4.8 Article

COVID-19-neutralizing antibodies predict disease severity and survival

Journal

CELL
Volume 184, Issue 2, Pages 476-+

Publisher

CELL PRESS
DOI: 10.1016/j.cell.2020.12.015

Keywords

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Funding

  1. Gilead Sciences Research Scholars Program in HIV
  2. Ruth L. Kirschstein National Research Service Award (NRSA) Individual Postdoctoral Fellowship [1F32AI143480]
  3. National Institute of General Medical Sciences [T32GM007753, T32AI007245]
  4. NIH [R01 AI146779]
  5. Massachusetts Consortium on Pathogenesis Readiness (MassCPR) grant
  6. Lambertus Family Foundation
  7. National Institute on Drug Abuse (NIDA) Avenir New Innovator Award [DP2DA040254]
  8. MGH Transformative Scholars Program
  9. Charles H. Hood Foundation

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Severe cases of COVID-19 show increased inflammatory markers, lymphopenia, pro-inflammatory cytokines, and high antibody levels. High neutralization potency is a predictor of survival. Patient sera can neutralize different strains, indicating cross-protection from reinfection.
Coronavirus disease 2019 (COVID-19) exhibits variable symptom severity ranging from asymptomatic to life-threatening, yet the relationship between severity and the humoral immune response is poorly understood. We examined antibody responses in 113 COVID-19 patients and found that severe cases resulting in intubation or death exhibited increased inflammatory markers, lymphopenia, pro-inflammatory cytokines, and high anti-receptor binding domain (RBD) antibody levels. Although anti-RBD immunoglobulin G (IgG) levels generally correlated with neutralization titer, quantitation of neutralization potency revealed that high potency was a predictor of survival. In addition to neutralization of wild-type SARS-CoV-2, patient sera were also able to neutralize the recently emerged SARS-CoV-2 mutant D614G, suggesting cross-protection from reinfection by either strain. However, SARS-CoV-2 sera generally lacked cross-neutralization to a highly homologous pre-emergent bat coronavirus, WIV1-CoV, which has not yet crossed the species barrier. These results highlight the importance of neutralizing humoral immunity on disease progression and the need to develop broadly protective interventions to prevent future coronavirus pandemics.

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