Something has been bothering me for a while, which means this post has been brewing (stewing?) for a while.
I’m going to talk about coronaviruses. I’m going to talk about feline coronavirus, in particular, which is a distinctly different coronavirus from COVID-19.
Talking about feline coronavirus, the coronavirus that I know the most about, helps me talk about coronaviruses in general. Which then allows me to talk, a little bit, about COVID-19.
This post is a departure for me. In talking/writing about feline coronavirus on this blog, I’m breaching the barrier between my two worlds. Between my relaxing world of creativity, where I indulge myself with poetry and photos and blog posts, and my anxious world of responsibilities, where I worry about knowledge and knowledge gaps and the idea that facts about the natural world exist but are seldom fully grasped.
I’ve been talking about coronaviruses for much of the past year, but only with friends and family. And cats. Marie and Dutch are attentive listeners.
Actually, they’re not very good listeners at all.
In this post, I’m going to explain some of what I know about feline coronavirus. Then I’m going to explain why I’ve been talking to my friends and family and cats about feline coronavirus during the COVID-19 pandemic.
The coronavirus family tree
To be clear, feline coronavirus is a distinctly different virus from COVID-19.
Taxonomically, both feline coronavirus and COVID-19 belong to the subfamily orthocoronavirinae (previously called coronavirinae), but they are in different genera. COVID-19 is in the genus betacoronavirus, while feline coronavirus is in the genus alphacoronavirus.
But what do these classifications mean? Obviously, they mean that feline coronavirus and COVID-19 are somewhat related, but does “somewhat related” mean anything useful for bloggers and readers and cats?
A linguist might say It depends on what you mean by ‘useful.’ An editor might say The question needs editing before it can be answerable. And a taxonomist would likely say Please stop before you even start, because viral taxonomy follows its own rules and should not be compared to cats.
The history of the taxonomy, classification, and nomenclature of viruses is an interesting study of its own. Efforts to classify viruses began in the 1960s and continue today, with a major expansion of the classification system having been proposed as recently as 2017. Currently, the family tree of coronaviruses looks something like this (Decaro & Lorusso 2020; Kipar & Meli, 2014):
- Order – Nidovirales
- Family – coronaviridae
- Subfamily – coronavirinae (as of 2014) or orthocoronavirinae (as of 2020)
- Genus – alphacoronavirus, betacoronavirus, deltacoronavirus, and gammacoronavirus
- Subfamily – coronavirinae (as of 2014) or orthocoronavirinae (as of 2020)
- Family – coronaviridae
Beyond the genus level of classification, the coronavirus family tree branches into subgenera, species, and subspecies, with some 39 species of coronaviruses distributed across 27 subgenera (Coronaviridae Study Group of the International Committee on Taxonomy of Viruses, 2020).
But again, what do these classifications mean?
In a desperate and thoroughly unscientific attempt to answer this question, I’m borrowing an example from mammalian taxonomy. (Remember the taxonomist’s warning, that viral taxonomy should not be compared to cats? Like I said, the following comparison is thoroughly unscientific. I’ll understand if the taxonomist, or any other reader, snorts in contempt and walks away.)
In viral taxonomy, feline coronavirus and COVID-19 are in the same subfamily, but in different genera.
In mammalian taxonomy, domestic cats and bobcats are in the same subfamily, but in different genera.
The feline family tree
Dutch and Marie are domestic cats. Spoiled, pampered, much loved house cats.
Taxonomically speaking, Dutch and Marie belong in subfamily Felinae, the genus Felis, and the species catus. Put in the more familiar binomial phrasing of genus-species, Dutch and Marie are Felis catus. By comparison, bobcats also belong to the subfamily Felinae, but are classified in the genus Lynx and species rufus. So, binomially, bobcats are Lynx rufus.
To add a third, and somewhat more complicated, data point (because everything is complicated in taxonomy), Pallas’s cats are also classified in the subfamily Felinae. But some sources place Pallas’s cats in the genus Felis and other sources separate them into the genus Otocolobus. All seem to agree on a species name for Pallas’s cats–manul. So Pallas’s cats are variously listed as Felis manul, Otocolobus manul, or Felis (Otocolobus) manul.
Marie and Dutch, being pair-bonded rescue Felis catus, are clearly related to each other. Littermates, maybe. But they are only distantly related to bobcats and Pallas’s cats. Some taxonomists, those who classify Pallas’s cats in the genus Felis, might consider Marie and Dutch more closely related to Pallas’s cats than they are to bobcats. Other taxonomists, those who classify Pallas’s cats in the genus Otocolobus, might consider Marie and Dutch no more closely related to Pallas’s cats than they are to bobcats. For my purposes, it is enough to note that domestic cats, bobcats, and Pallas’s cats are all cats, but they are all distinctly different cats.
Feline coronavirus and COVID-19 are both coronaviruses, but they are distinctly different coronaviruses.
(Back to the taxonomist’s concerns: Viral taxonomy and mammalian taxonomy are, indeed, different systems. The above comparison is flagrantly unscientific. I offer it as a metaphorical demonstration of the messiness inherent in trying to describe, measure, or quantify relatedness among viruses and/or cats.)
As recently as the early 1990s, when I first entered veterinary school, there were many knowledge gaps in the story of feline coronavirus. Now research has illuminated how the virus moves within cat populations and has unraveled some of the complex mechanisms that mediate how the virus affects individual cats.
From here, for the sake of brevity and clarity, I’m going to shorten “feline coronavirus” to FCoV. For one thing, I won’t have to keep typing the whole name. For another, I want to be as clear as possible that coronaviruses are a large and varied group of viruses, while FCoV is a very specific coronavirus that infects cats. Probably even Marie and Dutch, at some point in their lives.
Yes, even you, my dears. But it’s okay, because the overwhelming majority of cats that become infected with FCoV will have few or no symptoms. Perhaps some diarrhea or other gastrointestinal signs, perhaps some upper respiratory congestion.
(There’s more to the FCoV story, which I’ll come to later. For now, I’ll simply say that I’m grateful Marie and Dutch are among the overwhelming majority of cats who have avoided the “more” part of the FCoV story.)
Marie and Dutch have likely been infected with FCoV, perhaps on multiple occasions. Because FCoV is “worldwide and ubiquitous among virtually all cat populations”, found in more than 60% of pet cats in multi-cat households and in as many as 90% of kittens in shelters (Pedersen, 2009, p. 227).
FCoV is a single-stranded RNA virus
The particular feature of FCoV that is important to this post, and that has been important in my year-long discussions with friends and family, relates to the way coronaviruses carry their genetic information. Unlike humans and cats (and most other organisms), who carry their genetic information as double strands of DNA, coronaviruses carry their genetic information as single strands of RNA. So FCoV, like all other coronaviruses, employs single-stranded RNA as the primary molecule for carrying genetic information.
Dutch and Marie always go to sleep at this point. It’s okay if you do, too. I’ve fallen asleep several times, myself. But there is a point to this post. I’m getting close to it, and my next tangent about the differences between double-stranded DNA and single-stranded RNA will get even closer.
The double helix packaging of DNA provides a relatively stable structure for passing along genetic information. Each strand of DNA serves as a sort of back-up copy for its partner strand, and the process of DNA copying actually uses this back-up feature to proofread and correct mistakes. Should a strand of DNA break, or should mistakes occur in copying a strand, the back-up copy allows enzymes to repair the breaks and remedy the mistakes. This prevents mutations. Obviously, some mutations slip through, but at a far lower rate than would otherwise occur.
Single strands of RNA are less stable genetic carriers than double-stranded DNA. RNA is a more fragile molecule than DNA, and single-stranded RNA, lacking partner strands, has no back-up copies for enzymatic proofreading. Coronaviruses do have a unique mechanism for proofreading, a complex of enzymes and proteins that proofread key genes (Robson et al., 2020), and this unique mechanism provides some stability. But rapid and frequent mutations still occur.
As a single-stranded RNA virus, FCoV does a poor job of creating exact copies of itself. Every time FCoV copies itself, errors occur. Every time (Kipar & Meli, 2014, p. 507). For that matter, FCoV mutates so often that researchers characterize the array of viruses produced in the course of a single infection as a quasispecies–a group of “related genotypes” (Kipar & Meli, 2014, p. 507). Other researchers use the term “pseudo-strain” (Emmler et al., 2020, p. 792).
In short, within any FCoV infected cat, there are many mutated versions of the FCoV they originally contracted.
FCoV and feline infectious peritonitis
The overwhelming majority of cats that become infected with FCoV will have few or no symptoms. Perhaps some diarrhea or other gastrointestinal signs, perhaps some upper respiratory congestion. But there’s more to the story.
For somewhere between about 1% (Pedersen et al., 2012, p. 20) and 12% (Addie et al., 2009, p. 594) of infected cats, their particular FCoV quasispecies mutates into one of a number of forms that are able to cause a devastating and often fatal disease: feline infectious peritonitis (FIP).
I say “able to cause” because the FIP-able quasispecies do not always cause FIP. Some cats can resist FIP, even when their FCoV infection mutates into a form capable of causing FIP. Some cats are resistant at one point in their lives and later become susceptible, others perhaps follow an opposite path. In essence, FIP occurs at intersections between rapidly mutating FCoV quasispecies and the genetics and immune systems of individual cats. When an FCoV quasispecies gains the ability to cause FIP, in a cat that never had or has lost the ability to resist FIP, a deadly cascade of disease may begin.
What I’ve just described is the internal mutation theory of FIP. Put bluntly, this theory says that every case (or cluster of cases) of FIP represents a newly mutated variant of FCoV that is newly capable of causing FIP.
And now, all tangents complete, I come to the point of this post.
FIP is not rare.
- As of 2008, FIP was “one of the leading infectious causes of death among young cats from shelters and catteries” (Pedersen, 2009, p. 225).
- “In one study, FIP was the most common single cause of disease in cats younger than 2 years of age…. An average of 1-5% of young cattery or shelter cats in the US will die from FIP, with losses in catteries higher than from shelters” (Pedersen, 2009, p. 227).
- “Up to 12% of FCoV-infected cats may succumb to FIP, with stress predisposing to the development of disease” (Addie et al., 2009, p. 594).
This is the source of my bother. (Remember the bother, all those paragraphs ago, that started this post?)
What does it all mean?
I haven’t found much information about the mutation rates of COVID-19. I feel like the data exists, at least in some rough estimate, but I’ve not found it in a reliable and readily accessible format. And, without ready access to the mutation rates of COVID-19, my frame of reference reverts to my existing knowledge about FCoV.
FCoV and COVID-19 are only distantly related, but all coronaviruses share the genetic instability that comes from having a single-stranded RNA genome. Yes, coronaviruses have a unique mechanism for some stability, but this mechanism can’t completely compensate for the instability that leads to mutations.
A vague measure of the instability of FCoV can be seen in the incidence of FIP in cats around the world. Because each case (or cluster of cases) of FIP represents an FCoV quasispecies that has newly acquired one or more of the mutations that enable FIP.
Remember those word problems in math class?
- Think about how many kittens and young cats there are in the world. (While no one counts the number of kittens born each year, the ASPCA estimates that 3.2 million cats enter US animal shelters each year…)
- Narrow the number down to all the kittens and young cats in shelters and multi-cat environments, each year. (Hint: That’s still so very many cats.)
- Between 60% and 90% of the cats in shelters or in multi-cat environments will, at some point, become infected with FCoV.
- Calculate a number that would be between 1% and 12% of FCoV-infected kittens and young cats.
That’s how many cats will develop FIP each year.
According to the internal mutation theory, that’s how many times FCoV mutates, each year, into a form capable of causing FIP in a cat that is incapable of resisting FIP. (To determine the exact number of times FCoV mutates into a form capable of causing FIP, add the times such mutations occur in a resistant cat.)
As a word problem, the math itself is not too complicated. The scope of the problem is obvious, even without exact numbers.
Limiting the emergence of variants is the point
The incidence of FIP represents a direct measure of how often one specific group of FCoV variants emerge in cats. Each case (or cluster of cases) of FIP represents a newly mutated variant of FCoV that is newly capable of causing FIP. And FIP is not rare.
I’ve spent the last year lecturing my family and friends and cats about the mutation rate of FCoV, pleading for everyone to do as much as possible to limit COVID-19’s infection cycles.
Yes, it’s true that FCoV and COVID-19 are only distantly related. (Metaphorically, about as distantly related as domestic cats are to bobcats.) But if the mutation rate of COVID-19 is even a fraction of what is seen with FCoV, the risk of new variants surges with each surge of infections.
While it is scientifically inaccurate and somewhat irresponsible to claim that more dangerous COVID-19 variants are inevitable if infections continue, it is equally inaccurate and irresponsible to claim that more dangerous variants are impossible. This, also, is the point.
P.S. Marie and Duchess (Dutch) would like me to add that they are very good listeners, all the time. It’s just that they prefer listening to things other than my voice.
Addie, D., Belák, S., Boucraut-Baralon, C. Egberink, H., Frymus, T., Gruffydd-Jones, T., Hartmann, K., Hosie, M. J., Lloret, A., Lutz, H., Marsilio, F., Pennisi, M. G., Radford, A. D., Thiry, E., Truyen, U., & Horzinek, M. C. (2009). Feline infectious peritonitis: ABCD guidelines on prevention and management. Journal of Feline Medicine and Surgery 11, 594-604. doi: 10.1016/j.jfms.2009.05.08
Coronaviridae Study Group of the International Committee on Taxonomy of Viruses (2020). The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2. Nature Microbiology 5, 536-544. https://doi.org/10.1038/s41564-020-0695-z
Decaro, N. & Lorusso, A. (2020). Novel human coronaviruses (SARS-CoV-2): A lesson from animal coronaviruses. Veterinary Microbiology 244(2020). 1-18. doi: 10.1016/j.vetmic.2020.108693
Emmler, L., Felten, S., Matiasek, K., Balzer, H.-J., Pantchev, N., Leutenegger, C., & Hartmann, K. (2020) Feline coronavirus with and without spike gene mutations detected by real-time RT-PCRs in cats with feline infectious peritonitis. Journal of Feline Medicine and Surgery 22(8). 791-799. doi: 10.1177/1098612X19886671
Kipar, A. & Meli, M. L. (2014). Feline infectious peritonitis: Still an enigma? Veterinary Pathology 51(2). 505-526. doi: 10.1177/0300985814522077
Pedersen, N. C. (2009). A review of feline infectious peritonitis virus infection: 1963-2008. Journal of Feline Medicine and Surgery 11. 225-258. doi: 10.1016/j.jfms.2008.09.008.
Pedersen, N. C., Liu, H., Scarlett, J., Leutenegger, C. M., Golovko, L., Kennedy, H., & Kamal, F. M. (2012). Feline infectious peritonitis: Role of the feline coronavirus 3c gene in intestinal tropism and pathogenicity based upon isolates from resident and adopted shelter cats. Virus Research 165, 17-28. doi: 10.1016/j.virusres.2011.12.020
Robson, F., Khan, K. S., Le, T. K., Paris, C., Demirbag, S., Barfuss, P., Rocchi, P., & Ng, W.-L. (2020). Coronavirus RNA proofreading: Molecular basis and therapeutic targeting. Molecular Cell 79, 710-727. https://doi.org/10.1016/j.molcel.2020.07.027