​• Asymptomatic SARS-CoV-2 infected individuals don’t have weak antiviral immunity; on the contrary, they mount a highly functional virus-specific cellular immune response
• The study suggests that a balanced T cell response is key to avoiding COVID-19 symptoms

Even though they show no signs of COVID-19, people with asymptomatic infections mount a virus-specific T-cell immune response, scientists at Duke-NUS Medical School and NUS Saw Swee Hock School of Public Health, Singapore, reported in the Journal of Experimental Medicine. The study findings show that these people produce a robust virus-specific T-cell response, which, in combination with antibodies, protects them from developing severe COVID-19 disease.

To effectively fight off SARS-CoV-2, the immune system depends on both antibodies and T cells, a type of white blood cell, which work together to eradicate the virus. However, little was known about virus-specific T cells in asymptomatic patients.

“We now know that many people are getting infected with SARS-CoV-2 without realising it, as they stay healthy and don’t develop any symptoms. These asymptomatic infections may provide the key to understanding how the immune system can control the virus without triggering pathological processes,” explained Dr Nina Le Bert, Senior Research Fellow at the Duke-NUS’ Emerging Infectious Diseases (EID) Programme and the co-author of this study.

The study, done in collaboration with Assistant Professor Clarence C. Tam from the NUS Saw Swee Hock School of Public Health, compared the T-cell response in 85 asymptomatic and 75 symptomatic patients who were infected with SARS-CoV-2 around the same time.

They selected the asymptomatic individuals from a group of male workers living in a densely populated dormitory in Singapore where SARS-CoV-2 was actively spreading. The symptomatic patients were selected from cohorts of hospitalised COVID-19 patients with mild to severe symptoms, collected and studied by the Singapore General Hospital, National University Hospital and National Centre for Infectious Diseases. By using a test called rapid whole blood T-cell activation assay, they were able to study both the quantity and characteristics of the T-cell response, providing a snapshot of the cellular immunity of both groups.

The team found that the frequency of T cells recognising different viral proteins of SARS-CoV-2 was similar in both asymptomatic individuals and COVID-19 patients. Yet, their features differed: those patients who were asymptomatic produced higher quantities of IFN gamma and IL-2, which are important for viral control.

“Recently, more and more studies are suggesting that T cells may play a protective role in COVID-19 disease. It would be good news for patients to know that they are developing an efficient cellular immune response after a symptom-free infection. Our study opens the door for further large-scale T-cell testing, which could match the speed of antibody testing,” added Professor Antonio Bertoletti, from Duke-NUS’ EID programme, who is the corresponding author of this study.

“Studies such as this deepen our understanding of the body’s complex immune response to SARS-CoV-2. Such knowledge will be key in evaluating long-term immunity, which in part will guide countries’ exit strategies. This study will hopefully spur greater investment in ways to facilitate and scale T cell analysis so that it, along with antibodies, can become part of any first-line immune response assessment,” said Professor Patrick Casey, Senior Vice-Dean for Research at Duke-NUS.

Reference: Nina Le Bert, Hannah E Clapham, Anthony T Tan, Wan Ni Chia, Christine YL Tham, Jane M Lim, Kamini Kunasegaran, Linda WL Tan, Charles-Antoine Dutertre, Nivedita Shankar, Joey ME Lim, Louisa Jin Sun, Marina Zahari, Zaw Myo Tun, Vishakha Kumar, Beng Lee Lim, Siew Hoon Lim, Adeline Chia, Yee-Joo Tan, Paul Anantharajah Tambyah, Shirin Kalimuddin, David Lye, Jenny GH Low, Lin-Fa Wang, Wei Yee Wan, Li Yang Hsu, Antonio Bertoletti and Clarence C Tam (2021). Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection. Journal of Experimental Medicine.

Complete research paper available at this link: https://doi.org/10.1084/jem.20202617