Healthcare workers in the Singapore General Hospital isolation ward assisting in the transfer of a suspected Covid-19 patient to an isolation room. Photo: ST File

When a virus invades a body, the development of the disease is often determined by how the immune system reacts to the infection.

Most of the time, the immune system mounts a protective response. But sometimes, that response can be harmful too, experts say.

If the immune system kicks into overdrive, for instance, it could stimulate the overproduction of proteins called cytokines, which can cause inflammation.

Cytokines are molecular messengers of the immune system. For Covid-19 patients, this cytokine storm can lead to symptoms such as breathlessness or respiratory distress.

Now, a team of Singapore scientists have found that patients with Covid-19 could have a dynamic and fluctuating immune response to the virus, particularly in the early stages of the disease.

For instance, when the immune system responds in a way that causes the body to produce more cytokines, it correlates with the period when the patients become more sick and experience respiratory distress.

The study was published on March 28 in scientific journal Cell Host & Microbe.

The finding is important as it could pave the way for research into existing or new drugs that could help prevent harmful immune reactions that may worsen the disease, said Dr Eugenia Ong, a member of the team. She is senior research fellow at the Viral Research and Experimental Medicine Centre, a unit of the SingHealth Duke-NUS Academic Medical Centre, and at the Duke-NUS' Emerging Infectious Diseases programme.

In studying three Covid-19 patients in Singapore, the scientists found that the patients' immune systems showed marked changes in the way they dealt with the invading pathogen.

As molecular messengers, cytokines help to flag the presence of a foreign pathogen in the body, so other elements of the immune system can kick in to get rid of the virus.

But when the body produces too much of it, this can result in inflammation. This production of cytokines is regulated by genes, explained one of the study's lead authors, Associate Professor Jenny Low, a senior consultant at the Department of Infectious Diseases at Singapore General Hospital and co-director of the Viral Research and Experimental Medicine Centre.

The study noted that the processes that stimulate the production of cytokines in a patient differed from day to day.

The scientists found that one particular cytokine called Interleukin-1 was produced even before the patient showed clinical deterioration.

"In this study, we found that the early immune response following the start of symptoms is highly dynamic, which means that research needs to take into account the day-to-day fluctuations in activation or deactivation of immune genes that collectively shape disease severity in Covid-19 patients," said Prof Low, who is also an associate professor at the Emerging Infectious Diseases programme at Duke-NUS.

As the sensing of the foreign pathogen triggers a cascade of molecular events, characterising the immune response in the early phase of illness is thus important to understand how the final immune reaction is derived, said Prof Low.

Professor Lisa Ng, who was not involved in the research project, said the study of early stages of infection is interesting, as it may lead to opportunities for early interventions.

"Potentially, some clinically approved drugs could be used to target certain inflammatory pathways to control virus-induced inflammation," said Prof Ng, a senior principal investigator at the Agency for Science, Technology and Research's Singapore Immunology Network. However, she said it would be important to see if larger cohort groups from various countries will show similar patterns.