How a health care worker biobank shaped understanding of COVID-19 immunity

Five years ago, just months after South Africa’s first COVID-19 case was identified, two University of Cape Town (UCT) professors spearheaded a groundbreaking healthcare worker cohort study. Their goal was to track the threat to global public health by creating a repository of biological samples from healthcare workers who were most exposed to the disease.

Today, the store of samples collected since 2020 has become a goldmine for immunologists. It has deepened understanding of human immune responses to SARS-CoV-2, and shaped future infectious disease research, locally and globally.

Led by Ntobeko Ntusi, UCT’s former head of medicine and now president of the South African Medical Research Council, and UCT’s professor of virology, Wendy Burgers, the study followed 400 frontline health care workers from Groote Schuur Hospital in Cape Town.

Over the past five years, they have captured critical biological data to explore vaccine efficacy, immune memory, and the long-term effects of repeated SARS-CoV-2 infections.

“We realised that this was an unprecedented opportunity to follow the body’s reaction to a completely new virus,” Burgers explains.

Healthcare workers, among the most exposed groups during the pandemic, became a natural choice for studying immunity. In South Africa, they were the first to receive the Johnson & Johnson (J&J) vaccine, through the Sisonke study.

Participants included doctors, nurses, allied health professionals and other hospital employees – 75% of whom were women. They volunteered their own blood, plasma and nasal swabs for research. In the first month, samples were taken weekly. This moved to fortnightly for the next six months. They were sampled every three months for the following six months, and finally, every six months until the five-year mark since testing began. The last collection has now taken place.

Samples are stored in the Faculty of Health Sciences at UCT, both at the Cape Heart Institute and at the Institute of Infectious Diseases and Molecular Medicine.

“These health care workers put their bodies on the line not only in service of their patients, but also to advance science and deepen our understanding of immune system responses,” Ntusi says.

The data collected from this cohort led to 20 major publications in leading scientific journals, including Nature¹, New England Journal of Medicine² and Science Translational Medicine³.

These provided critical insights into the durability of immune responses, the impact of repeated exposure to the virus, and how hybrid immunity – gained from both infection and vaccination – enhanced protection against severe disease.

The confirmation of the durability of hybrid immunity was one of the most significant findings. The scientists were able to show that this pattern held true in African populations, adding critical data to the global understanding of COVID-19 immunity.

Another breakthrough was the role of T cells in long-term immunity. While much of the initial focus of COVID-19 research was on antibodies, the South African scientists demonstrated that T cells provided lasting immune protection, even as new variants emerged.

“Our findings showed that people who had both vaccination and prior infection had the strongest and most durable immune responses,” says Burgers. “This helped reinforce the importance of vaccines, even in populations that had already experienced widespread infection.”

As new variants emerged, the cohort study enabled researchers to assess pre-existing immunity, using stored samples.

“When Omicron first surfaced, there was global anxiety about whether our existing immunity would hold up,” Burgers explains. “Our data showed that while antibody responses declined with each new variant, T-cell responses remained highly cross-reactive.”

This ability of the immune system to recognise and respond effectively to the different variants “was a huge relief and helped explain why we didn’t see waves of severe disease and high mortality with every new variant.”

The research has laid the foundation for pandemic preparedness beyond COVID-19.

“We are now using these stored samples to study cross-reactivity to H5N1 avian influenza, assessing whether prior flu infections or vaccinations might provide some level of protection if this avian virus were to cause a human pandemic,” Burgers adds.

“If we can answer this, we’ll be better prepared for future pandemics.”

The study brought together scientists from across South Africa, including from the South African National Institute for Communicable Diseases. Partnerships with global institutions also amplified the impact of the research.

“This project was made possible by a network of dedicated researchers, funders and, most importantly, the healthcare workers who volunteered to be part of it,” says Ntusi.

Beyond answering urgent pandemic questions, the study also built crucial local research capacity.

“Many of our young scientists gained high-level technical skills, from running sophisticated immunology assays to analysing complex datasets,” explains Michael Zulu, a junior research fellow from UCT’s Institute of infectious Disease and Molecular Medicine, who is working on the project.

The infrastructure developed during the pandemic is being used to study immune responses to Mpox, RSV vaccines, and preclinical work on new mRNA vaccines developed in South Africa.

Historically, much of the world’s leading infectious disease research has been conducted in high-income countries. “We have shown that cutting-edge research can thrive in Africa,” says Ntusi. “Our work has informed global policy, influenced vaccine strategies, and demonstrated that African-led science can drive meaningful change.”

Source article: feature by Nature Africa, can be viewed here.