Examining Chronic Chikungunya and Potential Clues to Rheumatologic Symptoms

Chikungunya is a mosquito-borne virus that in some cases, can cause chronic symptoms including arthralgia and fatigue.¹ Globally, cases are increasing in regions that are not accustomed to seeing the virus. For example, France just reported there have been 382 cases of locally-acquired cases of chikungunya, which includes 81 cases from the past week alone, in addition to 966 travel-related cases. This is up dramatically from last year where there was just 1 locally-acquired case.²

China is also experiencing an unprecedented outbreak. Back in August, the Centers for Disease Control and Prevention (CDC) issued a Level 2 travel advisory (Practice Enhanced Precautions) for Guangdong Province, China, following an outbreak of chikungunya, with most cases concentrated in Foshan city.³

As of August 2025, 50 travel-related chikungunya cases and no locally-transmitted cases were reported in the US.⁴ This is much lower than last year. Through December 2024, CDC reported 173 Chikungunya cases in territories and non-US residents in Chikungunya 2024. From 2006 to 2023, 4,590 travel-related cases were reported in the US.⁴

Although in the US, cases are relatively low, year-to-year, there are no FDA approved or existing antivirals available. Treatment for symptoms include rest, fluids, and use of analgesics and antipyretics. Nonsteroidal anti-inflammatory drugs can be used to help with acute fever and pain.⁵

Additionally, although many cases of acute chikungunya resolve on their own, debilitating joint pain (chronic chikungunya disease or arthralgia) can remain. “Some patients will have a continuation or relapse of rheumatologic symptoms (eg, polyarthralgia, polyarthritis, tenosynovitis, Raynaud syndrome) in the months after acute illness. Studies have reported variable proportions, ranging from 5% to 80%, of patients with persistent joint pains and prolonged fatigue for months or years after illness,” writes the CDC.⁵

With interest around the connection between chikungunya and chronic arthralgia, a team of investigators led by Daniela Weiskopf, PhD, assistant professor, the La Jolla Institute for Immunology, examined the connection between how virus may lead to persistent rheumatologic symptoms.

In their study, Weiskopf and her team of investigators found a strong correlation between elevated disease specific CD4⁺ T-cell responses and individuals’ with chronic symptoms, despite no detectable viral antigen. This finding remains a mystery to the researchers.

“We do see more specific CD4⁺ T-cells in these people that still have chronic symptoms, but not in the ones that are recovered,” Weiskopf said.“So all of them had the infection, but some of them can clear the virus, and some of them clear the symptoms, and some of them still have symptoms. And we have no idea. So we are looking at this right now, this very specific question.”

Their findings were published in Cell Reports Medicine.

“This was surprising, because if you have been infected but recovered, we do see CD4⁺ T cell responses, but not a lot, so significantly lower. The interesting thing is that when we look more closely what do they recognize? There's seems to be no difference, so between recovered and chronic patients, they do recognize the same parts of the virus, but something keeps the T-cell response still around in the chronic patients.”

Weiskopf hopes the unusual findings inform future work in this area and leads to potential pathways for prospective therapeutics.

“I think it's important to point out we do see this predominantly TNF alpha response that is interesting—not what you would expect from a viral infection. So does this have anything to do with a potential target for therapeutics?”

References
1. Agarwal R, Chang J, Côrtes FH, et al. Chikungunya virus-specific CD4⁺ T cells are associated with chronic chikungunya viral arthritic disease in humans. Cell Rep Med. 2025;6(5):102134. doi:10.1016/j.xcrm.2025.102134
2. Chiappa C. Local chikungunya cases soar in France. Politico. September 10, 2025. Accessed September 13, 2025.
https://www.politico.eu/article/local-chikungunya-cases-soar-in-france/
3. Abene S. CDC Issues Level 2 Travel Advisory for Chikungunya Outbreak in Guangdong, China. Contagion. August 28, 2025. Accessed September 13, 2025.
4. Chikungunya Outbreaks. Vax Before Travel. Reviewed August 21, 2025. Accessed September 13, 2025.
https://www.vax-before-travel.com/chikungunya-outbreaks.
5. Chikungunya. CDC. Updated June 13, 2025. Accessed September 13, 2025. https://www.cdc.gov/yellow-book/hcp/travel-associated-infections-diseases/chikungunya.html