SARS-CoV-2 Infection of Rhesus Macaques Treated Early with Human COVID-19 Convalescent Plasma

Jesse D. Deere, Timothy D. Carroll, Joseph Dutra, Linda Fritts, Rebecca Lee Sammak, Jo Ann L. Yee, Katherine J. Olstad, J. Rachel Reader, Amy Kistler, Jack Kamm, Clara Di Germanio, Yashavanth Shaan Lakshmanappa, Sonny R. Elizaldi, Jamin W. Roh, Graham Simmons, Jennifer Watanabe, Rachel E. Pollard, Jodie Usachenko, Ramya Immareddy, Brian A. SchmidtShelby L. O'Connor, Joseph DeRisi, Michael P. Busch, Smita S. Iyer, Koen K.A. Van Rompay, Dennis J. Hartigan-O'Connor, Christopher J. Miller

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Human clinical studies investigating use of convalescent plasma (CP) for treatment of coronavirus disease 2019 (COVID-19) have produced conflicting results. Outcomes in these studies may vary at least partly due to different timing of CP administration relative to symptom onset. The mechanisms of action of CP include neutralizing antibodies but may extend beyond virus neutralization to include normalization of blood clotting and dampening of inflammation. Unresolved questions include the minimum therapeutic titer in the CP units or CP recipient as well as the optimal timing of administration. Here, we show that treatment of macaques with CP within 24 h of infection does not reduce viral shedding in nasal or lung secretions compared to controls and does not detectably improve any clinical endpoint. We also demonstrate that CP administration does not impact viral sequence diversity in vivo, although the selection of a viral sequence variant in both macaques receiving normal human plasma was suggestive of immune pressure. Our results suggest that CP, administered to medium titers, has limited efficacy, even when given very early after infection. Our findings also contribute information important for the continued development of the nonhuman primate model of COVID-19. These results should inform interpretation of clinical studies of CP in addition to providing insights useful for developing other passive immunotherapies and vaccine strategies.

Original languageEnglish (US)
Article numbere01397-21
JournalMicrobiology spectrum
Issue number3
StatePublished - Dec 2021


  • Animal models of infectious diseases
  • Convalescent plasma
  • COVID-19
  • Microbial pathogenesis
  • Nonhuman primate
  • Passive immunization
  • SARS-CoV-2
  • Virology

ASJC Scopus subject areas

  • Physiology
  • Ecology
  • Immunology and Microbiology(all)
  • Genetics
  • Microbiology (medical)
  • Cell Biology
  • Infectious Diseases


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