In brief

In Singapore, patients with persistent COVID symptoms had elevated levels of two key inflammatory biomarkers even up to six months after disease onset.

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Cracking the code of long COVID

5 Nov 2021

Elevated levels of inflammatory factors may be linked to persistent COVID-19 symptoms, researchers find.

For most COVID-19 patients, the infection resembles a sprint, with mild symptoms typically subside in a couple of weeks. But for those with ‘long COVID,’ it’s more of a marathon. Even months after initial symptoms have waned, these individuals are plagued by serious and ongoing health problems. Unfortunately, it remains unclear why some are predisposed to persistent symptoms and how best to address these lingering complications.

“Much is still unknown about why some patients with COVID-19 continue to show symptoms for months,” explained Lisa Ng, Executive Director at A*STAR’s Infectious Diseases Labs (ID Labs). “Long COVID has greatly impacted patients’ quality of life and has had a huge impact on healthcare costs and resource utilization.”

Taking a closer look at the biology behind this mysterious phenomenon, Ng and colleagues studied a cohort of nearly 300 Singaporean COVID patients up to six months after the onset of the disease. The researchers tracked and analyzed participants’ levels of circulating inflammatory cytokines in search of patterns linking particular immune responses with persistent symptoms.

The team discovered that patients with long COVID had elevated levels of two key inflammatory biomarkers previously associated with chronic respiratory conditions: a molecule called MCP-1 and PDGF-BB, a growth factor responsible for blood vessel formation.

Interestingly, it wasn’t just those affected by persistent COVID symptoms that had these tell-tale markers of chronic inflammation—the COVID ‘sprinters’ did too. “Our longitudinal analyses of cytokine responses in recovered patients revealed subclinical changes potentially underpinning the development of post-COVID-19 complications even in those who did not have persistent symptoms,” said Ng.

Additionally, their investigation revealed fascinating insights into the complex, multi-dimensional nature of long COVID. Ng’s team found that while prior studies conducted in Europe had indicated a 55 to 87 percent incidence rate of persistent COVID symptoms, only 10 percent of the Singaporean patient cohort were affected. “The differences in demographics and ethnicity may explain this discordance in the frequency of persistent symptoms,” suggested Ng.

Together, these findings contribute to our understanding of the long-term consequences of COVID and unlock new possibilities in the hunt for clinical interventions to slow or even stop the progression of persistent symptoms. Speaking on ongoing efforts by the team, Ng said, “We are still monitoring COVID-19 patients longitudinally to appreciate the dynamics of cytokine responses and study their associations with recovery trajectories and long-term outcomes of COVID-19.”

The A*STAR-affiliated researchers contributing to this research are from the Infectious Diseases Labs (ID Labs).

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Ong, S.W.X., Fong, S.W., Young, B.E., Chan, Y.H., Lee, B., et al. Persistent symptoms and association with inflammatory cytokine signatures in recovered coronavirus disease 2019 patients. Open Forum Infectious Diseases 8 (6), ofab156 (2021). | article

About the Researcher

Lisa F.P. Ng obtained her PhD in molecular virology in coronaviruses from the National University of Singapore (NUS) in 2002. After joining A*STAR’s Genome Institute of Singapore (GIS) in 2002 as a Postdoctoral Fellow, she worked on viral diseases such as hepatitis, severe acute respiratory syndrome and influenza. Ng is currently the Executive Director at A*STAR Infectious Diseases Labs (ID Labs) where she focuses on the immune responses to arthritic arboviruses that are epidemic or highly endemic in the tropical region. Ng has won numerous accolades for her research, including the ASEAN ‘International Young Scientist and Technologist Award’ in 2008 and A*STAR’s ‘Most Inspiring Mentor Award’ in March 2013.

This article was made for A*STAR Research by Wildtype Media Group