What Is Happening to the Cats of Cyprus?

By Lambert Strether of Corrente.

You’ve seen the horrifying headlines:

Feline coronavirus kills 300,000 cats in Cyprus – and many more could die if the strain reaches Britain Daily Mail (Links 7/13/2023).

Cyprus becomes ‘island of dead cats’ after outbreak of feline coronavirus kills 300,000 Daily Telegraph

The Mediterranean ‘island of cats’ is facing disaster as 300,000 felines are estimated to have died from COVID, say animal advocates Business Insider

Deadly virus kills 300,000 cats in Cyprus; Europe in danger of new coronavirus pandemic Greek City Times (an English-language media property located in Sydney, Australia).

However, that 300,000 figure is, as we say, baseless (or at least not entirely based). So the ailurophiles among us can heave a sigh of relief; although the cats are in danger, we don’t have a firm body count. Moreover, headlines that read “Coronavirus” (Daily Mail) are correct; headlines that read “COVID” (Business Insider) are wrong. This coronavirus is not SARS-Cov-2, but a very interesting virus in its own right; so I won’t be going all ultra virus, here, since coronaviruses seem to be my beat.

For fun, I will first look at the Cypriot cat. Then I will look at feline coronavirus infection, that 300,000 figure, how feline coronavirus is transmitted, whether it will spread beyond Cyprus, and finally the mechanism of the virus itself, which is unsettlingly intriguing.

Cypriot Cats

Here’s a photo of a Cypriot cat in Limassol, Cyprus:

About 6 kilometers to the east of Limassol there lies an archeological dig, Shillourokambos, which gives the earliest dating for a domesticated cat: 9500BC. From Science, 2004 (original, “Early Taming of the Cat in Cyprus“):

For the past decade Jean-Denis Vigne, an archaeologist at the Natural History Museum in Paris, and his colleagues have been analyzing animal bones from an archaeological dig at a town called Shillourokambos in Cyprus. The site had provided detailed evidence of the island’s first human residents, Neolithic farmers who arrived as early as 10,000 years ago, probably from Turkey.

[I]n 2001, a colleague working on the 9500-year-old burial of a 30-year-old human found the remains of a cat. The two sets of bones were less than a half-meter apart, buried at the same depth and in the same sediment, with the same degree of preservation, strongly suggesting that they were buried together…

The cat bones were articulated, indicating that the animal was intentionally buried with the human, possibly to accompany its owner to the hereafter, says Vigne. He argues that it was very likely a tame cat, because wild animals, when they were buried at all at this time, were represented only by isolated bones. If correct, that interpretation puts cat domestication about 3000 years after dogs became man’s best friend and very close to the time that wheat and sheep were domesticated.

“In lieu of finding a bell around its neck, this is about as solid evidence as one can have that cats held a special place in the lives and afterlives of residents of this site,” says zooarchaeologist Melinda Zeder of the Smithsonian National Museum of Natural History in Washington, D.C., who was not involved with the study. Until this find, the oldest evidence of tame cats came from Egypt, where 4000-year-old remains and paintings document cats’ place of honor in that culture.

Perhaps because Cyprus cats have had so long to co-evolve with humans, they are very sweet-natured. From the Greek Reporter, “The Adorable Native Cat Breeds of Greece and Cyprus“:

Cyprus cats, unlike most Aegean cats, tend to be extremely energetic and athletic. They have a thick coat, which can be short or semi-long.

They are extremely playful and social and love to be around humans. They’re also great hunters. Cyprus cats are commonly tabby with a mix of white but can be found in a variety of colors, ranging from ginger to black.

Like Aegean cats, Cyprus cats are common in their native country but very rare in the rest of the world.

The Infection: FCoV and FIP

Sky News gives a simplified explanation of the infection, which I will unsimplify below. But for now:

Feline Coronavirus (FCoV[1]) is a common and contagious virus in cats. Feline Infectious Peritonitis (FIP) is a disease caused by feline coronavirus (FCoV), which is almost always fatal.

Keep the acronyms and the sequence FCoV -> FIP in mind, because the coverage often conflates them. More:

Dr Nathalie Dowgray, head of the International Society of Feline Medicine, said the outbreak was “very concerning” for cats, cat owners and vets in Cyprus.

“For many, including stray cats, treatment will likely not be possible and sadly this will likely result in significant mortality.

You may wish to know the symptoms to watch for:

FIP is hard to diagnose but most cats with the virus will have a fever, appear lethargic and go off their food.

There are two types of the virus – wet FIP and dry FIP.

In cats with the former, fluid builds up in the abdomen or chest, causing swelling.

“We tend to see cats presenting with a large fluid-filled belly and breathing difficulties, who are increasingly lethargic and picky with their food,” Dr Lewis said.

Cats with dry FIP have less fluid build-up but may have a poor appetite, high temperature and vision problems.

FIP is more likely to develop in young cats between three months and two years old.

(When they say “hard to diagnose,” they’re not kidding.) You may also wish to know if there are treatments. From The Telegraph:

The drugs are remdesivir [ironically enough!], used for Covid-19, and the closely related GS-441524. Although it is approved for use in animals in the UK, and for importation into Cyprus, it is expensive – between £2,500 and £6,000 for a cat weighing between 3kg and 4kg.

Another potential option is a cheaper antiviral used to treat Covid-19 in humans, called molnupiravir. Dr Epaminondas estimates this would cost around £170 per animal – yet an application by the vets association to authorise the treatment for cats was rejected in May, because the government said human drugs cannot be imported for use for veterinary care.

Prof Gunn-Moore urged the Cypriot government to make GS-441524, remdesivir and molnupiravir available for all cats, but said the ultimate control measure would be a vaccine.

“This is a coronavirus, so on the back of the Covid outbreak this should be very possible if the drug companies want to do this,” she said.

In the absence of government actions, some people are buying drugs themselves – and Dr Epaminondas told a Cypriot news outlet in May that there is a “flourishing” black market of cheap, unlicensed drugs.

GS-441524 is apparently an effective treatment. From Nature 2021, from a study in Wuhan, amazingly enough:

Of the 30 cats treated with GS-441524 and/or GC376, 29 were clinically cured.

A second study on GS-441524, from Viruses:

27 households were identified containing 147 cats. Thirteen cats were treated for FIP, 109 cats shed FCoV and 25 did not; a 4–7-day course of oral GS-441524 antiviral stopped faecal FCoV shedding. Follow-up was from 6 months to 3.5 years; 11 of 147 cats died, but none developed FIP. A previous field study of 820 FCoV-exposed cats was used as a retrospective control group; 37 of 820 cats developed FIP.

(We’ll have more to say about fecal shedding when we look at transmission).

Molnupiravir, also, is apparently an effective treatment. From Pathogens, 2022:

The 26 cats treated with unlicensed molnupiravir as a rescue therapy were treated with an average starting dosage of 12.8 mg/kg and an average ending dosage of 14.7 mg/kg twice daily for a median of 12 weeks (IQR = 10–15). In total, 24 of 26 cats were still living disease-free at the time of writing…. This study provides a proof of principle for the use of molnupiravir in cats and supports the need for future studies to further evaluate molnupiravir as a potentially safe and effective therapy for FIP.

Let’s just hope that molnupiravir doesn’t drive the creation of new variants (unless it already has, some black market molnupiravir already did).

And there are no recommended vaccines.

Now let’s look at how FCoV is transmittted.

FCoV Transmission

From CatVirus.com:

CoV is a very contagious virus, infecting nearly all cats who encounter it. The major source of infection is the faeces of infected cats, and uninfected cats become infected by sharing litter trays with infected cats. The second major route of infection is the unintentional exposure of uninfected cats to tiny particles of infected faeces on people’s shoes or clothing, hands, poop scoops, etc. The infected cat likely swallows the virus when grooming, or when particles of faeces contaminate their food.

FCoV is occasionally shed in the saliva, early in infection, so sharing food bowls or inhaling sneezed droplets could possibly allow infection to occur. Close contact with infected cats, for example in mutual grooming, might, rarely, result in infection.

Feline coronavirus almost never crosses the placenta to the unborn kitten. Most kittens which become infected do so after protective antibody they receive in their mother’s milk has waned, usually when they are 5-7 weeks old.

And advice on litter tray hygiene:

If your cat uses a litter tray, then make sure it is declumped as often as possible and use dedicated poop scoops for each cat pen or tray. Better still, if possible, let the cat out to go to the toilet naturally outside (I am aware that this is not always possible or desirable where there is a lot of traffic). If you have several cats, make sure that you have enough litter trays, preferably one for each cat, and get covered or even self-cleaning litter trays. Site the litter tray away from food areas so that microscopic faecal particles cannot be blown onto the cat’s food. Use a Fuller’s Earth based non-tracking cat litter, to minimise spread of microscopic particles around the house. Once or twice a week, clean your litter tray with domestic bleach (sodium hypochlorite). Do stick to bleach disinfectants, as pine based ones are toxic to cats. Vacuum as often as possible to reduce the number of contaminated cat litter particles.

Now, this is stomping on my priors, since it sounds like fomite transmission. However, that GS-44152 stopped faecal shedding in all the cats that took it, and none of them died, does suggest that the faecal route is the major one.

That 300,000 Figure

I tracked down the 300,000 figure to its source. From the Cypress Mail:

Vice president of the NGO Voice for Animals, Dinos Agiomammitis, who was mentioned by France 24 as the source for the 300,000 number, said that his words had been lost in translation.

“I don’t want people to panic, cats are not about to go extinct from the island,” Agiomammitis said.

He explained that there is a very rough and hypothetical estimate that there are 1 million cats on the island. Extrapolating from there, if a mortality rate of 20-30 per cent of infected animals dying is applied, the resulting number is 300,000, he told CyBC’s morning programme.

The director of the Veterinary Services Charalmbos Pipis told CyBC that they cannot confirm the number of 300,000 dead cats from feline infectious peritonitis.

“These data are based on estimations, since there is not an official recorded number of the cats in Cyprus,” he said.

So, the 300,000 figure is a rational calculation, but that’s not how it’s being presented in our famously free press. From locals Charalampos Attipa et al. in a letter to the Royal (Dick) School of Veterinary Studies found in the University of Edinburgh Research Explorer, “Widespread outbreak of feline infectious peritonitis (FIP) in Cyprus, with a suspected highly virulent feline corona virus strain“:

Results: There were 3 and 4 PCR-confirmed FIP cases, in 2021 and 2022 respectively, whilst to date in 2023 (January – April) 98 PCR-confirmed FIP cases were reported, which is more than a 20-fold increase… We are in the process of analysing the FCoV before and during the outbreak and establishing an epidemiological monitoring system.

So, obviously this round of FCoV is new and different, very serious, to be watched carefully, and the precautionary principle applied. But I don’t think it’s minimizing to ask that clickbait headlines be deprecated.

How FCoV Mutates into FIP

Here is a more detailed description of FCoV -> FIP, along with a new acronym: Feline Enteric Coronavirus (FeCV) which is what cats get if they do not get FIP:

Feline infectious peritonitis (FIP) is a viral disease of cats caused by certain strains of a virus called the feline coronavirus. Most strains of feline coronavirus are found in the gastrointestinal tract and do not cause significant disease. These are referred to as feline enteric coronavirus (FeCV). Cats infected with FeCV usually do not show any symptoms during the initial viral infection, but may occasionally experience brief bouts of diarrhea and/or mild upper respiratory signs from which they recover spontaneously. FeCV-infected cats usually mount an immune response through which antibodies against the virus are produced within 7-10 days of infection. In approximately 10 percent of cats infected with FeCV, one or more mutations of the virus can alter its biological behavior, resulting in white blood cells becoming infected with virus and spreading it throughout the cat’s body. When this occurs, the virus is referred to as the FIPV. An intense inflammatory reaction to FIPV occurs around vessels in the tissues where these infected cells locate, often in the abdomen, kidney, or brain. It is this interaction between the body’s own immune system and the virus that is responsible for the development of FIP. Once a cat develops clinical FIP, the disease is usually progressive and almost always fatal without therapy that has recently become available.

But how, exactly, do these “one or more mutations of the virus” happen? That’s the unsettlingly intriguing part. From Merck’s MSD Veterinary Manual:

FIP is a sporadic disease thought to be caused by viral variants that develop within each specific cat.

Holy moley![2] More:

The pathogenesis of FIP is unclear, but there are two main hypotheses. The “internal mutation theory” states that cats are infected with the primarily avirulent FCoV that replicates in enterocytes; in some cats, a mutation occurs in a certain region of the FCoV genome that creates a new phenotype with the ability to replicate within macrophages. The presence of highly virulent strains of FCoV capable of consistently inducing FIP support this theory, albeit under experimental conditions. Several researchers speculate that some circulating feline enteric coronaviruses are closer to making critical mutations necessary for development of FIP, possibly explaining FIP outbreaks. No consistent mutation has yet been identified….

Here is a handy diagram for the first hypothesis:

(c) is where “the miracle occurs”; the individual mutation within the cat. Back to the MSD manual:

The second hypothesis for the development of FIP is the existence of distinct circulating virulent and avirulent strains in a population, and exposure to the pathogenic strain, the viral load, and the cat’s immune response determine whether FIP will develop. It is likely both viral genetics and host immunity play a role. In both hypotheses, the key pathogenic event in the development of FIP is the massive replication of FCoV in macrophages. If the cat does not eliminate macrophages infected with replication-competent virus early in infection, the presence of the virus within circulating macrophages initiates an ultimately fatal arthus-type immune-mediated reaction, which defines FIP.

Unfortunately:

A consistent mutation in FCoV that leads to FIP has not been identified. Rather, FIP develops sporadically within each individual cat that becomes affected.

Feline Coronavirus (FCoV) and Feline Infectious Peritonitis (FIP) | Animal Health Topics / School of Veterinary Medicine UC Davis

So if indeed internal mutation within the individual cat is the mechanism, that is indeed concerning:

[Dr Jo Lewis, a feline veterinary surgeon] said: “What’s concerning about the evidence from the Cyprus outbreak, is that a particularly nasty FCoV mutation seems to have already occurred.”

FCoV Spread

Spread can occur in two ways: Geographically, and zoonotically (that is, from cat to human, and vice versa).

First, geographic spread. Attipa et al. recommend the following travel guidance:

The implementation of travel requirements for cats travelling from Cyprus must be a priority for UK. This is due to the high numbers of animals traveling between the two countries reflecting the historic links that exist; parts of Cyprus are British overseas territories, and a notable number of British immigrants are based permanently or seasonally in Cyprus. Previously, we have seen introduction of other infectious agents to the UK via dogs travelling from Cyprus, such as Hepatozoon canis and Leishmania infantum.

FCoV may already have spread to Lebanon, and there have been previous outbreaks in Turkey. As a sidebar, I spent too much time looking at Istanbul cat videos, but

Istanbul and cats…

pic.twitter.com/w1nLK5OMC1

— Rez 🇪🇸 (@JrRezvani) September 12, 2021

End sidebar.

Second, zoonotic spread. From Transboundary and Emerging Diseases, 2020, we see that SARS-CoV-2 and FCoV are “kissing cousins”:

SARS-CoV-2 and FCoV are taxonomically distant viruses, and recombination events with other coronaviruses have been reported for FCoV and have been suggested for SARS-CoV-2. SARS-CoV-2 and FCoV differ in terms of some pathogenic, clinical and pathological features. However, some of the pathogenic and immunopathogenic events that are well known in cats FIP seem to be present also in people with COVID-19. Moreover, preventive measures currently recommended to prevent SARS-CoV-2 spreading have been shown to allow eradication of FIP in feline households. Finally, one of the most promising therapeutic compounds against FIP, GS-441524, is the active form of Remdesivir, which is being used as one therapeutic option for COVID-19.

And more disturbingly, from Gene:

Since SARS-CoV-2 emerged at the end of December 2019, researchers have also reported that cats can be infected by common SARS-CoV-2 strains and even (Delta) variant strains from humans (Garigliany et al., 2020, Curukoglu et al., 2021, Hosie et al., 2021, Kang et al., 2021, Mohebali et al., 2022), which revealed that the fACE2 receptor could be recognized by the variant strains. The information also indicates that cats may play a special role in the transmission of SARS-CoV-2, considering the three factors: similar cellular receptor, receptor binding domain (RBD) with similar furin cleavage sites, and especially the third factor, high risk of cross-transmission between humans and cats because cats are usually in close contact with humans, especially companion animals (Stout et al., 2020). In addition, it has been reported that FCoV can infect humans (Silva et al., 2014), which indicates that cat-infecting coronaviruses, including SARS-CoV-2, can also infect humans because of virus variability and evolution, although more in-depth studies are needed. Therefore, it should be pointed out that cats might be potential hosts for producing novel variant strains of SARS-CoV-2.

Virology mavens will talk me off the ledge here — I hope! — but I think it would be very bad if some cat got both SARS-CoV-2 and FCoV churning together in its bowels, and SARS-CoV-2 picked up FCoV’s clever trick of “internal mutation” with “viral variants that develop within each specific cat,” and then went on to infect humans.[3]

Conclusion

We love our affectionate, aloof, and playful little predators, but the virus so many of them are carrying is something to watch.

NOTES

[1] “FCoV is a nonsegmented, single-stranded RNA virus that belongs to the order Nidovirales, family Coronaviridae, subfamily Coronavirinae…. The genome of the virus, which is approximately 29 kb in size, includes 11 open reading frames (ORFs) and encodes four major structural proteins: the spike (S) protein, the nucleocapsid (N) protein, the envelope (E) protein and the membrane (M) protein.” Here is a handy diagram comparing FCoV to SARS-CoV-2:

FCoV apparently emerged in the early 1950s, in the United States.

[2] Reminds me of that unidentified but massive shedder commuting from Columbus to Washington Court House, OH.

[3] Nobody’s arguing that FCoV was created in a lab, oddly.