Previous COVID infection may not offer long-term protection – UK study

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Previous infection with coronavirus does not necessarily protect against COVID-19 in the longer term, especially when caused by new variants of concern, an Oxford University study of healthcare workers suggests, writes Ian Sample for The Guardian.

The Oxford researchers found marked differences in the immune responses of medical staff who contracted COVID, with some appearing far better equipped than others to combat the disease six months later.

Scientists on the study, conducted with the UK Coronavirus Immunology Consortium, said the findings reinforced the importance of everyone getting vaccinated regardless of whether they had been infected with the virus earlier in the pandemic.

“If you look at the trajectory of the immune response after infection, mostly it is still detectable six months later, but it’s highly variable between people,” said Professor Eleanor Barnes, a professor of hepatology and experimental medicine at Oxford and a senior author on the study.

The Guardian article of 17 June 2021 continues: “That is quite different to vaccination. If you vaccinate you get a really robust response, but with natural infection there’s much more diversity in responses.”

The researchers analysed blood samples from 78 healthcare workers who had COVID, with or without symptoms, between April and June last year. The blood was checked monthly for up to six months post-infection for a range of immune responses. These included different types of antibody that target the virus, B cells that make antibodies and retain a memory of the disease, and T cells, which reduce the severity of disease by killing off infected cells.

Writing in a preprint that has yet to be peer-reviewed, the authors describe how they used a machine learning system called Simon, for Sequential Iterative Modeling Over Night, to see whether a person’s early immune response and the severity of their infection could predict their longer-term immunity, writes Sample in The Guardian.

Dr Adriana Tomic, the first author on the study, said a signature in the antibody and T-cell response at one month predicted how robust the antibody response would be at six months.

The majority of people who produced a weak immune response at one month had no detectable antibodies that could neutralise the Alpha variant, first seen in Kent, at six months. None mounted neutralising antibodies against the Beta variant first spotted in South Africa. The researchers have yet to analyse data for the Delta variant now dominant in the UK.

While most of the healthcare workers who developed symptomatic disease had a measurable immune response six months later, more than a quarter did not. More than 90% of those who had asymptomatic infections had no measurable immune response six months later, the researchers found, writes The Guardian.

“In our view, previous infection does not necessarily protect you long-term from Sars-Cov-2, particularly variants of concern,” said Barnes. “You shouldn’t depend on it to protect you from subsequent disease, you should be vaccinated.”

Link to the full story in The Guardian below.


Study details

Divergent trajectories of antiviral memory after SARS-Cov-2 infection 

Adriana Tomic, Donal T Skelly, Ane Ogbe, Daniel O'Connor, Matthew Pace, Emily Adland, Frances Alexander, Mohammad Ali, Kirk Allott, M Azim Ansari, Sandra Belij-Rammerstorfer , Sagida Bibi, Luke Blackwell, Anthony Brown, Helen Brown, Breeze Cavell, Elizabeth A Clutterbuck, Thushan I de Silva, David Eyre, Amy Flaxman, James Grist, Carl-Philipp Hackstein, Rachel Halkerston, Adam C Harding, Jennifer Hill, Tim James, Cecilia Jay, Síle A Johnson, Barbara Kronsteiner, Yolanda Lie, Aline Linder, Stephanie Longet, Spyridoula Marinou, Philippa C Matthews, Jack Mellors, Christos Petropoulos, Patpong Rongkard, Cynthia Sedik, Laura Silva-Reyes, Holly Smith, Lisa Stockdale, Stephen Taylor, Stephen Thomas, Timothy Tipoe, Lance Turtle, Vinicius Adriano Vieira, Terri Wrin, OPTIC Clinical Group, PITCH Study Group, C-MORE Group, Andrew J Pollard, Teresa Lambe, Christopher P Conlon, Katie Jeffery, Simon Travis, Philip J Goulder, John Frater, Alexander J Mentzer, Lizzie Stafford, Miles W Carroll, William S James, Paul Klenerman, Eleanor Barnes, Christina Dold and Susanna J Dunachie.

Preprint published on Research Square



Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is normally controlled by effective host immunity including innate, humoral and cellular responses. However, the trajectories and correlates of acquired immunity, and the capacity of memory responses months after infection to neutralise variants of concern – which has important public health implications – is not fully understood.

To address this, we studied a cohort of 78 UK healthcare workers who presented in April to June 2020 with symptomatic PCR-confirmed infection or who tested positive during an asymptomatic screening programme and tracked virus-specific B and T cell responses longitudinally at 5-6 time points each over 6 months, prior to vaccination.

We observed a highly variable range of responses, some of which – T cell interferon-gamma (IFN-γ) ELISpot, N-specific antibody waned over time across the cohort, while others (spike-specific antibody, B cell memory ELISpot) were stable. In such cohorts, antiviral antibody has been linked to protection against re-infection.

We used integrative analysis and a machine-learning approach (SIMON – Sequential Iterative Modeling Over Night) to explore this heterogeneity and to identify predictors of sustained immune responses. Hierarchical clustering defined a group of high and low antibody responders, which showed stability over time regardless of clinical presentation.

These antibody responses correlated with IFN-γ ELISpot measures of T cell immunity and represent a subgroup of patients with a robust trajectory for longer term immunity. Importantly, this immune-phenotype associates with higher levels of neutralising antibodies not only against the infecting (Victoria) strain but also against variants B.1.1.7 (alpha) and B.1.351 (beta).

Overall memory responses to SARS-CoV-2 show distinct trajectories following early priming, that may define subsequent protection against infection and severe disease from novel variants.


The Guardian story – Previous COVID infection may not offer long-term protection, study finds (Open access)

Research article – Divergent trajectories of antiviral memory after SARS-Cov-2 infection (Open access)




COVID-19 immunity likely to be long lasting — studies

SA appears to be close to COVID-19 herd immunity

COVID-19 herd immunity may be unachievable — Spanish study of 61,000 people

Immunity to COVID-19 may be higher than tests have shown — Karolinska Institutet




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