Natural infection induces varied immune responses, reinforcing need for vaccination

Key findings:

  • Immune memory following COVID infection is measurable at 6 months but is highly variable between people

  • Previous infection does not necessarily protect you long term from SARS-CoV-2, particularly the Variants of Concern Alpha and Beta. People who show little or no evidence of immune memory to COVID 6 months after natural infection are not able to neutralise the Variants of Concern. 

  • Some features of the immune response can be measured one month after natural infection with SARS-CoV-2 and used to predict which people will have durable immune responses after six months.

  • People with COVID-19 symptoms have variable immune responses that may reduce over time and are not necessarily protected from SARS-CoV-2 variants.

  • People who experienced asymptomatic infection tended to have lower immune responses across the many immune parameters we have measured.


It remains important to understand the strength and of the immune response to natural infection with SARS-CoV-2 (i.e. COVID-19), as well as how long immunity lasts. Doing so will help us better understand how the immune system responds to vaccination and to new Variants of Concern (VOCs).

In this study, researchers examined the immune response of healthcare workers from 1-6 months after experiencing COVID-19 and looked for patterns in the ways immune responses differed over time. This study is available as a pre-print via Research Square and has not yet been peer-reviewed.

The study was led by researchers at the University of Oxford, in collaboration with the Universities of Liverpool, Sheffield, Newcastle, and Birmingham, with support from the UK Coronavirus Immunology Consortium, as part of the PITCH study (Protective Immunity from T cells to Covid-19 in Health workers).

Included in the study were:

  • 66 healthcare workers who experienced COVID-19 with symptoms
  • 12 healthcare workers who experienced asymptomatic COVID-19 (i.e., no symptoms)
  • 8 patients who experienced severe disease

The researchers took blood samples each month, from 1-6 months after infection, to study different aspects of the immune response. This included different types of antibodies which are produced to target different parts of the virus, B cells which manufacture these antibodies and keep the body’s memory of the disease, and several types of T cell.

The researchers used a new machine learning approach – nicknamed SIMON – to find patterns in the data and to see if the early immune response, and how severe a person’s early symptoms were, could predict the strength of their immune response later on.

They found an early immune signature, visible one month after infection, which predicted how strong the immune response to the virus was after 6 months. This was linked to both cellular (T cell) and antibody immunity, which are the two main ways the immune system tries to protect the body from infection. 

When the researcher tested serum samples (which contain antibodies) from 1 and 6 months after infection, most samples from people with a weak immune response signature at the first month failed to show any neutralising antibodies against the Alpha variant at six months. In addition, none of them showed a neutralising antibody response against the Beta variant. This raises the possibility that the immune memory of people with a weak immune signature does not provide enough protection to prevent reinfection by these variants. 

Most people who experienced symptomatic COVID-19 had measurable immune responses six months later, however a smaller but significant minority (17/66; 26%) did not. The vast majority of people who experienced no symptoms during their initial infection (11/12; 92%) did not show a measurable immune response six months later. 

These results suggest that people who have previously been infected with SARS-CoV-2, with or without symptoms, should not assume that they are automatically protected against reinfection. It also highlights the importance of everyone getting their COVID-19 vaccination when they are offered it. 

Overall, this study reinforces how important it is that everyone gets their COVID-19 vaccination when offered. This is because COVID-19 vaccines generate higher immune responses than natural infection, and it is important for everyone to get vaccinated for maximum protection against this disease and, in particular, against Variants of Concern. 



Comments from the authors of the study:


Dr Christina Dold, study author from University of Oxford, said:

“Our study is one of the most comprehensive accounts of the immune response following COVID-19 in both symptomatic and asymptomatic individuals.  We found that individuals showed very different immune responses from each other following COVID-19, with some people from both the symptomatic and asymptomatic groups showing no evidence of immune memory six months after infection or even sooner. Our concern is that these people may be at risk of contracting COVID-19 for a second time, especially with new variants circulating. This means that it is very important that we all get the COVID vaccine when offered even if you think you may have previously had COVID-19.”


Dr Adriana Tomic, study author from University of Oxford said:

“For this study, we wanted to try to understand if there are immune factors that can predict how likely it is that a person can maintain immunity against SARS-CoV-2 over time.  

“We found a signature present in the immune response one month after infection that can predict whether an individual will exhibit strong immune memory against SARS-CoV-2 six months later. This ‘immune signature’ comprises aspects of both T cell and antibodies responses, indicating that both immune components are important for strong and durable protection against SARS-CoV-2.”


Our grateful thanks go to all the healthcare workers who volunteered to take part in this study.

More details on this study are available via the publications section.