Reducing feline coronavirus antibody titer in cured cats

How Oliver’s reducing feline coronavirus antibody titre ruled out feline infectious peritonitis: and Skywise’s significant reduction in FCoV antibody titre showed that he had recovered from FIP, rather than being in remission

By: Diane D. Addie, Johanna Covell-Ritchie, Mark Fosbery

This short case study illustrates a couple of important points for both the veterinarians and guardians of cats who have recovered from feline infectious peritonitis (FIP).

The first point is huge anxiety about the health of one’s cats after an encounter with FIP, and a tendency to believe that any illness appearing in the FIP-recovered cat, or any of his housemates, is FIP: we call this syndrome post-FIP stress disorder or post-FIP PTSD.   The second point of this story is that a falling feline coronavirus (FCoV) antibody titre demonstrates conclusively that the cat is not suffering from FIP and has fully recovered from coronavirus infection, which brings relief to his or her guardian and frees up the veterinary surgeon’s attention to concentrate on discovering what is really wrong with the cat.

Johanna’s cat Skywise (before treatment, see left) was successfully treated for non-effusive FIP with an adenosine nucleoside analogue drug called Mutian (Nantong Biotechnology, China), followed by oral feline interferon (Virbagen Omega, Virbac, France). Addie et al, 2020b  Skywise had become blind in his one remaining eye due to FIP uveitis (he lost his other eye in kittenhood); happily he recovered his sight after treatment (see right), which also included a few days of prednisolone eye drops.

MOST CATS INFECTED WITH FELINE CORONAVIRUS DO NOT DEVELOP FIP

Skywise’s case study was published in the journal Viruses, Addie et al, 2020b and if you read that report, you’ll know that three of the four of Skywise’s housemates were also shedding feline coronavirus (FCoV)  in their faeces (see Table 1).  Although FCoV is the virus that causes FIP, most cats who get infected with FCoV do not develop FIP, just as most people who become infected with human coronavirus don’t get sick.

TREATING CATS IN CONTACT WITH AN FIP CAT TO STOP VIRUS SHEDDING PREVENTS RE-INFECTION OF THE FIP-RECOVERED CAT.

Skywise’s housemate cats were treated with a five day course of Mutian pills to stop virus shedding, in order to prevent re-infection of Skywise, because we didn’t want him to suffer a relapse of FIP.

Table 1. Feline coronavirus (FCoV) antibody titre and RT-qPCR C_T results.

yo—year old. C_T – Cycle threshold of FCoV RT-qPCR test performed on a faecal sample to detect viral RNA. Neg- negative.

Skywise was treated with a 50 day Mutian course beginning in April 2020, and the other FCoV-infected cats got a 5 day course. By May 2020 the household was clear of FCoV.

A SIGNIFICANTLY REDUCING FCOV ANTIBODY TITRE RULED OUT FIP IN OLIVER

In November 2020, Oliver (see right) presented to his attending veterinary surgeon, Mark, with acute back pain and a fever of 41oC.  Naturally, after her experience with Skywise, Johanna was extremely worried that Oliver might have developed FIP.  Diane was also concerned because a painful tail can be an early sign of coronavirus related hydrocephalus in the brain; although Oliver’s back pain was lumbar, not around the tail base.  So a FCoV antibody test was performed.  Previously, in March of 2020, Oliver had a very high FCoV antibody titre of over 10, 240 (see Table 1) but happily his November test showed that his FCoV antibody titre had fallen to only 40!  This result was conclusive evidence that Oliver’s back pain was not due to FIP.

Diane was especially delighted by Oliver having eradicated FCoV from his body, because when people use Mutian to stop their cats shedding FCoV, one of the questions that remains is whether or not FIP has been prevented in that cat?  Addie et al, 2020a    She was particularly  worried about the possibility of virus remaining in Oliver’s brain, because relapses in GC376-treated cats had often presented with neurological signs, Pedersen et al, 2018  likely due to failure of the GC-376 protease inhibitor to clear virus from the brain: some drugs don’t cross the blood-brain barrier very effectively.  Diane had seen a couple of relapsing FIP cases begin with painful tails prior to developing ataxia, then seizures.   However, a falling FCoV antibody titre indicated that coronavirus had been eliminated from everywhere in Oliver’s body, not just his gut.

Oliver was treated with antibiotics and painkillers, and made an excellent recovery.  We think that he had been bitten by a false widow spider, which are present in Johanna’s garden.

HUGE REDUCTIONS IN FCOV ANTIBODY TITRES SHOWED THAT CORONAVIRUS HAD BEEN ELIMINATED FROM JOHANNA’S CATS

Since Skywise had FIP, Johanna has been worried about whether the other cats in her household could develop FIP too, even though they were no longer shedding virus, we didn’t know if the short course of Mutian had cleared the whole body of virus, or only the gut. Addie et al, 2020a

Johanna was so pleased with Oliver’s FCoV antibody test result that she then had her other four cats FCoV antibody tested.  Paddy’s (see above) FCoV antibody titre had also dropped considerably: from over 10,240 to 80; Link’s had dropped to 160, and Zelda’s (see right) had stayed the same at 640 (Table 1).

In antibody testing, a more than three-fold dilution reduction is counted as being significant, in other words, not simply due to normal variations in the test. It would appear that the laboratory uses doubling dilutions of the cat’s plasma or serum, beginning with a one in ten (1:10) dilution, then doubling: 1:20, 1:40, 80, 160, 320, 640, 1280, 2560, 5120, 10,240.  Therefore – to take Skywise’s titre as an example – it had fallen four-fold from >10,240 to 640.

SKYWISE’S FCOV ANTIBODY TITRE REDUCTION WAS EVIDENCE THAT HE HAD RECOVERED FROM FIP, RATHER THAN BEING IN REMISSION

The big surprise was that Skywise’s FCoV antibody titre had reduced from over 10,240 to 640 so quickly (in just 8 months), showing that he had recovered from FIP (i.e. he wasn’t simply in remission), therefore it was safe for him to stop his oral Virbagen Omega treatment. These FCoV antibody test results reassured Johanna to know that coronavirus was no longer present in her cats.

When an animal encounters a coronavirus, he makes antibodies to it, but when the immune system (or treatment) successfully eliminates the virus from the body, gradually over time there are fewer and fewer anti-FCoV antibodies, although the body retains the blueprint and is able to quickly make antibodies again if it needs to.  Making antibodies costs the body energy, and of course the globulins themselves thicken the blood, so the body stops making antibodies when there is no longer antigenic stimulus, but it keeps memory T cells with the blueprint so it can rapidly make antibodies again if exposed again to the infectious agent.

Clearly it was important that the FCoV antibody test used for Johanna’s cats gave an accurate indication of antibody quantity (i.e. antibody titre), and did not simply report a positive or negative result. Addie et al, 2015

CONCLUSION

A negative FCoV antibody test, or significantly falling antibody titre, is useful in ruling out FIP in a sick cat.  A huge reduction in FCoV antibody titre differentiates a cat who has recovered from FIP from one who is simply in remission, and this brings comfort to FIP cat guardians who are worried about relapses in their FIP-recovered cats, or about a new case of FIP developing in one of the other cats in their household.

References

Addie DD, le Poder S,  Burr P, Decaro N, Graham E, Hofmann-Lehmann R, Jarrett O, McDonald M, Meli ML. 2015.  Utility of feline coronavirus antibody tests.  J. Feline Med Surg. 17(2):152-62.

Addie DD.  Curran S, Bellini F, Crowe B, Sheehan E,  Ukrainchuk L, Decaro N.  2020a. Oral Mutian® X stopped faecal feline coronavirus shedding by naturally infected cats.   Res. Vet. Sci. 130:222-229.. doi: 10.1016/j.rvsc.2020.02.012.

Addie DD, Covell-Ritchie J, Jarrett O, Fosbery M. 2020b. Rapid Resolution of Non-Effusive Feline Infectious Peritonitis Uveitis with an Oral Adenosine Nucleoside Analogue and Feline Interferon Omega. Viruses 12, 1216; doi:10.3390/v12111216

Pedersen NC, Kim Y, Liu H, Galasiti Kankanamalage AC, Eckstrand C, Groutas WC, Bannasch M, Meadows JM, Chang KO. 2018. Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis. J. Feline Med. Surg.  20 (4): 378-392.