In brief

Formerly hospitalised COVID-19 patients with long COVID symptoms exhibited distinct T cell differentiation signatures and elevated pro-inflammatory cytokine levels, which normalised by two years post-infection.

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Predicting persistence, and a glimmer of hope

31 Jan 2024

A two-year study uncovers potential immune biomarkers to detect long COVID, and evidence that its inflammatory symptoms may resolve over time.

Nearly four years since COVID-19 made headlines, new discoveries continue to reshape our assumptions about the disease. Siew-Wai Fong, a Senior Scientist at A*STAR Infectious Diseases Labs (ID Labs) cites the example of the populations we consider at high risk for ‘long COVID’: a constellation of changes to the body that can linger for months to years after infection, with potentially debilitating effects.

“Initially, the focus of long COVID research was on individuals who had severe acute illness; we now know it can also affect people who had mild or asymptomatic disease,” said Fong.

Many aspects of long COVID remain a mystery: its causes, why it impacts some individuals over others, or why it manifests in varied symptoms ranging from brain fog to cardiovascular disease. Even the question of how common it is can be difficult to answer: studies report between 13 to 87 percent of patients who had COVID-19 deal with persistent symptoms.

Part of the issue is that long COVID can be difficult to diagnose. According to Fong, some patients may appear completely recovered on the outside, but show subtle signs of COVID-linked inflammation in their pulmonary, cardiac and renal systems.

“If we can detect long COVID earlier in its course, we can start treatment before it further impacts a patient’s health,” said Fong.

Working with the National Centre for Infectious Diseases, Singapore; National University of Singapore; Changi General Hospital; and Tan Tock Seng Hospital; A*STAR researchers tracked how post-COVID complications progressed in survivors of severe disease. They also searched for immune biomarkers that can be used to identify patients likely to have persistent inflammation.

The researchers recruited 78 patients in Singapore who were hospitalised with COVID-19 in the pandemic’s early phases. Over two years after their discharge, the researchers collected blood samples and self-reported data on any symptoms experienced.

A year into the study, 29 participants reported symptoms such as lingering cough and fatigue. Their blood samples revealed high levels of cytokines: immune mediators known to promote inflammation. The team also noted that patients with persistent inflammation showed distinctive levels of T cell differentiation and higher levels of specific IgG antibodies.

“The good news is that prolonged inflammation seen in these patients reverted to healthy levels within two years after initial infection,” said Fong, who added that the study also provided much-needed insights on lingering effects experienced by high-risk patients who often had comorbidities like diabetes or high blood pressure.

“We believe our study offers some reassurance to affected individuals that their symptoms will resolve with time,” said Fong. “Hopefully, our findings will also accelerate the search for treatments that aid recovery from long COVID. Further studies are needed to identify the mechanisms behind the prolonged inflammation and immune activation caused by COVID-19.”

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

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Fong, S.-W., Goh, Y.S., Torres-Ruesta, A., Chang, Z.W., Chan, Y.-H., et al. Prolonged inflammation in patients hospitalized for coronavirus disease 2019 (COVID‐19) resolves 2 years after infection. Journal of Medical Virology 95 (5), e28774 (2023). | article

About the Researchers

Siew-Wai Fong obtained her PhD in human physiology from Universiti Sains Malaysia (USM). She joined A*STAR Infectious Diseases Labs to work on bridging the knowledge gap of vector-pathogen-host interactions in mosquito-borne virus transmission. Since 2020, she has conducted extensive research on the human immune response to SARS-CoV-2 infection. Key findings from her in-depth immunophenotyping of COVID-19 patients have aided Singapore’s efforts to tackle COVID-19. Her COVID-19 research works have been published in international scientific journals such as the Lancet, Nature and EMBO.
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