Natural SARS-CoV-2 infection in farmed minks causes lung pathology, systemic viral spread, and transmission risk, even in asymptomatic animals

Sandra Vreman^1*Giuseppe Giglia^2,3Robert-Jan Molenaar⁴Renate Hakze - Van Der Honing⁵Eveline Delemarre⁶Stefan Nierkens⁶Katrin E Wiese⁵Gianfilippo Agliani²Wim HM VanderPoel⁵Frank van Kuppeveld²Berend-Jan Bosch²Erwin de Bruin²Andrea Grone²Naomi D. De Bruijn⁴Judith van den Brand-Garritsen^2*

• ¹Wageningen Bioveterinary Research, Wageningen University and Research, Lelystad, Netherlands
• ²Department of Biomolecular Health Sciences, Universiteit Utrecht Faculteit Diergeneeskunde, Utrecht, Netherlands
• ³Universita degli Studi di Perugia Dipartimento di Medicina Veterinaria, Perugia, Italy
• ⁴Gezondheidsdienst voor Dieren BV, Deventer, Netherlands
• ⁵Wageningen Bioveterinary Research, Lelystad, Netherlands
• ⁶Center for Translational Immunology, Universitair Medisch Centrum Utrecht, Utrecht, Netherlands

Abstract In 2020, the first disease outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in farmed minks was reported in the Netherlands, followed by outbreaks in other countries. The disease in minks is characterized by interstitial pneumonia and viral replication in both the upper and lower respiratory tracts, resulting in respiratory disease and, in some cases, death. A major concern, besides animal health problems, is that minks are a potential reservoir for SARS-CoV-2, with a zoonotic impact for human Coronavirus Disease-19 (COVID-19), underscoring the need for close monitoring of infections. To better understand the dynamics of viral spread and disease progression after natural infection, this study investigates the pathology, immunohistochemistry, virology, serology, proteomics, and the presence of Aleutian Disease Virus (ADV) in minks from an infected farm. A total of 45 minks were divided into four groups based on clinical health status and time of sampling: found dead before culling (FD, n=15), clinically healthy during culling (NCSc, n=10), clinical signs during culling (CSc, n=10), and found dead during culling (FDc, n=10). Histopathological examination revealed that interstitial pneumonia was the most prominent SARS-CoV-2-related finding across all four groups, with more severe lesions seen in the FD and FDc groups. Histopathological changes were supported by viral antigen expression in the nose, trachea, and lungs, as well as in extra-respiratory tissues such as the intestine, spleen, and lymph nodes, in all groups. Highest viral RNA levels were found in nasal and throat swabs and nose and lung tissues. Lower levels were detected in the spleen, liver, and intestine, especially in the FDc animals. Serology confirmed the presence of SARS-CoV-2 specific antibodies in all groups, whereas immune-related proteomics on whole blood did not show a significant difference between the groups. Based on qPCR, over 57% of minks were co-infected with ADV. 13JAN2026-V2 In conclusion, minks naturally infected with SARS-CoV-2 exhibit severe lung pathology and high viral loads across multiple organs. Additionally, severe lung lesions are also observed in animals without clinical signs, suggesting a potential zoonotic risk and viral spread in the absence of any clinical signs.