Protective Immunity of the Primary SARS-CoV-2 Infection Reduces Disease Severity Post Re-Infection with Delta Variants in Syrian Hamsters

Abstract

The Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Delta variant has evolved to become the dominant SARS-CoV-2 lineage with multiple sub-lineages and there are also reports of re-infections caused by this variant. We studied the disease characteristics induced by the Delta AY.1 variant and compared it with the Delta and B.1 variants in Syrian hamsters. We also assessed the potential of re-infection by these variants in Coronavirus disease 2019 recovered hamsters 3 months after initial infection. The variants produced disease characterized by high viral load in the respiratory tract and interstitial pneumonia. The Delta AY.1 variant produced mild disease in the hamster model and did not show any evidence of neutralization resistance due to the presence of the K417N mutation, as speculated. Re-infection with a high virus dose of the Delta and B.1 variants 3 months after B.1 variant infection resulted in reduced virus shedding, disease severity and increased neutralizing antibody levels in the re-infected hamsters. The reduction in viral load and lung disease after re-infection with the Delta AY.1 variant was not marked. Upper respiratory tract viral RNA loads remained similar after re-infection in all the groups. The present findings show that prior infection could not produce sterilizing immunity but that it can broaden the neutralizing response and reduce disease severity in case of reinfection.

Pathogenicity of SARS-CoV-2 Omicron (R346K) variant in Syrian hamsters and its cross-neutralization with different variants of concern

“…The viral RNA shedding and live virus clearance observed here was similar to earlier VOCs studied in hamster model. 22 , 36 Replication competent virus could be detected in NW till 5 DPI. The clearance of virus was observed by 1 week in hamsters.…”

“… 10 , 11 The model have been effectively used for the studies on the vaccines, antivirals, pathogenesis, transmissibility, virus shedding and disease severity associated with SARS-CoV-2 VOC's. 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 Recently, few studies have been published on the pathogenesis aspect of Omicron variant in mice and Syrian hamsters in comparison with other VOC's demonstrating decreased severity of infection. 23 , 24 , 25 , 26 , 27 , 28 , 29 Abdelnabi et al.…”

Omicron breakthrough infections in vaccinated or previously infected hamsters

“…The Syrian golden hamster has become the preclinical animal model of choice to assess vaccine effectiveness against SARS-CoV-2 variants, as well as the likelihood of reinfections ( 16 , 21 – 28 ). Such information is critical for rational decisions around vaccine strain updates or other public health responses to the continuing emergence of new variants.…”

Nasal Mucosa Exploited by SARS-CoV-2 for Replicating and Shedding during Reinfection

“…Second, most COVID-19 vaccines that are currently in circulation were prepared from the native strain, therefore, research on SARS-CoV-2-KMS1/2020 reinfection would be useful in the immunological and protective evaluation of vaccines. In addition, reinfections were validated in homologous and heterologous VOC variants, including B.1.1.7 (Alpha), B.1.351 (Beta), and Delta variants [ 22 , 23 ]. Importantly, we demonstrated that nasal mucosa is exploited by SARS-CoV-2 for replication and shedding during reinfection.…”

“…In addition, the mean serum neutralizing antibody titer was approximately 1:427 at 14 dpi in infected animals, while the titer was just 1:16–1:32 in infected rhesus monkeys. Interestingly, Syrian hamsters are susceptible to reinfection, and the known data mainly demonstrated shedding in the upper respiratory tracts [ 22 , 23 ]. Here, we used Syrian hamsters to investigate the clinical and infectious features in the tissues in reinfection.…”