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. The emergence and global spread of SARS-CoV-2 variants of concern (VOCs) has expanded the range of susceptible host species. Previous experimental infection studies in cattle using Wuhan-like SARS-CoV-2 isolates suggested 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. 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. The co-infection resulted in a high proportion of calves shedding SARS-CoV-2 RNA at 1- and 2-days post-challenge (DPC). Extensive tissue distribution of SARS-CoV-2 RNA was observed at 3 and 7 DPC and infectious virus was recovered from two calves at 3 DPC. Next-generation sequencing revealed that only the SARS-CoV-2 Delta variant was detected in clinical samples and tissues. 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.
Acknowledgements
We thank the staff of KSU Biosecurity Research Institute, the histology laboratory at the Kansas State Veterinary Diagnostic Laboratory (KSVDL), members of the Histology and Immunohistochemistry sections at the Louisiana Animal Disease Diagnostic Laboratory (LADDL), the Comparative Medicine Group staff at Kansas State University and technical support from Yonghai Li and Baolin Wang. We also thank Kyeong-Ok Chang for the Vero E6/TMPRSS2 cells used in these studies, Roman Pogranichniy for providing the bovine coronavirus antibodies. The SARS-CoV-2/Delta (hCoV-19/USA/NYMSHPSP-PV29995/2021; lineage B.1.617.2, clade GK) strain was obtained from Viviana Simon (Mount Sinai Pathogen Surveillance program) via Michael Schotsaert (Icahn School of Medicine at Mount Sinai), and the SARS-CoV-2 Omicron BA.2 strain was acquired from BEI Resources (NR-56520; Manassas, VA, USA).
Disclosure statement
The J.A.R. laboratory received support from Tonix Pharmaceuticals, Xing Technologies and Zoetis, outside of the reported work. J.A.R. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections, owned by Kansas State University, Manhattan, KS, USA. The M.S. laboratory has received unrelated research funding in sponsored research agreements from ArgenX BV, Moderna, 7Hills Pharma and Phio Pharmaceuticals, which has no competing interest with this work. The A.G.-S. laboratory has received research support from GSK, Pfizer, Senhwa Biosciences, Kenall Manufacturing, Blade Therapeutics, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma, Applied Biological Laboratories and Merck, outside of the reported work. A.G.-S. has consulting agreements for the following companies involving cash and/or stock: Castlevax, Amovir, Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Pagoda, Accurius, Esperovax, Farmak, Applied Biological Laboratories, Pharmamar, CureLab Oncology, CureLab Veterinary, Synairgen, Paratus and Pfizer, outside of the reported work. A.G.-S. has been an invited speaker in meeting events organized by Seqirus, Janssen, Abbott and Astrazeneca. A.G.-S. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside of the reported work. Mention of trade names or commercial products in this publication is solely for the purpose of providing specific information and does not imply recommendation or endorsement by the U.S. Department of Agriculture. The conclusions in this report are those of the authors and do not necessarily represent the views of the USDA. USDA is an equal opportunity provider and employer.