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Immunity ; 55(7): 1299-1315.e4, 2022 07 12.
Article in English | MEDLINE | ID: covidwho-2076210


As the establishment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell memory in children remains largely unexplored, we recruited convalescent COVID-19 children and adults to define their circulating memory SARS-CoV-2-specific CD4+ and CD8+ T cells prior to vaccination. We analyzed epitope-specific T cells directly ex vivo using seven HLA class I and class II tetramers presenting SARS-CoV-2 epitopes, together with Spike-specific B cells. Unvaccinated children who seroconverted had comparable Spike-specific but lower ORF1a- and N-specific memory T cell responses compared with adults. This agreed with our TCR sequencing data showing reduced clonal expansion in children. A strong stem cell memory phenotype and common T cell receptor motifs were detected within tetramer-specific T cells in seroconverted children. Conversely, children who did not seroconvert had tetramer-specific T cells of predominantly naive phenotypes and diverse TCRαß repertoires. Our study demonstrates the generation of SARS-CoV-2-specific T cell memory with common TCRαß motifs in unvaccinated seroconverted children after their first virus encounter.

COVID-19 , SARS-CoV-2 , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , Epitopes, T-Lymphocyte , Humans , Immunologic Memory , Receptors, Antigen, T-Cell , Receptors, Antigen, T-Cell, alpha-beta/genetics , Spike Glycoprotein, Coronavirus
Lancet Reg Health West Pac ; 25: 100486, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1867463


Background: Early, rapid detection of SARS-CoV-2 is essential in healthcare settings in order to implement appropriate infection control precautions and rapidly assign patients to care pathways. Rapid testing methods, such as SARS-CoV-2 rapid antigen testing (RAT) may improve patient care, despite a lower sensitivity than real-time PCR (RT-PCR) testing. Methods: Patients presenting to an Emergency Department (ED) in Melbourne, Australia, were risk-stratified for their likelihood of active COVID-19 infection, and a non-randomised cohort of patients were tested by both Abbott Panbio™ COVID-19 Ag test (RAT) and SARS-CoV-2 RT-PCR. Patients with a positive RAT in the 'At or High Risk' COVID-19 group were moved immediately to a COVID-19 ward rather than waiting for a RT-PCR result. Clinical and laboratory data were assessed to determine test performance characteristics; and length of stay in the ED was compared for the different patient cohorts. Findings: Analysis of 1762 paired RAT/RT-PCR samples demonstrated an overall sensitivity of 75.5% (206/273; 95% CI: 69·9-80·4) for the Abbott Panbio™ COVID-12 Ag test, with specificity of 100% (1489/1489; 95% CI: 99·8-100). Sensitivity improved with increasing risk for COVID-19 infection, from 72·4% (95% CI: 52·8-87·3) in the 'No Risk' cohort to 100% (95% CI: 29·2-100) in the 'High Risk' group. Time in the ED for the 'At/High Risk' group decreased from 421 minutes (IQR: 281, 525) for those with a positive RAT result to 274 minutes (IQR:140, 425) for those with a negative RAT result, p = 0.02. Interpretation: The positive predictive value of a positive RAT in this setting was high, allowing more rapid instigation of COVID-19 care pathways and an improvement in patient flow within the ED. Funding: Royal Melbourne Hospital, Melbourne, Australia.