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Role of IgM and IgA Antibodies in the Neutralization of SARS-CoV-2

Jéromine Klingler1,2, Svenja Weiss1,2, Vincenza Itri1, Xiaomei Liu1,2, Kasopefoluwa Y. Oguntuyo3, Christian Stevens3, Satoshi Ikegame3, Chuan-Tien Hung3, Gospel Enyindah-Asonye1, Fatima Amanat3,4, Ian Baine5, Suzanne Arinsburg5,Juan C. Bandres2, Erna Milunka Kojic6, Jonathan Stoever7, Denise Jurczyszak3,4, Maria Bermudez-Gonzalez3, Arthur Nádas8, Sean Liu1,3, Benhur Lee3, Susan Zolla-Pazner1,3*, Catarina E. Hioe1,2,3* 

1Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY USA.

2James J. Peters VA Medical Center, Bronx, NY, USA.

3Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

4Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

5Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

6Division of Infectious Diseases, Department of Medicine, Mount Sinai West and Morningside, NY, USA.

7Pulmonary and Critical Care Medicine, Mount Sinai West, NY, USA.

8Department of Environment Medicine, NYU School of Medicine, New York, NY, USA

Background: SARS-CoV-2 has infected millions of people globally. Virus infection requires the receptor-binding domain (RBD) of the spike protein. Although studies have demonstrated anti-spike and -RBD antibodies to be protective in animal models, and convalescent plasma as a promising therapeutic option, little is known about immunoglobulin (Ig) isotypes capable of blocking infection.

Methods: We studied spike- and RBD-specific Ig isotypes in convalescent and acute plasma/sera using a multiplex bead assay. We also determined virus neutralization activities in plasma, sera, and purified Ig fractions using a VSV pseudovirus assay.

Results: Spike- and RBD-specific IgM, IgG1, and IgA1 were produced by all or nearly all subjects at variable levels and detected early after infection. All samples displayed neutralizing activity. Regression analyses revealed that IgM and IgG1 contributed most to neutralization, consistent with IgM and IgG fractions’ neutralization potency. IgA also exhibited neutralizing activity, but with lower potency.

Conclusion: IgG, IgM and IgA are critical components of convalescent plasma used for COVID-19 treatment.