15 research outputs found

    Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

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    [This corrects the article DOI: 10.1186/s13054-016-1208-6.]

    Local and systemic responses to SARS-CoV-2 infection in children and adults.

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    It is not fully understood why COVID-19 is typically milder in children1-3. Here, to examine the differences between children and adults in their response to SARS-CoV-2 infection, we analysed paediatric and adult patients with COVID-19 as well as healthy control individuals (total n = 93) using single-cell multi-omic profiling of matched nasal, tracheal, bronchial and blood samples. In the airways of healthy paediatric individuals, we observed cells that were already in an interferon-activated state, which after SARS-CoV-2 infection was further induced especially in airway immune cells. We postulate that higher paediatric innate interferon responses restrict viral replication and disease progression. The systemic response in children was characterized by increases in naive lymphocytes and a depletion of natural killer cells, whereas, in adults, cytotoxic T cells and interferon-stimulated subpopulations were significantly increased. We provide evidence that dendritic cells initiate interferon signalling in early infection, and identify epithelial cell states associated with COVID-19 and age. Our matching nasal and blood data show a strong interferon response in the airways with the induction of systemic interferon-stimulated populations, which were substantially reduced in paediatric patients. Together, we provide several mechanisms that explain the milder clinical syndrome observed in children

    Delayed diagnosis of spinal cord schistosomiasis in a non-endemic country: A tertiary referral centre experience.

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    BackgroundNeuroschistosomiasis is a severe complication of schistosomiasis, triggered by the local immune reaction to egg deposition, with spinal cord involvement the most well recognised form. Early treatment with praziquantel and high dose steroids leads to a reduction of neurological sequelae. The rarity of this condition in returning travellers to high income countries can result in delayed diagnosis and treatment. We aimed to evaluate the diagnosis and management of neuroschistosomiasis in a UK national referral centre.Materials/methodsA retrospective review of confirmed clinical cases of spinal schistosomiasis referred to the Hospital for Tropical Diseases, UK, between January 2016 and January 2020 was undertaken. Electronic referral records were interrogated and patient demographic, clinical, laboratory, and radiological data collected.ResultsFour cases of neuroschistosomiasis were identified. The median age at diagnosis was 28 (range 21 to 50) with three male patients. All patients had epidemiological risk factors for schistosomiasis based on travel history and freshwater exposure; two in Uganda (River Nile), one in Malawi and one in Nigeria. All patients presented with features of transverse myelitis including back pain, leg weakness, paraesthesia and urinary dysfunction. The mean time from presentation to health services to definitive treatment was 42.5 days (range 16-74 days). Diagnosis was confirmed with CSF serology for schistosomiasis in all cases. Radiological features on MRI spine included enhancement focused predominantly in the lower thoracic spinal cord in three cases and the conus in one patient. All patients received a minimum of three days of oral praziquantel and high dose steroids. At three-month follow-up, one patient had complete resolution of symptoms and three had residual deficit; one patient was left with urinary and faecal incontinence, another had urinary retention, and the final patient has persistent leg pains and constipation.ConclusionWe observed a marked delay in diagnosis of neuroschistosomiasis in a non-endemic country. We advocate undertaking a thorough travel history, early use of imaging and CSF schistosomal serology to ensure early diagnosis of neuroschistosomiasis in patients presenting with consistent symptoms. If schistosomal diagnostics are not immediately available, presumptive treatment under the guidance of a tropical medicine specialist should be considered to minimize the risk of residual disability. We advocate for consensus guidelines to be produced and reporting to be performed in a uniform way for patients with spinal schistosomiasis

    Delayed healthcare seeking and prolonged illness in healthcare workers during the COVID-19 pandemic: a single-centre observational study

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    Objectives To describe a cohort of self-isolating healthcare workers (HCWs) with presumed COVID-19.Design A cross-sectional, single-centre study.Setting A large, teaching hospital based in Central London with tertiary infection services.Participants 236 HCWs completed a survey distributed by internal staff email bulletin. 167 were women and 65 men.Measures Information on symptomatology, exposures and health-seeking behaviour were collected from participants by self-report.Results The 236 respondents reported illness compatible with COVID-19 and there was an increase in illness reporting during March 2020 Diagnostic swabs were not routinely performed. Cough (n=179, 75.8%), fever (n=138, 58.5%), breathlessness (n=84, 35.6%) were reported. Anosmia was reported in 42.2%. Fever generally settled within 1 week (n=110/138, 88%). Several respondents remained at home and did not seek formal medical attention despite reporting severe breathlessness and measuring hypoxia (n=5/9, 55.6%). 2 patients required hospital admission but recovered following oxygen therapy. 84 respondents (41.2%) required greater than the obligated 7 days off work and 9 required greater than 3 weeks off.Conclusion There was a significant increase in staff reporting illness compatible with possible COVID-19 during March 2020. Subsequent serology studies at the same hospital study site have confirmed sero-positivity for COVID-19 up to 45% by the end of April 2020 in frontline HCWs. The study revealed a concerning lack of healthcare seeking in respondents with significant red flag symptoms (severe breathlessness, hypoxia). This study also highlighted anosmia as a key symptom of COVID-19 early in the pandemic, prior to this symptom being more widely recognised as a feature of COVID-19

    36th International Symposium on Intensive Care and Emergency Medicine : Brussels, Belgium. 15-18 March 2016.

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    Single-cell multi-omics analysis of the immune response in COVID-19

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    Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy

    Single-cell multi-omics analysis of the immune response in COVID-19.

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    Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy

    Using trained dogs and organic semi-conducting sensors to identify asymptomatic and mild SARS-CoV-2 infections: an observational study

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    Background A rapid, accurate, non-invasive diagnostic screen is needed to identify people with SARS-CoV-2 infection. We investigated whether organic semi-conducting (OSC) sensors and trained dogs could distinguish between people infected with asymptomatic or mild symptoms, and uninfected individuals, and the impact of screening at ports-of-entry. Methods Odour samples were collected from adults, and SARS-CoV-2 infection status confirmed using RT-PCR. OSC sensors captured the volatile organic compound (VOC) profile of odour samples. Trained dogs were tested in a double-blind trial to determine their ability to detect differences in VOCs between infected and uninfected individuals, with sensitivity and specificity as the primary outcome. Mathematical modelling was used to investigate the impact of bio-detection dogs for screening. Results About, 3921 adults were enrolled in the study and odour samples collected from 1097 SARS-CoV-2 infected and 2031 uninfected individuals. OSC sensors were able to distinguish between SARS-CoV-2 infected individuals and uninfected, with sensitivity from 98% (95% CI 95–100) to 100% and specificity from 99% (95% CI 97–100) to 100%. Six dogs were able to distinguish between samples with sensitivity ranging from 82% (95% CI 76–87) to 94% (95% CI 89–98) and specificity ranging from 76% (95% CI 70–82) to 92% (95% CI 88–96). Mathematical modelling suggests that dog screening plus a confirmatory PCR test could detect up to 89% of SARS-CoV-2 infections, averting up to 2.2 times as much transmission compared to isolation of symptomatic individuals only. Conclusions People infected with SARS-CoV-2, with asymptomatic or mild symptoms, have a distinct odour that can be identified by sensors and trained dogs with a high degree of accuracy. Odour-based diagnostics using sensors and/or dogs may prove a rapid and effective tool for screening large numbers of people
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