what is sars-cov-2 serological testing and why do we need it? · what is sars-cov-2 serological...
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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
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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
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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?
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The spike protein is the main target of neutralizing antibodies for many coronaviruses
PBD # 6VXX
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The spike protein is the main target of neutralizing antibodies for many coronaviruses
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How does this work? – Negative serum:
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How does this work? – Positive serum:
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Types of tests
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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
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Human serum reactivity in RBD and spike ELISA
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R e c i p r o c a l d i l u t i o n
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R e c i p r o c a l d i l u t i o n
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Amanat et al., Nat. Med., in press
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Spike ELISA endpoint titers correlate well with virus neutralization
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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
s p i k e E L I S A e n d p o i n t t i t e r
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Amanat et al., Nat. Med., in press
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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
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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
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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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Wajnberg et al., under review
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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
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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)
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