Although the scientific community has made tremendous progress in our understanding of SARS-CoV-2, the virus that causes COVID-19, there are still many unanswered questions. Of these, one of the most urgent unknowns to address is: Does natural infection confer protection against subsequent infection and how long might this protection last?
One key measurement used to indicate a protective response is the levels of neutralizing antibodies (NAbs), which work by binding to the virus and preventing it from entering cells. However, antibodies could also theoretically worsen symptoms through a pathway called antibody-dependent enhancement, as seen in the case of diseases such as dengue.
To better understand the antibody responses in COVID-19 patients, researchers in Singapore examined 164 patients for 180 days following the onset of symptoms, measuring the amount and binding strength of the antibodies they produced. Then, using a machine learning algorithm, they classified the antibody responses into five groups and predicted how long NAbs would last for each group.
Patients who exhibited mild to no COVID-19 symptoms did not seem to have sustained immunity against the virus, with undetectable NAb levels by 180 days post-infection. On the other hand, those who suffered from moderate to severe symptoms tended to show persistent high levels of NAbs. This pattern is similar to the immune response of patients who had severe symptoms of the SARS virus in the early 2000s, said study co-author Lisa F.P. Ng, Executive Director at A*STAR’s Infectious Diseases Labs (ID Labs).
“Neutralizing antibody levels were also predictive of immune protection from re-infection or symptomatic SARS-CoV-2 infection,” she said, adding that low titers of NAbs are associated with symptomatic COVID-19 infection and subsequent re-infection.
NAb waning patterns varied widely depending on factors such as age, the presence of co-morbidities and clinical outcomes, with levels dropping off within 96 days on average for the rapid waning group compared to 1.5 years in the persistent group. “It is thus important to monitor NAbs strategically, stratifying by age, ethnicity and other factors, to determine optimal vaccine dosing strategies and improve vaccine design,” Ng said.
On the other hand, a different branch of immunity—conferred by T cells rather than antibody-producing B cells—appeared to be the same in all patients regardless of disease severity and NAb levels. “This shows that individuals may still be protected if they have a robust T cell immunity when the neutralizing antibody level is low,” Ng explained.
The team, including study corresponding authors David Lye at the National Centre for Infectious Diseases and Linfa Wang from Duke-NUS Medical School, are now studying the antibody responses in vaccinated individuals to understand the longevity of immunity provided by vaccination.