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

• Published in: Nature communications 2022-03, Vol.13 (1), p.1251-1251, Article 1251
• Main Authors: Tomic, Adriana, Skelly, Donal T., Ogbe, Ane, O’Connor, Daniel, Pace, Matthew, Adland, Emily, Alexander, Frances, Ali, Mohammad, Allott, Kirk, Azim Ansari, M., Belij-Rammerstorfer, Sandra, Bibi, Sagida, Blackwell, Luke, Brown, Anthony, Brown, Helen, Cavell, Breeze, Clutterbuck, Elizabeth A., de Silva, Thushan, Eyre, David, Lumley, Sheila, Flaxman, Amy, Grist, James, Hackstein, Carl-Philipp, Halkerston, Rachel, Harding, Adam C., Hill, Jennifer, James, Tim, Jay, Cecilia, Johnson, Síle A., Kronsteiner, Barbara, Lie, Yolanda, Linder, Aline, Longet, Stephanie, Marinou, Spyridoula, Matthews, Philippa C., Mellors, Jack, Petropoulos, Christos, Rongkard, Patpong, Sedik, Cynthia, Silva-Reyes, Laura, Smith, Holly, Stockdale, Lisa, Taylor, Stephen, Thomas, Stephen, Tipoe, Timothy, Turtle, Lance, Vieira, Vinicius Adriano, Wrin, Terri, Pollard, Andrew J., Lambe, Teresa, Conlon, Chris P., Jeffery, Katie, Travis, Simon, Goulder, Philip, Frater, John, Mentzer, Alex J., Stafford, Lizzie, Carroll, Miles W., James, William S., Klenerman, Paul, Barnes, Eleanor, Dold, Christina, Dunachie, Susanna J.
• Format: Article
• Language: English
• Subjects: 13; 13/1; 13/31; 631/250/2152/1566/1571; 631/250/254; 631/250/255/2514; 631/326/596/4130; Antibodies; Antibodies, Viral; Antiviral Agents; Coronaviruses; COVID-19; Enzyme-linked immunosorbent assay; Health care; Heterogeneity; Humanities and Social Sciences; Humans; Immunity; Immunological memory; Immunology; Infections; Interferon; Iterative methods; Longitudinal Studies; Lymphocytes; Lymphocytes T; Machine learning; Medical personnel; Memory cells; multidisciplinary; Priming; Respiratory diseases; SARS-CoV-2; Science; Science (multidisciplinary); Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus; Subgroups; Vaccination; Viral diseases; γ-Interferon
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-28898-1

The trajectories of acquired immunity to severe acute respiratory syndrome coronavirus 2 infection are not fully understood. We present a detailed longitudinal cohort study of UK healthcare workers prior to vaccination, presenting April-June 2020 with asymptomatic or symptomatic infection. Here we show a highly variable range of responses, some of which (T cell interferon-gamma ELISpot, N-specific antibody) wane over time, while others (spike-specific antibody, B cell memory ELISpot) are stable. We use integrative analysis and a machine-learning approach (SIMON - Sequential Iterative Modeling OverNight) to explore this heterogeneity. We identify a subgroup of participants with higher antibody responses and interferon-gamma ELISpot T cell responses, and a robust trajectory for longer term immunity associates with higher levels of neutralising antibodies against the infecting (Victoria) strain and also against variants B.1.1.7 (alpha) and B.1.351 (beta). These variable trajectories following early priming may define subsequent protection from severe disease from novel variants. The engagement of immunological memory is a key component to the protective anti-SARS-CoV-2 B and T cell responses. Here the authors assess the B and T cells of a cohort of UK healthcare workers in response to infection and longitudinally track the compartment showing distinct trajectories following early priming.