Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 1.455
Filter
1.
Anaesthesist ; 70(Suppl 1): 19-29, 2021 12.
Article in English | MEDLINE | ID: covidwho-1958962

ABSTRACT

Since December 2019 a novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) has rapidly spread around the world resulting in an acute respiratory illness pandemic. The immense challenges for clinicians and hospitals as well as the strain on many healthcare systems has been unprecedented.The majority of patients present with mild symptoms of coronavirus disease 2019 (COVID-19); however, 5-8% become critically ill and require intensive care treatment. Acute hypoxemic respiratory failure with severe dyspnea and an increased respiratory rate (>30/min) usually leads to intensive care unit (ICU) admission. At this point bilateral pulmonary infiltrates are typically seen. Patients often develop a severe acute respiratory distress syndrome (ARDS).So far, remdesivir and dexamethasone have shown clinical effectiveness in severe COVID-19 in hospitalized patients. The main goal of supportive treatment is to ascertain adequate oxygenation. Invasive mechanical ventilation and repeated prone positioning are key elements in treating severely hypoxemic COVID-19 patients.Strict adherence to basic infection control measures (including hand hygiene) and correct use of personal protection equipment (PPE) are essential in the care of patients. Procedures that lead to formation of aerosols should be carried out with utmost precaution and preparation.


Subject(s)
COVID-19 , Critical Illness , Humans , SARS-CoV-2
2.
Curr Opin Anaesthesiol ; 34(2): 187-198, 2021 Apr 01.
Article in English | MEDLINE | ID: covidwho-1956585

ABSTRACT

PURPOSE OF REVIEW: Hospitalizations for COVID-19 dramatically increase with age. This is likely because of increases in fragility across biological repair systems and a weakened immune system, including loss of the cardiorenal protective arm of the renin--angiotensin system (RAS), composed of angiotensin-converting enzyme-2 (ACE2)/angiotensin-(1--7) [Ang-(1--7)] and its actions through the Mas receptor. The purpose of this review is to explore how cardiac ACE2 changes with age, cardiac diseases, comorbid conditions and pharmaceutical regimens in order to shed light on a potential hormonal unbalance facilitating SARs-CoV-2 vulnerabilities in older adults. RECENT FINDINGS: Increased ACE2 gene expression has been reported in human hearts with myocardial infarction, cardiac remodeling and heart failure. We also found ACE2 mRNA in atrial appendage tissue from cardiac surgical patients to be positively associated with age, elevated by certain comorbid conditions (e.g. COPD and previous stroke) and increased in conjunction with patients' chronic use of antithrombotic agents and thiazide diuretics but not drugs that block the renin--angiotensin system. SUMMARY: Cardiac ACE2 may have bifunctional roles in COVID-19 as ACE2 not only mediates cellular susceptibility to SARS-CoV-2 infection but also protects the heart via the ACE2/Ang-(1--7) pathway. Linking tissue ACE2 from cardiac surgery patients to their comorbid conditions and medical regimens provides a unique latform to address the influence that altered expression of the ACE2/Ang-(1-7)/Mas receptor axis might have on SARs-CoV-2 vulnerability in older adults.


Subject(s)
Atrial Appendage , COVID-19 , Cardiac Surgical Procedures , Aged , Aging , Angiotensin-Converting Enzyme 2 , Angiotensins , Atrial Appendage/surgery , Humans , SARS-CoV-2
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 ; : 1-5, 2020 Jul 30.
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.

6.
J Matern Fetal Neonatal Med ; : 1-4, 2020 Jul 14.
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.

7.
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.

8.
Tanaffos ; 19(4): 291-299, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-1801409

ABSTRACT

BACKGROUND: Inflammatory mediators are an important component in the pathophysiology of the coronavirus disease 2019 (COVID-19). This study aimed to assess the effects of reducing inflammatory mediators using hemoperfusion (HP) and continuous renal replacement therapy (CRRT) on the mortality of patients with COVID-19. MATERIALS AND METHODS: Twelve patients with confirmed diagnosis of COVID-19 were included. All patients had acute respiratory distress syndrome (ARDS). Patients were divided into three groups, namely, HP, CRRT and HP+CRRT. The primary outcome was mortality and the secondary outcomes were oxygenation and reduction in inflammatory mediators at the end of the study. RESULTS: Patients were not different at baseline in demographics, inflammatory cytokine levels, and the level of acute phase reactants. Half of the patients (3 out of 6) in the HP+CRRT group survived along with the survival of one patient (1 out of 2) in the HP group. All four patients in the CRRT group died. Serum creatinine (SCr), Interleukin-1 (IL1), Interleukin-6 (IL6), Interleukin-8 (IL8), partial pressure of oxygen (PaO2), O2 saturation (O2 sat), and hemodynamic parameters improved over time in HP+CRRT and CRRT groups, but no significant difference was observed in the HP group (All Ps > 0.05). CONCLUSION: Combined HP and CRRT demonstrated the best result in terms of mortality, reduction of inflammatory mediators and oxygenation. Further investigations are needed to explore the role of HP+CRRT in COVID-19 patients.

9.
Crit Care Explor ; 2(9): e0207, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1795073

ABSTRACT

OBJECTIVES: To determine whether placental cell therapy PLacental eXpanded (PLX)-PAD (Pluristem Therapeutics, Haifa, Israel) may be beneficial to treating critically ill patients suffering from acute respiratory distress syndrome due to coronavirus disease 2019. DESIGN: Retrospective case report of critically ill coronavirus disease 2019 patients treated with PLacental eXpanded (PLX)-PAD from March 26, 2020, to April 4, 2020, with follow-up through May 2, 2020. SETTING: Four hospitals in Israel (Rambam Health Care Campus, Bnai Zion Medical Center, and Samson Assuta Ashdod University Hospital), and Holy Name Medical Center in New Jersey. PATIENTS: Eight critically ill patients on invasive mechanical ventilation, suffering from acute respiratory distress syndrome due to coronavirus disease 2019. INTERVENTIONS: Intramuscular injection of PLacental eXpanded (PLX)-PAD (300 × 106 cells) given as one to two treatments. MEASUREMENTS AND MAIN RESULTS: Mortality, time to discharge, and changes in blood and respiratory variables were monitored during hospitalization to day 17 posttreatment. Of the eight patients treated (median age 55 yr, seven males and one female), five were discharged, two remained hospitalized, and one died. By day 3 postinjection, mean C-reactive protein fell 45% (240.3-131.3 mg/L; p = 0.0019) and fell to 77% by day 5 (56.0 mg/L; p < 0.0001). Pao2/Fio2 improved in 5:8 patients after 24-hour posttreatment, with similar effects 48-hour posttreatment. A decrease in positive end-expiratory pressure and increase in pH were statistically significant between days 0 and 14 (p = 0.0032 and p = 0.00072, respectively). A decrease in hemoglobin was statistically significant for days 0-5 and 0-14 (p = 0.015 and p = 0.0028, respectively), whereas for creatinine, it was statistically significant between days 0 and 14 (p = 0.032). CONCLUSIONS: Improvement in several variables such as C-reactive protein, positive end-expiratory pressure, and Pao2/Fio2 was observed following PLacental eXpanded (PLX)-PAD treatment, suggesting possible therapeutic effect. However, interpretation of the data is limited due to the small sample size, use of concomitant investigational therapies, and the uncontrolled study design. The efficacy of PLacental eXpanded (PLX)-PAD in coronavirus disease 2019 should be further evaluated in a controlled clinical trial.

10.
Thromb J ; 18: 22, 2020.
Article in English | MEDLINE | ID: covidwho-1793931

ABSTRACT

BACKGROUND: Hospitals in the Middle East Gulf region have experienced an influx of COVID-19 patients to their medical wards and intensive care units. The hypercoagulability of these patients has been widely reported on a global scale. However, many of the experimental treatments used to manage the various complications of COVID-19 have not been widely studied in this context. The effect of the current treatment protocols on patients' diagnostic and prognostic biomarkers may thus impact the validity of the algorithms adopted. CASE PRESENTATION: In this case series, we report four cases of venous thromboembolism and 1 case of arterial thrombotic event, in patients treated with standard or intensified prophylactic doses of unfractionated heparin or low molecular weight heparin at our institution. Tocilizumab has been utilized as an add-on therapy to the standard of care to treat patients with SARS-CoV-2 associated acute respiratory distress syndrome, in order to dampen the hyperinflammatory response. It is imperative to be aware that this drug may be masking the inflammatory markers (e.g. IL6, CRP, fibrinogen, and ferritin), without reducing the risk of thrombotic events in this population, creating instead a façade of an improved prognostic outcome. However, the D-dimer levels remained prognostically reliable in these cases, as they were not affected by the drug and continued to be at the highest level until event occurrence. CONCLUSIONS: In the setting of tocilizumab therapy, traditional prognostic markers of worsening infection and inflammation, and thus potential risk of acute thrombosis, should be weighed carefully as they may not be reliable for prognosis and may create a façade of an improved prognostic outcome insteasd. Additionally, the fact that thrombotic events continued to be observed despite decrease in inflammatory markers and the proactive anticoagulative approach adopted, raises more questions about the coagulative mechanisms at play in COVID-19, and the appropriate management strategy.

11.
Indian J Crit Care Med ; 24(10): 914-918, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-1792087

ABSTRACT

BACKGROUND: The World Health Organization (WHO) has declared SARS-CoV-2 as pandemic. Patients with COVID-19 present mainly with respiratory symptoms. Prone position has been traditionally used in acute respiratory distress syndrome (ARDS) to improve oxygenation and prevent barotrauma in ventilated patients. Awake proning is being used as an investigational therapy in COVID to defer invasive ventilation, improve oxygenation, and outcomes. Hence, we conducted a retrospective case study to look for benefits of awake proning with oxygen therapy in non-intubated COVID patients. MATERIALS AND METHODS: A retrospective case study of 15 COVID patients admitted from June 15 to July 1, 2020 to HDU in our hospital was conducted. Cooperative patients who were hemodynamically stable and SpO2 < 90% on presentation were included. Oxygen was administered through facemask, non-rebreathing mask and noninvasive ventilation to patients as per requirement. Patients were encouraged to maintain prone position and target time was 10-12 hours/day. SpO2 and P/f ratio in supine and prone position was observed till discharge. Primary target was SpO2 > 95% and P/f > 200 mm Hg. Other COVID therapies were used according to institutional protocol. RESULTS: The mean SpO2 on room air on admission was 80%. In day 1 to 3, the mean P/f ratio in supine position was 98.8 ± 29.7 mm Hg which improved to 136.6 ± 38.8 mm Hg after proning (p = 0.005). The difference was significant from day 1 to 10. Two patients were intubated. The mean duration of stay was 11 days. CONCLUSION: Awake prone positioning showed marked improvement in P/f ratio and SpO2 in COVID-19 patients with improvement in clinical symptoms with reduced rate of intubation. HIGHLIGHTS: Prone position ventilation improves oxygenation by reducing V/Q mismatch.Awake prone positioning has been used along with high-flow oxygen therapy in recent pandemic of SARS-CoV-2 virus for management of mild to moderate cases. HOW TO CITE THIS ARTICLE: Singh P, Jain P, Deewan H. Awake Prone Positioning in COVID-19 Patients. Indian J Crit Care Med 2020;24(10):914-918.

12.
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
13.
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
14.
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.
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
16.
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
17.
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
18.
J Immunotoxicol ; 18(1): 23-29, 2021 12.
Article in English | MEDLINE | ID: covidwho-1593522

ABSTRACT

The coronavirus SARS-CoV-2 of 2019 (COVID-19) causes a pandemic that has been diagnosed in more than 70 million people worldwide. Mild-to-moderate COVID-19 symptoms include coughing, fever, myalgia, shortness of breath, and acute inflammatory lung injury (ALI). In contrast, acute respiratory distress syndrome (ARDS) and respiratory failure occur in patients diagnosed with severe COVID-19. ARDS is mediated, at least in part, by a dysregulated inflammatory response due to excessive levels of circulating cytokines, a condition known as the "cytokine-storm syndrome." Currently, there are FDA-approved therapies that attenuate the dysregulated inflammation that occurs in COVID-19 patients, such as dexamethasone or other corticosteroids and IL-6 inhibitors, including sarilumab, tocilizumab, and siltuximab. However, the efficacy of these treatments have been shown to be inconsistent. Compounds that activate the vagus nerve-mediated cholinergic anti-inflammatory reflex, such as the α7 nicotinic acetylcholine receptor agonist, GTS-21, attenuate ARDS/inflammatory lung injury by decreasing the extracellular levels of high mobility group box-1 (HMGB1) in the airways and the circulation. It is possible that HMGB1 may be an important mediator of the "cytokine-storm syndrome." Notably, high plasma levels of HMGB1 have been reported in patients diagnosed with severe COVID-19, and there is a significant negative correlation between HMGB1 plasma levels and clinical outcomes. Nicotine can activate the cholinergic anti-inflammatory reflex, which attenuates the up-regulation and the excessive release of pro-inflammatory cytokines/chemokines. Therefore, we hypothesize that low molecular weight compounds that activate the cholinergic anti-inflammatory reflex, such as nicotine or GTS-21, may represent a potential therapeutic approach to attenuate the dysregulated inflammatory responses in patients with severe COVID-19.


Subject(s)
Benzylidene Compounds/pharmacology , COVID-19/drug therapy , Cholinergic Agents/pharmacology , Inflammation/drug therapy , Nicotine/metabolism , Pyridines/pharmacology , SARS-CoV-2/physiology , Tobacco Use Disorder/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Cigarette Smoking/adverse effects , Dexamethasone/therapeutic use , HMGB1 Protein/blood , Humans , Pandemics , alpha7 Nicotinic Acetylcholine Receptor/agonists
19.
Ann Med ; 53(1): 410-412, 2021 12.
Article in English | MEDLINE | ID: covidwho-1573909

ABSTRACT

OBJECTIVE: Cytokine release syndrome is suggested to be the most important mechanism triggering acute respiratory distress syndrome and end organ damage in COVID-19. The severity of disease may be measured by different biomarkers. METHODS: We studied markers of inflammation and coagulation as recorded in 29 patients on admission to the hospital in order to identify markers of severe COVID-19 and need of ICU. RESULTS: Patients who were eventually admitted to ICU displayed significantly higher serum levels of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin. No statistical differences were found between the groups in median levels of lymphocytes, D-dimer or ferritin. CONCLUSIONS: IL-6 and CRP were the strongest predictors of severity in hospitalized patients with COVID-19.


Subject(s)
COVID-19/blood , COVID-19/diagnosis , Interleukin-6/blood , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Female , Humans , Male , Middle Aged , Severity of Illness Index , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL