Review 2: "Development of an automated chemiluminescence assay system for quantitative measurement of multiple anti-SARS-CoV-2 antibodies"

Massimo Pieri

doi:doi:10.1162/2e3983f5.18ba169e

The authors develop a new chemiluminescence assay system for measurement of SARS-CoV-2 antibodies. However, reviewers suggest that the study is potentially informative, though the lack of analytical validation in the study limits the generalizability of the findings.

by Massimo Pieri

Published onDec 09, 2020

Development of an automated chemiluminescence assay system for quantitative measurement of multiple anti-SARS-CoV-2 antibodies

by Sousuke Kubo, Norihisa Ohtake, Kei Miyakawa, Sundararaj Stanleyraj Jeremiah, Yutaro Yamaoka, Kota Murohashi, Eri Hagiwara, Takahiro Mihara, Atsushi Goto, Etsuko Yamazaki, Takashi Ogura, Takeshi Kaneko, Takeharu Yamanaka, and Akihide Ryo

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Published on Nov 06, 2020
www.medrxiv.org

Description

Objective: Serological tests for COVID-19 have been instrumental in studying the epidemiology of the disease. However, the performance of the currently available tests is plagued by the problem of variability. We have developed a high-throughput serological test capable of simultaneously detecting total immunoglobulins (Ig) and immunoglobulin G (IgG) against two of the most immunologically relevant SARS-CoV-2 antigens, nucleocapsid protein (NP) and spike protein (SP) and report its performance in detecting COVID-19 in clinical samples. Methods: We designed and prepared reagents for measuring NP-IgG, NP-Total Ig, SP-IgG, and SP-Total Ig (using N-terminally truncated NP (ΔN-NP) or receptor-binding domain (RBD) antigen) on the advanced chemiluminescence enzyme immunoassay system TOSOH AIA-CL. After determining the basal thresholds based on 17 sera obtained from confirmed COVID-19 patients and 600 negative sera. Subsequently, the clinical validity of the assay was evaluated using independent 202 positive samples and 1,000 negative samples from healthy donors. Results: All of the four test parameters showed 100% specificity individually (1,000/1,000; 95%CI, 99.63-100). The sensitivity of the assay increased proportionally to the elapsed time from symptoms onset, and all the tests achieved 100% sensitivity (153/153; 95%CI, 97.63-100) after 13 days from symptoms onset. NP-Total Ig was the earliest to attain maximal sensitivity among the other antibodies tested. Conclusion: Our newly developed serological testing exhibited 100% sensitivity and specificity after 13 days from symptoms onset. Hence, it could be used as a reliable method for accurate detection of COVID-19 patients and to evaluate seroprevalence and possibly for surrogate assessment of herd immunity.

RR:C19 Evidence Scale rating by reviewer:

Strong. The main study claims are very well-justified by the data and analytic methods used. There is little room for doubt that the study produced has very similar results and conclusions as compared with the hypothetical ideal study. The study’s main claims should be considered conclusive and actionable without reservation.

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Review:

The authors in this paper developed a new chemiluminescence assay system for quantitative measurement of multiple anti-SARS-CoV-2 antibodies. The developed serological testing exhibited 100% sensitivity and specificity after 13 days from the onset of symptoms. The work is clearly and accurately presented, is well-structured, and well-written. The work used a proper number of healthy donors and good statistics.

The article can be suitable for publication but needs some minor revision:
Since the test is new and developed by the authors, they should insert the accuracy data (within run and between run precision) and, if available, data of linearity.

Review 2: "Development of an automated chemiluminescence assay system for quantitative measurement of multiple anti-SARS-CoV-2 antibodies"

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