Vitalant Research Institute San Francisco, California, United States
Background/Case Studies: In January 2022, the FDA revised the Emergency Use Authorization for use of COVID-19 convalescent plasma (CCP) to restrict use to immunocompromised patients who are unable to mount a sufficiently protective antibody response, resulting in viral persistence and increased morbidity and mortality. In a randomized trial, immunosuppressed patients in the CCP arm tended to exhibit worsening pulmonary function at day 4 post-infusion but maintained the positive impact of CCP on survival (Lacombe et al. 2022). In a hamster model of SARS-CoV-2 infection, we characterized viral replication, lung pathology and disease progression in SARS-CoV-2 infected hamsters treated with CCP, including with CCP from recovered COVID patients who were subsequently vaccinated (Vaxplas).
Study
Design/Methods: Forty male, 8–10-week-old Syrian Golden hamsters were intranasally inoculated with a mixture containing of 5000 PFU of seven SARS-CoV-2 variant strains. Twenty-four hours after inoculation, four groups of 10 inoculated hamsters each were treated with 2ml peritoneal injections of: 1) Vaxplas; 2) CCP from unvaccinated, recovered COVID patients; 3) plasma from SARS-CoV-2 naïve human donors; group 4) was untreated controls. Change in body weight was used to assess disease severity. Effect on virus replication was assessed by determining SARS-CoV-2 subgenomic RNA (sgRNA) levels in upper respiratory tract (URT) washes and lungs collected at necropsy. Lung histology was characterized in five necropsied animals from each group at days 3 and 6 post infection (PI).
Results/Findings: Body weight declined transiently in all SARS-CoV-2 inoculated hamsters with larger body weight declines in the virus only and control plasma treated animals at day 6 PI; body weights in Vaxplas treated animals at day 3 did not decline further at day 6. Very high upper respiratory tract (URT) sg RNA levels (> 106 copies/ug total RNA) were seen on day 3 PI in all 4 animals groups. Day 6 PI sg RNA levels in UTR were lower and more variable but still similar among the 4 groups indicating CCP and Vaxplas had minimal effect on URT virus replication. Day 3 PI sgRNA levels were significantly lower in lungs of Vaxplas-treated animals compared to control plasma and virus-only animals. In all groups, similar pulmonary microscopic features were observed, including necrotizing neutrophilic and histiocytic broncho-interstitial pneumonia. At days 3 and 6 PI, there was significantly more lung disease in the Vaxplas group compared to the control groups; by day 6 inflammation and hemorrhage in the Vaxplas animals had resolved. Conclusions: Infusion of hamsters with Vaxplas 24 hours after SARS-CoV-2 infection blunts virus replication in the lungs but not the URT, and improves the course of disease despite transient enhancement of lung inflammation due to immune complex formation at sites of virus replication.
Importance of research: Viral replication and lung disease progression were studied in SARS-CoV-2 infected hamsters treated with COVID-19 convalescent plasma from recovered patients subsequently vaccinated with an mRNA vaccine (Vaxplas). Vaxplas reduced virus replication and improved clinical outcomes. However, Vaxplas transiently enhanced lung pathology in treated animals due to deposition of immune complexes, activation of complement and recruitment of proinflammatory macrophages into the lung parenchyma.
