RESUMO
Accurate assessment of SARS-CoV-2 immunity is critical in evaluating vaccine efficacy and devising public health policies. Whilst the exact nature of effective immunity remains incompletely defined, SARS-CoV-2-specific T-cell responses are a critical feature that will likely form a key correlate of protection against COVID-19. Here, we developed and optimized a high-throughput whole blood-based assay to determine the T-cell response associated with prior SARS-CoV-2 infection and/or vaccination amongst 231 healthy donors and 68 cancer patients. Following overnight in vitro stimulation with SARS-CoV-2-specific peptides, blood plasma samples were analysed for TH 1-type cytokines. Highly significant differential IFN-γ+ /IL-2+ SARS-CoV-2-specific T-cell responses were seen amongst previously infected COVID-19-positive healthy donors in comparison with unknown / naïve individuals (p < 0·0001). IFN-γ production was more effective at identifying asymptomatic donors, demonstrating higher sensitivity (96·0% vs. 83·3%) but lower specificity (84·4% vs. 92·5%) than measurement of IL-2. A single COVID-19 vaccine dose induced IFN-γ and/or IL-2 SARS-CoV-2-specific T-cell responses in 116 of 128 (90·6%) healthy donors, reducing significantly to 27 of 56 (48·2%) when measured in cancer patients (p < 0·0001). A second dose was sufficient to boost T-cell responses in the majority (90·6%) of cancer patients, albeit IFN-γ+ responses were still significantly lower overall than those induced in healthy donors (p = 0·034). Three-month post-vaccination T-cell responses also declined at a faster rate in cancer patients. Overall, this cost-effective standardizable test ensures accurate and comparable assessments of SARS-CoV-2-specific T-cell responses amenable to widespread population immunity testing, and identifies individuals at greater need of booster vaccinations.
Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/imunologia , Portador Sadio/imunologia , Imunidade Celular , Imunogenicidade da Vacina , SARS-CoV-2/imunologia , Células Th1/imunologia , Vacinação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/prevenção & controle , Feminino , Humanos , Interferon gama/imunologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Risk profile assessment and corrective interventions using optimisation of health status and prehabilitation represent an important strategy in the management of patients with a suspected cancer diagnosis. AIM: To determine the feasibility of pre-treatment optimisation and prehabilitation commenced at index primary care consultation, to improve patients' preparation for treatment by maximising the time available. DESIGN & SETTING: Between January 2015 and May 2016, 195 patients presenting to 12 GP practices were deemed eligible to enter the study, of which 189 (96.9%, median age 60 [21-91] years and 65 months; 124 female) were recruited and consented to the prehabilitation bundle. METHOD: All patients were simultaneously referred to secondary care using urgent suspected cancer (USC) pathways. The primary outcome measures were definitive diagnosis and treatment plan. RESULTS: Fifteen patients (7.9%) were diagnosed with cancer (three breast, three colon, two lung, two skin [one melanoma, one sarcoma], one tonsil, one vocal cord, one pancreas, one prostate, one ependymoma) and 62 were diagnosed with other significant medical conditions (47 gastrointestinal, 13 sepsis, two respiratory) requiring secondary care assessment and treatment. Of the 15 patients with cancer, 11 (73.3%) underwent potentially curative treatment, and four (26.7%) palliative treatment. Of the total study cohort, 84 (44%) required a form of optimisation in primary care, and patients with cancer were more likely to require optimisation than others (n = 10 [63%] versus n = 74 [43%], χ2 9.384, P = 0.002). CONCLUSION: One in 12 primary care USC patients had cancer (5.6% receiving potentially curative treatment), one in three had other systemic health issues, and overall two in five benefited from healthcare intervention. Primary care optimisation was feasible and associated with important allied health benefits.