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1.
Clin Infect Dis ; 2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1973126

ABSTRACT

Long COVID (LC) constitutes a potential health emergency as millions of SARS-CoV-2 infections lead to chronic symptoms. We must understand whether vaccines reduce LC as this has major implications for health policy. We report a 79% reduction in LC referrals correlating with reinfections and vaccination in the UK.

2.
EBioMedicine ; 81: 104129, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1906949

ABSTRACT

BACKGROUND: There is currently no consensus on the diagnosis, definition, symptoms, or duration of COVID-19 illness. The diagnostic complexity of Long COVID is compounded in many patients who were or might have been infected with SARS-CoV-2 but not tested during the acute illness and/or are SARS-CoV-2 antibody negative. METHODS: Given the diagnostic conundrum of Long COVID, we set out to investigate SARS-CoV-2-specific T cell responses in patients with confirmed SARS-CoV-2 infection and/or Long COVID from a cohort of mostly non-hospitalised patients. FINDINGS: We discovered that IL-2 release (but not IFN-γ release) from T cells in response to SARS-CoV-2 peptides is both sensitive (75% +/-13%) and specific (88%+/-7%) for previous SARS-CoV-2 infection >6 months after a positive PCR test. We identified that 42-53% of patients with Long COVID, but without detectable SARS-CoV-2 antibodies, nonetheless have detectable SARS-CoV-2 specific T cell responses. INTERPRETATION: Our study reveals evidence (detectable T cell mediated IL-2 release) of previous SARS-CoV-2 infection in seronegative patients with Long COVID. FUNDING: This work was funded by the Addenbrooke's Charitable Trust (900276 to NS), NIHR award (G112259 to NS) and supported by the NIHR Cambridge Biomedical Research Centre. NJM is supported by the MRC (TSF MR/T032413/1) and NHSBT (WPA15-02). PJL is supported by the Wellcome Trust (PRF 210688/Z/18/Z, 084957/Z/08/Z), a Medical Research Council research grant MR/V011561/1 and the United Kingdom Research and a Innovation COVID Immunology Consortium grant (MR/V028448/1).


Subject(s)
COVID-19 , Antibodies, Viral , COVID-19/complications , Humans , Interleukin-2 , SARS-CoV-2
3.
Cell Rep ; 38(7): 110393, 2022 02 15.
Article in English | MEDLINE | ID: covidwho-1719435

ABSTRACT

B cells are important in immunity to both severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and vaccination, but B cell receptor (BCR) repertoire development in these contexts has not been compared. We analyze serial samples from 171 SARS-CoV-2-infected individuals and 63 vaccine recipients and find the global BCR repertoire differs between them. Following infection, immunoglobulin (Ig)G1/3 and IgA1 BCRs increase, somatic hypermutation (SHM) decreases, and, in severe disease, IgM and IgA clones are expanded. In contrast, after vaccination, the proportion of IgD/M BCRs increase, SHM is unchanged, and expansion of IgG clones is prominent. VH1-24, which targets the N-terminal domain (NTD) and contributes to neutralization, is expanded post infection except in the most severe disease. Infection generates a broad distribution of SARS-CoV-2-specific clones predicted to target the spike protein, while a more focused response after vaccination mainly targets the spike's receptor-binding domain. Thus, the nature of SARS-CoV-2 exposure differentially affects BCR repertoire development, potentially informing vaccine strategies.


Subject(s)
COVID-19/immunology , Receptors, Antigen, B-Cell/immunology , Vaccination , B-Lymphocytes/immunology , COVID-19/prevention & control , Clonal Evolution , Humans , Immunoglobulin Heavy Chains/genetics , Immunoglobulin Heavy Chains/immunology , Immunoglobulin Isotypes/genetics , Immunoglobulin Isotypes/immunology , Immunoglobulin Variable Region/genetics , Immunoglobulin Variable Region/immunology , Kinetics , Receptors, Antigen, B-Cell/genetics , SARS-CoV-2/immunology , Severity of Illness Index , Somatic Hypermutation, Immunoglobulin/immunology , Spike Glycoprotein, Coronavirus/immunology
4.
Cell reports ; 2022.
Article in English | EuropePMC | ID: covidwho-1661209

ABSTRACT

Kotagiri et al. find that SARS-CoV-2 infection versus vaccination induces distinct changes in the B cell receptor repertoire, including prominent clonal expansion in IgA and IgM after infection, but IgG after vaccination. A broad anti-spike response to infection contrasts with a narrower RBD-focused one after vaccination, potentially informing vaccination strategies.

5.
Immunity ; 54(6): 1257-1275.e8, 2021 06 08.
Article in English | MEDLINE | ID: covidwho-1230571

ABSTRACT

The kinetics of the immune changes in COVID-19 across severity groups have not been rigorously assessed. Using immunophenotyping, RNA sequencing, and serum cytokine analysis, we analyzed serial samples from 207 SARS-CoV2-infected individuals with a range of disease severities over 12 weeks from symptom onset. An early robust bystander CD8+ T cell immune response, without systemic inflammation, characterized asymptomatic or mild disease. Hospitalized individuals had delayed bystander responses and systemic inflammation that was already evident near symptom onset, indicating that immunopathology may be inevitable in some individuals. Viral load did not correlate with this early pathological response but did correlate with subsequent disease severity. Immune recovery is complex, with profound persistent cellular abnormalities in severe disease correlating with altered inflammatory responses, with signatures associated with increased oxidative phosphorylation replacing those driven by cytokines tumor necrosis factor (TNF) and interleukin (IL)-6. These late immunometabolic and immune defects may have clinical implications.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , COVID-19/virology , Host-Pathogen Interactions/immunology , Lymphocyte Activation/immunology , SARS-CoV-2/immunology , Biomarkers , CD8-Positive T-Lymphocytes/metabolism , COVID-19/diagnosis , COVID-19/genetics , Cytokines/metabolism , Disease Susceptibility , Gene Expression Profiling , Humans , Inflammation Mediators/metabolism , Longitudinal Studies , Lymphocyte Activation/genetics , Oxidative Phosphorylation , Phenotype , Prognosis , Reactive Oxygen Species/metabolism , Severity of Illness Index , Transcriptome
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