Efficient direct and limited environmental transmission of SARS-CoV-2 lineage B.1.22 in domestic cats (preprint)

Susceptibility of domestic cats for infection with SARS-CoV-2 has been demonstrated by several experimental studies and field observations. We performed an extensive study to further characterize transmission of SARS-CoV-2 between cats, both by direct contact as well as by indirect contact. To that end, we estimated the transmission rate parameter and the decay parameter for infectivity in the environment. Using four groups of pair-transmission experiment, all donor (inoculated) cats became infected, shed virus and seroconverted, while three out of four direct contact cats got infected, shed virus and two of those seroconverted. One out of eight cats exposed to a SARS-CoV-2-contaminated environment became infected but did not seroconvert. Statistical analysis of the transmission data gives a reproduction number R0 of 2.18 (95% CI: (0.92-4.08), a transmission rate parameter {beta} of 0.23 day-1 (95% CI: 0.06-0.54), and a virus decay rate parameter of 2.73 day-1 (95% CI: 0.77-15.82). These data indicate that transmission between cats can be sustained (R0>1), however, infectiousness of a contaminated environment decays rapidly (mean duration of infectiousness 1/2.73 days). Infections of cats via exposure to a SARS-CoV-2-contaminated environment cannot be excluded if cats are exposed shortly after contamination.

Influenza infection in ferrets with SARS-CoV-2 infection history (preprint)

Non-pharmaceutical interventions (NPIs) to contain the SARS-CoV-2 pandemic drastically reduced human-to-human interactions, decreasing the circulation of other respiratory viruses as well. As a consequence, influenza virus circulation - normally responsible for 3-5 million hospitalizations per year globally - was significantly reduced. With downscaling the NPI countermeasures, there is a concern for increased influenza disease, particularly in individuals suffering from post-acute effects of SARS-CoV-2 infection. To investigate this possibility, we performed a sequential influenza H1N1 infection 4 weeks after an initial SARS-CoV-2 infection in the ferret model. Upon H1N1 infection, ferrets that were previously infected with SARS-CoV-2 showed an increased tendency to develop clinical symptoms compared to the control H1N1 infected animals. Histopathological analysis indicated only a slight increase for type II pneumocyte hyperplasia and bronchitis. The effects of the sequential infection thus appeared minor. However, ferrets were infected with B.1.351-SARS-CoV-2, the beta variant of concern, which replicated poorly in our model. The histopathology of the respiratory organs was mostly resolved 4 weeks after SARS-CoV-2 infection, with only reminiscent histopathological features in the upper respiratory tract. Nevertheless, SARS-CoV-2 specific cellular and humoral responses were observed, confirming an established infection. Thus, there may likely be a SARS-CoV-2 variant-dependent effect on the severity of disease upon a sequential influenza infection as we observed mild effects upon a mild infection. It, however, remains to be determined what the impact is of more virulent SARS-CoV-2 variants.

Rapid Application of the Molecular Clamp Platform for SARS-CoV-2 (preprint)

Efforts to develop and deploy effective vaccines against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continue at pace. Here we describe rational antigen design through to manufacturability and vaccine efficacy, of a prefusion-stabilised Spike (S) protein, Sclamp. This strategy uses an orthogonal stabilisation approach compared to canonical vaccines, in combination with the licensed adjuvant MF59 (Seqirus). In mice, the Sclamp vaccine elicits high levels of neutralising antibodies, as well as broadly reactive and polyfunctional S-specific CD4+ and cytotoxic CD8+ T cells in vivo. In the Syrian hamster challenge model (n = 70), vaccination results in reduced viral load within the lung, protection from pulmonary disease, and decreased viral shedding in daily throat swabs which correlated strongly with the neutralising antibody level. The Sclamp vaccine candidate is currently completing Phase 1 clinical evaluation, in parallel with large-scale commercial manufacture for pivotal efficacy trials and potential widespread distribution.Funding: This work was funded by CEPI.Conflict of Interest: K.J.C., D.W. and P.R.Y. are inventors of the “Molecular Clamp” patent, US 2020/0040042.