SARS-CoV-2 Antibody Responses Correlate with Resolution of RNAemia But Are Short-Lived in Patients with Mild Illness

Katharina Röltgen; Oliver F Wirz; Bryan A Stevens; Abigail E Powell; Catherine A Hogan; Javaria Najeeb; Molly Hunter; Malaya K Sahoo; ChunHong Huang; Fumiko Yamamoto; Justin Manalac; Ana R Otrelo-Cardoso; Tho D Pham; Arjun Rustagi; Angela J Rogers; Nigam H Shah; Catherine A Blish; Jennifer R Cochran; Kari C Nadeau; Theodore S Jardetzky; James L Zehnder; Taia T Wang; Peter S Kim; Saurabh Gombar; Robert Tibshirani; Benjamin A Pinsky; Scott D Boyd

doi:10.1101/2020.08.15.20175794

SARS-CoV-2 Antibody Responses Correlate with Resolution of RNAemia But Are Short-Lived in Patients with Mild Illness

medRxiv [Preprint]. 2020 Aug 17:2020.08.15.20175794. doi: 10.1101/2020.08.15.20175794.

Authors

Katharina Röltgen¹, Oliver F Wirz¹, Bryan A Stevens¹, Abigail E Powell², Catherine A Hogan¹, Javaria Najeeb³, Molly Hunter⁴, Malaya K Sahoo¹, ChunHong Huang¹, Fumiko Yamamoto¹, Justin Manalac¹, Ana R Otrelo-Cardoso³, Tho D Pham^{1

5}, Arjun Rustagi⁶, Angela J Rogers⁷, Nigam H Shah⁸, Catherine A Blish^{6

9}, Jennifer R Cochran¹⁰, Kari C Nadeau^{7

11}, Theodore S Jardetzky³, James L Zehnder¹, Taia T Wang^{6

9

12}, Peter S Kim^{2

9}, Saurabh Gombar¹, Robert Tibshirani^{13

14}, Benjamin A Pinsky^{1

6}, Scott D Boyd^{1

11}

Affiliations

¹ Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
² Stanford ChEM-H and Department of Biochemistry, Stanford University School of Medicine, Stanford, CA, USA.
³ Department of Structural Biology, Stanford University, Stanford, USA.
⁴ ATUM, Newark, CA, USA.
⁵ Stanford Blood Center, Palo Alto, CA, USA.
⁶ Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA, USA.
⁷ Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Stanford University, Stanford, CA, USA.
⁸ Stanford Center for Biomedical Informatics Research, Stanford University, Stanford, California, USA.
⁹ Chan Zuckerberg Biohub, San Francisco, CA, USA.
¹⁰ Department of Bioengineering, Stanford University, Stanford, CA, USA.
¹¹ Sean N. Parker Center for Allergy and Asthma Research, Stanford, CA, USA.
¹² Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
¹³ Department of Biomedical Data Sciences, Stanford University, Stanford, CA, USA.
¹⁴ Department of Statistics, Stanford University, Stanford, CA, USA.

Abstract

SARS-CoV-2-specific antibodies, particularly those preventing viral spike receptor binding domain (RBD) interaction with host angiotensin-converting enzyme 2 (ACE2) receptor, could offer protective immunity, and may affect clinical outcomes of COVID-19 patients. We analyzed 625 serial plasma samples from 40 hospitalized COVID-19 patients and 170 SARS-CoV-2-infected outpatients and asymptomatic individuals. Severely ill patients developed significantly higher SARS-CoV-2-specific antibody responses than outpatients and asymptomatic individuals. The development of plasma antibodies was correlated with decreases in viral RNAemia, consistent with potential humoral immune clearance of virus. Using a novel competition ELISA, we detected antibodies blocking RBD-ACE2 interactions in 68% of inpatients and 40% of outpatients tested. Cross-reactive antibodies recognizing SARS-CoV RBD were found almost exclusively in hospitalized patients. Outpatient and asymptomatic individuals' serological responses to SARS-CoV-2 decreased within 2 months, suggesting that humoral protection may be short-lived.

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