Studying the immune system’s response to COVID-19

The COVID-19 pandemic has directly affected more than 700 000 South Africans, and each patient experienced the virus differently – many paid the ultimate price. While the infection rate in the country has slowed down, pressing questions remain: How long does immunity last? What accounts for the differences in the disease’s severity?

In recent weeks globally, a handful of patients have reportedly been reinfected with COVID-19.  Therefore, understanding how the immune system responds to the virus and whether it provides previously infected patients with a level of protection should they be re-exposed to the virus are two critical questions scientists at the University of Cape Town (UCT) are trying to answer.

This research is led by Associate Professor Wendy Burgers, a viral immunologist in the Division of Medical Virology in the Department of Pathology in UCT’s Faculty of Health Sciences, in partnership with a team of researchers.

When studying the immune system’s response to a virus, scientists focus on the two major arms of the immune system: antibodies and T cells. Both, Associate Professor Burgers explained, provide immune memory, which refers to the immune system’s ability to quickly and specifically recognise antigens (components of a foreign virus or bacteria) that the body has previously encountered to help the body initiate an immune response.

 

“We’re trying to understand whether those patients who have been exposed to the common cold viruses (viruses related to COVID-19) build a level of immunity.”

Currently, researchers are interested in establishing how long immune memory lasts in COVID-19 patients, and whether cross-reactive immunity in patients who have been exposed to other related coronaviruses, which typically cause the common cold, protects patients from developing severe forms of COVID-19.  

“We’re trying to understand whether those patients who have been exposed to the common cold viruses (viruses related to COVID-19) build a level of immunity. In this case, T cells that can recognise SARS-CoV-2 might protect [patients] from contracting severe COVID-19,” Burgers said.

“These are important questions and because this is new research, we don’t have any of the answers yet.”

Establishing an assay

The research team has established an antibody assay – a biochemical test that measures the presence or concentration of antibodies in a patient’s blood, recognises the virus and signals that infection has occurred and an immune response has formed.

Following an in-depth study which spanned a period of 12 weeks (May to July), the findings were presented in a research paper by lead author Dr Stephen Makatsa, a postdoctoral fellow in the Division of Medical Virology.

The research involved collecting COVID-19-positive samples from infected volunteers in Cape Town and Johannesburg, recruited by the National Health Laboratory Services (NHLS). Once the scientists received the participants’ samples, they measured their antibody responses to the virus.   

Of the 77 participants surveyed, 23 volunteers reported that they had experienced mild disease symptoms; 38 volunteers reported moderate symptoms; five were asymptomatic and three were admitted to hospital with severe disease.

Results indicate that antibodies to the viral spike protein, and to its receptor binding domain (a key part of a virus that allows it to dock to body receptors to gain entry into cells and cause infection), were detected in 51 and 48 participants respectively.

“Results show that our test works really well in measuring antibodies in people who have been infected,” Burgers said.

“We are working with the NHLS who are validating commercial antibody assays for regulatory purposes. Our test shows excellent concordance when we compare it with their results.”

The goal now, she explained, is to use the test to measure antibody responses and see how long they last in patients who have been previously infected.

Studying healthcare workers

Burgers and her team have partnered with a healthcare worker study in UCT’s Department of Medicine, headed by Professor Ntobeko Ntusi. The study involves regularly sampling a group of healthcare workers who were infected with COVID-19, as well as a group of their peers who have not been infected with the virus, to study their immune responses.

Healthcare workers have been identified as primary participants for this study because of their high risk of exposure to the virus. The study spans a period of three years and study visits will occur every six months to obtain samples and perform tests.

From the antibody data available, Burgers said, scientists are able to measure antibodies in most people who have been infected with COVID-19. However, she added, in some cases, patients have displayed very low antibody responses post-infection, which may be related to the time period after infection, and whether they experienced mild or severe disease.

 

“This has caused quite a lot of alarm, but it’s important to remember that this is a normal immune response.”

“This has caused quite a lot of alarm, but it’s important to remember that this is a normal immune response, where antibodies wane after the initial infection is cleared.”

While scientists may not be able to measure the antibody response 100% of the time, Burgers said that if previously infected patients were to be re-exposed to the virus, immune memory could kick in, expand to very high levels and protect the person from reinfection.

For those volunteers who have not been infected with the virus, the group will study whether any “cross-reactive” T cells (from previous common cold coronavirus infection) have any effect in modulating the outcome of infection or the course of COVID-19 disease, should they become infected over the course of the study.

“This is what we are trying to understand and the reason we have committed to this study to follow healthcare workers,” she said.

Questions, questions, questions

At this stage, scientists have more questions than answers, one of which is: Can patients become reinfected with COVID-19?

“Maybe they’ve developed a good immune response to the virus as a result of the first infection. Our basic understanding of immunology and our experience of the pandemic thus far suggest that there certainly are some months of immunity because there are no widespread reports of people becoming reinfected,” she said.

“So, we can safely say that we do build a certain amount of immunity that protects us. We just don’t know for sure how long it lasts.”

Understanding immune responses in South Africans  

Burgers said that while research into the immune response to COVID-19 has begun globally since the onset of the pandemic, research specific to South Africa is essential.

“It’s important to understand the immune responses in South Africans. We need to determine whether findings are the same or different with South Africans compared to elsewhere in the world.”  

The results will give researchers insight into how long immune responses last, and how strong those immune responses are, as well as provide clarity into whether prior exposure to other related coronaviruses helps patients build a level of immunity to COVID-19.

“These insights are critical and will tell us a lot about how we need to respond overall and will be especially useful as we conduct clinical trials for a [COVID-19] vaccine here in the country.”

The power of collaboration

Burgers has lauded her colleagues and students for their commitment to the ongoing COVID-19 research project, and for pressing on despite “exceptionally difficult” circumstances.   

 

“This pandemic has highlighted the power of collaboration.”

“This pandemic has highlighted the power of collaboration. We are working with wonderful colleagues who are both caring for patients and at the same time recruiting patients in order to perform critical research,” she said.

“And [thanks go] to my incredible students who are working under very difficult circumstances, but regardless they continue to learn and ... do the research. To survive this pandemic will be an achievement for all of us.”

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