Rapid Resolution of severe feline infectious peritonitis using natural products


 This is the first report of a successful treatment of a severe feline infectious peritonitis (FIP) case using Lianhuaqingwen (LH) capsule, a Chinese patent medicine （natural products）and it has been used for the treatment of coronavirus disease 2019. A 1-year-old cat was diagnosed FIP and presented with severe ascites, aphagia, inflammation, breathing difficulties and weight loss. Within 22 days of LH capsule treatment, all indicators of the cat eventually returned to normal, and the ascites gradually disappeared. This case report is the first description of the clinical recovery features of a cat with a systemic FCoV infection using LH capsules.

of lymphocyte rate (Lym%) signi cantly decreased, which indicated that the lymphocytes depletion caused by the virus. Given the cat's diarrhea and breathing di culties, the SAA (markers of in ammation and tissue injury) was tested (Fig 2A). The patient received supportive care, including normal saline and protein for nutrition. Given the serve clinical presentation, the veterinarian recommends euthanasia or experimental drug GS-441524 for the cat. In consideration of the high price of the treatment with GS-441524, cat guardians have to seek to other therapies.
The guardian turned to look for help from traditional Chinese medicine. Given the cat's coronavirus infection and breathing di culties, the LH capsule was recommended, which has been prescribed in treating disease of respiratory system and endorsed by the National Heath Commission for treatment of covid-19. The FCoV and SARS-CoV-2 share partly RNA sequence identity, therefore, drug targeting viral of SARS-CoV-2 are likely to be effective for FCoV.
On November 17, 2020, the Cat "Big tangerine" was given LH capsule (table 2) three times a day, 4 capsules at a time (0.35 g per capsule) combined with antipyretics, no adverse events were observed. 24 hours later (Nov, 18, day 1), his shortness of breath relieved. He just received liquid food during these times for his continued anorexia and diarrhea. 48 hours after taking medicine (Nov, 19, day 2), the patient's condition remained largely stable, and his rst loose stools was reported; meanwhile his mental state is a bit better. He could sit licking his hair, instead of lying on the ground and panting just like a few days before. 3 days after taking the medicine (Nov, 20th), he was observed to feed himself (though in small amounts). Within the next 7 days of treatment, his appetite improved and ascites gradually decreased. His stools have been loose during this time. At the beginning of December, he was given a palpation examination, which showed the ascites almost completely disappeared. As shown in Fig.1, with the disappearance of ascites, he was estimated to be about 1.5 kg lighter, which was the lightest weight during the whole process. On Dec, 2nd, all symptoms have resolved. He began to run and play with the other cats.

Outcome and Follow-up
The patient continues to take LH capsule medication daily until on Dec.9 th . The medication period lasted for 3weeks and the symptoms did not recur after the drug withdrawal. He was taken to Guaiguai Pet Hospital on Jan, 3 rd and his blood counts and SAA level lie within the normal range, apart from total protein (8.2g/dL, Normal 5.4-8.2) and blood urea nitrogen (42mg/dL, Normal 10-30). (table 3 & Fig. 2). His specimens later tested negative by FCoV RT-PCR which meant the FCoV viral load was lower than the limit of detection. The symptoms did not recur until the report submission (Mar.17 th ).

Discussion
FIP is a fatal disease in cats caused by FCoV, which is lurking in the intestinal system. FIP is still a terminal disease with a variable time of death, over 95% of cats cat died in days to months after diagnosis [9] . The symptoms of FIP in cats comes in two forms: dry and wet [10] . The most prominent symptom of wet FIP is large effusion in the chest and abdomen [11] . The glucocorticoids such as prednisolone are used to attenuate symptoms. While once FIP ascites is diagnosed, veterinarian may generally recommend euthanasia, as there are few successful cure cases.
At present, some effective therapies have been evaluated. For instance, the successful treatment of FIP using GS441 [12] , GC376 [13] , or oral adenosine nucleoside analogue [14] was reported recently. GS441 combined with antibiotic therapy, recommended by many veterinarians, have shown good therapeutic effect. GS441 is the precursor of remdesivir, which is previously used in the COVID-19 treatment. The course of GS441 treatment takes 1-3 months, which may spend about $5,000 to $9,000 in China. Unfortunately, because of price and access channel (GS441 is not o cially listed yet), many cat guardians give up this proven effective treatment.
In this case, the veterinarian fears it's hard to survive a week without using GS441. Hence the cat guardians hoped to seek other therapies. LH Capsule, a Chinese patent medicine composed of 13 herbs is a commonly used broad-spectrum antiviral medicine developed from traditional Chinese medicine formula [15] . It has been used to treat a series of in uenza viruses such as viral cold, pneumonia and so on [16,17] Pharmacological and clinical trials showed that it can signi cantly relieve the in ammatory response by inhibiting virus replication and reducing the cytokine release from host cells [17] . And is also recommended as one of the COVID-19 adjuvant therapy drugs [6,18,19] . Hence, we initially tried to use this medicine to alleviate the in ammatory response and symptoms caused by FIP. Surprisingly, within the rst week of treatment, there was a signi cant improvement on a daily basis. Therefore, we reported this case in detail for the reference of researchers.
It is worthy to mention several strengths of this case report. First, it is cheap and easily available for the cat guardians, which can bene t more animals. Especially in China, where pet populations have skyrocketed in the last decade, while the existing pet hospitals are inadequate to meet the needs of pet medical care. Meanwhile, many pets have to face euthanasia since their guardians cannot afford the expensive drugs. Second, LH takes effect within a week and heals FIP in about a month. While the recommended duration of administration of GS-441524 was 84 days.
Although a decision to administer LH for compassionate use was based on the case cat's worsening clinical status and an optimistic result obtained, we should treat it with caution. Further study are needed to determine the safety and e cacy of LH for treatment of cat's with feline infection. It is notable that although the specimens were negative for FCoV, the TP and BUN is a little higher than the normal value.
We cannot yet be sure it's due to LH capsules or the virus. According to the previous clinical studies, we did not nd that LH capsule has the side effect of causing liver injury in human. But obviously, more cases and BUN levels in future cases following this FIP treatment protocol require further investigation. In order to avoid the special reaction, we extended the trial to 3 cats, and all of them recovered in about a month. Due to incomplete test data of some cats, we could only put them in supplementary materials for reference.

Conclusions
To our knowledge, this is the rst case of nature products being used to remit (or clinical cure) a cat of FIP. More cases following this FIP treatment protocol require further investigation. The animal medication was approved by the Committee of Ethics of Animal Experimentation of the Beijing University of Chinese Medicine.

Consent for publication
All the co-authors were aware of this submission and approve for publication.

Availability of data and materials
Data sharing is applicable to this article.

Competing interests
The authors have no other relevant a liations or nancial involvement with any organization or entity with a nancial interest in or nancial con ict with the subject matter or materials discussed in the manuscript apart from those disclosed.    Figure 1 Body weight of the cat before, during and after recovery from FIP and the timeline. The cat's weight is shown on the graph above: Day 0 represents FIP diagnosis at the clinic. LH treatment was given between Days 1 to 22. The cat lost 1.5 kg of weight during drain ascites treatment using LH (Day 1 to 15). The cat's weight rapidly increased following the body returning to normal, and continually increased after the treatment stopped, until leveled out at around 7.2 kg now.