Yue Zhang, Yuanfeng Zhang, Lili Zhu, Fang Lu, Xin Du, Xin Zhao, Tao Lu
Original article: Rapid Resolution of severe feline infectious peritonitis using natural products
This is the first report of the successful treatment of a serious case of feline infectious peritonitis (FIP) with Lianhuaqingwen Capsule (LH), a Chinese natural products medicine that has also been used to treat Covid-19. The one-year-old cat was diagnosed with FIP - strong ascites, aphasia, inflammation, difficulty breathing and weight loss. After 22 days of treatment with LH capsules, all indicators of the cat returned to normal and the ascites gradually disappeared. This case report is the first description of the clinical recovery of a cat with systemic FCoV infection using LH capsules.
KEY WORDS: coronavirus, inflammation, feline infectious peritonitis, FIP, natural products, TCM
Feline coronavirus (FCoV), RNA alpha coronavirus, is a highly infectious enteric virus that is epidemiologically a member of the Coronaviridae family of the Nidovirales family. [1,2], and can infect cats of all ages. Most cases occur in cats aged 1-2 years and older than 11 years. May lurk in the intestines for a long time and cause feline infectious peritonitis (FIP) in a weakened immune or stress state , which is known to cats as an "incurable disease" with almost 100% mortality.
Although treatment of FIP with new therapies has been published , further investigation is needed into the efficacy and safety of FCoV-targeted broad-spectrum antiviral drugs. GS441524 is a great promise in the treatment of cats with FIP , but is not currently FDA approved. What's more, the cost of FIP treatment costs $ 5,000 to $ 9,000, which is a big financial burden for most ordinary families. The LH capsule, one of the natural products of TCM (Traditional Chinese Medicine), was made to inhibit SARS-CoV-2 replication. . The LH capsule exerts its anti-influenza activity by regulating the immune response in order to influence both viral and host responses. . The LH capsule was approved by the National Board of Health for Covid-19, a prospective randomized study involving 284 patients conducted in a multicenter environment suggests that treatment with LH capsules for 14 days significantly improved the rate of symptom relief. .
"Big Tangerine" is a one-year-old neutered Chinese domestic cat (Felis catus) from a household of four cats (2 Felis catus, 2 British Shorthair). "Big Tangerine" developed an appetite loss and weight loss lasting several weeks. The other cats showed no signs of disease. On November 15, 2020, the cat was transferred to Guaiguai Pet Hospital (Tianjin, China). Abdominocentesis showed a large amount of ascites. FCoV was detected by RT-PCR in ascites and was thus diagnosed with FIP. Symptoms included aphasia (inability to swallow), diarrhea, ascites, lethargy, weight loss and difficulty breathing (Figure 1)
RT-PCR of ascites showed a high FCoV load (Ct value 21.73). Laboratory test results showed elevated levels of white blood cells (WBC) and neutrophilic granulocytes (Neu), indicating severe inflammation (Table 1). In addition, the immune response was altered: lymphocyte levels (Lym%) were significantly reduced, indicating virus-induced lymphocyte depletion. SAA (marker of inflammation and tissue damage) was tested for cat diarrhea and respiratory distress (Fig. 2A). The patient received saline and protein as supportive care. Due to the clinical condition, the veterinarian recommended euthanasia or the experimental drug GS-441524 for the cat. Due to the high cost of GS-441524 treatment, cat owners decided to look for other therapy options.
|Title||Day 0||Day 30||Reference range||Units|
|Leukocytes (WBC)||44.8||13.85||5.5-19.5||10 ^ 9 / L|
|Neutrophilic granulocytes (Neu%)||94.1||76.2||38-80||%|
|Neutrophilic granulocytes (Neu#)||42.16||10.56||3.12-12.58||10 ^ 9 / L|
|Lymphocytes (LYM#)||0.98||2.38||0.73-7.86||10 ^ 9 / L|
|Monocytes (Mon#)||1.04||0.36||0.07-1.36||10 ^ 9 / L|
|Eosinophils (Eos#)||0.62||0.54||0.06-1.93||10 ^ 9 / L|
|Basophils (Bas#)||0||0.01||0.00-0.12||10 ^ 9 / L|
|Erythrocytes (RBC)||5.83||7.23||4.62-10.20||10 ^ 12 / L|
|Hemoglobin (HGB)||85||117||85.0-153.0||g / L|
|Mean erythrocyte volume (MCV)||42.5||47.9||38.00-54.00||fL|
|Mean erythrocyte hemoglobin (MCH)||14.6||16.1||11.89-18.00||pg|
|Mean erythrocyte hemoglobin (MCHC) concentration||342||337||290.0-360.0||g / L|
|Erythrocyte distribution width - coefficient of variation (RDW-CV)||20.6||16||6.50-23.00||%|
|Erythrocyte distribution width - standard deviation (RDW-SD)||40.5||35.5||19.30-43.10||fL|
|Platelets (PLT)||187||333||100.0-518.0||10 ^ 9 / L|
|Mean platelet volume (MPV)||11||11.7||9.90-16.30||fL|
|Platelet distribution width (PDW)||10.2||14.7||12.00-17.50|
|Platelet hematocrit (PTC)||0.21||0.39||0.09-0.70||%|
The cat's caregiver sought help in traditional Chinese medicine. Due to feline coronavirus infection and respiratory distress, he was recommended an LH capsule, which was prescribed for the treatment of respiratory diseases and approved by the National Animal Health Commission for the treatment of covid-19. FCoV and SARS-CoV-2 share partially identical RNA sequences, so antivirals targeting SARS-CoV-2 are likely to be effective against FCoV as well.
On 17 November 2020, 'Big Tangerine' began receiving 4 LH capsules (Table 2) three capsules a day (0.35 g per capsule) in combination with antipyretics; no side effects were observed. Shortly afterwards (November 18, day 1), shortness of breath improved. At that time, he received a liquid diet for his ongoing anorexia and diarrhea. 48 hours after taking the drug (November 19, day 2), the patient's condition was largely stabilized and the first soft stool appeared; his mental condition also improved. He was able to sit up, lick his fur while he was still lying on the ground a few days ago, gasping for breath. 3 days after starting treatment (November 20), he started eating on his own (albeit in small amounts). During the next 7 days of treatment, his appetite improved and the effusion began to decrease. During this time he had soft stools. In early December, the cat underwent a palpation examination, which showed that the effusion had almost completely disappeared. As shown in Figure 1, with ascites disappearing, it was estimated to be about 1.5 kg lighter, which was the lowest weight throughout the treatment. On December 2, all symptoms subsided. The cat started running and playing with the other cats.
|Forsythia suspensa (Zlatovka overhang)||Dried fruit||12.7|
|Lonicera japonica (Japanese earthworm)||Dried flower bud or flower||12.7|
|Ephedra sinica (Chinese wormwood)||Dried herb stem||4.2|
|Isatis indigotica (Boryt dyeing)||Dried root||12.7|
|Pogostemon cablin (Patchouli)||Dried above ground part||4.2|
|Rheum palmatum (Rhubarb||Dried root and rhizome||2.5|
|Glycyrrhiza uralensis (Ural Malt)||Dried root and rhizome||4.2|
|Dryopteris crassirhizoma||Dried rhizomes and leaves||12.7|
|Rhodiola crenulata (Rozchodnica)||Dried root and rhizome||4.2|
|Houttuynia cordata (Hutinia)||Dried above ground part||12.7|
|Prunus sibirica (Siberian apricot)||Dried ripe seed||4.2|
|gypsum||CaSO4 · 2H2O||12.7|
* LH capsules have been manufactured according to the Pharmacopoeia of the People's Republic of China.
Result and next steps
The patient continued to take LH capsules every day until December 9. The treatment period lasted 3 weeks and the symptoms did not return after discontinuation of the drug. On January 3, he was examined at a pet clinic in Guaiguai and his blood count and SAA levels were already in the normal range, except for total protein (8.2 g / dl, normally 5.4 to 8.2) and urea (42 mg / dl, normally 10-30). (Table 3 and Figure 2). The samples were subsequently tested by FCoV RT-PCR with a negative result, which means that the FCoV viral load was below the limit of detection. The symptoms of the FIP did not recur until the report was submitted (March 17).
|Title||Day 30||Reference range||Units|
|ALB albumin||4||2.2-4.0||g / dL|
|Alkaline phosphatase ALP||38||10-90||U / L|
|Alanine aminotransferase ALT||60||20-100||U / L|
|AMY amylase||1082||300-1100||U / L|
|Total bilirubin TBIL||0.5||0.1-0.6||mg / dL|
|Urea BUN||42||10.0-30.0||mg / dL|
|Calcium CA||11.7||8.0-11.8||mg / dL|
|Phosphorus PHOS||4.5||3.4-8.5||mg / dL|
|Creatinine CRE||1.5||0.3-2.1||mg / dL|
|Glucose GLU||101||70-150||mg / dL|
|NA +||146||142-164||mmol / L|
|K +||4||3.7-5.8||mmol / L|
|Total TP protein||8.2||5.4-8.2||g / dL|
|GLOB globulin||4.2||1.5-5.7||g / dL|
FIP is a fatal disease in cats caused by FCoV, which lurks in the intestinal system. FIP is still a terminal disease with a variable death time, with more than 95% feline cats dying several days to months after diagnosis . The symptoms of FIP in cats take two forms: dry and moist. The most prominent symptom of wet FIP is effusion in the abdomen and thoracic cavity . Glucocorticoids such as prednisolone are used to relieve symptoms. After diagnosing FIP ascites, a veterinarian may recommend euthanasia because there are few cases of successful treatment.
There are currently several effective therapies. For example, the successful treatment of FIP with GS441524 has recently been published , GC376  or an oral adenosine nucleoside analog . GS441524 in combination with antibiotic treatment, recommended by many veterinarians, has shown a good therapeutic effect. GS441524 is a precursor of remdesivir used in the treatment of COVID-19. GS441524 treatment lasts for 1-3 months, which can mean approximately $ 5,000 to $ 9,000 in China. Unfortunately, due to price and availability (GS441524 not yet officially approved), many cat owners are giving up this proven and effective treatment option.
In this case, the veterinarian feared that without the use of GS441524, the cat would not survive even a week. Cat owners hoped to find another therapy. LH Capsule, a Chinese patent drug composed of 13 herbs, is a commonly used broad-spectrum antiviral drug developed on the example of traditional Chinese medicine . It is used to treat a series of influenza viruses, such as viral rhinitis, pneumonia and the like. [16, 17] Pharmacological and clinical studies have shown that it can significantly alleviate the inflammatory response by inhibiting viral replication and reducing the release of cytokines from host cells. . It is also recommended as one of the supportive drugs in the treatment of COVID-19 [6, 18, 19]. Therefore, we tried to use this drug to alleviate the inflammatory response and symptoms caused by FIP. Surprisingly, there was a significant daily improvement during the first week of treatment. Therefore, we have recorded this case in detail for scientific purposes.
Several strengths of this case study need to be mentioned. First, it is a cheap and readily available drug for cat owners, which can benefit more cats. Especially in China, where the pet population has risen sharply in the last decade, while current pet clinics do not have sufficient capacity to meet the medical care needs of pets. Many pets have to face euthanasia because their owners cannot afford expensive drugs. Second, LH will take effect within a week and the FIP will heal in about a month, while the recommended duration of administration of GS-441524 is 84 days.
Although the decision to administer LH was based on the worsening of the cat's clinical condition and the optimistic results achieved with LH use, we should handle it with caution. Further studies are needed to determine the safety and efficacy of LH in the treatment of feline feline infections. Notably, although the samples were negative for FCoV, the TP and BUN values were slightly higher than normal. We cannot yet be sure whether the cause was LH capsules or a virus. Previous clinical studies have not shown whether the LH capsule has side effects causing liver damage in humans. Clearly, further research and data on BUN levels are needed in future cases. In order to find out whether this was not just an isolated case, 3 other cats also underwent experimental treatment and all of them recovered after about a month. Due to incomplete test data for some cats, we were only able to list them in supplementary materials.
To our knowledge, this is the first use of natural products to reverse (or cure) a cat with FIP. A study with multiple cats undergoing this treatment protocol is required.
FCoV: feline coronavirus;
FIP: Infectious feline peritonitis
LH capsule: Lianhuaqingwen capsule
TCM: Traditional Chinese Medicine
- Pedersen NC, Sato R, Foley JE, Poland AM. Common virus infections in cats, before and after being placed in shelters, with emphasis on feline enteric coronavirus. Journal of feline medicine and surgery. 2004;6(2):83-88.
- Felten S, Hartmann K. Diagnosis of Feline Infectious Peritonitis: A Review of the Current Literature. Viruses. 2019;11(11).
- Rissi DR. A retrospective study of the neuropathology and diagnosis of naturally occurring feline infectious peritonitis. Journal of veterinary diagnostic investigation: official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc. 2018;30(3):392-399.
- Kim Y, Shivanna V, Narayanan S, et al. Broad-spectrum inhibitors against 3C-like proteases of feline coronaviruses and feline caliciviruses. Journal of virology. 2015;89(9):4942-4950.
- Ko WC, Rolain JM, Lee NY, et al. Arguments in favor of remdesivir for treating SARS-CoV-2 infections. International journal of antimicrobial agents. 2020;55(4):105933.
- Runfeng L, Yunlong H, Jicheng H, et al. Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2). Pharmacological research. 2020;156:104761.
- Zhang ZJ, Morris-Natschke SL, Cheng YY, Lee KH, Li RT. Development of anti-influenza agents from natural products. Medicinal research reviews. 2020;40(6):2290-2338.
- Hu K, Guan WJ, Bi Y, et al. Efficacy and safety of Lianhuaqingwen capsules, a repurposed Chinese herb, in patients with coronavirus disease 2019: A multicenter, prospective, randomized controlled trial. Phytomedicine: international journal of phytotherapy and phytopharmacology. 2020:153242.
- Dickinson PJ, Bannasch M, Thomasy SM, et al. Antiviral treatment using the adenosine nucleoside analogue GS-441524 in cats with clinically diagnosed neurological feline infectious peritonitis. Journal of veterinary internal medicine. 2020;34(4):1587-1593.
- Hartmann K. Feline infectious peritonitis. The Veterinary clinics of North America Small animal practice. 2005; 35 (1): 39-79, vi.
- Giori L, Giordano A, Giudice C, Grieco V, Paltrinieri S. Performances of different diagnostic tests for feline infectious peritonitis in challenging clinical cases. The Journal of small animal practice. 2011;52(3):152-157.
- Pedersen NC, Perron M, Bannasch M, et al. Efficacy and safety of the nucleoside analog GS-441524 for the treatment of cats with naturally occurring feline infectious peritonitis. Journal of feline medicine and surgery. 2019;21(4):271-281.
- Pedersen NC, Kim Y, Liu H, et al. Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis. Journal of feline medicine and surgery. 2018;20(4):378-392.
- Sharun K, Tiwari R, Dhama K. Protease inhibitor GC376 for COVID-19: Lessons learned from feline infectious peritonitis. Annals of medicine and surgery (2012). 2021;61:122-125.
- Addie DD, Curran S, Bellini F, et al. Oral Mutian®X stopped faecal feline coronavirus shedding by naturally infected cats. Research in veterinary science. 2020;130:222-229.
- Ding Y, Zeng L, Li R, et al. The Chinese prescription lianhuaqingwen capsule exerts anti-influenza activity through the inhibition of viral propagation and impacts immune function. BMC complementary and alternative medicine. 2017;17(1):130.
- Liu L, Shi F, Tu P, et al. Arbidol combined with the Chinese medicine Lianhuaqingwen capsule versus arbidol alone in the treatment of COVID-19. Medicine. 2021; 100 (4): e24475.
- Duan ZP, Jia ZH, Zhang J, et al. Natural herbal medicine Lianhuaqingwen capsule anti-influenza A (H1N1) trial: a randomized, double blind, positive controlled clinical trial. Chinese medical journal. 2011;124(18):2925-2933.
- Ren JL, Zhang AH, Wang XJ. Traditional Chinese medicine for COVID-19 treatment. Pharmacological research. 2020;155:104743.