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3.
Int J Mol Sci ; 21(14)2020 Jul 08.
Article in English | MEDLINE | ID: covidwho-1934087

ABSTRACT

Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) are characterized by an inflammatory response, alveolar edema, and hypoxemia. ARDS occurs most often in the settings of pneumonia, sepsis, aspiration of gastric contents, or severe trauma. The prevalence of ARDS is approximately 10% in patients of intensive care. There is no effective remedy with mortality high at 30-40%. Most functional proteins are dynamic and stringently governed by ubiquitin proteasomal degradation. Protein ubiquitination is reversible, the covalently attached monoubiquitin or polyubiquitin moieties within the targeted protein can be removed by a group of enzymes called deubiquitinating enzymes (DUBs). Deubiquitination plays an important role in the pathobiology of ALI/ARDS as it regulates proteins critical in engagement of the alveolo-capillary barrier and in the inflammatory response. In this review, we provide an overview of how DUBs emerge in pathogen-induced pulmonary inflammation and related aspects in ALI/ARDS. Better understanding of deubiquitination-relatedsignaling may lead to novel therapeutic approaches by targeting specific elements of the deubiquitination pathways.


Subject(s)
Acute Lung Injury/metabolism , Deubiquitinating Enzymes/metabolism , Respiratory Distress Syndrome/metabolism , Animals , Humans , Pneumonia/metabolism , Signal Transduction/physiology , Ubiquitin/metabolism , Ubiquitination/physiology
4.
Lancet Respir Med ; 9(5): 533-544, 2021 05.
Article in English | MEDLINE | ID: covidwho-1931217

ABSTRACT

Cough is one of the most common presenting symptoms of COVID-19, along with fever and loss of taste and smell. Cough can persist for weeks or months after SARS-CoV-2 infection, often accompanied by chronic fatigue, cognitive impairment, dyspnoea, or pain-a collection of long-term effects referred to as the post-COVID syndrome or long COVID. We hypothesise that the pathways of neurotropism, neuroinflammation, and neuroimmunomodulation through the vagal sensory nerves, which are implicated in SARS-CoV-2 infection, lead to a cough hypersensitivity state. The post-COVID syndrome might also result from neuroinflammatory events in the brain. We highlight gaps in understanding of the mechanisms of acute and chronic COVID-19-associated cough and post-COVID syndrome, consider potential ways to reduce the effect of COVID-19 by controlling cough, and suggest future directions for research and clinical practice. Although neuromodulators such as gabapentin or opioids might be considered for acute and chronic COVID-19 cough, we discuss the possible mechanisms of COVID-19-associated cough and the promise of new anti-inflammatories or neuromodulators that might successfully target both the cough of COVID-19 and the post-COVID syndrome.


Subject(s)
COVID-19/complications , COVID-19/physiopathology , Cough/etiology , Inflammation/etiology , Nervous System Diseases/etiology , Neuroimmunomodulation , Cough/physiopathology , Humans , Inflammation/physiopathology , Nervous System Diseases/physiopathology , SARS-CoV-2 , Syndrome
5.
J Matern Fetal Neonatal Med ; 35(16): 3044-3048, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1908605

ABSTRACT

There is a global problem of increment of the number of children with clinical features that mimic Kawasaki Disease (KD) during the ongoing Coronavirus Disease 2019 (COVID-19) pandemic. The disease was first reported by Tomisaku Kawasaki, a Japanese pediatrician, in a four-year-old child with a rash and fever at the Red Cross Hospital in Tokyo in January 1961. Now Kawasaki disease is recognized worldwide. The complexity of symptoms was defined as an «acute febrile mucocutaneous lymphnode syndrome". At the moment, it is still unclear whether the coronavirus itself can lead to development of mucocutaneous lymph node syndrome. However, it is believed that COVID-19 virus infection worsens the course of Kawasaki disease, and in some cases, children affected by SARS-V-2 may develop a disease that has a clinical picture similar to Kawasaki disease.


Subject(s)
COVID-19 , Mucocutaneous Lymph Node Syndrome , COVID-19/complications , Child , Child, Preschool , Fever , Humans , Mucocutaneous Lymph Node Syndrome/complications , Mucocutaneous Lymph Node Syndrome/diagnosis , Mucocutaneous Lymph Node Syndrome/epidemiology , Pandemics , SARS-CoV-2
6.
J Matern Fetal Neonatal Med ; 35(15): 2976-2979, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1900908

ABSTRACT

INTRODUCTION: The covid-19 pandemic has meant a change in working protocols, as well as in Personal Protective Equipment (PPE). Obstetricians have had to adapt quickly to these changes without knowing how they affected their clinical practice. The aim of the present study was to evaluate how COVID-19 pandemic and PPE can affect operative time, operating room time, transfer into the operating room to delivery time and skin incision to delivery time in cesarean section. METHODS: This is a single-center retrospective cohort study. Women with confirmed or suspected SARS-CoV-2 infection having a cesarean section after March 7th, 2020 during the COVID-19 pandemic were included in the study. For each woman with confirmed or suspected SARS-CoV-2 infection, a woman who had a cesarean section for the same indication during the COVID-19 pandemic and with similar clinical history but not affected by SARS-CoV-2 was included. RESULTS: 42 cesarean sections were studied. The operating room time was longer in the COVID-19 confirmed or suspected women: 90 (73.0 to 110.0) versus 61 (48.0 to 70.5) minutes; p < .001. The transfer into the operating room to delivery time was longer, but not statistically significant, in urgent cesarean sections in COVID-19 confirmed or suspected women: 25.5 (17.5 to 31.75) versus 18.0 (10.0 to 26.25) minutes; p = .113. CONCLUSIONS: There were no significant differences in the operative time, transfer into the operating room to delivery time and skin incision to delivery time when wearing PPE in cesarean section. The COVID-19 pandemic and the use of PPE resulted in a significant increase in operating room time.


Subject(s)
COVID-19 , Personal Protective Equipment , COVID-19/epidemiology , COVID-19/prevention & control , Cesarean Section/methods , Female , Humans , Operative Time , Pandemics/prevention & control , Pregnancy , Retrospective Studies , SARS-CoV-2
7.
Minerva Cardiol Angiol ; 70(3): 303-309, 2022 06.
Article in English | MEDLINE | ID: covidwho-1841790

ABSTRACT

BACKGROUND: The Lombardy region, in Northern Italy, suffered a major outbreak of Coronavirus disease 2019 (COVID-19) at the end of February 2020. The health system was rapidly overwhelmed by the pandemic. It became evident that patients suffering from time-sensitive medical emergencies like stroke, cerebral hemorrhage, trauma and acute myocardial infarction required timely, effective and safe pathways to be treated. The problem was addressed by a regional decree that created a hub-and-spoke system for time-sensitive medical emergencies. METHODS: We report the re-organizational changes adopted at a hub hospital (despite having already destined to COVID-19 patients most resources), and the number of emergent procedures for medical emergencies on the first 30-day of activity. These data were compared with the hospital activity in the same period of the previous year. RESULTS: Organizational changes were implemented in few hours. Dedicated pathways for non-COVID-19 patients affected by a medical emergency were set up in the emergency department, in the labs and in the operating theater. Ten intensive beds were implemented from a high-dependency unit; two operating rooms were reserved 24 h/day to neurosurgical or trauma emergencies. The number of emergent procedures was not different from that of the previous year, no admission refusal, no treatment delay and no viral transmission to the treated patients were recorded. No viral transmission to health care workers was observed. CONCLUSIONS: Re-organization of a hospital in order to adopt a hub-and-spoke model resulted feasible and allowed to face acute coronary syndrome and other time-sensitive medical emergencies timely and safely.


Subject(s)
Acute Coronary Syndrome , COVID-19 , COVID-19/epidemiology , Emergencies , Humans , Pandemics , SARS-CoV-2
8.
J Atheroscler Thromb ; 29(5): 597-607, 2022 May 01.
Article in English | MEDLINE | ID: covidwho-1818582

ABSTRACT

AIM: The coronavirus disease 2019 (COVID-19) pandemic has left negative spillover effects on the entire health care system. Previous studies have suggested significant declines in cases of acute coronary syndrome (ACS) and primary percutaneous coronary intervention (PCI) during the COVID-19 pandemic. METHODS: We performed a quasi-experimental, retrospective cohort study of ACS hospitalisations by using a multi-institutional administrative claims database in Japan. We used interrupted time series analyses to ascertain impacts on cases, treatment approaches, and in-hospital mortality before and after Japan's state of emergency to respond to COVID-19. The primary outcome was the change in ACS cases per week. RESULTS: A total of 30,198 ACS cases (including 21,612 acute myocardial infarction and 8,586 unstable angina) were confirmed between 1st July 2018 and 30th June 2020. After the state of emergency, an immediate decrease was observed in ACS cases per week (-18.3%; 95% confidence interval, -13.1 to -23.5%). No significant differences were found in the severity of Killip classification (P=0.51) or cases of fibrinolytic therapy (P=0.74). The impact of the COVID-19 pandemic on in-hospital mortality in ACS patients was no longer observed after adjustment for clinical characteristics (adjusted odds ratio, 0.93; 95% confidence interval, 0.78 to 1.12; P=0.49). CONCLUSIONS: We demonstrated the characteristics and trends of ACS cases in a Japanese population by applying interrupted time series analyses. Our findings provide significant insights into the association between COVID-19 and decreases in ACS hospitalisations during the pandemic.


Subject(s)
Acute Coronary Syndrome , COVID-19 , Percutaneous Coronary Intervention , Acute Coronary Syndrome/drug therapy , COVID-19/epidemiology , Hospital Mortality , Humans , Japan/epidemiology , Pandemics , Retrospective Studies
10.
QJM ; 114(9): 625-635, 2021 Nov 13.
Article in English | MEDLINE | ID: covidwho-1746245

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been linked to the Guillain-Barré syndrome (GBS). The objective of the present study is to identify specific clinical features of cases of GBS reported in the literature associated with SARS-CoV-2 infection. We searched Pubmed, and included single case reports and case series with full text in English, reporting original data of patients with GBS and a confirmed recent SARS-CoV-2 infection. Clinical data were extracted. We identified 28 articles (22 single case reports and 6 case series), reporting on a total of 44 GBS patients with confirmed SARS-CoV-2 infection. SARS-CoV-2 infection was confirmed through serum reverse transcriptase-polymerase chain reaction in 72.7% of cases. A total of 40 patients (91%) had symptoms compatible with SARS-CoV-2 infection before the onset of the GBS. The median period between the onset of symptoms of SARS-CoV-2 infection and symptoms of the GBS was 11.2 days (range, 2-23). The most common clinical features were: leg weakness (61.4%), leg paresthesia (50%), arm weakness (50.4%), arm paresthesia (50.4%), hyporeflexia/areflexia (48%) and ataxia (22.7%). In total, 38.6% (n = 17) were found to have facial paralysis. Among 37 patients in whom nerve-conduction studies and electromyography were performed, of which 26 patients (59.1%) were consistent with the acute inflammatory demyelinating polyneuropathy subtype of the GBS. The present retrospective analysis support the role of the SARS-CoV-2 infection in the development of the GBS, may trigger GBS as para-infectious disease, and lead to SARS-CoV-2-associated GBS.


Subject(s)
COVID-19 , Communicable Diseases , Guillain-Barre Syndrome , Guillain-Barre Syndrome/complications , Humans , Retrospective Studies , SARS-CoV-2
11.
J Clin Rheumatol ; 28(2): e623-e625, 2022 03 01.
Article in English | MEDLINE | ID: covidwho-1703382

ABSTRACT

BACKGROUND: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection produces a wide variety of inflammatory responses in children, including multisystem inflammatory syndrome in children, which has similar clinical manifestations as Kawasaki disease (KD). METHODS: We performed a chart review of all patients with KD-like illnesses from January 1, 2016, to May 31, 2020, at a tertiary care children's hospital within a larger health system. Relevant symptoms, comorbid illnesses, laboratory results, imaging studies, treatment, and outcomes were reviewed. Descriptive analyses to compare features over time were performed. RESULTS: We identified 81 cases of KD-like illnesses from January 1, 2016, to May 31, 2020. Few clinical features, such as gallbladder involvement, were more prevalent in 2020 than in previous years. A few patients in 2020 required more intensive treatment with interleukin 1 receptor antagonist therapy. There were no other clear differences in incidence, laboratory parameters, number of doses of intravenous immunoglobulin, or outcomes over the years of the study. CONCLUSIONS: There was no difference in incidence, laboratory parameters, or number of doses of intravenous immunoglobulin required for treatment of KD-like illnesses during the COVID-19 pandemic when compared with previous years at our institution. Kawasaki disease-like illnesses, including multisystem inflammatory syndrome in children, may not have changed substantially during the COVID-19 pandemic.


Subject(s)
COVID-19 , Mucocutaneous Lymph Node Syndrome , COVID-19/complications , Child , Humans , Medical Records , Mucocutaneous Lymph Node Syndrome/diagnosis , Mucocutaneous Lymph Node Syndrome/drug therapy , Mucocutaneous Lymph Node Syndrome/epidemiology , Pandemics , SARS-CoV-2 , Systemic Inflammatory Response Syndrome
12.
Pediatr Infect Dis J ; 40(7): e274-e276, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1700567

ABSTRACT

Underlying mechanisms on the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and neurologic complications are still poorly understood. Cases of Guillain-Barré Syndrome (GBS) have been linked to the SARS-CoV-2 infection as the result of dysregulated immune response with damage in neuronal tissues. In the current report, we present the first pediatric case of GBS with detection of SARS-CoV-2 in the cerebrospinal fluid (CFS). This unique case of COVID-19-associated GBS with detection of SARS-CoV-2 RNA in the CSF indicates direct viral involvement inducing peripheral nerve inflammation.


Subject(s)
COVID-19/cerebrospinal fluid , COVID-19/diagnosis , Guillain-Barre Syndrome/complications , RNA, Viral/cerebrospinal fluid , Adolescent , COVID-19/complications , Cauda Equina/diagnostic imaging , Cauda Equina/pathology , Cauda Equina/virology , Female , Guillain-Barre Syndrome/virology , Humans , Inflammation/virology , Magnetic Resonance Imaging , SARS-CoV-2/isolation & purification
13.
Clin Infect Dis ; 74(3): 479-489, 2022 02 11.
Article in English | MEDLINE | ID: covidwho-1684541

ABSTRACT

BACKGROUND: Increased inflammation has been well defined in coronavirus disease 2019 (COVID-19), while definitive pathways driving severe forms of this disease remain uncertain. Neutrophils are known to contribute to immunopathology in infections, inflammatory diseases, and acute respiratory distress syndrome, a primary cause of morbidity and mortality in COVID-19. Changes in neutrophil function in COVID-19 may give insight into disease pathogenesis and identify therapeutic targets. METHODS: Blood was obtained serially from critically ill COVID-19 patients for 11 days. Neutrophil extracellular trap formation (NETosis), oxidative burst, phagocytosis, and cytokine levels were assessed. Lung tissue was obtained immediately postmortem for immunostaining. PubMed searches for neutrophils, lung, and COVID-19 yielded 10 peer-reviewed research articles in English. RESULTS: Elevations in neutrophil-associated cytokines interleukin 8 (IL-8) and interleukin 6, and general inflammatory cytokines IFN-inducible protien-19, granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin 1ß, interleukin 10, and tumor necrosis factor, were identified both at first measurement and across hospitalization (P < .0001). COVID-19 neutrophils had exaggerated oxidative burst (P < .0001), NETosis (P < .0001), and phagocytosis (P < .0001) relative to controls. Increased NETosis correlated with leukocytosis and neutrophilia, and neutrophils and NETs were identified within airways and alveoli in lung parenchyma of 40% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected lungs available for examination (2 of 5). While elevations in IL-8 and absolute neutrophil count correlated with disease severity, plasma IL-8 levels alone correlated with death. CONCLUSIONS: Literature to date demonstrates compelling evidence of increased neutrophils in the circulation and lungs of COVID-19 patients. Importantly, neutrophil quantity and activation correlates with severity of disease. Similarly, our data show that circulating neutrophils in COVID-19 exhibit an activated phenotype with enhanced NETosis and oxidative burst.


Subject(s)
COVID-19 , Extracellular Traps , Critical Illness , Humans , Neutrophil Activation , Neutrophils , Phenotype , SARS-CoV-2
15.
Curr Pharmacol Rep ; 6(5): 228-240, 2020.
Article in English | MEDLINE | ID: covidwho-1682288

ABSTRACT

The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for causing coronavirus disease 2019 (COVID-19), marked the third time in the twenty-first century when a new, highly pathogenic human coronavirus outbreak has led to an epidemic. The COVID-19 epidemic has emerged in late December 2019 in Wuhan city of China and spread rapidly to other parts of the world. This quick spread of SARS-CoV-2 infection to many states across the globe affecting many people has led WHO to declare it a pandemic on March 12, 2020. As of July 4, 2020, more than 523,011 people lost their lives worldwide because of this deadly SARS-CoV-2. The current situation becomes more frightening as no FDA-approved drugs or vaccines are available to treat or prevent SARS-CoV-2 infection. The current therapeutic options for COVID-19 are limited only to supportive measures and non-specific interventions. So, the need of the hour is to search for SARS-CoV-2-specific antiviral treatments and to develop vaccines for SARS-CoV-2. Also, it is equally important to maintain our immunity, and natural products and Ayurvedic medicines are indispensable in this regard. In this review, we discuss recent updates regarding various therapeutic approaches to combat COVID-19 pandemic and enlist the major pipeline drugs and traditional medicines that are under trial for COVID-19. Also, possible mechanisms involved in viral pathogenesis are discussed, which further allow us to understand various drug targets and helps in discovering novel therapeutic approaches for COVID-19. Altogether, the information provided in this review will work as an intellectual groundwork and provides an insight into the ongoing development of various therapeutic agents.

16.
J Clin Gastroenterol ; 56(2): e149-e152, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1672370

ABSTRACT

GOALS: The goal of this study was to describe the influence of the COVID-19 pandemic on ability to engage in activities and the influence on psychological distress and gastrointestinal symptoms among individuals with irritable bowel syndrome (IBS) and comorbid anxiety and/or depression. BACKGROUND: Individuals with IBS and comorbid anxiety and/or depression report increased symptoms and decreased quality of life compared with individuals with IBS alone. The current COVID-19 pandemic has the potential to further influence symptoms among individuals with IBS and comorbid anxiety and/or depression. STUDY: Individuals who met the Rome-IV IBS criteria and reported mild to severe anxiety and/or depression were included. Participants completed an online survey with questions about anxiety, depression, impact of COVID on activities and symptoms, and demographics. RESULTS: Fifty-five individuals participated in the study. The COVID-19 pandemic most commonly influenced their ability to spend time with friends and family, shop for certain types of food, and access health care. Participants also reported increased stress (92%), anxiety (81%), and depressive symptoms (67%). Finally, around half the sample reported increases in abdominal pain (48%), diarrhea (45%), or constipation (44%). CONCLUSIONS: The COVID-19 pandemic is related to self-reported increases in psychological distress and gastrointestinal symptoms among individuals with IBS and comorbid anxiety and/or depression. Additional research is needed to intervene on these symptoms.


Subject(s)
COVID-19 , Irritable Bowel Syndrome , Anxiety/epidemiology , Depression/epidemiology , Humans , Irritable Bowel Syndrome/complications , Irritable Bowel Syndrome/epidemiology , Pandemics , Quality of Life , SARS-CoV-2 , Surveys and Questionnaires
17.
Cardiol Young ; 32(1): 138-141, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1655373

ABSTRACT

A 17-year-old adolescent with severe multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease-2019 developed reduced left ventricular function and left ventricular thrombus. With treatment, his condition improved and the thrombus was dissolved. This case illustrates the risk of severe intra-cardiac thrombotic complications in patients with MIS-C.


Subject(s)
COVID-19 , Thrombosis , Adolescent , COVID-19/complications , Child , Humans , SARS-CoV-2 , Systemic Inflammatory Response Syndrome , Thrombosis/diagnosis , Thrombosis/etiology
18.
Br J Nutr ; 127(6): 896-903, 2022 03 28.
Article in English | MEDLINE | ID: covidwho-1651089

ABSTRACT

Coronavirus disease 2019 (COVID-19) has caused mild illness in children, until the emergence of the novel hyperinflammatory condition paediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PIMS-TS). PIMS-TS is thought to be a post-SARS-CoV-2 immune dysregulation with excessive inflammatory cytokine release. We studied 25 hydroxyvitamin D (25OHD) concentrations in children with PIMS-TS, admitted to a tertiary paediatric hospital in the UK, due to its postulated role in cytokine regulation and immune response. Eighteen children (median (range) age 8·9 (0·3-14·6) years, male = 10) met the case definition. The majority were of Black, Asian and Minority Ethnic (BAME) origin (89 %, 16/18). Positive SARS-CoV-2 IgG antibodies were present in 94 % (17/18) and RNA by PCR in 6 % (1/18). Seventy-eight percentage of the cohort were vitamin D deficient (< 30 nmol/l). The mean 25OHD concentration was significantly lower when compared with the population mean from the 2015/16 National Diet and Nutrition Survey (children aged 4-10 years) (24 v. 54 nmol/l (95 % CI -38·6, -19·7); P < 0·001). The paediatric intensive care unit (PICU) group had lower mean 25OHD concentrations compared with the non-PICU group, but this was not statistically significant (19·5 v. 31·9 nmol/l; P = 0·11). The higher susceptibility of BAME children to PIMS-TS and also vitamin D deficiency merits contemplation. Whilst any link between vitamin D deficiency and the severity of COVID-19 and related conditions including PIMS-TS requires further evidence, public health measures to improve vitamin D status of the UK BAME population have been long overdue.


Subject(s)
COVID-19 , COVID-19/complications , Child , Child, Preschool , Humans , Male , SARS-CoV-2 , Systemic Inflammatory Response Syndrome , Vitamin D
19.
Trials ; 22(1): 172, 2021 Mar 01.
Article in English | MEDLINE | ID: covidwho-1622253

ABSTRACT

OBJECTIVES: The primary objective of this study is to test the hypothesis that administration of dexamethasone 20 mg is superior to a 6 mg dose in adult patients with moderate or severe ARDS due to confirmed COVID-19. The secondary objective is to investigate the efficacy and safety of dexamethasone 20 mg versus dexamethasone 6 mg. The exploratory objective of this study is to assess long-term consequences on mortality and quality of life at 180 and 360 days. TRIAL DESIGN: REMED is a prospective, phase II, open-label, randomised controlled trial testing superiority of dexamethasone 20 mg vs 6 mg. The trial aims to be pragmatic, i.e. designed to evaluate the effectiveness of the intervention in conditions that are close to real-life routine clinical practice. PARTICIPANTS: The study is multi-centre and will be conducted in the intensive care units (ICUs) of ten university hospitals in the Czech Republic. INCLUSION CRITERIA: Subjects will be eligible for the trial if they meet all of the following criteria: 1. Adult (≥18 years of age) at time of enrolment; 2. Present COVID-19 (infection confirmed by RT-PCR or antigen testing); 3. Intubation/mechanical ventilation or ongoing high-flow nasal cannula (HFNC) oxygen therapy; 4. Moderate or severe ARDS according to Berlin criteria: • Moderate - PaO2/FiO2 100-200 mmHg; • Severe - PaO2/FiO2 < 100 mmHg; 5. Admission to ICU in the last 24 hours. EXCLUSION CRITERIA: Subjects will not be eligible for the trial if they meet any of the following criteria: 1. Known allergy/hypersensitivity to dexamethasone or excipients of the investigational medicinal product (e.g. parabens, benzyl alcohol); 2. Fulfilled criteria for ARDS for ≥14 days at enrolment; 3. Pregnancy or breastfeeding; 4. Unwillingness to comply with contraception measurements from enrolment until at least 1 week after the last dose of dexamethasone (sexual abstinence is considered an adequate contraception method); 5. End-of-life decision or patient is expected to die within next 24 hours; 6. Decision not to intubate or ceilings of care in place; 7. Immunosuppression and/or immunosuppressive drugs in medical history: a) Systemic immunosuppressive drugs or chemotherapy in the past 30 days; b) Systemic corticosteroid use before hospitalization; c) Any dose of dexamethasone during the present hospital stay for COVID-19 for ≥5 days before enrolment; d) Systemic corticosteroids during present hospital stay for conditions other than COVID-19 (e.g. septic shock); 8. Current haematological or generalized solid malignancy; 9. Any contraindication for corticosteroid administration, e.g. • intractable hyperglycaemia; • active gastrointestinal bleeding; • adrenal gland disorders; • presence of superinfection diagnosed with locally established clinical and laboratory criteria without adequate antimicrobial treatment; 10. Cardiac arrest before ICU admission; 11. Participation in another interventional trial in the last 30 days. INTERVENTION AND COMPARATOR: Dexamethasone solution for injection/infusion is the investigational medicinal product as well as the comparator. The trial will assess two doses, 20 mg (investigational) vs 6 mg (comparator). Patients in the intervention group will receive dexamethasone 20 mg intravenously once daily on day 1-5, followed by dexamethasone 10 mg intravenously once daily on day 6-10. Patients in the control group will receive dexamethasone 6 mg day 1-10. All authorized medicinal products containing dexamethasone in the form of solution for i.v. injection/infusion can be used. MAIN OUTCOMES: Primary endpoint: Number of ventilator-free days (VFDs) at 28 days after randomisation, defined as being alive and free from mechanical ventilation. SECONDARY ENDPOINTS: a) Mortality from any cause at 60 days after randomisation; b) Dynamics of inflammatory marker (C-Reactive Protein, CRP) change from Day 1 to Day 14; c) WHO Clinical Progression Scale at Day 14; d) Adverse events related to corticosteroids (new infections, new thrombotic complications) until Day 28 or hospital discharge; e) Independence at 90 days after randomisation assessed by Barthel Index. The long-term outcomes of this study are to assess long-term consequences on mortality and quality of life at 180 and 360 days through telephone structured interviews using the Barthel Index. RANDOMISATION: Randomisation will be carried out within the electronic case report form (eCRF) by the stratified permuted block randomisation method. Allocation sequences will be prepared by a statistician independent of the study team. Allocation to the treatment arm of an individual patient will not be available to the investigators before completion of the whole randomisation process. The following stratification factors will be applied: • Age <65 and ≥ 65; • Charlson Comorbidity index (CCI) <3 and ≥3; • CRP <150 mg/L and ≥150 mg/L • Trial centre. Patients will be randomised in a 1 : 1 ratio into one of the two treatment arms. Randomisation through the eCRF will be available 24 hours every day. BLINDING (MASKING): This is an open-label trial in which the participants and the study staff will be aware of the allocated intervention. Blinded pre-planned statistical analysis will be performed. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size is calculated to detect the difference of 3 VFDs at 28 days (primary efficacy endpoint) between the two treatment arms with a two-sided type I error of 0.05 and power of 80%. Based on data from a multi-centre randomised controlled trial in COVID-19 ARDS patients in Brazil and a multi-centre observational study from French and Belgian ICUs regarding moderate to severe ARDS related to COVID-19, investigators assumed a standard deviation of VFD at 28 days as 9. Using these assumptions, a total of 142 patients per treatment arm would be needed. After adjustment for a drop-out rate, 150 per treatment arm (300 patients per study) will be enrolled. TRIAL STATUS: This is protocol version 1.1, 15.01.2021. The trial is due to start on 2 February 2021 and recruitment is expected to be completed by December 2021. TRIAL REGISTRATION: The study protocol was registered on EudraCT No.:2020-005887-70, and on December 11, 2020 on ClinicalTrials.gov (Title: Effect of Two Different Doses of Dexamethasone in Patients With ARDS and COVID-19 (REMED)) Identifier: NCT04663555 with a last update posted on February 1, 2021. FULL PROTOCOL: The full protocol (version 1.1) is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the standard formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.


Subject(s)
COVID-19/therapy , Dexamethasone/administration & dosage , Glucocorticoids/administration & dosage , Respiration, Artificial , Respiratory Distress Syndrome/therapy , COVID-19/complications , Clinical Trials, Phase II as Topic , Disease Progression , Dose-Response Relationship, Drug , Equivalence Trials as Topic , Humans , Length of Stay , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Respiratory Distress Syndrome/etiology , SARS-CoV-2
20.
Eur J Neurol ; 28(10): 3289-3302, 2021 10.
Article in English | MEDLINE | ID: covidwho-1605352

ABSTRACT

BACKGROUND AND PURPOSE: The full spectrum of neurological sequelae in COVID-19 is beginning to emerge. SARS-CoV-2 has the potential to cause both direct and indirect brain vascular endothelial damage through infection and inflammation that may result in long-term neurological signs and symptoms. We sought to illuminate persistent neuro-ophthalmological deficits that may be seen following posterior reversible encephalopathy syndrome (PRES) due to COVID-19. METHODS: We identified three individuals with PRES due to COVID-19 in our hospital system. One patient was identified on presentation to our neuro-ophthalmology clinic. The other patients were identified through internal records search. These cases were compared to published reports of PRES in COVID-19 identified through systematic literature search of PubMed/LitCOVID. RESULTS: All three patients were hospitalized with severe COVID-19 and developed altered mental status with new onset seizures that led to the recognition of PRES through diagnostic imaging. During recovery, two patients had persistent visual dysfunction including visual field deficits. One patient also experienced hallucinatory palinopsia and visual hallucinations. Literature search identified 32 other cases of PRES in the context of COVID-19. Visual disturbances were described in 14 cases (40%), with only seven cases (50%) reporting full recovery by the time of publication. CONCLUSIONS: As we learn about enduring neurological complications of COVID-19, it is possible that complications may be underrecognized and underreported. Understanding the range of complications can help in postcare evaluation and management changes in the critical care setting to potentially allow intervention before persistent deficits occur due to COVID-19.


Subject(s)
COVID-19 , Posterior Leukoencephalopathy Syndrome , Critical Care , Humans , Posterior Leukoencephalopathy Syndrome/complications , Posterior Leukoencephalopathy Syndrome/diagnostic imaging , SARS-CoV-2 , Vision Disorders/etiology
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