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1.
Brain ; 2022 Feb 18.
Article in English | MEDLINE | ID: covidwho-1705039

ABSTRACT

Vaccination against viruses has rarely been associated with Guillain-Barré syndrome (GBS). An association with the COVID-19 vaccine is unknown. We performed a population-based study of National Health Service data in England and a multicentre surveillance study from UK hospitals, to investigate the relationship between COVID-19 vaccination and GBS. Firstly, case dates of GBS identified retrospectively in the National Immunoglobulin Database from 8 December 2021 to 8 July 2021 were linked to receipt dates of a COVID-19 vaccines using data from the National Immunisation Management System in England. For the linked dataset, GBS cases temporally associated with vaccination within a 6-week risk window of any COVID-19 vaccine were identified. Secondly, we prospectively collected incident UK-wide (four nations) GBS cases from 1 January 2021 to 7 November 2021 in a separate UK multicentre surveillance database. For this multicentre UK-wide surveillance dataset, we explored phenotypes of reported GBS cases to identify features of COVID-19 vaccine-associated GBS. 996 GBS cases were recorded in the National Immunoglobulin Database from January to October 2021. A spike of GBS cases above the 2016-2020 average occurred in March-April 2021. 198 GBS cases occurred within 6 weeks of the first-dose COVID-19 vaccination in England (0.618 cases per 100,000 vaccinations, 176 ChAdOx1 nCoV-19 (AstraZeneca), 21 tozinameran (Pfizer), 1 mRNA-1273 (Moderna)). The 6-week excess of GBS (compared to the baseline rate of GBS cases 6-12 weeks after vaccination) occurs with a peak at 24 days post-vaccination; first-doses of ChAdOx1 nCoV-19 accounted for the excess. No excess was seen for second-dose vaccination. The absolute number of excess GBS cases from January-July 2021 was between 98-140 cases for first-dose ChAdOx1 nCoV-19 vaccination. First-dose tozinameran and second-dose of any vaccination showed no excess GBS risk. Detailed clinical data from 121 GBS patients were reported in the separate multicentre surveillance dataset during this timeframe. No phenotypic or demographic differences identified between vaccine-associated and non-vaccinated GBS cases occurring in the same timeframe. Analysis of the linked NID/NIMS dataset suggests that first-dose ChAdOx1 nCoV-19 vaccination is associated with an excess GBS risk of 0.576 (95%CI 0.481-0.691) cases per 100,000 doses. However, examination of a multicentre surveillance dataset suggests that no specific clinical features, including facial weakness, are associated with vaccination-related GBS compared to non-vaccinated cases. The pathogenic cause of the ChAdOx1 nCoV-19 specific first dose link warrants further study.

2.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-305830

ABSTRACT

Background: For a targeted therapeutic strategy to show outcome benefit, there needs to be a strong biological and pathogenic rationale to underpin and direct personalised treatments. Relevant biological disease features and biomarkers identify patients for the correct therapeutic, delivered at an appropriate time, dose and duration for maximal efficacy. We evaluated whether serum levels of a wide range of proposed therapeutic targets in COVID-19 discriminated between patients with mild and severe disease or death.Methods: A search of clinicaltrials.gov identified immunological drug targets in COVID-19. We subsequently conducted an observational study investigating the association of serum biomarkers relating to putative therapeutic biomarkers with illness severity and outcome.Results: A search of clinicaltrials.gov identified 477 randomized trials assessing immunomodulatory therapies, including 168 different therapies against 83 different pathways. We measured levels of ten cytokines/signalling proteins including those related to the most common therapeutic targets (GM-CSF, IFN-α2a, IFN-β, IFN-γ, IL-1β, IL-1ra, IL-6, IL-7, IL-8, TNF-α), immunoglobulin G ( IgG) antibodies directed against either the COVID-19 spike protein (S1) or nucleocapsid protein (N), and neutralization titres of antibodies within the first 5 days of hospital admission in 86 patients, 44 (51%) with mild disease and 42 (49%) with severe disease. Six of the ten cytokine/signalling protein markers measured (IL-6, IL-7, IL-8, interferon- a, interferon- b, IL -1ra ) discriminated between patients with mild and severe disease, although most were similar or only modestly raised above that seen in healthy volunteers. A similar proportion of patients with mild or severe disease had detectable S1 or N IgG antibodies with equivalent levels between groups. Neutralization titres were higher among patients with severe disease.Interpretation: Some therapeutic and prognostic biomarkers may be potentially useful in identifying patients who may benefit from specific immunomodulatory therapies in COVID-19 disease, particularly interleukin-6. It is however noteworthy that absolute values of a number of identified biomarkers were either appropriately elevated or within the normal range. This implies that these immunomodulatory treatments may be of limited benefit.Funding: National Institute for Health Research UCLH Biomedical Research Centre (BRC756/HI/MS/101440) and the UCL Coronavirus Response Fund.Declaration of Interests: MeS reports grants and advisory board fees from NewB, grants from the Defence Science and Technology Laboratory, Critical Pressure, Apollo Therapeutics, advisory board and speaker fees (paid to his institution) from Amormed, Biotest, GE, Baxter, Roche, and Bayer, and honorarium for chairing a data monitoring and safety committee from Shionogi. All other authors have nothing to declare. Ethics Approval Statement: Ethical approval was received from the London-Westminster Research Ethics Committee, the Health Research Authority and Health and Care Research Wales (HCRW) on 2nd July 2020 (REC reference 20/HRA/2505, IRAS ID 284088). The SAFER study protocol was approved by the NHS Health Research Authority (ref 20/SC/0147) on 26 March 2020. Ethical oversight was provided by the South- Central Berkshire Research Ethics Committee.

3.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296749

ABSTRACT

Vaccination against viruses has rarely been associated with Guillain-Barré syndrome (GBS). An association with the COVID-19 vaccine is unknown. We performed a population-based study of National Health Service (NHS) data in England and a multicentre surveillance study from UK hospitals, to investigate the relationship between COVID-19 vaccination and GBS. Firstly, we present a retrospective analysis of every GBS patient in England in the National Immunoglobulin Database (NID) linked with their COVID-19 vaccination data. Cases of GBS identified in the National Immunoglobulin Database (NID) from 8 December 2021 to 8 July 2021 were linked to data from the National Immunisation Management System (NIMS) in England to identify exposure to a COVID-19 vaccine. For the NID/NIMS linked dataset, GBS cases temporally associated with vaccination within a 6-week risk window of any COVID-19 vaccine were identified. Secondly, we prospectively collected incident UK GBS cases from 1 January 2021 to 7 November 2021 in a separate UK multicentre surveillance database, regardless of vaccine exposure, with vaccine timings and GBS phenotypic data. For this multicentre UK surveillance dataset, we explored phenotypes of reported GBS cases to identify features of COVID-19 vaccine-associated GBS. 996 GBS cases were recorded in the NID from January to October 2021. A spike of GBS cases above the 2016-2020 average occurred in March-April 2021. In England, among all cases of GBS, 198 occurred within 6 weeks of the first-dose COVID-19 vaccination (0.618 cases per 100,000 vaccinations, 176 ChAdOx1 nCoV-19 (AstraZeneca), 21 tozinameran (Pfizer), 1 mRNA-1273 (Moderna)). The excess of GBS occurs with a peak at 24 days;first-doses of ChAdOx1 nCoV-19 accounted for the excess. No excess was seen for second-dose vaccination. The absolute number of excess GBS cases was between 98-140 cases for first-dose ChAdOx1 nCoV-19 vaccination from January-July 2021. First-dose tozinameran and second-dose of any vaccination showed no excess GBS risk. 121 patients were reported in the separate multicentre surveillance dataset with no phenotypic or demographic differences identified between vaccinated and non-vaccinated GBS cases. Data from the linked NID/NIMS dataset suggest that first-dose ChAdOx1 nCoV-19vaccination is associated with an excess GBS risk of 0.576 (95%CI 0.481-0.691) cases per 100,000 doses. However, further data reported from a multicentre surveillance dataset suggest that no specific clinical features, including facial weakness, are associated with vaccination-related GBS compared to non-vaccinated cases. The pathogenic cause of the ChAdOx1 nCoV-19specific first dose link warrants further study.

5.
Brain Commun ; 3(3): fcab168, 2021.
Article in English | MEDLINE | ID: covidwho-1364745

ABSTRACT

SARS-CoV-2 is associated with new-onset neurological and psychiatric conditions. Detailed clinical data, including factors associated with recovery, are lacking, hampering prediction modelling and targeted therapeutic interventions. In a UK-wide cross-sectional surveillance study of adult hospitalized patients during the first COVID-19 wave, with multi-professional input from general and sub-specialty neurologists, psychiatrists, stroke physicians, and intensivists, we captured detailed data on demographics, risk factors, pre-COVID-19 Rockwood frailty score, comorbidities, neurological presentation and outcome. A priori clinical case definitions were used, with cross-specialty independent adjudication for discrepant cases. Multivariable logistic regression was performed using demographic and clinical variables, to determine the factors associated with outcome. A total of 267 cases were included. Cerebrovascular events were most frequently reported (131, 49%), followed by other central disorders (95, 36%) including delirium (28, 11%), central inflammatory (25, 9%), psychiatric (25, 9%), and other encephalopathies (17, 7%), including a severe encephalopathy (n = 13) not meeting delirium criteria; and peripheral nerve disorders (41, 15%). Those with the severe encephalopathy, in comparison to delirium, were younger, had higher rates of admission to intensive care and a longer duration of ventilation. Compared to normative data during the equivalent time period prior to the pandemic, cases of stroke in association with COVID-19 were younger and had a greater number of conventional, modifiable cerebrovascular risk factors. Twenty-seven per cent of strokes occurred in patients <60 years. Relative to those >60 years old, the younger stroke patients presented with delayed onset from respiratory symptoms, higher rates of multi-vessel occlusion (31%) and systemic thrombotic events. Clinical outcomes varied between disease groups, with cerebrovascular disease conferring the worst prognosis, but this effect was less marked than the pre-morbid factors of older age and a higher pre-COVID-19 frailty score, and a high admission white cell count, which were independently associated with a poor outcome. In summary, this study describes the spectrum of neurological and psychiatric conditions associated with COVID-19. In addition, we identify a severe COVID-19 encephalopathy atypical for delirium, and a phenotype of COVID-19 associated stroke in younger adults with a tendency for multiple infarcts and systemic thromboses. These clinical data will be useful to inform mechanistic studies and stratification of patients in clinical trials.

6.
Brain Commun ; 3(3): fcab099, 2021.
Article in English | MEDLINE | ID: covidwho-1358433

ABSTRACT

Preliminary pathological and biomarker data suggest that SARS-CoV-2 infection can damage the nervous system. To understand what, where and how damage occurs, we collected serum and CSF from patients with COVID-19 and characterized neurological syndromes involving the PNS and CNS (n = 34). We measured biomarkers of neuronal damage and neuroinflammation, and compared these with non-neurological control groups, which included patients with (n = 94) and without (n = 24) COVID-19. We detected increased concentrations of neurofilament light, a dynamic biomarker of neuronal damage, in the CSF of those with CNS inflammation (encephalitis and acute disseminated encephalomyelitis) [14 800 pg/ml (400, 32 400)], compared to those with encephalopathy [1410 pg/ml (756, 1446)], peripheral syndromes (Guillain-Barré syndrome) [740 pg/ml (507, 881)] and controls [872 pg/ml (654, 1200)]. Serum neurofilament light levels were elevated across patients hospitalized with COVID-19, irrespective of neurological manifestations. There was not the usual close correlation between CSF and serum neurofilament light, suggesting serum neurofilament light elevation in the non-neurological patients may reflect peripheral nerve damage in response to severe illness. We did not find significantly elevated levels of serum neurofilament light in community cases of COVID-19 arguing against significant neurological damage. Glial fibrillary acidic protein, a marker of astrocytic activation, was not elevated in the CSF or serum of any group, suggesting astrocytic activation is not a major mediator of neuronal damage in COVID-19.

7.
Crit Care Explor ; 3(8): e0488, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1356719

ABSTRACT

OBJECTIVES: Multiple mechanisms have been proposed to explain disease severity in coronavirus disease 2019. Therapeutic approaches need to be underpinned by sound biological rationale. We evaluated whether serum levels of a range of proposed coronavirus disease 2019 therapeutic targets discriminated between patients with mild or severe disease. DESIGN: A search of ClinicalTrials.gov identified coronavirus disease 2019 immunological drug targets. We subsequently conducted a retrospective observational cohort study investigating the association of serum biomarkers within the first 5 days of hospital admission relating to putative therapeutic biomarkers with illness severity and outcome. SETTING: University College London, a tertiary academic medical center in the United Kingdom. PATIENTS: Patients admitted to hospital with a diagnosis of coronavirus disease 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Eighty-six patients were recruited, 44 (51%) with mild disease and 42 (49%) with severe disease. We measured levels of 10 cytokines/signaling proteins related to the most common therapeutic targets (granulocyte-macrophage colony-stimulating factor, interferon-α2a, interferon-ß, interferon-γ, interleukin-1ß, interleukin-1 receptor antagonist, interleukin-6, interleukin-7, interleukin-8, tumor necrosis factor-α), immunoglobulin G antibodies directed against either coronavirus disease 2019 spike protein or nucleocapsid protein, and neutralization titers of antibodies. Four-hundred seventy-seven randomized trials, including 168 different therapies against 83 different pathways, were identified. Six of the 10 markers (interleukin-6, interleukin-7, interleukin-8, interferon-α2a, interferon-ß, interleukin-1 receptor antagonist) discriminated between patients with mild and severe disease, although most were similar or only modestly raised above that seen in healthy volunteers. A similar proportion of patients with mild or severe disease had detectable spike protein or nucleocapsid protein immunoglobulin G antibodies with equivalent levels between groups. Neutralization titers were higher among patients with severe disease. CONCLUSIONS: Some therapeutic and prognostic biomarkers may be useful in identifying coronavirus disease 2019 patients who may benefit from specific immunomodulatory therapies, particularly interleukin-6. However, biomarker absolute values often did not discriminate between patients with mild and severe disease or death, implying that these immunomodulatory treatments may be of limited benefit.

8.
EClinicalMedicine ; 39: 101070, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1351631

ABSTRACT

BACKGROUND: A high prevalence of antiphospholipid antibodies has been reported in case series of patients with neurological manifestations and COVID-19; however, the pathogenicity of antiphospholipid antibodies in COVID-19 neurology remains unclear. METHODS: This single-centre cross-sectional study included 106 adult patients: 30 hospitalised COVID-neurological cases, 47 non-neurological COVID-hospitalised controls, and 29 COVID-non-hospitalised controls, recruited between March and July 2020. We evaluated nine antiphospholipid antibodies: anticardiolipin antibodies [aCL] IgA, IgM, IgG; anti-beta-2 glycoprotein-1 [aß2GPI] IgA, IgM, IgG; anti-phosphatidylserine/prothrombin [aPS/PT] IgM, IgG; and anti-domain I ß2GPI (aD1ß2GPI) IgG. FINDINGS: There was a high prevalence of antiphospholipid antibodies in the COVID-neurological (73.3%) and non-neurological COVID-hospitalised controls (76.6%) in contrast to the COVID-non-hospitalised controls (48.2%). aPS/PT IgG titres were significantly higher in the COVID-neurological group compared to both control groups (p < 0.001). Moderate-high titre of aPS/PT IgG was found in 2 out of 3 (67%) patients with acute disseminated encephalomyelitis [ADEM]. aPS/PT IgG titres negatively correlated with oxygen requirement (FiO2 R=-0.15 p = 0.040) and was associated with venous thromboembolism (p = 0.043). In contrast, aCL IgA (p < 0.001) and IgG (p < 0.001) was associated with non-neurological COVID-hospitalised controls compared to the other groups and correlated positively with d-dimer and creatinine but negatively with FiO2. INTERPRETATION: Our findings show that aPS/PT IgG is associated with COVID-19-associated ADEM. In contrast, aCL IgA and IgG are seen much more frequently in non-neurological hospitalised patients with COVID-19. Characterisation of antiphospholipid antibody persistence and potential longitudinal clinical impact are required to guide appropriate management. FUNDING: This work is supported by UCL Queen Square Biomedical Research Centre (BRC) and Moorfields BRC grants (#560441 and #557595). LB is supported by a Wellcome Trust Fellowship (222102/Z/20/Z). RWP is supported by an Alzheimer's Association Clinician Scientist Fellowship (AACSF-20-685780) and the UK Dementia Research Institute. KB is supported by the Swedish Research Council (#2017-00915) and the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), and theUK Dementia Research Institute at UCL. BDM is supported by grants from the MRC/UKRI (MR/V007181/1), MRC (MR/T028750/1) and Wellcome (ISSF201902/3). MSZ, MH and RS are supported by the UCL/UCLH NIHR Biomedical Research Centre and MSZ is supported by Queen Square National Brain Appeal.

9.
Blood ; 136(Supplement 1):27-27, 2020.
Article in English | PMC | ID: covidwho-1339001

ABSTRACT

IntroductionSevere COVID-19 disease is associated with a hyperinflammatory, pro-thrombotic state and a high mortality. A thrombotic phenotype rather than a coagulopathy is suggested and we undertook plasma exchange to determine its effects on organ function and thrombo-inflammatory markers.MethodsPlasma exchange was carried out in seven critically ill adults with severe COVID-19 respiratory failure (PaO2:FiO2 ratio <200 mmHg) requiring invasive or non-invasive ventilatory support and elevated thrombo-inflammatory markers (LDH>800 IU/L and D dimer>1000 µg/L (or doubling from baseline). Patients received a daily single volume 3 litre plasma exchange for a minimum of five days. No other immunomodulatory medications were initiated during this period. Effects on organ function, thrombo-inflammatory markers and complications were monitored. Seven patients matched for age and baseline biochemistry were a comparator group.ResultsCoagulation screening revealed no evidence of coagulopathy. However, von Willebrand Factor (VWF) activity, antigen and VWF antigen:ADAMTS13 ratio, Factor VIII and D-dimers were all elevated. Following five days of plasma exchange, plasma levels of all the above, and ferritin levels, were significantly reduced (p<0.05, Figure 1) while lymphocyte count normalized (p<0.05). The PaO2:FiO2 ratio increased from a median(IQR) of 11.6 (10.8- 19.7) kPa to 18.1 (16.0-25.9) kPa (p<0.05). Similar improvements were not observed in controls. Acute kidney injury (AKI) occurred among 5 patients in the control arm but not in patients who underwent plasma exchange.ConclusionPlasma exchange was associated with an improvement in oxygenation, decreased incidence of AKI, normalisation of lymphocytes and reduction in circulating thrombo-inflammatory markers including D-Dimer and VWF Ag:ADAMTS13 ratio.

12.
Brain ; 143(10): 3104-3120, 2020 10 01.
Article in English | MEDLINE | ID: covidwho-1066271

ABSTRACT

Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms that will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.


Subject(s)
Coronavirus Infections , Nervous System Diseases , Pandemics , Pneumonia, Viral , Adolescent , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Aged, 80 and over , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Drug Utilization/statistics & numerical data , Female , Humans , Immunoglobulins, Intravenous/therapeutic use , London/epidemiology , Magnetic Resonance Imaging , Male , Middle Aged , Nervous System Diseases/cerebrospinal fluid , Nervous System Diseases/diagnostic imaging , Nervous System Diseases/drug therapy , Nervous System Diseases/epidemiology , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Retrospective Studies , SARS-CoV-2 , Young Adult
16.
Brain ; 144(2): 682-693, 2021 03 03.
Article in English | MEDLINE | ID: covidwho-975205

ABSTRACT

Reports of Guillain-Barré syndrome (GBS) have emerged during the Coronavirus disease 2019 (COVID-19) pandemic. This epidemiological and cohort study sought to investigate any causative association between COVID-19 infection and GBS. The epidemiology of GBS cases reported to the UK National Immunoglobulin Database was studied from 2016 to 2019 and compared to cases reported during the COVID-19 pandemic. Data were stratified by hospital trust and region, with numbers of reported cases per month. UK population data for COVID-19 infection were collated from UK public health bodies. In parallel, but separately, members of the British Peripheral Nerve Society prospectively reported incident cases of GBS during the pandemic at their hospitals to a central register. The clinical features, investigation findings and outcomes of COVID-19 (definite or probable) and non-COVID-19 associated GBS cases in this cohort were compared. The incidence of GBS treated in UK hospitals from 2016 to 2019 was 1.65-1.88 per 100 000 individuals per year. GBS incidence fell between March and May 2020 compared to the same months of 2016-19. GBS and COVID-19 incidences during the pandemic also varied between regions and did not correlate with one another (r = 0.06, 95% confidence interval: -0.56 to 0.63, P = 0.86). In the independent cohort study, 47 GBS cases were reported (COVID-19 status: 13 definite, 12 probable, 22 non-COVID-19). There were no significant differences in the pattern of weakness, time to nadir, neurophysiology, CSF findings or outcome between these groups. Intubation was more frequent in the COVID-19 affected cohort (7/13, 54% versus 5/22, 23% in COVID-19-negative) attributed to COVID-19 pulmonary involvement. Although it is not possible to entirely rule out the possibility of a link, this study finds no epidemiological or phenotypic clues of SARS-CoV-2 being causative of GBS. GBS incidence has fallen during the pandemic, which may be the influence of lockdown measures reducing transmission of GBS inducing pathogens such as Campylobacter jejuni and respiratory viruses.


Subject(s)
COVID-19/epidemiology , Guillain-Barre Syndrome/epidemiology , Adult , Aged , Aged, 80 and over , Cohort Studies , Female , Humans , Male , Middle Aged , Prospective Studies , Retrospective Studies , SARS-CoV-2 , United Kingdom/epidemiology , Young Adult
17.
EJHaem ; 2(1): 26-32, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-950770

ABSTRACT

Severe COVID-19 disease is a hyperinflammatory, pro-thrombotic state. We undertook plasma exchange (PEX) to determine its effects on organ function and thrombo-inflammatory markers. Seven critically ill adults with severe COVID-19 respiratory failure (PaO2:FiO2 ratio < 200 mm Hg) requiring invasive or noninvasive ventilatory support and elevated thrombo-inflammatory markers (LDH >800 IU/L and D-dimer >1000 µg/L (or doubling from baseline) received PEX, daily, for a minimum of 5 days. No other immunomodulatory medications were initiated during this period. Seven patients matched for age and baseline biochemistry were a comparator group. Coagulation screening revealed no evidence of coagulopathy. However, von Willebrand Factor (VWF) activity, antigen and VWF antigen: ADAMTS13 ratio, Factor VIII and D-dimers were all elevated. Following 5 days of PEX, plasma levels of all the above, and ferritin levels, were significantly reduced (P < .05) while lymphocyte counts normalized (P < .05). The PaO2:FiO2 ratio increased from a median interquartile range (IQR) of 11.6 (10.8-19.7) kPa to 18.1 (16.0-25.9) kPa (P < .05). Similar improvements were not observed in controls. Acute kidney injury (AKI) occurred among five patients in the control arm but not in patients receiving PEX. PEX improved oxygenation, decreased the incidence of AKI, normalized lymphocyte counts and reduced circulating thrombo-inflammatory markers including D-Dimer and VWF Ag:ADAMTS13 ratio.

19.
J Neurol Neurosurg Psychiatry ; 91(6): 568-570, 2020 06.
Article in English | MEDLINE | ID: covidwho-96709
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