Rapid seroconversion and persistent functional IgG antibodies in severe COVID-19 patients correlates with an IL-12p70 and IL-33 signature

Ariel Munitz; L. Edry-Botzer; M. Itan; R. Tur-Kaspa; D. Dicker; D. Marcoviciu; M. G. Goren; M. Mor; S. Lev; T. Gottesman; K. Muhsen; D. Cohen; M. Stein; U. Qimron; N. T. Freund; Y. Wine; Motti Gerlic

doi:10.1038/s41598-021-83019-0

Rapid seroconversion and persistent functional IgG antibodies in severe COVID-19 patients correlates with an IL-12p70 and IL-33 signature

Ariel Munitz, L. Edry-Botzer, M. Itan, R. Tur-Kaspa, D. Dicker, D. Marcoviciu, M. G. Goren, M. Mor, S. Lev, T. Gottesman, K. Muhsen, D. Cohen, M. Stein, U. Qimron, N. T. Freund, Y. Wine, Motti Gerlic

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

Despite ongoing efforts to characterize the host response toward SARS-CoV-2, a major gap in our knowledge still exists regarding the magnitude and duration of the humoral response. Analysis of the antibody response in mild versus moderate/severe patients, using our new developed quantitative electrochemiluminescent assay for detecting IgM/IgA/IgG antibodies toward SARS-CoV-2 antigens, revealed a rapid onset of IgG/IgA antibodies, specifically in moderate/severe patients. IgM antibodies against the viral receptor binding domain, but not against nucleocapsid protein, were detected at early stages of the disease. Furthermore, we observed a marked reduction in IgM/IgA antibodies over-time. Adapting our assay for ACE2 binding-competition, demonstrated that the presence of potentially neutralizing antibodies is corelated with IgG/IgA. Finally, analysis of the cytokine profile in COVID-19 patients revealed unique correlation of an IL-12p70/IL33 and IgG seroconversion, which correlated with disease severity. In summary, our comprehensive analysis has major implications on the understanding and monitoring of SARS-CoV-2 infections.

Original language	English
Article number	3461
Journal	Scientific Reports
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41598-021-83019-0
State	Published - 10 Feb 2021
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2021, The Author(s).

Funding

MA acknowledges funding from the US-BSF grant #2011244, ISF grant #886/15, ICRF, and the Cancer Biology Research Center, Tel Aviv University. GM acknowledges funding from Alpha-1 foundation grant #615533 and US-BSF grant #2017176, ISF grant #818/18, the Recanati Foundation, and the Varda and Boaz Dotan Research Center in Hemato-Oncology. MA and GM acknowledge a development grant from Biological Industries, Beit Haemek, Israel; QU acknowledges funding from CoG-ERC grant #818878. FNT acknowledges funding from ISF grant # 1422/18 and Israeli Innovation Authority # grant 65029 and the Milner Foundation. WY acknowledges funding from US-BSF grant #2017359 and ISF grant #1282/17.

Funders	Funder number
Biological Industries
Cancer Biology Research Center
CoG-ERC	1422/18
Israeli Innovation Authority	65029
Milner Foundation	1282/17, 2017359
Recanati Foundation
US-BSF	2011244
Varda and Boaz Dotan Research Center in Hemato-oncology
Alpha-1 Foundation	2017176, 615533, 818/18
Israel Cancer Research Fund
Horizon 2020 Framework Programme
H2020 European Research Council	818878
United States-Israel Binational Science Foundation
Israel Science Foundation	886/15
Tel Aviv University
Varda and Boaz Dotan Research Center for Hemato-Oncology Research, Tel Aviv University

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Munitz, A., Edry-Botzer, L., Itan, M., Tur-Kaspa, R., Dicker, D., Marcoviciu, D., Goren, M. G., Mor, M., Lev, S., Gottesman, T., Muhsen, K., Cohen, D., Stein, M., Qimron, U., Freund, N. T., Wine, Y., & Gerlic, M. (2021). Rapid seroconversion and persistent functional IgG antibodies in severe COVID-19 patients correlates with an IL-12p70 and IL-33 signature. Scientific Reports, 11(1), Article 3461. https://doi.org/10.1038/s41598-021-83019-0

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title = "Rapid seroconversion and persistent functional IgG antibodies in severe COVID-19 patients correlates with an IL-12p70 and IL-33 signature",

abstract = "Despite ongoing efforts to characterize the host response toward SARS-CoV-2, a major gap in our knowledge still exists regarding the magnitude and duration of the humoral response. Analysis of the antibody response in mild versus moderate/severe patients, using our new developed quantitative electrochemiluminescent assay for detecting IgM/IgA/IgG antibodies toward SARS-CoV-2 antigens, revealed a rapid onset of IgG/IgA antibodies, specifically in moderate/severe patients. IgM antibodies against the viral receptor binding domain, but not against nucleocapsid protein, were detected at early stages of the disease. Furthermore, we observed a marked reduction in IgM/IgA antibodies over-time. Adapting our assay for ACE2 binding-competition, demonstrated that the presence of potentially neutralizing antibodies is corelated with IgG/IgA. Finally, analysis of the cytokine profile in COVID-19 patients revealed unique correlation of an IL-12p70/IL33 and IgG seroconversion, which correlated with disease severity. In summary, our comprehensive analysis has major implications on the understanding and monitoring of SARS-CoV-2 infections.",

author = "Ariel Munitz and L. Edry-Botzer and M. Itan and R. Tur-Kaspa and D. Dicker and D. Marcoviciu and Goren, {M. G.} and M. Mor and S. Lev and T. Gottesman and K. Muhsen and D. Cohen and M. Stein and U. Qimron and Freund, {N. T.} and Y. Wine and Motti Gerlic",

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Munitz, A, Edry-Botzer, L, Itan, M, Tur-Kaspa, R, Dicker, D, Marcoviciu, D, Goren, MG, Mor, M, Lev, S, Gottesman, T, Muhsen, K, Cohen, D, Stein, M, Qimron, U, Freund, NT, Wine, Y & Gerlic, M 2021, 'Rapid seroconversion and persistent functional IgG antibodies in severe COVID-19 patients correlates with an IL-12p70 and IL-33 signature', Scientific Reports, vol. 11, no. 1, 3461. https://doi.org/10.1038/s41598-021-83019-0

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T1 - Rapid seroconversion and persistent functional IgG antibodies in severe COVID-19 patients correlates with an IL-12p70 and IL-33 signature

AU - Munitz, Ariel

AU - Edry-Botzer, L.

AU - Itan, M.

AU - Tur-Kaspa, R.

AU - Dicker, D.

AU - Marcoviciu, D.

AU - Goren, M. G.

AU - Mor, M.

AU - Lev, S.

AU - Gottesman, T.

AU - Muhsen, K.

AU - Cohen, D.

AU - Stein, M.

AU - Qimron, U.

AU - Freund, N. T.

AU - Wine, Y.

AU - Gerlic, Motti

PY - 2021/2/10

Y1 - 2021/2/10

N2 - Despite ongoing efforts to characterize the host response toward SARS-CoV-2, a major gap in our knowledge still exists regarding the magnitude and duration of the humoral response. Analysis of the antibody response in mild versus moderate/severe patients, using our new developed quantitative electrochemiluminescent assay for detecting IgM/IgA/IgG antibodies toward SARS-CoV-2 antigens, revealed a rapid onset of IgG/IgA antibodies, specifically in moderate/severe patients. IgM antibodies against the viral receptor binding domain, but not against nucleocapsid protein, were detected at early stages of the disease. Furthermore, we observed a marked reduction in IgM/IgA antibodies over-time. Adapting our assay for ACE2 binding-competition, demonstrated that the presence of potentially neutralizing antibodies is corelated with IgG/IgA. Finally, analysis of the cytokine profile in COVID-19 patients revealed unique correlation of an IL-12p70/IL33 and IgG seroconversion, which correlated with disease severity. In summary, our comprehensive analysis has major implications on the understanding and monitoring of SARS-CoV-2 infections.

AB - Despite ongoing efforts to characterize the host response toward SARS-CoV-2, a major gap in our knowledge still exists regarding the magnitude and duration of the humoral response. Analysis of the antibody response in mild versus moderate/severe patients, using our new developed quantitative electrochemiluminescent assay for detecting IgM/IgA/IgG antibodies toward SARS-CoV-2 antigens, revealed a rapid onset of IgG/IgA antibodies, specifically in moderate/severe patients. IgM antibodies against the viral receptor binding domain, but not against nucleocapsid protein, were detected at early stages of the disease. Furthermore, we observed a marked reduction in IgM/IgA antibodies over-time. Adapting our assay for ACE2 binding-competition, demonstrated that the presence of potentially neutralizing antibodies is corelated with IgG/IgA. Finally, analysis of the cytokine profile in COVID-19 patients revealed unique correlation of an IL-12p70/IL33 and IgG seroconversion, which correlated with disease severity. In summary, our comprehensive analysis has major implications on the understanding and monitoring of SARS-CoV-2 infections.

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Rapid seroconversion and persistent functional IgG antibodies in severe COVID-19 patients correlates with an IL-12p70 and IL-33 signature

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