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1.
Pediatr Infect Dis J ; 41(5): e246-e248, 2022 05 01.
Article in English | MEDLINE | ID: covidwho-1853265

ABSTRACT

A 6-year-old boy with autistic spectrum disorder was diagnosed with tuberculosis infection following contact tracing of his mother who had isoniazid-resistant pulmonary tuberculosis. He progressed to develop mediastinal lymphadenopathy causing a persistent cough. He was too small to undergo endobronchial ultrasound-guided biopsy. As an alternative, he underwent esophageal endoscopic ultrasound-guided biopsy, leading to confirmation of the diagnosis. We believe this approach to diagnostic biopsy is underrecognized in pediatric practice, and highlight its utility with this case and a brief literature review.


Subject(s)
Lung Neoplasms , Tuberculosis , Bronchoscopy , Child , Endoscopic Ultrasound-Guided Fine Needle Aspiration , Humans , Lung Neoplasms/pathology , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Male , Mediastinum/diagnostic imaging , Mediastinum/pathology , Tuberculosis/pathology , Ultrasonography
2.
Front Allergy ; 2: 668781, 2021.
Article in English | MEDLINE | ID: covidwho-1779928

ABSTRACT

The nose provides a route of access to the body for inhalants and fluids. Unsurprisingly it has a strong immune defense system, with involvement of innate (e.g., epithelial barrier, muco- ciliary clearance, nasal secretions with interferons, lysozyme, nitric oxide) and acquired (e.g., secreted immunoglobulins, lymphocytes) arms. The lattice network of dendritic cells surrounding the nostrils allows rapid uptake and sampling of molecules able to negotiate the epithelial barrier. Despite this many respiratory infections, including SARS-CoV2, are initiated through nasal mucosal contact, and the nasal mucosa is a significant "reservoir" for microbes including Streptococcus pneumoniae, Neisseria meningitidis and SARS -CoV-2. This review includes consideration of the augmentation of immune defense by the nasal application of interferons, then the reduction of unnecessary inflammation and infection by alteration of the nasal microbiome. The nasal mucosa and associated lymphoid tissue (nasopharynx-associated lymphoid tissue, NALT) provides an important site for vaccine delivery, with cold-adapted live influenza strains (LAIV), which replicate intranasally, resulting in an immune response without significant clinical symptoms, being the most successful thus far. Finally, the clever intranasal application of antibodies bispecific for allergens and Intercellular Adhesion Molecule 1 (ICAM-1) as a topical treatment for allergic and RV-induced rhinitis is explained.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323307

ABSTRACT

The primary objective of MATIS is to determine the efficacy of ruxolitinib (RUX) or fostamatinib (FOS) compared to standard of care (SOC) with respect to reducing the proportion of hospitalised patients progressing from mild or moderate to severe COVID-19 pneumonia. Secondary objectives, at 14 and 28 days, are to: · Determine the efficacy of RUX or FOS to reduce mortality · Determine the efficacy of RUX or FOS to reduce the need for invasive ventilation or ECMO· Determine the efficacy of RUX or FOS to reduce the need for non-invasive ventilation · Determine the efficacy of RUX or FOS to reduce the proportion of participants suffering significant oxygen desaturationDetermine the efficacy of RUX or FOS to reduce the need for renal replacement therapy · Determine the efficacy of RUX and FOS to reduce the incidence of venous thromboembolism · Determine the efficacy of RUX and FOS to reduce the severity of COVID-19 pneumonia [graded by a 9-point modified WHO Ordinal Scale*· Determine the efficacy of RUX or FOS to reduce systemic inflammation· Determine the efficacy of RUX or FOS to the incidence of renal impairment · Determine the efficacy of RUX or FOS to reduce duration of hospital stay · Evaluate the safety of RUX and FOS for treatment of COVID-19 pneumonia. Trial design A multi-arm, multi-stage (3-arm parallel-group, 2-stage) randomised controlled trial that allocates participants 1:1:1 and tests for superiority in experimental arms versus standard of care.

4.
Eur Respir J ; 2021 Nov 25.
Article in English | MEDLINE | ID: covidwho-1538052

ABSTRACT

INTRODUCTION: The success of case isolation and contact tracing for the control of SARS-CoV-2 transmission depends on the accuracy and speed of case identification. We assessed whether inclusion of additional symptoms alongside three canonical symptoms (CS) - fever; cough; loss or change in smell or taste - could improve case definitions and accelerate case identification in SARS-CoV-2 contacts. METHODS: Two prospective longitudinal London-based cohorts of community SARS-CoV-2 contacts, recruited within 5 days of exposure, provided independent training and test datasets. Infected and uninfected contacts completed daily symptom diaries from the earliest possible time-points. Diagnostic information gained by adding symptoms to the CS was quantified using likelihood ratios and AUC-ROC. Improvements in sensitivity and time-to-detection were compared to penalties in terms of specificity and number-needed-to-test. RESULTS: Of 529 contacts within two cohorts, 164 (31%) developed PCR-confirmed infection and 365 (69%) remained uninfected. In the training dataset (n=168), 29% of infected contacts did not report the CS. Four symptoms (sore throat, muscle aches, headache and appetite loss) were identified as early-predictors (EP) which added diagnostic value to the CS. The broadened symptom criterion "≥1 of the CS, or ≥2 of the EP" identified PCR-positive contacts in the test dataset on average 2 days earlier after exposure (p=0.07) than "≥1 of the CS", with only modest reduction in specificity (5.7%). CONCLUSIONS: Broadening symptom criteria to include individuals with at least 2 of muscle aches, headache, appetite loss and sore throat identifies more infections and reduces time-to-detection, providing greater opportunities to prevent SARS-CoV-2 transmission.

6.
Trials ; 22(1): 270, 2021 Apr 12.
Article in English | MEDLINE | ID: covidwho-1181120

ABSTRACT

OBJECTIVES: The primary objective of MATIS is to determine the efficacy of ruxolitinib (RUX) or fostamatinib (FOS) compared to standard of care (SOC) with respect to reducing the proportion of hospitalised patients progressing from mild or moderate to severe COVID-19 pneumonia. Secondary objectives, at 14 and 28 days, are to: Determine the efficacy of RUX or FOS to reduce mortality Determine the efficacy of RUX or FOS to reduce the need for invasive ventilation or ECMO Determine the efficacy of RUX or FOS to reduce the need for non-invasive ventilation Determine the efficacy of RUX or FOS to reduce the proportion of participants suffering significant oxygen desaturation Determine the efficacy of RUX or FOS to reduce the need for renal replacement therapy Determine the efficacy of RUX and FOS to reduce the incidence of venous thromboembolism Determine the efficacy of RUX and FOS to reduce the severity of COVID-19 pneumonia [graded by a 9-point modified WHO Ordinal Scale* Determine the efficacy of RUX or FOS to reduce systemic inflammation Determine the efficacy of RUX or FOS to the incidence of renal impairment Determine the efficacy of RUX or FOS to reduce duration of hospital stay Evaluate the safety of RUX and FOS for treatment of COVID-19 pneumonia. TRIAL DESIGN: A multi-arm, multi-stage (3-arm parallel-group, 2-stage) randomised controlled trial that allocates participants 1:1:1 and tests for superiority in experimental arms versus standard of care. PARTICIPANTS: Patients will be recruited while inpatients during hospitalisation for COVID-19 in multiple centres throughout the UK including Imperial College Healthcare NHS Trust. INCLUSION: Patients age ≥ 18 years at screening Patients with mild or moderate COVID-19 pneumonia, defined as Grade 3 or 4 severity by the WHO COVID-19 Ordinal Scale Patients meeting criteria: Hospitalization AND SARS-CoV2 infection (clinically suspected or laboratory confirmed) AND Radiological change consistent with COVID-19 disease CRP ≥ 30mg/L at any time point Informed consent from patient or personal or professional representative Agreement to abstain from sexual intercourse or use contraception that is >99% effective for all participants of childbearing potential for 42 days after the last dose of study drug. For male participants, agreement to abstain from sperm donation for 42 days after the last dose of study drug. EXCLUSION: Requiring either invasive or non-invasive ventilation including CPAP or high flow nasal oxygen at any point after hospital admission but before baseline, not related to a pre-existing condition (e.g., obstructive sleep apnoea) Grade ≥ 5 severity on the modified WHO COVID-19 Ordinal Scale, i.e. SpO2 < 90% on ≥ 60% inspired oxygen by facemask at baseline; non-invasive ventilation; or invasive mechanical ventilation In the opinion of the investigator, progression to death is inevitable within the next 24 hours, irrespective of the provision of therapy Known severe allergic reactions to the investigational agents Child-Pugh B or C grade hepatic dysfunction Use of drugs within the preceding 14 days that are known to interact with any study treatment (FOS or RUX), as listed in the Summary of Product Characteristics Pregnant or breastfeeding Any medical condition or concomitant medication that in the opinion of the investigator would compromise subjects' safety or compliance with study procedures. Any medical condition which in the opinion of the principal investigator would compromise the scientific integrity of the study Non-English speakers will be able to join the study. If participants are unable to understand verbal or written information in English, then hospital translation services will be requested at the participating site for the participant where possible. INTERVENTION AND COMPARATOR: RUXOLITINIB (RUX) (14 days): An oral selective and potent inhibitor of Janus Associated Kinases (JAK1 and JAK2) and cell proliferation (Verstovek, 2010). It is approved for the treatment of disease-related splenomegaly or constitutional symptoms in myelofibrosis, polycythaemia vera and graft-versus-host-disease. RUX will be administered orally 10mg bd Day 1-7 and 5mg bd Day 8-14. FOSTAMATINIB (FOS) (14 days): An oral spleen tyrosine kinase inhibitor approved for the treatment of thrombocytopenia in adult participants with chronic immune thrombocytopenia. FOS will be administered orally 150mg bd Day 1-7 and 100mg bd Day 8-14. Please see protocol for recommended dose modifications where required. COMPARATOR (Standard of Care, SOC): experimental arms will be compared to participants receiving standard of care. It is accepted that SOC may change during a rapidly evolving pandemic. Co-enrolment to other trials and rescue therapy, either pre- or post-randomisation, is permitted and will be accounted for in the statistical analysis. MAIN OUTCOMES: Pairwise comparison (RUX vs SOC and FOS vs SOC) of the proportion of participants diagnosed with severe COVID-19 pneumonia within 14 days. Severe COVID-19 pneumonia is defined by a score ≥ 5 on a modified WHO COVID-19 Ordinal Scale, comprising the following indicators of disease severity: Death OR Requirement for invasive ventilation OR Requirement for non-invasive ventilation including CPAP or high flow oxygen OR O2 saturation < 90% on ≥60% inspired oxygen RANDOMISATION: Participants will be allocated to interventions using a central web-based randomisation service that generates random sequences using random permuted blocks (1:1:1), with stratification by age (<65 and ≥65 years) and site. BLINDING (MASKING): No participants or caregivers are blinded to group assignment. Clinical outcomes will be compared blind to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): For an early informal dose examination by the Data Monitoring Committee a minimum of 30 participants will be recruited. For Stage 1 of this multi-arm multi-stage study, 171 participants will be randomised, with 57 participants in each arm. If at least one experimental intervention shows promise, then Stage 2 will recruit a further 95 participants per arm. Sample size calculations are given in the protocol. TRIAL STATUS: Recruitment is ongoing and started 2nd October 2020. We anticipate completion of Stage 1 by July 2021 and Stage 2 by April 2022. The current protocol version 2.0 of 11th February 2021 is appended. TRIAL REGISTRATION: EudraCT: 2020-001750-22 , 9th July 2020 ClinicalTrials.gov: NCT04581954 , 9th October 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
COVID-19/drug therapy , Oxazines/therapeutic use , Pyrazoles/therapeutic use , Pyridines/therapeutic use , Adult , Aminopyridines , Humans , Morpholines , Nitriles , Pandemics , Pyrimidines , Randomized Controlled Trials as Topic , Respiration, Artificial , Treatment Outcome , Venous Thromboembolism/prevention & control
7.
BMJ Open Respir Res ; 8(1)2021 04.
Article in English | MEDLINE | ID: covidwho-1172762

ABSTRACT

BACKGROUND: The symptoms, radiography, biochemistry and healthcare utilisation of patients with COVID-19 following discharge from hospital have not been well described. METHODS: Retrospective analysis of 401 adult patients attending a clinic following an index hospital admission or emergency department attendance with COVID-19. Regression models were used to assess the association between characteristics and persistent abnormal chest radiographs or breathlessness. RESULTS: 75.1% of patients were symptomatic at a median of 53 days post discharge and 72 days after symptom onset and chest radiographs were abnormal in 47.4%. Symptoms and radiographic abnormalities were similar in PCR-positive and PCR-negative patients. Severity of COVID-19 was significantly associated with persistent radiographic abnormalities and breathlessness. 18.5% of patients had unscheduled healthcare visits in the 30 days post discharge. CONCLUSIONS: Patients with COVID-19 experience persistent symptoms and abnormal blood biomarkers with a gradual resolution of radiological abnormalities over time. These findings can inform patients and clinicians about expected recovery times and plan services for follow-up of patients with COVID-19.


Subject(s)
Aftercare , Biomarkers/analysis , COVID-19 , Patient Discharge/standards , Radiography, Thoracic , Symptom Assessment , Aftercare/methods , Aftercare/organization & administration , COVID-19/blood , COVID-19/diagnostic imaging , COVID-19/epidemiology , COVID-19/physiopathology , Female , Humans , Male , Middle Aged , Patient Acceptance of Health Care/statistics & numerical data , Radiography, Thoracic/methods , Radiography, Thoracic/statistics & numerical data , Recovery of Function , Retrospective Studies , SARS-CoV-2 , Severity of Illness Index , Symptom Assessment/methods , Symptom Assessment/statistics & numerical data , Time Factors , United Kingdom/epidemiology
8.
Eur Heart J ; 42(19): 1866-1878, 2021 05 14.
Article in English | MEDLINE | ID: covidwho-1087735

ABSTRACT

BACKGROUND: Troponin elevation is common in hospitalized COVID-19 patients, but underlying aetiologies are ill-defined. We used multi-parametric cardiovascular magnetic resonance (CMR) to assess myocardial injury in recovered COVID-19 patients. METHODS AND RESULTS: One hundred and forty-eight patients (64 ± 12 years, 70% male) with severe COVID-19 infection [all requiring hospital admission, 48 (32%) requiring ventilatory support] and troponin elevation discharged from six hospitals underwent convalescent CMR (including adenosine stress perfusion if indicated) at median 68 days. Left ventricular (LV) function was normal in 89% (ejection fraction 67% ± 11%). Late gadolinium enhancement and/or ischaemia was found in 54% (80/148). This comprised myocarditis-like scar in 26% (39/148), infarction and/or ischaemia in 22% (32/148) and dual pathology in 6% (9/148). Myocarditis-like injury was limited to three or less myocardial segments in 88% (35/40) of cases with no associated LV dysfunction; of these, 30% had active myocarditis. Myocardial infarction was found in 19% (28/148) and inducible ischaemia in 26% (20/76) of those undergoing stress perfusion (including 7 with both infarction and ischaemia). Of patients with ischaemic injury pattern, 66% (27/41) had no past history of coronary disease. There was no evidence of diffuse fibrosis or oedema in the remote myocardium (T1: COVID-19 patients 1033 ± 41 ms vs. matched controls 1028 ± 35 ms; T2: COVID-19 46 ± 3 ms vs. matched controls 47 ± 3 ms). CONCLUSIONS: During convalescence after severe COVID-19 infection with troponin elevation, myocarditis-like injury can be encountered, with limited extent and minimal functional consequence. In a proportion of patients, there is evidence of possible ongoing localized inflammation. A quarter of patients had ischaemic heart disease, of which two-thirds had no previous history. Whether these observed findings represent pre-existing clinically silent disease or de novo COVID-19-related changes remain undetermined. Diffuse oedema or fibrosis was not detected.


Subject(s)
COVID-19 , Myocarditis , Contrast Media , Female , Gadolinium , Humans , Magnetic Resonance Imaging, Cine , Magnetic Resonance Spectroscopy , Male , Myocarditis/diagnostic imaging , Myocardium , Predictive Value of Tests , SARS-CoV-2 , Troponin , Ventricular Function, Left
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