneutralization, fluorescent focus reduction assays, microneutralization assays, and plaque reduction neutralization tests (PRNT). Pseudoparticle neutralization tests are convenient and do not require bio-safety level 3 containment, but it is not clear how closely different types of virus pseudoparticles expressing SARS-CoV-2 spike protein mimics authentic virus, or how results from one pseudoparticle assay compares with another.

Even with neutralization of live virus, microneutralization tests were found to be less sensitive than plaque reduction neutralization assays, which are regarded as the “gold-standard” for neutralizing antibody testing. The major outstanding question is the duration of these neutralizing antibody responses. There are reports of rapid waning of antibody with some reports claiming that a third of patients have lost pseudoparticle neutralizing antibody by around 1–2 months after onset of illness. If true, such findings have major implications for the duration of protective immunity from reinfection, and the likely success of vaccination in prevention from reinfection and disease. It is therefore essential that the duration of neutralizing antibody responses are assessed using live virus neutralization assays.

Fig. 1: Antibody responses (PRNT90) in COVID-19 patients by days after illness onset and severity, Hong Kong (n = 293 samples).

The black lines showed the fitted values and gray areas showed the 95% confidence intervals. Neutralization tests were carried out in duplicate.


Fig. 2: Antibody responses (PRNT50) in COVID-19 patients by days after illness onset and severity, Hong Kong (n = 293 samples).

The black lines showed the fitted values and gray areas showed the 95% confidence intervals. Neutralization tests were carried out in duplicate.

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