Long COVID is real. Tens of thousands of scientific publications have investigated its biological mechanisms and global prevalence. Other research has focused on describing its debilitating health implications and understanding the possible social and economic burdens. This is the reason why there are ongoing pursuits to find effective treatments. Hence, as part of these emerging research undertakings, a particular research on Feline Infectious Peritonitis, a severe coronavirus disease in cats, provides a framework for understanding and treating long COVID in humans.
FIP in Cats and COVID in Humans: What Cats Can Teach Us About Treating Long COVID and Long COVID Recovery
Background: Understanding FCoV in Cats and SARS-CoV-2 in Humans
Feline Infectious Peritonitis or FIP is a severe and often fatal viral disease in cats caused by certain strains of feline coronavirus or FCoV. Moss strains are relatively harmless and only cause mild infections. However, in a small percentage of cats, the FCoV undergoes a mutation in the body of a particular cat. This mutated form is known as Feline Infectious Peritonitis Virus.
The mutated FCoV strain infects macrophages and causes intense inflammatory reactions around blood vessels in various organs due to a cytokine storm. The overall immune response is overactive but ineffective. This is because FIP is an immune-mediated disease that dysregulates the immune response of an infected cat and renders its immune system suppressed.
SARS-CoV-2, the causative pathogen behind COVID-19, can also cause immune dysregulation because it can evade or delay the innate immune response and exhaust the adaptive immune response. The immune dysregulation does not resolve in many individuals. This contributes to the biological mechanisms behind long COVID or Post COVID-19 Condition.
The persistent immune system abnormalities in long COVID cases include uncoordinated adaptive immune response due to ongoing changes in immune cell populations, chronic inflammation due to persistent T cell activation, exhaustion, or altered function, triggering or exacerbation of certain autoimmune conditions, and induction of mitochondrial dysfunction.
Translational Research: FIP in Cats as a Model for Long COVID in Humans
Researchers P. Wanakumjorn et al. from UC Davis Health first outlined how FIP resembles severe coronavirus infections in humans in their paper, which was published in Stem Cells Translational Medicine in July 2025. The comparison was based on how both infections result in widespread inflammation, T cell exhaustion, and persistent immune dysfunction.
Hence, in consideration of the similarities, the researchers have been investigating FIP in cats as a valuable model for severe coronavirus infections in humans. They focused on a combination of treatment involving the antiviral drug GS‑441524 and a novel cell therapy using mesenchymal stromal cells to help immune system recovery and reduce inflammation.
The antiviral GS‑441524 drug was observed to be effective in treating FIP back in 2017. However, due to hurdles in government regulation, its availability was delayed. Moreover, even after clinical recovery, some cats exhibited lingering immune dysregulation. P. Wanakumjorn et al. noted that this persistent immune system issue is reminiscent of long COVID in humans.
Designing a new treatment approach that combines antiviral therapy with mesenchymal stromal cell or MSC therapy was warranted. The researchers chose MSC therapy because of its established immunomodulatory properties. Stromal cells are known to regulate immune responses by reducing inflammation, increasing T cells, and reversing immune exhaustion.
Findings: Effectiveness of Mesenchymal Stromal Cell Therapy
The researchers conducted a controlled therapeutic study on cats diagnosed with systemic feline infectious peritonitis. There were two treatment groups. The first involved cats that were given a standard course of the antiviral GS-441524 drug plus MSC therapy. The second included cats that were given the same antiviral drug and placebo infusions.
Biological samples were collected and analyzed at baseline, during treatment, and after therapy completion. Important parameters were flow cytometry to count and characterize different immune cell populations, clinical observations, and serological testing to measure inflammatory markers, immune cell counts, and other indicators of systemic immune activation.
The researchers compared immune profiles between the two groups over time. Statistical analyses were conducted to determine the significance of changes in immune markers. This well-controlled study design allowed researchers to isolate the specific immune-repair effects of MSC therapy in a natural coronavirus model. Below are the key findings:
• MSC Therapy Accelerated Immune Recovery: The group that received GS-441524 along with MSC therapy showed faster immune normalization than those who received the antiviral alone. MSCs corrected immune imbalances.
• Reduced Activated T and B Cells in MSC Group: A significant decrease in T cell and B cell hyperactivity in the MSC group compared to the placebo group was observed. MSCs were effective at dampening excessive immune response.
• Significant Increase in Regulatory T Cells: The MSC group showed a notable increase in regulatory T cells. This helped in suppressing inflammation, maintaining immune balance, and restoring a normalized immune system environment.
• Notable Reversal of T Cell Exhaustion: A notable reduction in the expression of PD-1, a marker associated with T cell exhaustion, was observed in the MSC group. There were also signs of a developing memory T cell population.
• Persistent Immune Activation Without MSCs: The placebo group treated with antiviral alone still showed lingering immune dysregulation like enlarged lymph nodes and elevated inflammatory cells. Clearing the virus did not resolve the immune issue.
• MSC Therapy Was Safe and Well-Tolerated: No serious side effects were reported from the MSC group. All cats tolerated the treatment well. MSC therapy appears to be safe. This supports potential application in human medicine.
Implications: Insights from FIP in Cats and Long COVID Immune Recovery
Note that the researchers underscored that cross-species insights can hasten therapeutic discovery for both veterinary and human medicine. The aforementioned approach to treating severe and persistent coronavirus disease in cats provides a translational framework for solving the emerging problems associated with COVID-19 and long COVID in humans.
The findings align with a growing body of evidence suggesting that long COVID may result from a maladaptive immune response rather than continued viral presence. The observed immune rebalancing in cats offers a promising template for human clinical trials. It provides an avenue for using MSC therapy to tackle long-term symptoms of COVID-19.
It is also worth mentioning the larger implication of MSC therapy. This approach can be explored further in addressing immune dysfunction and supporting durable immune recovery in severe viral diseases characterized by chronic inflammation and immune dysregulation. Viral clearance might not be enough due to the impacts of viral infection on the immune system.
The research also highlights the importance of focusing treatment not only on survival but also on full recovery. Diseases like FIP in domestic cats and COVID-19 in humans demonstrate persistent health impacts of infections. Long-term health outcomes need to be addressed to mitigate other health-associated risks and socioeconomic burdens.
FURTHER READINGS AND REFERENCES
- Baxa, M. 29 April 2024. “An Incomplete Picture: Understanding the Burden of Long Covid.” Economist Impact. The Economist. Available online
- Cutler, D. 2022. “The Economic Cost of Long COVID: An Update.” Harvard Kennedy School. Harvard University. Available online
- Wanakumjorn, P., Kimura, K., Castillo, D., McLarty, E., Formaker, R., Qiao, R., Farrell, K., Brostoff, T., Ramarapu, R., Pires, J., Cohen-Davidyan, T., Cassano, J., Murphy, B., Reagan, K., and Kol, A. 2025. “Mesenchymal Stem/Stromal Cell Therapy Improves Immune Recovery in a Feline Model of Severe Coronavirus Infection.” Stem Cells Translational Medicine. 14(7). DOI: 1093/stcltm/szaf025