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Mid-titer human convalescent plasma administration results in suboptimal prophylaxis against SARS-CoV-2 infection in
Brandon J Beddingfield1, Nicholas J Maness1,2, Skye Spencer1
1Divisions of Microbiology, Tulane National Primate Research Center, Covington, LA, United States.
Introduction:
ARS-CoV-2 is a respiratory pathogen currently causing a worldwide pandemic, with resulting pathology of differing severity in humans, from mild illness to severe disease and death. The rhesus macaque model of COVID-19 was utilized to evaluate the added benefit of prophylactic administration of human post-SARS-CoV-2 infection convalescent plasma (CP) on disease progression and severity.
Methods:
A pharmacokinetic (PK) study using CP in rhesus monkeys preceded the challenge study and revealed the optimal time of tissue distribution for maximal effect. Thereafter, CP was administered prophylactically three days prior to mucosal SARS-CoV-2 viral challenge.
Results:
Results show similar viral kinetics in mucosal sites over the course of infection independent of administration of CP or normal plasma, or historic controls with no plasma. No changes were noted upon necropsy via histopathology, although there were differences in levels of vRNA in tissues, with both normal and CP seemingly blunting viral loads.
Discussion:
Results indicate that prophylactic administration with mid-titer CP is not effective in reducing disease severity of SARS-CoV-2 infection in the rhesus COVID-19 disease model.
Insights
Prophylactic administration of convalescent plasma (CP) did not reduce disease severity in rhesus macaques with SARS-CoV-2 infection. This study found no significant difference in viral kinetics or pathology, suggesting CP is not an effective treatment for COVID-19 in this model.
Area of Science:
- Virology
- Immunology
- Preclinical research
Background:
- Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic with variable human disease severity.
- The rhesus macaque is a relevant animal model for studying SARS-CoV-2 infection and potential therapeutics.
Purpose of the Study:
- To evaluate the efficacy of prophylactic human convalescent plasma (CP) in mitigating SARS-CoV-2 disease progression and severity in rhesus macaques.
- To assess the impact of CP on viral kinetics and histopathological outcomes.
Main Methods:
- A pharmacokinetic study determined optimal CP dosing timing.
- Rhesus macaques received prophylactic CP three days before SARS-CoV-2 challenge.
- Viral loads, viral kinetics, and necropsy findings were analyzed.
Main Results:
- Viral kinetics in mucosal sites were similar across groups (CP, normal plasma, no plasma).
- Histopathology showed no significant changes, but tissue vRNA levels suggested a blunting effect from both normal and CP.
- Prophylactic mid-titer CP did not reduce overall disease severity.
Conclusions:
- Prophylactic administration of mid-titer convalescent plasma is ineffective in reducing SARS-CoV-2 disease severity in the rhesus macaque model.
- Further research may be needed to explore different CP titers or therapeutic timing for COVID-19 treatment.
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