'Immune memory' may explain why some people don't catch COVID-19

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An immune memory from past coronavirus infections may explain why some people never test positive to COVID-19 despite being in high risk scenarios.  UK researchers tested 58 healthcare workers from hospitals in London, who never tested positive for COVID-19 despite being at very high risk and having other markers of viral infection. They compared the T cell responses in this group with those in matched healthcare workers who did develop COVID-19. They found that the people who escaped infection had stronger T cell responses, particularly against a part of the virus also found in other coronaviruses known as the replication–transcription complex (RTC). This 'immune memory' may be helping to clear the virus quickly before it can take hold. The discovery could pave the way for new vaccines which target the T-cell response.

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From: Springer Nature

Resistance to detectable SARS-CoV-2 infection highlights new vaccine targets

Past exposure to other coronaviruses may speed up the clearance of SARS-CoV-2 because the immune system remembers viral replication proteins that are highly conserved across coronaviruses, a paper in Nature indicates. Healthcare workers at high risk of SARS-CoV-2 exposure were studied, and, despite testing negative for SARS-CoV-2 infection or antibodies, they showed signs of elevated memory T cell response against the conserved complex, suggesting that they were able to rapidly clear SARS-CoV-2. The findings highlight the highly conserved proteins as targets for future vaccines against endemic and emerging coronaviruses.

Some individuals at high risk of exposure to the highly infectious SARS-CoV-2 display negative results with standard diagnostic tests. Previous research has suggested that exposure to coronaviruses produces memory T cells that may be effective in attenuating SARS-CoV-2 infection. Mala Maini, Leo Swadling and colleagues hypothesize that pre-existing memory T cells that recognize the proteins of the replication–transcription complex (RTC), a conserved structure involved in viral replication, might facilitate the rapid control of SARS-CoV-2. Designing vaccines that could mimic this expansion of cross-reactive T cells may offer protection against a range of endemic or emerging coronaviruses, the authors conclude.

The authors studied 58 healthcare workers from hospitals in London, UK, who did not test positive for SARS-CoV-2 infection despite high risk of exposure during the first wave of the pandemic in the UK. They compared T cell responses in this cohort with those in matched healthcare workers who did develop laboratory-confirmed SARS-CoV-2 infection. Those individuals who seemed to evade infection had stronger T cell responses, particularly directed against the RTC, than those of individuals who tested positive.

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Organisation/s: University College London, UK
Funder: The COVIDsortium is supported by funding donated by individuals, charitable Trusts, and corporations including Goldman Sachs, Citadel and Citadel Securities, The GUy Foundation, GW Pharmaceuticals, Kusuma Trust, and Jagclif Charitable Trust, and enabled by Barts Charity with support from UCLH Charity. Wider support is acknowledged on the COVIDsortium website. Institutional support from Barts Health NHS Trust and Royal Free NHS Foundation Trust facilitated study processes, in partnership with University College London and Queen Mary University London. This study was funded by UKRI/NIHR UK-CIC (supporting LS and MKM). MKM is also supported by Wellcome Trust Investigator Award (214191/Z/18/Z) and CRUK Immunology grant (26603) and LS by a Medical Research Foundation fellowship (044-0001). MN is supported by the Wellcome Trust (207511/Z/17/Z) and by NIHR Biomedical Research Funding to UCL and UCLH. AB is supported by Grant support a Special NUHS COVID-19 Seed Grant Call, Project NUHSRO/2020/052/RO5+5/NUHS-COVID/6 (WBS R-571-000-077-733). JCM, CM and TAT are directly and indirectly supported by the University College London Hospitals (UCLH) and Barts NIHR Biomedical Research Centres and through the British Heart Foundation (BHF) Accelerator Award (AA/18/6/34223). TAT is funded by a BHF Intermediate Research Fellowship (FS/19/35/34374). AMV, ÁM, CM and JCM were supported by the UKRI/MRC Covid-19 Rapid response grant COV0331. ÁM and CP are supported by Rosetrees Trust, The John Black Charitable Foundation, and Medical College of St Bartholomew’s Hospital Trust and NIHR-MRC grant MR/V027883/1. RJB and DMA are supported by MRC (MR/S019553/1, MR/R02622X/1, MR/V036939/1, MR/W020610/1), NIHR Imperial Biomedical Research Centre (BRC): ITMAT, Cystic Fibrosis Trust SRC (2019SRC015), and Horizon 2020 Marie Skłodowska-Curie Innovative Training Network (ITN) European Training Network (No 860325). Funding for the HLA imputed data was provided by UKRI/MRC Covid-19 rapid response grant (Cov-0331 - MR/V027883/1). LEM is supported by a Medical Research Council Career Development Award (MR/R008698/1). LVD is supported by a UCL Excellence Fellowship. The funders had no role in study design data collection, data analysis, data interpretation, or writing of the report.
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