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What is SARS-CoV-2 serological testing and why do we need it? Florian Krammer Mount Sinai Professor in Vaccinology Icahn School of Medicine at Mount Sinai ICAP ‘SARS-CoV-2 serological testing: What is it and what does it mean?’ Webinar May 13th, 2020
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What is SARS-CoV-2 serological testing and why do we need it? · What is SARS-CoV-2 serological testing and why do we need it? Florian Krammer Mount Sinai Professor in Vaccinology.

Aug 16, 2020

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Page 1: What is SARS-CoV-2 serological testing and why do we need it? · What is SARS-CoV-2 serological testing and why do we need it? Florian Krammer Mount Sinai Professor in Vaccinology.

What is SARS-CoV-2 serological testing and why do we need it?

Florian KrammerMount Sinai Professor in Vaccinology

Icahn School of Medicine at Mount Sinai

ICAP ‘SARS-CoV-2 serological testing: What is it and what does it mean?’

WebinarMay 13th, 2020

Page 2: What is SARS-CoV-2 serological testing and why do we need it? · What is SARS-CoV-2 serological testing and why do we need it? Florian Krammer Mount Sinai Professor in Vaccinology.

What is serology?• When we get infected with viruses or other pathogens, our B-cells make

antibodies to the invading microbe to ‘neutralize it’• There antibodies can be found in the blood serum, hence the name

PCR Testing Serology Testing

Page 3: What is SARS-CoV-2 serological testing and why do we need it? · What is SARS-CoV-2 serological testing and why do we need it? Florian Krammer Mount Sinai Professor in Vaccinology.

Why is serology useful?• Finding donors for convalescent plasma therapy

• Sero-surveys to determine true infection rates

• Tool to understand dynamics of antibody responses to SARS-CoV-2

• Establish correlates of protection• Is somebody protected by the antibody response?• Does the antibody response need to reach a certain level to be protective?

Page 4: What is SARS-CoV-2 serological testing and why do we need it? · What is SARS-CoV-2 serological testing and why do we need it? Florian Krammer Mount Sinai Professor in Vaccinology.

The spike protein is the main target of neutralizing antibodies for many coronaviruses

PBD # 6VXX

Page 5: What is SARS-CoV-2 serological testing and why do we need it? · What is SARS-CoV-2 serological testing and why do we need it? Florian Krammer Mount Sinai Professor in Vaccinology.

The spike protein is the main target of neutralizing antibodies for many coronaviruses

Page 6: What is SARS-CoV-2 serological testing and why do we need it? · What is SARS-CoV-2 serological testing and why do we need it? Florian Krammer Mount Sinai Professor in Vaccinology.

How does this work? – Negative serum:

Page 7: What is SARS-CoV-2 serological testing and why do we need it? · What is SARS-CoV-2 serological testing and why do we need it? Florian Krammer Mount Sinai Professor in Vaccinology.

How does this work? – Positive serum:

Page 8: What is SARS-CoV-2 serological testing and why do we need it? · What is SARS-CoV-2 serological testing and why do we need it? Florian Krammer Mount Sinai Professor in Vaccinology.

Types of tests

Page 9: What is SARS-CoV-2 serological testing and why do we need it? · What is SARS-CoV-2 serological testing and why do we need it? Florian Krammer Mount Sinai Professor in Vaccinology.

Sensitivity and specificity• Sensitivity: How many real positives are detected

• For serology that is often influenced by when sample is taken

• Specificity: How many false positives are detected

• Both should be in the high 90% range• Only use tests with known performances and at least an FDA EUA• Different tests are useful for different things

Page 10: What is SARS-CoV-2 serological testing and why do we need it? · What is SARS-CoV-2 serological testing and why do we need it? Florian Krammer Mount Sinai Professor in Vaccinology.

Human serum reactivity in RBD and spike ELISA

1 0 0 1 0 0 0 1 0 0 0 0

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Amanat et al., Nat. Med., in press

Page 11: What is SARS-CoV-2 serological testing and why do we need it? · What is SARS-CoV-2 serological testing and why do we need it? Florian Krammer Mount Sinai Professor in Vaccinology.

Spike ELISA endpoint titers correlate well with virus neutralization

1 0 1 0 0 1 0 0 0 1 0 0 0 0 1 0 0 0 0 0

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1

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C o r r e l a t i o n

m S p i k e E L I S A a n d m i c r o n e u t r a l i z a t i o n a s s a y

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Amanat et al., Nat. Med., in press

Page 12: What is SARS-CoV-2 serological testing and why do we need it? · What is SARS-CoV-2 serological testing and why do we need it? Florian Krammer Mount Sinai Professor in Vaccinology.

Mount Sinai Plasma Donors• >22,000 donors screened by ELISA

• Mostly mild cases• PCR confirmed donors• Donors with suspected COVID19 (but without PCR confirmation)

• >250 patients treated with convalescent plasma

• ELISA and PCR results from the ~1350 donors can be found at: https://www.medrxiv.org/content/10.1101/2020.04.30.20085613v1

Page 13: What is SARS-CoV-2 serological testing and why do we need it? · What is SARS-CoV-2 serological testing and why do we need it? Florian Krammer Mount Sinai Professor in Vaccinology.

C O V I D 1 9 - s u s p e c t e d d o n o r s

A n t i b o d y p o s i t i v e ( n = 2 6 9 , 3 8 . 2 % )

A n t i b o d y n e g a t i v e ( n = 4 3 6 , 6 1 . 8 % )

P C R - c o n f i r m e d d o n o r s

A n t i b o d y p o s i t i v e ( n = 5 6 8 , 9 9 . 5 % )

A n t i b o d y n e g a t i v e ( n = 3 , 0 . 5 % )

Proportion of antibody positive donors

Wajnberg et al., under review

Page 14: What is SARS-CoV-2 serological testing and why do we need it? · What is SARS-CoV-2 serological testing and why do we need it? Florian Krammer Mount Sinai Professor in Vaccinology.

Proportion of antibody positive donors

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E L I S A t i t e r p o s t s y m p t o m o n s e t

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I n c r e a s e i n t i t e r s o f P C R c o n f i r m e d / A b l o w i n d i v i d u a l s

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Page 15: What is SARS-CoV-2 serological testing and why do we need it? · What is SARS-CoV-2 serological testing and why do we need it? Florian Krammer Mount Sinai Professor in Vaccinology.

What does this all mean?• Usually, antibodies are a good thing• Antibodies protect from (re)infection for most viruses• Neutralizing antibodies are usually associated with protection

from viruses• We know that antibodies protect from human CoV infections

• We need to now proof that antibodies against SARS-CoV-2 protect from infection

• What titer is protective?• Important for vaccine development

Page 16: What is SARS-CoV-2 serological testing and why do we need it? · What is SARS-CoV-2 serological testing and why do we need it? Florian Krammer Mount Sinai Professor in Vaccinology.

Acknowledgements

Adolfo Garcia-SastreLisa Miorin

Teresa Aydillo

Tom Moran

Viviana SimonMaria Bermudez-Gonzalez

Denise Jurczyszak

Katherine Kedzierska (U Melbourne)Jussi Hepojoki (U Helsinki)Olli Vapalahti (U Helsinki)

Department of Microbiology/ Icahn School of Medicine at Mount Sinai

Florian Krammer, [email protected]://labs.icahn.mssm.edu/krammerlab/Twitter: @florian_krammer

Ania Wajnberg(Mount Sinai Hospital)

Page 17: What is SARS-CoV-2 serological testing and why do we need it? · What is SARS-CoV-2 serological testing and why do we need it? Florian Krammer Mount Sinai Professor in Vaccinology.