ABSTRACT
Little is known about T-cell responses during acute coronavirus disease-2019 (COVID-19). We measured T-cell interferon gamma (IFN-{gamma}) responses to spike 1 (S1), spike 2 (S2), nucleocapsid (N) and membrane (M) SARS-CoV-2 antigens using the T-SPOT(R) Discovery SARS-CoV-2 assay, a proven EliSPOT technology, in 114 hospitalised adult COVID-19 patients and assessed their association with clinical disease phenotype. T-SPOT(R) Discovery SARS-CoV-2 responses were detectable within 2 days of a positive PCR and did not correlate with vaccination status or symptom duration. Higher responses to S1 protein associated with a higher symptom burden, and serum IL-6 levels. Despite treatment with dexamethasone this subgroup was also at greater risk of requiring continuous positive airway pressure (CPAP) in the days following sampling. Higher T-cell responses measured using T-SPOT(R) Discovery SARS-CoV-2 associate with progressive disease in acute COVID-19 disease and may have utility as a prognostic biomarker that should be evaluated in larger cohorts.
Subject(s)
Coronavirus Infections , COVID-19ABSTRACT
ImportanceThe association of ethnicity with outcomes in patients with COVID-19 is unclear. ObjectiveTo determine whether the risk of SARS-CoV-2 infection, COVID-19 intensive care unit (ICU) admission and mortality are associated with ethnicity. Data SourcesWe searched all English language articles published 1st December 2019 - 30th June 2020 within MEDLINE, EMBASE, PROSPERO and the Cochrane library using indexing terms for COVID-19 and ethnicity, as well as manuscripts awaiting peer review on MedRxiv during the same period. Study SelectionIncluded studies reported original clinical data, disaggregated by ethnicity, on patients with confirmed or suspected COVID-19. We excluded correspondence, area level, modelling and basic science articles. Two independent reviewers screened articles for inclusion. Of 926 identified articles, 35 were included in the meta-analyses. Data Extraction and SynthesisThe review was conducted according to PRISMA guidelines. Reviewers independently extracted data using a piloted form on: (1) rates of infection, ICU admission and mortality by ethnicity; and (2) unadjusted and adjusted data comparing ethnic minority and White groups. Data were pooled using random effects models. Main Outcomes and MeasuresOutcomes were: (1) infection with SARS-CoV-2 confirmed on molecular testing; (2) ICU admission; and (3) mortality in COVID-19 confirmed and suspected cases. Results13,535,562 patients from 35 studies were included in the meta-analyses. Black, Asian and Hispanic individuals had a greater risk of infection compared to White individuals (Black: pooled adjusted RR: 2.06, 95% CI: 1.59-2.67; Asian: 1.35, 95%CI: 1.15-1.59; Hispanic: 1.77, 95% CI: 1.39-2.25). Black individuals were significantly more likely to be admitted to ICU than White individuals (pooled adjusted RR: 1.61, 95% CI: 1.02-2.55). Risk of mortality was similar across ethnicities among hospitalised patients, but increased among Asian and Mixed ethnic groups in the general population. ConclusionsBlack, Asian and Hispanic ethnic groups are at increased risk of SARS-CoV-2 infection. Black individuals may be more likely to require ICU admission for COVID-19. There may also be disparities in risk of death from COVID-19 at a population level. Our findings are of critical public health importance and should inform policy on minimising SARS-CoV-2 exposure in ethnic minority groups. KEY POINTSO_ST_ABSQuestionC_ST_ABSIs ethnicity associated with vulnerability to, and outcomes from, coronavirus disease 2019 (COVID-19)? FindingsIn this systematic review and meta-analysis, rates of infection and outcomes from COVID-19 were compared between ethnic groups. Individuals from Black, Asian and Hispanic ethnicity were significantly more vulnerable to SARS-CoV-2 infection than those of White ethnicity. Black individuals were more likely to need intensive care unit (ICU) admission for COVID-19 than White individuals. Risk of mortality was similar across ethnicities among hospitalised patients, but increased among Asian and Mixed ethnic groups in the general population. MeaningThere is strong evidence for an increased risk of SARS-CoV-2 infection amongst ethnic minorities, and targeted public health policies are required to reduce this risk.
Subject(s)
COVID-19ABSTRACT
Background Nasopharyngeal samples (NPS) are the mainstay of COVID-19 diagnosis. However, the extent to which assay signals relate to exhaled virus is unknown. We investigated the use of novel, non-invasive face-mask sampling (FMS) to detect exhaled SARS-CoV-2 RNA in two studies. Methods In an outbreak study (cohort 1), we performed FMS and NPS for 21 consecutive days after diagnosis on six healthcare workers who were screened positive for SARS-CoV-2. In a second hospitalised cohort (cohort 2), we performed FMS on 47 patients within 24 hours of a positive diagnosis. COVID-19 severity was graded according to WHO recommendations. Findings In cohort 1, SARS-COV-2 was detected by FMS in 10/40 (25%) samples (4/6 individuals), with no correlation between NPS and FMS RNA signals. All samples were negative by day 14 post diagnosis. Sustained FMS positivity with higher viral RNA signals showed a trend towards disease severity. In cohort 2, 19/47 (40%) individuals exhaled SARS-CoV-2 RNA extending over five orders of magnitude. FMS positive participants were older (positive: median age [IQR] 71 [61-84] vs negative: 61 [45-73], p=0.04) with more comorbidities (positive: 2 [1-3] vs negative: 1 [0-2], p<0.001) and have active cough (positive: 68% vs negative: 24%, p=0.003) and breathlessness (positive: 74% vs negative: 32%, p=0.005) during sampling, compared to FMS negative patients. Of five patients who were FMS positive and asymptomatic at time of sampling, two died of severe COVID-19 pneumonia within one month of follow up. Interpretation FMS detects exhaled SARS-COV-2, with stronger signals in those who develop severe disease.