Delayed Production of Neutralizing Antibodies Correlates with Fatal COVID-19

Details

• Personal Author:
  Campbell M ; Casanovas-Massana A ; Chang C-H ; Chun HJ ; Dela Cruz C ; Farhadian S ; Fournier JB ; Grubaugh ND ; Huang J ; Israelow B ; Iwasaki A ; Klein J ; Ko AI ; Lee AI ; Liu F ; Lu P ; Lucas C ; Mao T ; Mohanty S ; Moore AJ ; Muenker MC ; Oh JE ; Omer SB ; Park A ; Ring AM ; Schulz WL ; Shaw AC ; Silva J ; Sundaram ME ; Tokuyama M ; Venkataraman A ; Vogels CBF ; Wisnewski AV ; Wong P ; Wyllie AL ; Yildirim I ; Zell J
• Corporate Authors:
  Yale University. IMPACT Research Team
• Description:
  Recent studies have provided insights into innate and adaptive immune dynamics in coronavirus disease 2019 (COVID-19). However, the exact features of antibody responses that govern COVID-19 disease outcomes remain unclear. In this study, we analyzed humoral immune responses in 229 patients with asymptomatic, mild, moderate and severe COVID-19 over time to probe the nature of antibody responses in disease severity and mortality. We observed a correlation between anti-spike (S) immunoglobulin G (IgG) levels, length of hospitalization and clinical parameters associated with worse clinical progression. Although high anti-S IgG levels correlated with worse disease severity, such correlation was time dependent. Deceased patients did not have higher overall humoral response than discharged patients. However, they mounted a robust, yet delayed, response, measured by anti-S, anti-receptor-binding domain IgG and neutralizing antibody (NAb) levels compared to survivors. Delayed seroconversion kinetics correlated with impaired viral control in deceased patients. Finally, although sera from 85% of patients displayed some neutralization capacity during their disease course, NAb generation before 14 d of disease onset emerged as a key factor for recovery. These data indicate that COVID-19 mortality does not correlate with the cross-sectional antiviral antibody levels per se but, rather, with the delayed kinetics of NAb production. Author correction published online: 18 June 2021, https://doi.org/10.1038/s41591-021-01416-4. In the version of this article initially published, two author names (Alfred Lee and Saad Omer) were missing the middle initial. The correct names are 'Alfred I. Lee' and 'Saad B. Omer' (respectively). The errors have been corrected in the HTML and PDF versions of the article. [Description provided by NIOSH]
• Subjects:
  Antibodies Communicable Diseases Immune System Mortality Occupational Health Safety Viral Diseases
• Keywords:
  Antibody Response Antiviral Cellular Effects Cellular Reactions Coronavirus COVID-19 Cytometric Analysis Disease Incidence Humans Immune Reaction Immunoglobulins Immunology Infectious Diseases Kinetics Medical Research Mortality Data Proteins SARS-CoV-2 Serology Therapeutic Agents Viral Diseases Viral Infections

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• ISSN:
  1078-8956
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Connecticut ; Maryland ; OSHA Region 1 ; OSHA Region 3
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  27
• Issue:
  7
• NIOSHTIC Number:
  nn:20063162
• Citation:
  Nat Med 2021 Jul; 27(7):1178-1186
• Contact Point Address:
  Akiko Iwasaki, Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA
• Email:
  akiko.iwasaki@yale.edu
• Federal Fiscal Year:
  2021
• Performing Organization:
  Yale University School of Medicine
• Peer Reviewed:
  True
• Start Date:
  20010701
• Source Full Name:
  Nature Medicine
• End Date:
  20260630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:09fc9dca0f2e415d5e69f46fd5f0493f4586a09539026a187854c47dcc45dece1cb9f4db3b39d3edb9898cca753f87c24921e0d54d56b9e1a839c36f47fe6202
• Download URL:
  https://stacks.cdc.gov/view/cdc/226277/cdc_226277_DS1.pdf
• File Type:
  [PDF - 6.97 MB ]