ABSTRACT
Identification of protective T cell responses against SARS-CoV-2 requires distinguishing people infected with SARS-CoV-2 from those with cross-reactive immunity to other coronaviruses. Here we show a range of T cell assays that differentially capture immune function to characterise SARS-CoV-2 responses. Strong ex vivo ELISpot and proliferation responses to multiple antigens (including M, NP and ORF3) are found in 168 PCR-confirmed SARS-CoV-2 infected volunteers, but are rare in 119 uninfected volunteers. Highly exposed seronegative healthcare workers with recent COVID-19-compatible illness show T cell response patterns characteristic of infection. By contrast, >90% of convalescent or unexposed people show proliferation and cellular lactate responses to spike subunits S1/S2, indicating pre-existing cross-reactive T cell populations. The detection of T cell responses to SARS-CoV-2 is therefore critically dependent on assay and antigen selection. Memory responses to specific non-spike proteins provide a method to distinguish recent infection from pre-existing immunity in exposed populations.
Subject(s)
Antiviral Agents/pharmacology , COVID-19/immunology , COVID-19/virology , Cross Reactions/immunology , Immunoassay/methods , SARS-CoV-2/physiology , T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/epidemiology , Cell Proliferation , Cytokines/metabolism , HEK293 Cells , Health Personnel , Humans , Immunoglobulin G/immunology , Immunologic Memory , Interferon-gamma/metabolism , Pandemics , Peptides/metabolism , SARS-CoV-2/drug effectsABSTRACT
INTRODUCTION: The emergence and rapid spread of COVID-19 have caused widespread and catastrophic public health and economic impact, requiring governments to restrict societal activity to reduce the spread of the disease. The role of household transmission in the population spread of SARS-CoV-2, and of host immunity in limiting transmission, is poorly understood. This paper describes a protocol for a prospective observational study of a cohort of households in Liverpool City Region, UK, which addresses the transmission of SARS-CoV-2 between household members and how immunological response to the infection changes over time. METHODS AND ANALYSIS: Households in the Liverpool City Region, in which members have not previously tested positive for SARS-CoV-2 with a nucleic acid amplification test, are followed up for an initial period of 12 weeks. Participants are asked to provide weekly self-throat and nasal swabs and record their activity and presence of symptoms. Incidence of infection and household secondary attack rates of COVID-19 are measured. Transmission of SARS-CoV-2 will be investigated against a range of demographic and behavioural variables. Blood and faecal samples are collected at several time points to evaluate immune responses to SARS-CoV-2 infection and prevalence and risk factors for faecal shedding of SARS-CoV-2, respectively. ETHICS AND DISSEMINATION: The study has received approval from the National Health Service Research Ethics Committee; REC Reference: 20/HRA/2297, IRAS Number: 283 464. Results will be disseminated through scientific conferences and peer-reviewed open access publications. A report of the findings will also be shared with participants. The study will quantify the scale and determinants of household transmission of SARS-CoV-2. Additionally, immunological responses before and during the different stages of infection will be analysed, adding to the understanding of the range of immunological response by infection severity.