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1.
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
2.
Lancet ; 398(10303): 843-855, 2021 09 04.
Article in English | MEDLINE | ID: covidwho-1599473

ABSTRACT

BACKGROUND: A previous efficacy trial found benefit from inhaled budesonide for COVID-19 in patients not admitted to hospital, but effectiveness in high-risk individuals is unknown. We aimed to establish whether inhaled budesonide reduces time to recovery and COVID-19-related hospital admissions or deaths among people at high risk of complications in the community. METHODS: PRINCIPLE is a multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial done remotely from a central trial site and at primary care centres in the UK. Eligible participants were aged 65 years or older or 50 years or older with comorbidities, and unwell for up to 14 days with suspected COVID-19 but not admitted to hospital. Participants were randomly assigned to usual care, usual care plus inhaled budesonide (800 µg twice daily for 14 days), or usual care plus other interventions, and followed up for 28 days. Participants were aware of group assignment. The coprimary endpoints are time to first self-reported recovery and hospital admission or death related to COVID-19, within 28 days, analysed using Bayesian models. The primary analysis population included all eligible SARS-CoV-2-positive participants randomly assigned to budesonide, usual care, and other interventions, from the start of the platform trial until the budesonide group was closed. This trial is registered at the ISRCTN registry (ISRCTN86534580) and is ongoing. FINDINGS: The trial began enrolment on April 2, 2020, with randomisation to budesonide from Nov 27, 2020, until March 31, 2021, when the prespecified time to recovery superiority criterion was met. 4700 participants were randomly assigned to budesonide (n=1073), usual care alone (n=1988), or other treatments (n=1639). The primary analysis model includes 2530 SARS-CoV-2-positive participants, with 787 in the budesonide group, 1069 in the usual care group, and 974 receiving other treatments. There was a benefit in time to first self-reported recovery of an estimated 2·94 days (95% Bayesian credible interval [BCI] 1·19 to 5·12) in the budesonide group versus the usual care group (11·8 days [95% BCI 10·0 to 14·1] vs 14·7 days [12·3 to 18·0]; hazard ratio 1·21 [95% BCI 1·08 to 1·36]), with a probability of superiority greater than 0·999, meeting the prespecified superiority threshold of 0·99. For the hospital admission or death outcome, the estimated rate was 6·8% (95% BCI 4·1 to 10·2) in the budesonide group versus 8·8% (5·5 to 12·7) in the usual care group (estimated absolute difference 2·0% [95% BCI -0·2 to 4·5]; odds ratio 0·75 [95% BCI 0·55 to 1·03]), with a probability of superiority 0·963, below the prespecified superiority threshold of 0·975. Two participants in the budesonide group and four in the usual care group had serious adverse events (hospital admissions unrelated to COVID-19). INTERPRETATION: Inhaled budesonide improves time to recovery, with a chance of also reducing hospital admissions or deaths (although our results did not meet the superiority threshold), in people with COVID-19 in the community who are at higher risk of complications. FUNDING: National Institute of Health Research and United Kingdom Research Innovation.


Subject(s)
Budesonide/administration & dosage , COVID-19/drug therapy , Glucocorticoids/administration & dosage , Administration, Inhalation , Aged , Bayes Theorem , COVID-19/mortality , Female , Hospitalization , Humans , Male , Middle Aged , Prospective Studies , Risk Factors , SARS-CoV-2 , Treatment Outcome
3.
Prague Med Rep ; 122(4): 257-268, 2021.
Article in English | MEDLINE | ID: covidwho-1597646

ABSTRACT

This paper briefly reviews the safety and efficacy of liposteroid in different inflammatory and non-inflammatory diseases. Corticosteroids (CS) are the first-line therapy in many inflammatory and autoimmune disorders. Although highly efficacious, long-term use of CS is limited due to the occurrence of significant side effects. Liposteroid, which is a liposomal formulation of dexamethasone palmitate, possess more potent anti-inflammatory and immunosuppressive properties compared to dexamethasone sodium phosphate. These two formulations have markedly different lipid solubility, resulting in different pharmacokinetic and pharmacodynamic properties. Liposteroid has been used with success in patients with rheumatoid arthritis, macrophage activation syndrome, and idiopathic pulmonary hemosiderosis. In addition, liposteroid has been used in some non-inflammatory diseases. Moreover, we conceive that liposteroid may have a beneficial effect in patients, who are critically ill due to COVID-19, and suffer from the macrophage activation syndrome.


Subject(s)
COVID-19 , Hemosiderosis , Lung Diseases , Glucocorticoids , Humans , SARS-CoV-2
4.
N Engl J Med ; 385(1): 11-22, 2021 07 01.
Article in English | MEDLINE | ID: covidwho-1585668

ABSTRACT

BACKGROUND: Evidence is urgently needed to support treatment decisions for children with multisystem inflammatory syndrome (MIS-C) associated with severe acute respiratory syndrome coronavirus 2. METHODS: We performed an international observational cohort study of clinical and outcome data regarding suspected MIS-C that had been uploaded by physicians onto a Web-based database. We used inverse-probability weighting and generalized linear models to evaluate intravenous immune globulin (IVIG) as a reference, as compared with IVIG plus glucocorticoids and glucocorticoids alone. There were two primary outcomes: the first was a composite of inotropic support or mechanical ventilation by day 2 or later or death; the second was a reduction in disease severity on an ordinal scale by day 2. Secondary outcomes included treatment escalation and the time until a reduction in organ failure and inflammation. RESULTS: Data were available regarding the course of treatment for 614 children from 32 countries from June 2020 through February 2021; 490 met the World Health Organization criteria for MIS-C. Of the 614 children with suspected MIS-C, 246 received primary treatment with IVIG alone, 208 with IVIG plus glucocorticoids, and 99 with glucocorticoids alone; 22 children received other treatment combinations, including biologic agents, and 39 received no immunomodulatory therapy. Receipt of inotropic or ventilatory support or death occurred in 56 patients who received IVIG plus glucocorticoids (adjusted odds ratio for the comparison with IVIG alone, 0.77; 95% confidence interval [CI], 0.33 to 1.82) and in 17 patients who received glucocorticoids alone (adjusted odds ratio, 0.54; 95% CI, 0.22 to 1.33). The adjusted odds ratios for a reduction in disease severity were similar in the two groups, as compared with IVIG alone (0.90 for IVIG plus glucocorticoids and 0.93 for glucocorticoids alone). The time until a reduction in disease severity was similar in the three groups. CONCLUSIONS: We found no evidence that recovery from MIS-C differed after primary treatment with IVIG alone, IVIG plus glucocorticoids, or glucocorticoids alone, although significant differences may emerge as more data accrue. (Funded by the European Union's Horizon 2020 Program and others; BATS ISRCTN number, ISRCTN69546370.).


Subject(s)
COVID-19/drug therapy , Glucocorticoids/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Systemic Inflammatory Response Syndrome/drug therapy , Adolescent , Antibodies, Viral , COVID-19/immunology , COVID-19/mortality , COVID-19/therapy , Child , Child, Preschool , Cohort Studies , Confidence Intervals , Drug Therapy, Combination , Female , Hospitalization , Humans , Immunomodulation , Male , Propensity Score , Regression Analysis , Respiration, Artificial , SARS-CoV-2/immunology , Systemic Inflammatory Response Syndrome/immunology , Systemic Inflammatory Response Syndrome/mortality , Systemic Inflammatory Response Syndrome/therapy , Treatment Outcome
6.
Ann Med ; 53(1): 181-188, 2021 12.
Article in English | MEDLINE | ID: covidwho-1575964

ABSTRACT

OBJECTIVE: To illustrate the effect of corticosteroids and heparin, respectively, on coronavirus disease 2019 (COVID-19) patients' CD8+ T cells and D-dimer. METHODS: In this retrospective cohort study involving 866 participants diagnosed with COVID-19, patients were grouped by severity. Generalized additive models were established to explore the time-course association of representative parameters of coagulation, inflammation and immunity. Segmented regression was performed to examine the influence of corticosteroids and heparin upon CD8+ T cell and D-dimer, respectively. RESULTS: There were 541 moderate, 169 severe and 156 critically ill patients involved in the study. Synchronous changes of levels of NLR, D-dimer and CD8+ T cell in critically ill patients were observed. Administration of methylprednisolone before 14 DFS compared with those after 14 DFS (ß = 0.154%, 95% CI=(0, 0.302), p=.048) or a dose lower than 40 mg per day compared with those equals to 40 mg per day (ß = 0.163%, 95% CI=(0.027, 0.295), p=.020) significantly increased the rising rate of CD8+ T cell in 14-56 DFS. CONCLUSIONS: The parameters of coagulation, inflammation and immunity were longitudinally correlated, and an early low-dose corticosteroid treatment accelerated the regaining of CD8+ T cell to help battle against SARS-Cov-2 in critical cases of COVID-19.


Subject(s)
CD8-Positive T-Lymphocytes/drug effects , COVID-19/drug therapy , Glucocorticoids/administration & dosage , Inflammation/drug therapy , Adult , Aged , Aged, 80 and over , Blood Coagulation/drug effects , Blood Coagulation/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/blood , COVID-19/diagnosis , COVID-19/immunology , Dose-Response Relationship, Drug , Female , Fibrin Fibrinogen Degradation Products/analysis , Fibrin Fibrinogen Degradation Products/immunology , Heparin/administration & dosage , Humans , Inflammation/blood , Inflammation/diagnosis , Inflammation/immunology , Linear Models , Longitudinal Studies , Lymphocyte Count , Male , Methylprednisolone/administration & dosage , Middle Aged , Models, Biological , Retrospective Studies , SARS-CoV-2/immunology , SARS-CoV-2/isolation & purification , Severity of Illness Index , Time Factors , Time-to-Treatment , Young Adult
7.
Ann Med ; 53(1): 295-301, 2021 12.
Article in English | MEDLINE | ID: covidwho-1575822

ABSTRACT

INTRODUCTION: Critically ill patients with COVID-19 are at increased risk of developing a hypercoagulable state due to haemostatic changes directly related to the SARS-CoV-2 infection or to the consequence of the cytokine storm. Anticoagulation is now recommended to reduce the thrombotic risk. Ilio-psoas haematoma (IPH) is a potentially lethal condition that can arise during the hospitalization, especially in intensive care units (ICUs) and frequently reported as a complication of anticoagulation treatment. MATERIALS AND METHODS: We report a case series of seven subjects with SARS-CoV-2 pneumonia complicated by Ilio-psoas haematomas (IPHs) at our COVID-Hospital in Rome, Italy. RESULTS: Over the observation period, 925 subjects with confirmed SARS-CoV-2 infection were admitted to our COVID-hospital. Among them, we found seven spontaneous IPHs with an incidence of 7.6 cases per 1000 hospitalization. All the reported cases had a severe manifestation of COVID-19 pneumonia, with at least one comorbidity and 5/7 were on treatment with low weight molecular heparin for micro or macro pulmonary thrombosis. CONCLUSIONS: Given the indications to prescribe anticoagulant therapy in COVID-19 and the lack of solid evidences on the optimal dose and duration, it is important to be aware of the iliopsoas haematoma as a potentially serious complication in COVID-19 inpatients. KEY MESSAGE Critically ill patients with COVID-19 are at increased risk of hypercoagulability state and anticoagulation therapy is recommended. Ilio-psoas haematoma (IPH) is found to be a complication of anticoagulation regimen especially in severe COVID-19 cases. An incidence of 7.6 cases per 1000 admission of IPHs was reported. Hypoesthesia of the lower limbs, pain triggered by femoral rotation, hypovolaemia and anaemia are the most common symptoms and signs of IPHs that should alert physician.


Subject(s)
Anticoagulants/adverse effects , COVID-19/complications , Hematoma/epidemiology , Psoas Muscles/diagnostic imaging , Thrombophilia/drug therapy , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/virology , Critical Illness/mortality , Critical Illness/therapy , Female , Glucocorticoids/therapeutic use , Hematoma/chemically induced , Hematoma/diagnosis , Hematoma/drug therapy , Heparin, Low-Molecular-Weight , Hospital Mortality , Humans , Incidence , Intensive Care Units , Italy/epidemiology , Magnetic Resonance Imaging , Male , Middle Aged , Muscular Diseases , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Severity of Illness Index , Thrombophilia/etiology , Tomography, X-Ray Computed , Treatment Outcome
8.
Int J Environ Res Public Health ; 18(24)2021 12 15.
Article in English | MEDLINE | ID: covidwho-1572481

ABSTRACT

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) pandemic, affecting all age groups with a wide spectrum of clinical presentation ranging from asymptomatic to severe interstitial pneumonia, hyperinflammation, and death. Children and infants generally show a mild course of the disease, although infants have been observed to have a higher risk of hospitalization and severe outcomes. Here, we report the case of a preterm infant with a severe form of SARS-CoV-2 infection complicated by cerebral venous thrombosis successfully treated with steroids, hyperimmune plasma, and remdesivir.


Subject(s)
COVID-19 , Venous Thrombosis , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , COVID-19/drug therapy , Child , Glucocorticoids/therapeutic use , Humans , Infant , Infant, Newborn , Infant, Premature , SARS-CoV-2 , Venous Thrombosis/drug therapy
9.
Biomed Pharmacother ; 144: 112353, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1544808

ABSTRACT

Almost 80% of people confronting COVID-19 recover from COVID-19 disease without any particular treatments. They experience heterogeneous symptoms; a wide range of respiratory symptoms, cough, dyspnea, fever, and viral pneumonia. However, some others need urgent intervention and special treatment to get rid of this widespread disease. So far, there isn't any unique drug for the potential treatment of COVID 19. However, some available therapeutic drugs used for other diseases seem beneficial for the COVID-19 treatment. On the other hand, there is a robust global concern for developing an efficient COVID-19 vaccine to control the COVID-19 pandemic sustainably. According to the WHO report, since 8 October 2021, 320 vaccines have been in progress. 194 vaccines are in the pre-clinical development stage that 126 of them are in clinical progression. Here, in this paper, we have comprehensively reviewed the most recent and updated information about coronavirus and its mutations, all the potential therapeutic approaches for treating COVID-19, developed diagnostic systems for COVID- 19 and the available COVID-19 vaccines and their mechanism of action.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/drug therapy , COVID-19/prevention & control , Biosensing Techniques/methods , COVID-19/diagnosis , COVID-19 Nucleic Acid Testing/methods , Dexamethasone/therapeutic use , Glucocorticoids/therapeutic use , Humans , Molecular Diagnostic Techniques/methods , Mutation , Nucleic Acid Amplification Techniques/methods , Point-of-Care Testing , SARS-CoV-2/genetics , World Health Organization
11.
JAMA ; 326(18): 1807-1817, 2021 11 09.
Article in English | MEDLINE | ID: covidwho-1527380

ABSTRACT

Importance: A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. Objective: To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. Design, Setting, and Participants: A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. Interventions: Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and ≥1 serious adverse reactions at 28 days). Results: Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). Conclusions and Relevance: Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT04509973 and ctri.nic.in Identifier: CTRI/2020/10/028731.


Subject(s)
COVID-19/drug therapy , Dexamethasone/administration & dosage , Glucocorticoids/administration & dosage , Life Support Care , Aged , COVID-19/complications , COVID-19/mortality , Dexamethasone/adverse effects , Dose-Response Relationship, Drug , Female , Glucocorticoids/adverse effects , Humans , Hypoxia/etiology , Hypoxia/therapy , Male , Middle Aged , Mycoses/etiology , Respiration, Artificial , Shock, Septic/etiology , Single-Blind Method
13.
Retina ; 41(8): 1709-1714, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1503647

ABSTRACT

PURPOSE: To describe endogenous endophthalmitis in the setting of COVID-19 pneumonia. METHODS: Patients recovering from COVID-19 pneumonia who presented to our department with any or all of the following complaints: pain, watering, redness, and decreased vision were identified. All relevant data were collected for analysis. RESULTS: Three patients with endogenous endophthalmitis were identified. All patients had been treated for COVID-19 pneumonia and therefore had received remdesivir and systemic steroids; 2 of the 3 patients received tocilizumab. All patients received vitreous biopsy, vitrectomy, and intraocular antibiotic injection. Patient 1 demonstrated Klebsiella pneumoniae in blood culture, K. pneumoniae and Escherichia coli in urine culture, and K. pneumoniae in vitreous fluid, whereas Patients 2 and 3 demonstrated Stenotrophomonas maltophilia and methicillin-resistant Staphylococcus aureus in the blood and nasopharyngeal culture, respectively. Correspondingly, the same organism was cultured from vitreous in Patients 2 and 3. The visual acuity at the last follow-up in Patients 1 to 3 was 20/100, 20/80, and 20/40, respectively. The probable source of infection was identified in each as renal calculi, dental caries, and the pharynx, respectively. Real-time polymerase chain reaction demonstrated the presence of Severe Acute Respiratory Syndrome Coronavirus 2 in the vitreous fluid of Patient 1. CONCLUSION: We report good outcomes of early intervention for endogenous endophthalmitis in the setting of COVID-19 infection. We also document the presence of SARS-CoV-2 in vitreous.


Subject(s)
COVID-19/complications , Endophthalmitis/microbiology , Eye Infections, Bacterial/microbiology , Klebsiella pneumoniae/isolation & purification , Methicillin-Resistant Staphylococcus aureus/isolation & purification , SARS-CoV-2/isolation & purification , Stenotrophomonas maltophilia/isolation & purification , Adult , Aged , Anti-Bacterial Agents/therapeutic use , COVID-19 Nucleic Acid Testing , Endophthalmitis/diagnosis , Endophthalmitis/drug therapy , Eye Infections, Bacterial/diagnosis , Eye Infections, Bacterial/drug therapy , Female , Glucocorticoids/therapeutic use , Gram-Negative Bacterial Infections/diagnosis , Gram-Negative Bacterial Infections/drug therapy , Gram-Negative Bacterial Infections/microbiology , Humans , Klebsiella Infections/diagnosis , Klebsiella Infections/drug therapy , Klebsiella Infections/microbiology , Male , Middle Aged , Staphylococcal Infections/diagnosis , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Vitrectomy , Vitreous Body/microbiology , Vitreous Body/virology
14.
Am J Case Rep ; 22: e933462, 2021 Nov 02.
Article in English | MEDLINE | ID: covidwho-1497918

ABSTRACT

BACKGROUND COVID-19 can be complicated by kidney disease, including focal segmental glomerulosclerosis (FSGS), interstitial nephritis, and acute kidney injury (AKI). Almost all known cases of COVID-19-associated glomerulonephritis have been in patients of African descent, with G1 or G2 apolipoprotein L1 (APOL1) risk alleles, and they presented collapsing type of FSGS. CASE REPORT We report a case of biopsy-confirmed non-collapsing FSGS with secondary acute interstitial nephritis and AKI in a young White man with APOL1 low-risk genotype, who had COVID-19 pneumonia. His past history included arterial hypertension, anabolic steroids, and high-protein diet. He fully recovered from type 1 respiratory failure and AKI after transfusion of COVID-19 convalescent plasma and intravenous treatment with dexamethasone administered for 16 days in a dose reduced from 16 to 2 mg/day. Due to progressing severe nephrotic proteinuria (22.6 g/24 h), intravenous methylprednisolone was administered (1500 mg divided in 3 pulses over 3 days) immediately followed by oral prednisone (0.6 mg/kg body weight), with dose reduced 19 weeks later and switched to cyclosporine A (4 mg/kg body weight). Kidney re-biopsy, at that time, showed a decrease in proportion of glomeruli affected with podocytopathy, but progression of interstitial lesions. After 23 weeks of therapy, partial remission of FSGS was attained and proteinuria dropped to 3.6 g/24 h. After 43 weeks, proteinuria decreased to 0.4 g/24 h and the serum creatinine concentration remained steady. CONCLUSIONS High-dose glucocorticoid therapy was effective in the initial treatment of COVID-19-related non-collapsing FSGS, but had no effect on interstitial changes. Introduction of cyclosporine A to the therapy contributed to remission of disease.


Subject(s)
Acute Kidney Injury , COVID-19 , Glomerulosclerosis, Focal Segmental , Nephritis, Interstitial , Acute Kidney Injury/etiology , Apolipoprotein L1/genetics , COVID-19/therapy , Genotype , Glomerulosclerosis, Focal Segmental/drug therapy , Glucocorticoids/therapeutic use , Humans , Immunization, Passive , Male , SARS-CoV-2
15.
Intensive Care Med ; 46(12): 2284-2296, 2020 12.
Article in English | MEDLINE | ID: covidwho-1451948

ABSTRACT

Current literature addressing the pharmacological principles guiding glucocorticoid (GC) administration in ARDS is scant. This paucity of information may have led to the heterogeneity of treatment protocols and misinterpretation of available findings. GCs are agonist compounds that bind to the GC receptor (GR) producing a pharmacological response. Clinical efficacy depends on the magnitude and duration of exposure to GR. We updated the meta-analysis of randomized trials investigating GC treatment in ARDS, focusing on treatment protocols and response. We synthesized the current literature on the role of the GR in GC therapy including genomic and non-genomic effects, and integrated current clinical pharmacology knowledge of various GCs, including hydrocortisone, methylprednisolone and dexamethasone. This review addresses the role dosage, timing of initiation, mode of administration, duration, and tapering play in achieving optimal response to GC therapy in ARDS. Based on RCTs' findings, GC plasma concentration-time profiles, and pharmacodynamic studies, optimal results are most likely achievable with early intervention, an initial bolus dose to achieve close to maximal GRα saturation, followed by a continuous infusion to maintain high levels of response throughout the treatment period. In addition, patients receiving similar GC doses may experience substantial between-patient variability in plasma concentrations affecting clinical response. GC should be dose-adjusted and administered for a duration targeting clinical and laboratory improvement, followed by dose-tapering to achieve gradual recovery of the suppressed hypothalamic-pituitary-adrenal (HPA) axis. These findings have practical clinical relevance. Future RCTs should consider these pharmacological principles in the study design and interpretation of findings.


Subject(s)
Glucocorticoids , Respiratory Distress Syndrome , Humans , Hypothalamo-Hypophyseal System , Methylprednisolone , Pituitary-Adrenal System , Respiratory Distress Syndrome/drug therapy
16.
Semin Respir Crit Care Med ; 42(5): 672-682, 2021 10.
Article in English | MEDLINE | ID: covidwho-1493295

ABSTRACT

While the use of vitamin C as a therapeutic agent has been investigated since the 1950s, there has been substantial recent interest in the role of vitamin C supplementation in critical illness and particularly, sepsis and septic shock. Humans cannot synthesize vitamin C and rely on exogenous intake to maintain a plasma concentration of approximately 70 to 80 µmol/L. Vitamin C, in healthy humans, is involved with antioxidant function, wound healing, endothelial function, and catecholamine synthesis. Its function in the human body informs the theoretical basis for why vitamin C supplementation may be beneficial in sepsis/septic shock.Critically ill patients can be vitamin C deficient due to low dietary intake, increased metabolic demands, inefficient recycling of vitamin C metabolites, and loss due to renal replacement therapy. Intravenous supplementation is required to achieve supraphysiologic serum levels of vitamin C. While some clinical studies of intravenous vitamin C supplementation in sepsis have shown improvements in secondary outcome measures, none of the randomized clinical trials have shown differences between vitamin C supplementation and standard of care and/or placebo in the primary outcome measures of the trials. There are some ongoing studies of high-dose vitamin C administration in patients with sepsis and coronavirus disease 2019; the majority of evidence so far does not support the routine supplementation of vitamin C in patients with sepsis or septic shock.


Subject(s)
Ascorbic Acid/pharmacology , Ascorbic Acid/therapeutic use , Shock, Septic/drug therapy , Vitamins/pharmacology , Vitamins/therapeutic use , Animals , Antioxidants/pharmacology , Ascorbic Acid/administration & dosage , Ascorbic Acid/adverse effects , Ascorbic Acid Deficiency/physiopathology , Clinical Trials as Topic , Critical Illness , Dose-Response Relationship, Drug , Glucocorticoids/pharmacology , Humans , Inflammation Mediators/metabolism , Vasoconstrictor Agents/pharmacology , Vitamins/administration & dosage , Vitamins/adverse effects
17.
Semin Respir Crit Care Med ; 42(2): 316-326, 2021 04.
Article in English | MEDLINE | ID: covidwho-1493288

ABSTRACT

Venous thromboembolism, occlusion of dialysis catheters, circuit thrombosis in extracorporeal membrane oxygenation (ECMO) devices, acute limb ischemia, and isolated strokes, all in the face of prophylactic and even therapeutic anticoagulation, are features of novel coronavirus disease 2019 (COVID-19) coagulopathy. It seems well established at this time that a COVID-19 patient deemed sick enough to be hospitalized, should receive at least prophylactic dose anticoagulation. However, should some hospitalized patients have dosage escalation to intermediate dose? Should some be considered for full-dose anticoagulation without a measurable thromboembolic event and how should that anticoagulation be monitored? Should patients receive postdischarge anticoagulation and with what medication and for how long? What thrombotic issues are related to the various medications being used to treat this coagulopathy? Is antiphospholipid antibody part of this syndrome? What is the significance of isolated ischemic stroke and limb ischemia in this disorder and how does this interface with the rest of the clinical and laboratory features of this disorder? The aims of this article are to explore these questions and interpret the available data based on the current evidence.


Subject(s)
Anticoagulants/administration & dosage , COVID-19/drug therapy , Thrombophilia/drug therapy , Thrombosis/prevention & control , Venous Thromboembolism/prevention & control , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Ambulatory Care , Antibodies, Antiphospholipid/immunology , Antibodies, Monoclonal, Humanized/therapeutic use , Antirheumatic Agents/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/blood , COVID-19/complications , COVID-19/immunology , COVID-19/therapy , Dose-Response Relationship, Drug , Drug Combinations , Duration of Therapy , Glucocorticoids/therapeutic use , Hospitalization , Humans , Hydroxychloroquine/therapeutic use , Immunization, Passive , Lopinavir/therapeutic use , Ritonavir/therapeutic use , SARS-CoV-2 , Thrombolytic Therapy , Thrombophilia/blood , Thrombophilia/etiology , Thrombosis/drug therapy , Thrombosis/immunology , Venous Thromboembolism/drug therapy , Venous Thromboembolism/immunology
18.
J Postgrad Med ; 67(3): 174-176, 2021.
Article in English | MEDLINE | ID: covidwho-1485286

ABSTRACT

Scleredema adultorum of Buschke is a rare disorder of the connective tissue, involving the skin. Here, we present a 61-year-old male, who is a known case of compensated liver cirrhosis with a past history of being treated for autoimmune thyrotoxicosis, who presented with complaints of alopecia, skin tightening, dry skin, pruritus, and woody indurated plaques on the skin of the upper back, shoulder, and arms. Skin biopsy of the arm revealed the characteristic features of scleredema. He was extensively evaluated for known literature-cited causes of scleredema, and the work up revealed a negative result. He was also found to be hypothyroid on presentation. Hence, we present a case of scleredema occurring in a patient with hypothyroidism and chronic liver disease, which to our knowledge is being described for the first time in literature.


Subject(s)
Hypothyroidism/complications , Liver Cirrhosis/complications , Scleredema Adultorum/diagnosis , Alopecia/etiology , Betamethasone/therapeutic use , COVID-19/drug therapy , Fusidic Acid/therapeutic use , Glucocorticoids/therapeutic use , Humans , Male , Middle Aged , Pruritus/etiology , Thyrotoxicosis/complications
19.
Front Endocrinol (Lausanne) ; 12: 711612, 2021.
Article in English | MEDLINE | ID: covidwho-1485047

ABSTRACT

The ongoing coronavirus disease 2019 (COVID-19) pandemic forced a change in the way we provide medical treatment. Endocrinology in the era of COVID-19 had to transform and reduce its vast potential to the absolute necessities. Medical professionals needed to update their clinical practice to provide their patients as much support and as little harm as possible in these increasingly difficult times. International expert statements were published to offer guidance regarding proper care. It was suggested to simplify the diagnostic scheme of hypercortisolemia and to modify the approach to treatment. Hypercortisolemic patients with COVID-19 and iatrogenic hypercortisolemia due to glucocorticoid use are important clinical scenarios - we aimed to provide a cohesive summary of issues to consider.


Subject(s)
Adrenocortical Hyperfunction/therapy , COVID-19/complications , COVID-19/therapy , Adrenocortical Hyperfunction/chemically induced , Adrenocortical Hyperfunction/complications , Cushing Syndrome/complications , Cushing Syndrome/therapy , Glucocorticoids/adverse effects , Glucocorticoids/therapeutic use , Humans , Hydrocortisone/blood , Pandemics , Pituitary ACTH Hypersecretion/complications , Pituitary ACTH Hypersecretion/therapy
20.
JAMA ; 326(18): 1807-1817, 2021 11 09.
Article in English | MEDLINE | ID: covidwho-1482066

ABSTRACT

Importance: A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. Objective: To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. Design, Setting, and Participants: A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. Interventions: Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and ≥1 serious adverse reactions at 28 days). Results: Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). Conclusions and Relevance: Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT04509973 and ctri.nic.in Identifier: CTRI/2020/10/028731.


Subject(s)
COVID-19/drug therapy , Dexamethasone/administration & dosage , Glucocorticoids/administration & dosage , Life Support Care , Aged , COVID-19/complications , COVID-19/mortality , Dexamethasone/adverse effects , Dose-Response Relationship, Drug , Female , Glucocorticoids/adverse effects , Humans , Hypoxia/etiology , Hypoxia/therapy , Male , Middle Aged , Mycoses/etiology , Respiration, Artificial , Shock, Septic/etiology , Single-Blind Method
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