Delayed production of neutralizing antibodies correlates with fatal COVID-19

Details

• Alternative Title:
  Nat Med
• Personal Author:
  Lucas, Carolina ; Klein, Jon ; Sundaram, Maria E. ; Liu, Feimei ; Wong, Patrick ; Silva, Julio ; Mao, Tianyang ; Oh, Ji Eun ; Mohanty, Subhasis ; Huang, Jiefang ; Tokuyama, Maria ; Lu, Peiwen ; Venkataraman, Arvind ; Park, Annsea ; Israelow, Benjamin ; Vogels, Chantal B. F. ; Muenker, M. Catherine ; Chang, C-Hong ; Casanovas-Massana, Arnau ; Moore, Adam J. ; Zell, Joseph ; Fournier, John B. ; Wyllie, Anne L. ; Campbell, Melissa ; Lee, Alfred I. ; Chun, Hyung J. ; Grubaugh, Nathan D. ; Schulz, Wade L. ; Farhadian, Shelli ; Cruz, Charles Dela ; Ring, Aaron M. ; Shaw, Albert C. ; Wisnewski, Adam V. ; Yildirim, Inci ; Ko, Albert I. ; Omer, Saad B. ; Iwasaki, Akiko
• Corporate Authors:
  Yale 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.
• Subjects:
  Aged Aged, 80 And Over Antibodies, Neutralizing Antibodies, Viral Article Carrier State COVID-19 COVID-19 Vaccines Female Humans Immunity, Humoral Immunoglobulin G Kinetics Length Of Stay Male Middle Aged SARS-CoV-2 Severity Of Illness Index Spike Glycoprotein, Coronavirus Time Factors

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• Source:
  Nat Med. 27(7):1178-1186
• Pubmed ID:
  33953384
• Pubmed Central ID:
  PMC8785364
• Document Type:
  Journal Article
• Funding:
  I01 BX004661/BX/BLRD VAUnited States/ ; T03 OH008607/OH/NIOSH CDC HHSUnited States/ ; T32 AI007517/AI/NIAID NIH HHSUnited States/ ; NIAID 2T32AI007517/U.S. Department of Health & Human Services ; NIH ; National Institute of Allergy and Infectious Diseases (NIAID)/
• Volume:
  27
• Issue:
  7
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:f4ca250ff228bf7a3e2a63fe64ba41d2a4f15e770577b050321162e62c246858
• Download URL:
  https://stacks.cdc.gov/view/cdc/113768/cdc_113768_DS1.pdf
• File Type:
  [PDF - 3.31 MB ]