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COVID-19 Neutralizing Antibodies Predict Disease Severity and Survival

44 Pages Posted: 27 Oct 2020 Publication Status: Published

See all articles by Wilfredo Francisco Garcia-Beltran

Wilfredo Francisco Garcia-Beltran

Massachusetts General Hospital - Department of Pathology

Evan Christopher Lam

Ragon Institute of MGH, MIT and Harvard

Michael Gerino Astudillo

Harvard University - Department of Pathology

Diane Yang

Massachusetts General Hospital - Department of Pathology

Tyler E. Miller

Massachusetts General Hospital - Department of Pathology

Jared Feldman

Ragon Institute of MGH, MIT and Harvard

Blake M. Hauser

Ragon Institute of MGH, MIT and Harvard

Timothy M. Caradonna

Ragon Institute of MGH, MIT and Harvard

Kiera Leigh Clayton

Ragon Institute of MGH, MIT and Harvard

Adam Douglas Nitido

Ragon Institute of MGH, MIT and Harvard

Mandakolathur R. Murali

Massachusetts General Hospital - Department of Pathology

Galit Alter

The Ragon Institute of MGH, MIT and Harvard

Richelle C. Charles

Massachusetts General Hospital - Division of Infectious Diseases

Anand Dighe

Massachusetts General Hospital - Department of Pathology

John A. Branda

Massachusetts General Hospital - Department of Pathology

Jochen K. Lennerz

Massachusetts General Hospital - Department of Pathology

Daniel Lingwood

Ragon Institute of MGH, MIT and Harvard

Aaron Schmidt

Ragon Institute of MGH, MIT and Harvard

A. John Iafrate

Massachusetts General Hospital - Department of Pathology

Alejandro Benjamin Balazs

Ragon Institute of MGH, MIT and Harvard

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Abstract

COVID-19 exhibits variable symptom severity ranging from asymptomatic to life-threatening, yet the relationship between severity and the humoral immune response is poorly understood. We examined antibody responses in 113 COVID-19 patients and found that severe cases resulting in intubation or death exhibited increased inflammatory markers, lymphopenia, and high anti-RBD antibody levels. While anti-RBD IgG levels generally correlated with neutralization titer, quantitation of neutralization potency revealed that high potency was a predictor of survival. In addition to neutralization of wild-type SARS-CoV-2, patient sera were also able to neutralize the recently emerged SARS-CoV-2 mutant D614G, suggesting protection from reinfection by this strain. However, SARS-CoV-2 sera was unable to cross-neutralize a highly-homologous pre-emergent bat coronavirus, WIV1-CoV, that has not yet crossed the species barrier. These results highlight the importance of neutralizing humoral immunity on disease progression and the need to develop broadly protective interventions to prevent future coronavirus pandemics.

Funding: K.L.C. is supported by Ruth L. Kirschstein National Research Service Award (NRSA) Individual Postdoctoral Fellowship 1F32AI143480. T.M.C. and B.M.H. were supported by award Number T32GM007753 from the National Institute of General Medical Sciences. J.F. was supported by T32AI007245. A.G.S. was supported by NIH R01 AI146779 and a Massachusetts Consortium on Pathogenesis Readiness (MassCPR) grant. J.A.B. has received research support from Zeus Scientific, bioMerieux, Immunetics, Alere, DiaSorin, the Bay Area Lyme Foundation (BALF), and the National Institute of Allergy and Infectious Diseases (NIAID; Award 1R21AI119457-01) for unrelated projects. J.A.B. has served as a paid consultant to T2 Biosystems, DiaSorin and Roche Diagnostics. A.J.I. is supported by the Lambertus Family Foundation. A.B.B. is supported by the National Institutes for Drug Abuse (NIDA) Avenir New Innovator Award DP2DA040254, the MGH Transformative Scholars Program as well as funding from the Charles H. Hood Foundation. This independent research was supported by the Gilead Sciences Research Scholars Program in HIV.

Ethical Approval: Use of patient samples for the development and validation of SARS-CoV-2 diagnostic tests was approved by Partners Institutional Review Board (protocol 2020P000895).

Keywords: COVID-19, SARS-CoV-2, ELISA, neutralizing antibodies, disease severity, WIV1-CoV

Suggested Citation

Garcia-Beltran, Wilfredo Francisco and Lam, Evan Christopher and Astudillo, Michael Gerino and Yang, Diane and Miller, Tyler E. and Feldman, Jared and Hauser, Blake M. and Caradonna, Timothy M. and Clayton, Kiera Leigh and Nitido, Adam Douglas and Murali, Mandakolathur R. and Alter, Galit and Charles, Richelle C. and Dighe, Anand and Branda, John A. and Lennerz, Jochen K. and Lingwood, Daniel and Schmidt, Aaron and Iafrate, A. John and Balazs, Alejandro Benjamin, COVID-19 Neutralizing Antibodies Predict Disease Severity and Survival. Available at SSRN: https://ssrn.com/abstract=3720298 or http://dx.doi.org/10.2139/ssrn.3720298
This version of the paper has not been formally peer reviewed.

Wilfredo Francisco Garcia-Beltran

Massachusetts General Hospital - Department of Pathology ( email )

Boston, MA
United States

Evan Christopher Lam

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Michael Gerino Astudillo

Harvard University - Department of Pathology ( email )

Boston, MA
United States

Diane Yang

Massachusetts General Hospital - Department of Pathology

Boston, MA
United States

Tyler E. Miller

Massachusetts General Hospital - Department of Pathology

Boston, MA
United States

Jared Feldman

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Blake M. Hauser

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Timothy M. Caradonna

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Kiera Leigh Clayton

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Adam Douglas Nitido

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Mandakolathur R. Murali

Massachusetts General Hospital - Department of Pathology ( email )

Boston, MA
United States

Galit Alter

The Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Richelle C. Charles

Massachusetts General Hospital - Division of Infectious Diseases

MA
United States

Anand Dighe

Massachusetts General Hospital - Department of Pathology ( email )

Boston, MA
United States

John A. Branda

Massachusetts General Hospital - Department of Pathology

Boston, MA
United States

Jochen K. Lennerz

Massachusetts General Hospital - Department of Pathology ( email )

Boston, MA
United States

Daniel Lingwood

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

Aaron Schmidt

Ragon Institute of MGH, MIT and Harvard ( email )

Boston, MA
United States

A. John Iafrate

Massachusetts General Hospital - Department of Pathology ( email )

Boston, MA
United States

Alejandro Benjamin Balazs (Contact Author)

Ragon Institute of MGH, MIT and Harvard

25 Shattuck St
Boston, MA 02115
United States

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