What the cat tells us about Covid-19

Original article: What the cat tells us about Covid-19

Jean-Marc Sabatier

The article uses the term FIP repeatedly for the common non-mutated enteric coronavirus FCoV, probably for simplicity. However, the essence remains the same. (Translator's note)

The scientific community is concerned about a new coronavirus that appeared a year and a half ago in China. Jean-Marc Sabatier * first makes an analogy between coronavirus infectious peritonitis in cats or FIP (non-human transmissible) and SARS-CoV-2, which is caused by Covid-19. A better understanding of the complex physiological phenomena common to both viruses may provide a definitive medical response to a pandemic in the future. An interview.

In collaboration with the heads of the State Virology Laboratory in Wuhan (China), professors Zhijian Cao and Yingliang Wu and veterinarians Pierre Petruzzi (Clinique Vétérinaire de l'Albanne in Barberaz, Savoie) and Philippe Durieux (CHV Les Cordeliers, Meaux), you pointed out the striking similarities between feline disease and Covid-19. Can you explain that to us?

Feline infectious peritonitis (FIP) is a feline viral disease caused by alpha-coronavirus, while SARS-CoV-2 responsible for Covid-19 is a beta-coronavirus. These are related viruses. FIP is contagious to cats, but is not transmitted to other species, including humans. The FIP has been well known and documented since the 1980s. FIP viruses are known to be enteric coronaviruses that have become pathogenic due to mutation (s) and affect either young cats (aged 3 months to 3 years) or older cats (aged 10 to 15 years). FIP-related pathologies are similar to Covid-19 diseases.

What does it mean?

The clinical signs of FIP are very diverse, as in Covid-19, and the disease is divided into "dry" and "wet" forms. The dry form can affect the eyes, can cause granulomatous inflammation of the lungs, kidneys, liver, central nervous system, ganglia, intestines with possible neurological disorders…
The wet form is manifested by effusions in the abdomen or chest, pleurisy (pleurisy), peritonitis (peritonitis), which are also well defined in the case of Covid-19.
Other clinical manifestations are common to both forms of disease: organ inflammation, thrombosis, thrombocytopenia, coagulopathy, etc.
Dry and wet forms can coexist or follow each other. FIP virus infection of macrophages is responsible for the fatal granulomatous vasculitis of cats.

What else do we know about this feline disease?

The FIP virus can be latent and harmless for years (up to 14 or 15 years) or it can multiply and become fatal in a short period of time. Progression to severe form takes an average of 2 to 5 weeks. Cats cannot transmit the FIP virus to humans, but cats can be (exceptionally) infected with SARS-CoV-2, which causes Covid-19. The latency observed with FIP raises the question of the possible latency of Sars-CoV-2 given the similarity between the two viruses.

How is the virus transmitted between cats?

The virus is transmitted from mother to kittens. The virus is present in feces and can easily infect other cats, especially in shelters and kennels.

What are the similarities between feline viruses and SARS-CoV-2?

FIP and SARS-CoV-2 viruses are single-stranded, positive RNA-coated coronaviruses. This means that although one is of the alpha genus and the other of the beta genus, both are closely related and have a zoonotic origin.
In reality both viruses attack the host renin-angiotensin system (RAS) and over-activation of this system causes comparable disorders and pathologies, even though the two viruses act on different cellular receptors.
The FIP virus has a molecule called aminopeptidase N (APN) as a cellular receptor. It is a surface receptor found in the intestines, kidneys, lungs, epithelial and endothelial cells, etc. APN converts angiotensin-3 to angiotensin-4. Angiotensin 3 targets the AT1R receptor, which is responsible for Covid-19.

And what about another virus, SARS-CoV-2?

SARS-CoV-2 binds to the ACE2 receptor and leads to an increase in angiotensin 2, which in turn leads to overactivation of the AT1R receptor, which is very harmful because it is responsible for Covid-19. In other words, the two viruses target the AT1R receptor (feline or human) in different ways.
It is important to understand that APN and ACE2 are components of RAS, which is the main physiological system important for the functioning of the body, whether it is renal, cardiovascular or pulmonary functions. It is also involved in the intestinal microbiota and innate immunity, both in cats and humans.

What do you deduce from this?

FIP diseases caused by the FIP virus are comparable to diseases caused by SARS-CoV-2. There is no specific treatment for the cat other than symptomatic medications. RAS inhibitors are needed.We already know, of course, that there is a cure (Translator's note).

Is there no vaccine for FIP?

Vaccination experiments were performed using inactivated FIP virus. Young cats were vaccinated with an avirulent strain of the virus. However, this vaccination did not protect them from the oral route of virulent virus infection. In contrast, vaccinated animals were more easily infected than unvaccinated cats.
This lack of protection suggests the existence of a phenomenon called ADE (antibody-dependent amplification). ADE leads to a sequence of events that can be found in several viral diseases (HIV, Dengue, Ebola…). Viruses infect cells by a mechanism that relies on the interaction between so-called "facilitating" antibodies (as opposed to protective "neutralizing" antibodies) and the virus.

This is unexpected. So can the vaccine support the disease?

Indeed, "facilitating" antibodies allow the virus to better penetrate target cells. This mechanism to facilitate virus infection of cells would be problematic if it were also present during SARS-CoV-2 vaccination. Treatment would then be worse than the disease. However, the problem posed by ADE during vaccination can be circumvented.

* Jean-Marc Sabatier, Director of Research at CNRS and Doctor of Cell Biology and Microbiology, working with the Institute of Neurophysiopathology (INP), University of Aix-Marseille. Editor-in-Chief of the international scientific journals "Coronaviruses" and "Infectious Disorders - Drug Targets" (DR)