In brief

Asymptomatic COVID-19 patients have unique protective immune responses not seen in symptomatic patients, such as more active T cells and elevated tissue healing factors.

Immune secrets of the symptom-free

26 Nov 2021

Unique immune responses shield some COVID-19 patients from the disease’s worst effects.

Not all SARS-CoV-2 infections are created equal. Some infected individuals bounce back quickly after mild symptoms subside, while others bear severe, life-threatening symptoms and long recovery times. Curiously, yet another group gets off completely scot-free. Though these asymptomatic individuals test positive, they are spared from the fever, cough and fatigue commonly associated with the disease.

Symptomatic patients have borne the brunt of research into COVID-19’s inner workings, but studying their asymptomatic counterparts could support the creation of better therapies. “It is important to identify what are the mechanisms underlying disease tolerance and disease progression during SARS-CoV-2 infection,” said Lisa Ng, Executive Director at A*STAR's Infectious Diseases Labs (ID Labs).

Unfortunately, existing studies on asymptomatic COVID-19 cases have not yielded any clear answers. Until now, scientists continue to debate whether this ability to fend off the coronavirus can be attributed to the body’s first line of defense known as the innate immune system or the adaptive arm responsible for immune memory.

In search of more conclusive answers, Ng and colleagues analyzed a cohort of 263 Singaporean COVID-19 patients, 48 of whom were asymptomatic. The team looked for clues from multiple angles, tracking gene signatures, characterizing immune cells as well as measuring antibody and cytokine levels in samples obtained from the participants.

Crucially, the researchers identified an immunological tipping point that could be responsible for triggering the onset of COVID-19 symptoms. “We found that excessive pro-inflammatory responses and the regulation of T cell responses in COVID-19 patients are important factors that can influence symptom development in COVID-19,” explained Ng.

The study also uncovered unique protective immune responses in asymptomatic patients that set them apart from their symptomatic equivalents: lower levels of inflammation, more active T cells and elevated tissue healing factors.

According to Ng, these findings set the stage for novel therapeutics that mirror the immune responses of asymptomatic patients by dampening pro-inflammatory immune pathways, while boosting levels of protective growth factors.

For now, the team will continue to track health outcomes in the asymptomatic group. “We are monitoring the asymptomatic patients longitudinally to study the longevity of the immunity raised from the primary SARS-CoV-2 infection and evaluating its efficacy in long-term protection against subsequent exposures to SARS-CoV-2,” explained Ng.

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

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Chan, Y.H., Fong, S.W., Poh, C.M., Carissimo, G., Yeo, N.K., et al. Asymptomatic COVID-19: disease tolerance with efficient anti-viral immunity against SARS-CoV-2. EMBO Molecular Medicine 13 (6), e14045 (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