Prior SARS-CoV-2 Infection Prevents Acute Disease and Lung Pathology in Reinfected Syrian Hamsters but not Virus Replication in the Upper Respiratory Tract

Abstract

Human cases of SARS-CoV-2 reinfection have been documented throughout the pandemic but are likely underreported. In the current study, we used the Syrian hamster SARS-CoV-2 model to assess reinfection with homologous (Washington WA1) and heterologous (United Kingdom B.1.1.7 (alpha) and South Africa B.1.351 (beta)) SARS-CoV-2 variants over time. Upon primary infection with SARS-CoV-2 WA1, hamsters rapidly developed a strong and long-lasting humoral immune response. Following reinfection with homologous and heterologous SARS-CoV-2 variants, this immune response protected hamsters from clinical disease, virus replication in the lower respiratory tract and acute lung pathology. However, reinfection led to SARS-CoV-2 replication in the upper respiratory tract with the potential for virus shedding. Our findings indicate that reinfection results in restricted SARS-CoV-2 replication despite substantial levels of humoral immunity, denoting the potential for transmission through reinfected asymptomatic individuals.Funding: This study was funded by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH). Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: Work with infectious SARS-CoV-2 was approved by the Institutional Biosafety Committee (IBC) and performed in the high biocontainment facilities at Rocky Mountain Laboratories (RML), NIAID, NIH. Sample removal from high biocontainment followed IBC-approved Standard Operating Protocols (44). Animal work was approved by the Institutional Animal Care and Use Committee and performed by certified staff in an Association for Assessment and Accreditation of Laboratory Animal Care International accredited facility. Work followed the institution’s guidelines for animal use, the guidelines and basic principles in the NIH Guide for the Care and Use of Laboratory Animals, the Animal Welfare Act, United States Department of Agriculture and the United States Public Health Service Policy on Humane Care and Use of Laboratory Animals.