key: cord-0710903-leel1kz1
authors: Lippi, Giuseppe; Plebani, Mario
title: The presence of anti-SARS-CoV-2 antibodies does not necessarily reflect efficient neutralization
date: 2022-01-31
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2022.01.057
sha: f5ba37953947fbcea4b7519ec4a4e4a986ec73ef
doc_id: 710903
cord_uid: leel1kz1

nan

We read with interest the article of Gargouria et al. (Gargouria et al., 2022) , who described the cases of four patients with recurrent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection despite "the presence of (anti-SARS-CoV-2 S1 IgG) antibodies". Although continuous emergence of new and highly mutated SARS-CoV-2 variants is posing paramount challenges to adaptative immunity (Lippi et al., 2021) , the message delivered by the authors is not supported by data and thus potentially misleading.

The analysis of data published by Gargouria et al. (Gargouria et al., 2022) reveals first that anti-SARS-CoV-2 S1 IgG antibodies were measured with a commercial immunoassay displaying suboptimal negative predictive value for neutralizing antibodies (i.e., 71% vs. 80-95% of other IgG immunoassays) (Montesinos et al., 2021) . It is hence likely that several samples of patients with low values of these antibodies may retain significant neutralizing potential. The second aspect concerns the anti-S1 IgG antibodies values in the patients. In one case (case #4), serological assessment could be performed one week after molecular testing become positive, as admitted by Gargouria and colleagues (Gargouria et al., 2022) , so that no reliable indications can be garnered on anti-S1 IgG antibodies titer immediately before second infection. Then, in cases #2 and #3 the samples were collected between 12-14 days before recurrent infection, with anti-S1 IgG antibodies levels appearing only 2.49 to 3.75 folds higher than the method-specific cut-off, while it is clear that efficient viral neutralization could only be achieved with higher values. To this end, Bubonja-Šonje et al. reported that >80% neutralizing activity of anti-S1 IgG antibodies (measured with the same test) could only be reached with values around 10, achieving up to 100% neutralization when anti-S1 IgG antibodies values were >20 (Bubonja-Šonje et al., 2021) . Therefore, while we would formally agree that "reinfection occurred despite the presence of antibodies" (Gargouria et al., 2022) , the authors should have instead concluded that "reinfection occurred with the presence of low values of anti-S1 IgG antibodies" in both these cases. The same concept applies to the single case (#1) where serological testing could be performed the same day of reinfection episode, since anti-S1 IgG antibodies level was 3.46, thus around the same threshold associated with just 60% viral neutralization (Bubonja-Šonje et al., 2021) .

In conclusion, major caution shall be used in interpreting results of anti-SARS-CoV-2 antibodies testing, wherein the presence of anti-SARS-CoV-2 antibodies does not necessarily reflect efficient neutralization.

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Evidence of SARS-CoV-2 Symptomatic Reinfection in Four Health Care Professionals from the Same Hospital Despite the Presence of Antibodies

Updated picture of SARS-CoV-2 variants and mutations. Diagnosis (Berl)

Neutralizing antibody responses following natural SARS-CoV-2 infection: Dynamics and correlation with commercial serologic tests

Funding Source: none Ethical Approval statement: not required.