Experimental co-infection of calves with SARS-CoV-2 Delta and Omicron variants of concern

Authors: COOL, KONNER - Kansas State University; GAUDREAULT, NATASHA - Kansas State University; TRUJILLO, JESSIE - Kansas State University; MOROZOZ, IGOR - Kansas State University; MCDOWELL, CHESTER - Kansas State University; BOLD, DASHZEVEG - Kansas State University; SOUZA-NETO, JAYME - Kansas State University; MATIAS-FERRERYA, FRANCO - Kansas State University; RETALLICK, JAIME - Kansas State University; SINGH, GAGANDEEP - Mount Sinai School Of Medicine; SCHOTSAERT, MICHAEL - The Icahn School Of Medicine At Mount Sinai; CAROSSINO, MARIANO - Louisana State University; BALASURIYA, UDENI - Louisana State University; Wilson, William - Bill

Submitted to: Emerging Microbes & Infections
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/4/2023
Publication Date: 12/30/2023
Citation: Cool, K., Gaudreault, N.N., Trujillo, J.D., Morozoz, I., McDowell, C., Bold, D., Souza-Neto, J., Matias-Ferrerya, F., Retallick, J., Singh, G., Schotsaert, M., Carossino, M., Balasuriya, U.B., Wilson, W.C. 2023. Experimental co-infection of calves with SARS-CoV-2 Delta and Omicron variants of concern. Emerging Microbes & Infections. 13(1). Article 2281356. https://doi.org/10.1080/22221751.2023.2281356.
DOI: https://doi.org/10.1080/22221751.2023.2281356

Interpretive Summary: COVID-19 disease is caused by a virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has repeatedly crossed the species barrier with natural infections reported in various domestic and wild animal species. Previous experimental infection studies in cattle using original strain of SARS-CoV-2 resulted in limited virus replication and no transmission to contact animals, suggesting that cattle were not likely amplifying hosts for SARS-CoV-2. However, new strains of SARS-CoV-2 have emerged. This study investigated the susceptibility and transmission of the two new variants of concern in cattle. The results suggest that cattle are more permissive to infection with the new variant strains of SARS-CoV-2 but, in the absence of horizontal transmission, are not likely to be reservoir hosts for currently circulating two SARS-CoV-variants.

Technical Abstract: Since emerging in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has repeatedly crossed the species barrier with natural infections reported in various domestic and wild animal species. High rates of SARS-CoV-2 infection and viral mutation have resulted in the emergence and global spread (dissemination) of SARS-CoV-2 variants of concern (VOCs), several of which have an expanded range of susceptible host species. It is therefore necessary to continue surveillance of species which have close contact with humans and could potentially act as a reservoir for SARS-CoV-2. Previous experimental infection studies in cattle using Wuhan-like SARS-CoV-2 isolates resulted in limited virus replication and no transmission to contact animals, suggesting that cattle were not likely amplifying hosts for SARS-CoV-2. However, SARS-CoV-2 sero- and RNA-positive cattle have since been identified in Europe, India, and Africa, all coinciding with the Delta wave of SARS-CoV-2 emergence and transmission in humans. Here, we investigated the susceptibility and transmission of the Delta and Omicron SARS-CoV-2 VOCs in cattle. Eight Holstein calves were co-infected orally and intranasally with a mixed inoculum of SARS-CoV-2 VOCs Delta and Omicron BA.2. Twenty-four hours post challenge, two sentinel calves were introduced to evaluate virus transmission. During the 20-day study period, clinical signs were monitored daily, and clinical samples and tissues were collected at defined time points post challenge. Serological, histological, and molecular methods, including next-generation sequencing, were used to evaluate samples and determine the extent of SARS-CoV-2 infection and examine the competition of the two SARS-CoV-2 VOC isolates. Our results indicate that calves are permissive to infection with the SARS-CoV-2 Delta variant, whereas the SARS-CoV-2 Omicron BA.2 variant was not detected in clinical samples nor tissues. Infection with the SARS-CoV-2 Delta VOC resulted in a high proportion of calves shedding SARS-CoV-2 RNA at 1- and 2-days post-challenge (DPC), with extensive tissue distribution of the virus at 3 and 7 DPC. However, similar to previous experimental infection studies in cattle, we observed only limited seroconversion and no clear evidence of transmission to sentinel calves. Together, our findings suggest that cattle are more permissive to infection with SARS-CoV-2 Delta than Omicron BA.2 and Wuhan-like isolates but, in the absence of horizontal transmission, are not likely to be reservoir hosts for currently circulating SARS-CoV-2 variants.