Tessa Prince

COVID-19 is a spectrum of clinical symptoms in humans caused by infection with SARS-CoV-2. The coalescence of SARS-CoV-2 with seasonal respiratory viruses, particularly influenza viruses, is a global health concern. To understand this, transgenic mice expressing the human ACE2 receptor (K18-hACE2) were infected with influenza A virus (IAV) followed by SARS-CoV-2 and the host response and effect on virus biology was compared to K18-hACE2 mice infected with IAV or SARS-CoV-2 alone. The sequentially infected mice showed reduced SARS-CoV-2 RNA synthesis, yet exhibited more rapid weight loss, more severe lung damage and a prolongation of the innate response compared to the singly infected or control mice. Sequential infection also exacerbated the extrapulmonary encephalitic manifestations associated with SARS-CoV-2 infection. Conversely, prior infection with a commercially available, multivalent live-attenuated influenza vaccine (Fluenz Tetra) elicited the same reduction in SARS-CoV-2 RNA synthesis, albeit without the associated increase in disease severity. This suggests that the innate immune response stimulated by IAV inhibits SARS-CoV-2. Interestingly, infection with an attenuated, apathogenic influenza vaccine does not result in an aberrant immune response and enhanced disease severity. Taken together, the data suggest coinfection (‘twinfection’) is deleterious and mitigation steps should be instituted as part of the comprehensive public health and management strategy of COVID-19.

The recent SARS-CoV-2 pandemic has brought many questions over the origin of the virus, the threat it poses to animals both in the wild and captivity, and the risks of a permanent viral reservoir developing in animals. Animal experiments have shown that a variety of animals can become infected with the virus. While coronaviruses have been known to infect animals for decades, the true intermediate host of the virus has not been identified, with no cases of SARS-CoV-2 in wild animals. The screening of wild, farmed, and domesticated animals is necessary to help us understand the virus and its origins and prevent future outbreaks of both COVID-19 and other diseases. There is intriguing evidence that farmed mink infections (acquired from humans) have led to infection of other farm workers in turn, with a recent outbreak of a mink variant in humans in Denmark. A thorough examination of the current knowledge and evidence of the ability of SARS-CoV-2 to infect different animal species is therefore vital to evaluate the threat of animal to human transmission and reverse zoonosis.