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1.
Chest ; 161(2): e71-e73, 2022 02.
Article in English | MEDLINE | ID: covidwho-1664778

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterized by progressive scar tissue formation. An acute exacerbation of IPF (AE-IPF) is a clinically significant respiratory decompensation that accounts for a significant proportion of IPF-related morbidity and mortality. AE-IPF can be idiopathic or associated with pulmonary embolism, infection, aspiration, surgery, and drug toxicity. In this novel case report, we describe a potential association between AE-IPF and BNT162b2 mRNA COVID-19 vaccination that was successfully treated with a short course of glucocorticoids. While our aim is to raise awareness for this yet-to-be-described adverse event, immunization against vaccine-preventable disease remains widely recommended in vulnerable patients with chronic lung disease such as IPF.


Subject(s)
COVID-19/prevention & control , Idiopathic Pulmonary Fibrosis , Lung/diagnostic imaging , Methylprednisolone/administration & dosage , Respiratory Insufficiency , Aged , /adverse effects , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , Disease Progression , Drug Tapering/methods , Glucocorticoids/administration & dosage , Humans , Idiopathic Pulmonary Fibrosis/diagnosis , Idiopathic Pulmonary Fibrosis/physiopathology , Idiopathic Pulmonary Fibrosis/therapy , Male , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/etiology , Risk Assessment/methods , SARS-CoV-2 , Tomography, X-Ray Computed/methods , Treatment Outcome
2.
Mol Biol Rep ; 49(3): 2321-2324, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1664478

ABSTRACT

Numerous studies demonstrate parallels between CVD, type 2 diabetes mellitus (T2DM) and COVID-19 pathology, which accentuate pre-existing complications in patients infected with COVID-19 and potentially exacerbate the infection course. Antidiabetic drugs such as sodium-glucose transporter-2 (SGLT-2) inhibitors have garnered substantial attention recently due to their efficacy in reducing the severity of cardiorenal disease. The effect of SGLT-2 inhibitors in patients with COVID-19 remains unclear particularly since SGLT-2 inhibitors contribute to altering the RAAS cascade activity, which includes ACE-2, the major cell entry receptor for SARS-CoV2. A study, DARE-19, was carried out to unveil the effects of SGLT-2 inhibitor treatment on comorbid disease complications and concomitant COVID-19 outcomes and demonstrated no statistical significance. However, the need for further studies is essential to provide conclusive clinical findings.


Subject(s)
Benzhydryl Compounds/therapeutic use , COVID-19/complications , Glucosides/therapeutic use , Renin-Angiotensin System/drug effects , Respiratory Insufficiency/drug therapy , SARS-CoV-2 , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Angiotensin-Converting Enzyme 2/physiology , Clinical Trials, Phase III as Topic , Double-Blind Method , Drug Repositioning , Heart Diseases/prevention & control , Humans , Kidney Diseases/prevention & control , Mitochondria/drug effects , Multicenter Studies as Topic , Oxidative Stress/drug effects , Randomized Controlled Trials as Topic , Receptors, Virus/physiology , Respiratory Insufficiency/etiology , Sodium-Glucose Transporter 2/physiology , Sodium-Glucose Transporter 2 Inhibitors/pharmacology
3.
Lancet Respir Med ; 9(12): 1427-1438, 2021 12.
Article in English | MEDLINE | ID: covidwho-1621131

ABSTRACT

BACKGROUND: Infections with SARS-CoV-2 continue to cause significant morbidity and mortality. Interleukin (IL)-1 and IL-6 blockade have been proposed as therapeutic strategies in COVID-19, but study outcomes have been conflicting. We sought to study whether blockade of the IL-6 or IL-1 pathway shortened the time to clinical improvement in patients with COVID-19, hypoxic respiratory failure, and signs of systemic cytokine release syndrome. METHODS: We did a prospective, multicentre, open-label, randomised, controlled trial, in hospitalised patients with COVID-19, hypoxia, and signs of a cytokine release syndrome across 16 hospitals in Belgium. Eligible patients had a proven diagnosis of COVID-19 with symptoms between 6 and 16 days, a ratio of the partial pressure of oxygen to the fraction of inspired oxygen (PaO2:FiO2) of less than 350 mm Hg on room air or less than 280 mm Hg on supplemental oxygen, and signs of a cytokine release syndrome in their serum (either a single ferritin measurement of more than 2000 µg/L and immediately requiring high flow oxygen or mechanical ventilation, or a ferritin concentration of more than 1000 µg/L, which had been increasing over the previous 24 h, or lymphopenia below 800/mL with two of the following criteria: an increasing ferritin concentration of more than 700 µg/L, an increasing lactate dehydrogenase concentration of more than 300 international units per L, an increasing C-reactive protein concentration of more than 70 mg/L, or an increasing D-dimers concentration of more than 1000 ng/mL). The COV-AID trial has a 2 × 2 factorial design to evaluate IL-1 blockade versus no IL-1 blockade and IL-6 blockade versus no IL-6 blockade. Patients were randomly assigned by means of permuted block randomisation with varying block size and stratification by centre. In a first randomisation, patients were assigned to receive subcutaneous anakinra once daily (100 mg) for 28 days or until discharge, or to receive no IL-1 blockade (1:2). In a second randomisation step, patients were allocated to receive a single dose of siltuximab (11 mg/kg) intravenously, or a single dose of tocilizumab (8 mg/kg) intravenously, or to receive no IL-6 blockade (1:1:1). The primary outcome was the time to clinical improvement, defined as time from randomisation to an increase of at least two points on a 6-category ordinal scale or to discharge from hospital alive. The primary and supportive efficacy endpoints were assessed in the intention-to-treat population. Safety was assessed in the safety population. This study is registered online with ClinicalTrials.gov (NCT04330638) and EudraCT (2020-001500-41) and is complete. FINDINGS: Between April 4, and Dec 6, 2020, 342 patients were randomly assigned to IL-1 blockade (n=112) or no IL-1 blockade (n=230) and simultaneously randomly assigned to IL-6 blockade (n=227; 114 for tocilizumab and 113 for siltuximab) or no IL-6 blockade (n=115). Most patients were male (265 [77%] of 342), median age was 65 years (IQR 54-73), and median Systematic Organ Failure Assessment (SOFA) score at randomisation was 3 (2-4). All 342 patients were included in the primary intention-to-treat analysis. The estimated median time to clinical improvement was 12 days (95% CI 10-16) in the IL-1 blockade group versus 12 days (10-15) in the no IL-1 blockade group (hazard ratio [HR] 0·94 [95% CI 0·73-1·21]). For the IL-6 blockade group, the estimated median time to clinical improvement was 11 days (95% CI 10-16) versus 12 days (11-16) in the no IL-6 blockade group (HR 1·00 [0·78-1·29]). 55 patients died during the study, but no evidence for differences in mortality between treatment groups was found. The incidence of serious adverse events and serious infections was similar across study groups. INTERPRETATION: Drugs targeting IL-1 or IL-6 did not shorten the time to clinical improvement in this sample of patients with COVID-19, hypoxic respiratory failure, low SOFA score, and low baseline mortality risk. FUNDING: Belgian Health Care Knowledge Center and VIB Grand Challenges program.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal/therapeutic use , COVID-19 , Cytokine Release Syndrome , Respiratory Insufficiency , Aged , Belgium , COVID-19/drug therapy , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/virology , Female , Ferritins , Humans , Hypoxia , Interleukin-1/antagonists & inhibitors , Interleukin-6/antagonists & inhibitors , Male , Middle Aged , Oxygen , Prospective Studies , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/virology , SARS-CoV-2 , Treatment Outcome
4.
Chest ; 161(3): 710-727, 2022 03.
Article in English | MEDLINE | ID: covidwho-1491838

ABSTRACT

BACKGROUND: Pulmonary vascular microthrombi are a proposed mechanism of COVID-19 respiratory failure. We hypothesized that early administration of tissue plasminogen activator (tPA) followed by therapeutic heparin would improve pulmonary function in these patients. RESEARCH QUESTION: Does tPA improve pulmonary function in severe COVID-19 respiratory failure, and is it safe? STUDY DESIGN AND METHODS: Adults with COVID-19-induced respiratory failure were randomized from May14, 2020 through March 3, 2021, in two phases. Phase 1 (n = 36) comprised a control group (standard-of-care treatment) vs a tPA bolus (50-mg tPA IV bolus followed by 7 days of heparin; goal activated partial thromboplastin time [aPTT], 60-80 s) group. Phase 2 (n = 14) comprised a control group vs a tPA drip (50-mg tPA IV bolus, followed by tPA drip 2 mg/h plus heparin 500 units/h over 24 h, then heparin to maintain aPTT of 60-80 s for 7 days) group. Patients were excluded from enrollment if they had not undergone a neurologic examination or cross-sectional brain imaging within the previous 4.5 h to rule out stroke and potential for hemorrhagic conversion. The primary outcome was Pao2 to Fio2 ratio improvement from baseline at 48 h after randomization. Secondary outcomes included Pao2 to Fio2 ratio improvement of > 50% or Pao2 to Fio2 ratio of ≥ 200 at 48 h (composite outcome), ventilator-free days (VFD), and mortality. RESULTS: Fifty patients were randomized: 17 in the control group and 19 in the tPA bolus group in phase 1 and eight in the control group and six in the tPA drip group in phase 2. No severe bleeding events occurred. In the tPA bolus group, the Pao2 to Fio2 ratio values were significantly (P < .017) higher than baseline at 6 through 168 h after randomization; the control group showed no significant improvements. Among patients receiving a tPA bolus, the percent change of Pao2 to Fio2 ratio at 48 h (16.9% control [interquartile range (IQR), -8.3% to 36.8%] vs 29.8% tPA bolus [IQR, 4.5%-88.7%]; P = .11), the composite outcome (11.8% vs 47.4%; P = .03), VFD (0.0 [IQR, 0.0-9.0] vs 12.0 [IQR, 0.0-19.0]; P = .11), and in-hospital mortality (41.2% vs 21.1%; P = .19) did not reach statistically significant differences when compared with those of control participants. The patients who received a tPA drip did not experience benefit. INTERPRETATION: The combination of tPA bolus plus heparin is safe in severe COVID-19 respiratory failure. A phase 3 study is warranted given the improvements in oxygenation and promising observations in VFD and mortality. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04357730; URL: www. CLINICALTRIALS: gov.


Subject(s)
COVID-19/complications , Pandemics , Respiratory Insufficiency/drug therapy , SARS-CoV-2 , Thrombosis/complications , Tissue Plasminogen Activator/administration & dosage , Adolescent , Adult , Aged , COVID-19/blood , COVID-19/epidemiology , Cross-Sectional Studies , Female , Fibrinolytic Agents/administration & dosage , Follow-Up Studies , Humans , Male , Middle Aged , Partial Thromboplastin Time , Respiratory Insufficiency/blood , Respiratory Insufficiency/etiology , Retrospective Studies , Thrombosis/blood , Thrombosis/drug therapy , Treatment Outcome , Young Adult
6.
J Med Virol ; 93(9): 5432-5437, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1363681

ABSTRACT

This case series describes three patients affected by severe acute respiratory syndrome coronavirus 2, who developed polyradiculoneuritis as a probable neurological complication of coronavirus disease 2019 (COVID-19). A diagnosis of Guillain Barré syndrome was made on the basis of clinical symptoms, cerebrospinal fluid analysis, and electroneurography. In all of them, the therapeutic approach included the administration of intravenous immunoglobulin (0.4 gr/kg for 5 days), which resulted in the improvement of neurological symptoms. Clinical neurophysiology revealed the presence of conduction block, absence of F waves, and in two cases, a significant decrease in amplitude of compound motor action potential cMAP. Due to the potential role of inflammation on symptoms development and prognosis, interleukin-6 (IL-6) and IL-8 levels were measured in serum and cerebrospinal fluid during the acute phase, while only serum was tested after recovery. Both IL-6 and IL-8 were found increased during the acute phase, both in the serum and cerebrospinal fluid, whereas 4 months after admission (at complete recovery), only IL-8 remained elevated in the serum. These results confirm the inflammatory response that might be linked to peripheral nervous system complications and encourage the use of IL-6 and IL-8 as prognostic biomarkers in COVID-19.


Subject(s)
COVID-19/complications , Guillain-Barre Syndrome/complications , Interleukin-6/cerebrospinal fluid , Interleukin-8/cerebrospinal fluid , Respiratory Insufficiency/complications , SARS-CoV-2/pathogenicity , Action Potentials/drug effects , Acute Disease , Aged , Anti-Bacterial Agents/therapeutic use , Biomarkers/blood , Biomarkers/cerebrospinal fluid , COVID-19/cerebrospinal fluid , COVID-19/drug therapy , COVID-19/virology , Convalescence , Darunavir/therapeutic use , Drug Combinations , Guillain-Barre Syndrome/cerebrospinal fluid , Guillain-Barre Syndrome/drug therapy , Guillain-Barre Syndrome/virology , Humans , Hydroxychloroquine/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Interleukin-6/blood , Interleukin-8/blood , Lopinavir/therapeutic use , Male , Neural Conduction/drug effects , Peripheral Nervous System/drug effects , Peripheral Nervous System/pathology , Peripheral Nervous System/virology , Prognosis , Respiratory Insufficiency/cerebrospinal fluid , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/virology , Ritonavir/therapeutic use , SARS-CoV-2/drug effects
7.
J Med Virol ; 93(9): 5416-5424, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1363679

ABSTRACT

The kinetics of IgG antibodies after coronavirus disease 2019 (COVID-19) remain poorly understood. We investigated factors influencing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibody levels and time to seronegativation during the follow-up of severe and critically ill patients. We retrospectively reviewed serological evaluations drawn during the follow-up of severe or critical laboratory-proven COVID-19 patients hospitalized at a large academic hospital. Specific IgG titers were measured using a chemiluminescent assay targeting anti-spike and anti-nucleocapsid protein IgG. The influence of time, demographic factors, clinical and paraclinical characteristics, and COVID-19 therapeutics on IgG levels were assessed through linear regression using a mixed-effect model, and delay until IgG negativation through a Weibull regression model. The cohort included 116 patients with a total of 154 IgG measurements drawn at a median of 79 days after diagnosis. IgG antibodies were increased with age (p = 0.005) and decreased significantly over time (p = 0.0002). Using elapsed time and age as covariates, we demonstrated higher IgG levels in patients with a higher body mass index (BMI) (p = 0.0026) and lower IgG levels in immunocompromised patients (p = 0.032). A high BMI was further found to delay and immunodeficiency to hasten significantly seronegativation, whereas no significant effect was observed with corticosteroids. These data highlight the waning over time of IgG antibodies after severe or critical COVID-19. Age, BMI, and immunosuppression also appear to influence the IgG kinetics, while short-term corticotherapy does not. Those data improve the understanding of SARS-CoV-2 serology while further research should determine the determinants of long-term seroprotection.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Immunocompromised Host , Immunoglobulin G/blood , Respiratory Insufficiency/immunology , SARS-CoV-2/immunology , Adrenal Cortex Hormones/therapeutic use , Aged , Body Mass Index , COVID-19/blood , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19 Serological Testing , Convalescence , Female , Humans , Hydroxychloroquine/therapeutic use , Male , Middle Aged , Respiratory Insufficiency/blood , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/drug therapy , Retrospective Studies , Sensitivity and Specificity , Severity of Illness Index , Time Factors
8.
Respir Med ; 187: 106571, 2021 10.
Article in English | MEDLINE | ID: covidwho-1347816

ABSTRACT

Since the beginning of COVID-19 pandemic, clinical, radiological and histopathological features consistent with viral-induced organizing pneumonia (OP) have been reported as hallmark characteristics of the disease. Here, we describe the case of ten patients with severe COVID-19 pneumonia treated with methylprednisolone 1mg/kg for showing clinical and radiological features suggestive of OP at least 20 days after symptom onset and despite standard treatment for COVID-19.


Subject(s)
COVID-19/complications , COVID-19/therapy , Dexamethasone/administration & dosage , Glucocorticoids/administration & dosage , Methylprednisolone/administration & dosage , Respiratory Insufficiency/drug therapy , Aged , Drug Administration Schedule , Drug Therapy, Combination , Female , Humans , Male , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/virology
9.
Ann Pharmacother ; 56(3): 237-244, 2022 03.
Article in English | MEDLINE | ID: covidwho-1285161

ABSTRACT

BACKGROUND: Severe hypoxic respiratory failure from COVID-19 pneumonia carries a high mortality risk. There is uncertainty surrounding which patients benefit from corticosteroids in combination with tocilizumab and the dosage and timing of these agents. The balance of controlling inflammation without increasing the risk of secondary infection is difficult. At present, dexamethasone 6 mg is the standard of care in COVID-19 hypoxia; whether this is the ideal choice of steroid or dosage remains to be proven. OBJECTIVES: The primary objective was to assess the impact on mortality of tocilizumab only, corticosteroids only, and combination therapy in patients with COVID-19 respiratory failure. METHODS: A multihospital, retrospective study of adult patients with severe respiratory failure from COVID-19 who received supportive therapy, corticosteroids, tocilizumab, or combination therapy were assessed for 28-day mortality, biomarker improvement, and relative risk of infection. Propensity-matched analysis was performed between corticosteroid alone and combination therapies to further assess mortality benefit. RESULTS: The steroid-only, tocilizumab-only, and combination groups showed hazard reduction in mortality at 28 days when compared with supportive therapy. In a propensity-matched analysis, the combination group (daily equivalent dexamethasone 10 mg and tocilizumab 400 mg) had an improved 28-day mortality compared with the steroid-only group (daily equivalent dexamethasone 10 mg; hazard ratio (95% CI) = 0.56 (0.38-0.84), P = 0.005] without increasing the risk of infection. CONCLUSION AND RELEVANCE: Combination of tocilizumab and corticosteroids was associated with improved 28-day survival when compared with corticosteroids alone. Modification of steroid dosing strategy as well as steroid type may further optimize therapeutic effect of the COVID-19 treatment.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19 , Respiratory Insufficiency , Adult , COVID-19/drug therapy , COVID-19/mortality , Hospital Mortality , Humans , Hypoxia/drug therapy , Hypoxia/virology , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/virology , Retrospective Studies , Treatment Outcome
10.
Acta Haematol ; 144(6): 620-626, 2021.
Article in English | MEDLINE | ID: covidwho-1263968

ABSTRACT

INTRODUCTION: Currently, severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is a major public health problem worldwide. Although most patients present a mild infection, effective strategies are required for patients who develop the severe disease. Anti-inflammatory treatment with JAK inhibitors has been considered in SARS-CoV-2. METHODS: In this study, we presented our experience in a group of severe SARS-CoV-2 Chilean patients. This prospective study was performed on consecutive patients presenting severe respiratory failure owing to COVID-19 or high-risk clinical condition associated with SARS-CoV-2, and who were treated with ruxolitinib for management of associated inflammation. Overall, 18 patients presenting SARS-CoV-2 viral-induced hyperinflammation were treated with ruxolitinib, with 16 patients previously treated with steroids, 4 with tocilizumab, and 3 with both treatments. RESULTS: Ten patients evolved with favorable response, including 7 patients admitted with severe respiratory failure (PaFi less than 200 mm Hg in high-flow nasal cannula), presenting complete regression of hyperinflammation, regression of the lung lesions, and subsequent discharge. In the remaining 8 patients, 25% showed reduced inflammation, but early discharge was not achieved owing to the slow evolution of respiratory failure. Unfortunately, 3 patients demonstrated a severe respiratory failure. The early initiation of ruxolitinib was found to be associated with better clinical evolution (p < 0.005). CONCLUSION: In this study, ruxolitinib resolved hyperinflammatory state in 55% of the patients, regardless of the previous steroid or tocilizumab therapy. Unfortunately, few patients demonstrated severe evolution despite ruxolitinib therapy. Notably, the treatment starting time appears to play an important role in achieving good outcomes. Further validation in randomized controlled trials is crucial.


Subject(s)
COVID-19/complications , Inflammation/drug therapy , Nitriles/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/pathology , COVID-19/virology , Chile , Female , Humans , Inflammation/etiology , Male , Middle Aged , Nitriles/adverse effects , Prospective Studies , Protein Kinase Inhibitors/adverse effects , Pyrazoles/adverse effects , Pyrimidines/adverse effects , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/etiology , SARS-CoV-2/isolation & purification , Steroids/therapeutic use , Thrombocytopenia/etiology , Treatment Outcome
11.
J Med Virol ; 93(9): 5432-5437, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1258081

ABSTRACT

This case series describes three patients affected by severe acute respiratory syndrome coronavirus 2, who developed polyradiculoneuritis as a probable neurological complication of coronavirus disease 2019 (COVID-19). A diagnosis of Guillain Barré syndrome was made on the basis of clinical symptoms, cerebrospinal fluid analysis, and electroneurography. In all of them, the therapeutic approach included the administration of intravenous immunoglobulin (0.4 gr/kg for 5 days), which resulted in the improvement of neurological symptoms. Clinical neurophysiology revealed the presence of conduction block, absence of F waves, and in two cases, a significant decrease in amplitude of compound motor action potential cMAP. Due to the potential role of inflammation on symptoms development and prognosis, interleukin-6 (IL-6) and IL-8 levels were measured in serum and cerebrospinal fluid during the acute phase, while only serum was tested after recovery. Both IL-6 and IL-8 were found increased during the acute phase, both in the serum and cerebrospinal fluid, whereas 4 months after admission (at complete recovery), only IL-8 remained elevated in the serum. These results confirm the inflammatory response that might be linked to peripheral nervous system complications and encourage the use of IL-6 and IL-8 as prognostic biomarkers in COVID-19.


Subject(s)
COVID-19/complications , Guillain-Barre Syndrome/complications , Interleukin-6/cerebrospinal fluid , Interleukin-8/cerebrospinal fluid , Respiratory Insufficiency/complications , SARS-CoV-2/pathogenicity , Action Potentials/drug effects , Acute Disease , Aged , Anti-Bacterial Agents/therapeutic use , Biomarkers/blood , Biomarkers/cerebrospinal fluid , COVID-19/cerebrospinal fluid , COVID-19/drug therapy , COVID-19/virology , Convalescence , Darunavir/therapeutic use , Drug Combinations , Guillain-Barre Syndrome/cerebrospinal fluid , Guillain-Barre Syndrome/drug therapy , Guillain-Barre Syndrome/virology , Humans , Hydroxychloroquine/therapeutic use , Immunoglobulins, Intravenous/therapeutic use , Interleukin-6/blood , Interleukin-8/blood , Lopinavir/therapeutic use , Male , Neural Conduction/drug effects , Peripheral Nervous System/drug effects , Peripheral Nervous System/pathology , Peripheral Nervous System/virology , Prognosis , Respiratory Insufficiency/cerebrospinal fluid , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/virology , Ritonavir/therapeutic use , SARS-CoV-2/drug effects
12.
Crit Care ; 25(1): 178, 2021 05 25.
Article in English | MEDLINE | ID: covidwho-1243817

ABSTRACT

A growing consensus seems to be emerging that dexamethasone is a crucial component in the treatment of COVID-19-associated oxygen-dependent respiratory failure. Although dexamethasone has an undeniably beneficial effect on the inflammatory response in a subgroup of patients, the potential negative effects of corticosteroids must also be considered. In view of these negative effects, we argue that a one-size-fits-all dexamethasone approach may be potentially harmful in specific subsets of patients with COVID-19-associated ARDS. We propose a different individually tailored treatment strategy based on the patient's inflammatory response.


Subject(s)
COVID-19/drug therapy , Critical Care/methods , Dexamethasone/therapeutic use , Inflammation/prevention & control , Respiratory Insufficiency/drug therapy , COVID-19/complications , Dexamethasone/adverse effects , Humans , Intensive Care Units , Respiratory Insufficiency/virology , Treatment Outcome
13.
BMC Infect Dis ; 21(1): 427, 2021 May 07.
Article in English | MEDLINE | ID: covidwho-1219337

ABSTRACT

PURPOSE: Hyperinflammation in severe COVID-19 infection increases the risk of respiratory failure and one of the cogent reasons of mortality associated with COVID-19. Baricitinib, a janus kinases inhibitor, can potentially suppress inflammatory cascades in severe COVID-19 pneumonia. METHODS: The objective of this study was to compare the clinical outcomes of high dose of baricitinib with its usual dose in patients with severe COVID-19 pneumonia. This prospective cohort study was conducted on 238 adult patients with severe COVID-19 pneumonia. Eight milligram and 4 mg of baricitinib was given orally to 122 patients in the high dose (HD) group and 116 patients the usual dose (UD) group, respectively daily for 14 days, and clinical outcomes were compared among the groups. RESULTS: Blood oxygen saturation level was stabilized (≥94% on room air) earlier in the HD group compared to the UD group [5 (IQR: 4-5)/8 (IQR: 6-9), P < 0.05]. Patients in the HD group required intensive care unit (ICU) and intubation supports more in the UD group than that in patients of the HD group [17.2%/9%, P < 0.05; 11.2%/4.1%, P > 0.05; N = 116/122, respectively]. The 30-day mortality and 60-day rehospitalization rate were higher in the UD group than the HD group [6%/3.3%, P < 0.01; 11.9%/7.6%, P > 0.05; N = 116/122, respectively]. CONCLUSION: The daily high dose of baricitinib in severe COVID-19 results in early stabilization of the respiratory functions, declined requirements of critical care supports, reduced rehospitalization with mortality rate compared to its daily usual dose.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Azetidines/administration & dosage , COVID-19/drug therapy , Purines/administration & dosage , Pyrazoles/administration & dosage , Sulfonamides/administration & dosage , Administration, Oral , Aged , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Azetidines/therapeutic use , Bangladesh , COVID-19/mortality , Comorbidity , Critical Care , Female , Hospital Mortality , Humans , Male , Middle Aged , Patient Readmission , Prospective Studies , Purines/therapeutic use , Pyrazoles/therapeutic use , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/virology , Sulfonamides/therapeutic use , Treatment Outcome
14.
Clin Exp Hypertens ; 43(7): 587-596, 2021 Oct 03.
Article in English | MEDLINE | ID: covidwho-1217770

ABSTRACT

INTRODUCTION: We have aimed to investigate the relationship between use of angiotensin-converting-enzyme inhibitor (ACEI) or angiotensin-receptor-blocker (ARB) drugs and acute hypoxemic respiratory failure (AHRF) and in-hospital mortality in hypertensive Covid-19 patients. MATERIAL AND METHOD: Consecutive 1345 patients diagnosed with Covid-19 between April and October 2020 who met inclusion criteria were divided into two groups based on presence and absence of AHRF and mortality. The groups were compared regarding epidemiological, clinical, radiological, laboratory findings and treatments methods. The patient groups ACEI, ARB and other antihypertensive drugs (non-ACEI/ARB) were compared regarding same parameters. RESULTS: Median age was 68 (60-76) years in the patient group including 805 (59.9.1%) females. Of the patients, 475 (35.3%), 644 (47.9%) and 226 (16.8%) were using ACEIs, ARBs and non-ACEI/ARB, respectively. AHRF and in-hospital mortality developed in 1053 (78.3%) and 290 (21.6%) patients, respectively. Age, gender, coronary artery disease, diabetes mellitus (DM), neutrophil, lymphocyte, creatinine, D-dimer, C-reactive protein (CRP), ACEI, beta blocker and aspartate transaminase (AST) found statistically significant in the univariable logistic regression performed to identify independent predictors of mortality were included multivariable logistic regression model. Age (OR: 1.066, 95%CI: 1.049-1.083; p < .001), DM (OR: 1.682, 95%CI: 1.238-2.286; p = .001), neutrophil (OR: 1.041, 95%CI: 1.007-1.077; p = .019), creatinine (OR: 1.178, 95%CI: 1.048-1.325; p = .006), CRP (OR: 1.008, 95%CI: 1.006-1.010; p < .001), ACEI (OR: 0.718, 95%CI: 0.521-0.988; p = .042), AST (OR: 1.005, 95%CI: 1.001-1.010; p = .010) were found associated with in-hospital mortality. CONCLUSION: In our study, it was not detected clinically significant difference between three groups with regard to their relation with in-hospital mortality.


Subject(s)
Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors , COVID-19 , Hospital Mortality , Hypertension , Respiratory Insufficiency , Aged , Angiotensin Receptor Antagonists/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/drug therapy , COVID-19/mortality , Female , Humans , Hypertension/drug therapy , Male , Middle Aged , Renin-Angiotensin System , Respiratory Insufficiency/drug therapy , Retrospective Studies
15.
Carbohydr Res ; 505: 108326, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1213065

ABSTRACT

The viral infection caused by SARS-CoV-2 has increased the mortality rate and engaged several adverse effects on the affected individuals. Currently available antiviral drugs have found to be unsuccessful in the treatment of COVID-19 patients. The demand for efficient antiviral drugs has created a huge burden on physicians and health workers. Plasma therapy seems to be less accomplishable due to insufficient donors to donate plasma and low recovery rate from viral infection. Repurposing of antivirals has been evolved as a suitable strategy in the current treatment and preventive measures. The concept of drug repurposing represents new experimental approaches for effective therapeutic benefits. Besides, SARS-CoV-2 exhibits several complications such as lung damage, blood clot formation, respiratory illness and organ failures in most of the patients. Based on the accumulation of data, sulfated marine polysaccharides have exerted successful inhibition of virus entry, attachment and replication with known or unknown possible mechanisms against deadly animal and human viruses so far. Since the virus entry into the host cells is the key process, the prevention of such entry mechanism makes any antiviral strategy effective. Enveloped viruses are more sensitive to polyanions than non-enveloped viruses. Besides, the viral infection caused by RNA virus types embarks severe oxidative stress in the human body that leads to malfunction of tissues and organs. In this context, polysaccharides play a very significant role in providing shielding effect against the virus due to their polyanionic rich features and a molecular weight that hinders their reactive surface glycoproteins. Significantly the functional groups especially sulfate, sulfate pattern and addition, uronic acids, monosaccharides, glycosidic linkage and high molecular weight have greater influence in the antiviral activity. Moreover, they are very good antioxidants that can reduce the free radical generation and provokes intracellular antioxidant enzymes. Additionally, polysaccharides enable a host-virus immune response, activate phagocytosis and stimulate interferon systems. Therefore, polysaccharides can be used as candidate drugs, adjuvants in vaccines or combination with other antivirals, antioxidants and immune-activating nutritional supplements and antiviral materials in healthcare products to prevent SARS-CoV-2 infection.


Subject(s)
Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Immunologic Factors/therapeutic use , Polysaccharides/therapeutic use , Pulmonary Embolism/drug therapy , Respiratory Insufficiency/drug therapy , Anticoagulants/chemistry , Anticoagulants/isolation & purification , Antiviral Agents/chemistry , Antiviral Agents/isolation & purification , Blood Platelets/drug effects , Blood Platelets/pathology , Blood Platelets/virology , COVID-19/complications , COVID-19/diagnosis , COVID-19/virology , Humans , Immunologic Factors/chemistry , Immunologic Factors/isolation & purification , Lung/blood supply , Lung/drug effects , Lung/pathology , Lung/virology , Phaeophyta/chemistry , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Pulmonary Embolism/complications , Pulmonary Embolism/diagnosis , Pulmonary Embolism/virology , Respiratory Insufficiency/complications , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/virology , Rhodophyta/chemistry , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , Sulfuric Acid Esters/chemistry , Virus Attachment/drug effects , Virus Internalization/drug effects
16.
Crit Care Med ; 49(6): e624-e633, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1191503

ABSTRACT

OBJECTIVES: No standard therapy, including anticoagulation regimens, is currently recommended for coronavirus disease 2019. Aim of this study was to evaluate the efficacy of anticoagulation in coronavirus disease 2019 hospitalized patients and its impact on survival. DESIGN: Multicenter international prospective registry (Health Outcome Predictive Evaluation for Corona Virus Disease 2019). SETTING: Hospitalized patients with coronavirus disease 2019. PATIENTS: Five thousand eight hundred thirty-eight consecutive coronavirus disease 2019 patients. INTERVENTIONS: Anticoagulation therapy, including prophylactic and therapeutic regimens, was obtained for each patient. MEASUREMENTS AND MAIN RESULTS: Five thousand four hundred eighty patients (94%) did not receive any anticoagulation before hospitalization. Two-thousand six-hundred one patients (44%) during hospitalization received anticoagulation therapy and it was not associated with better survival rate (81% vs 81%; p = 0.94) but with higher risk of bleeding (2.7% vs 1.8%; p = 0.03). Among patients admitted with respiratory failure (49%, n = 2,859, including 391 and 583 patients requiring invasive and noninvasive ventilation, respectively), anticoagulation started during hospitalization was associated with lower mortality rates (32% vs 42%; p < 0.01) and nonsignificant higher risk of bleeding (3.4% vs 2.7%; p = 0.3). Anticoagulation therapy was associated with lower mortality rates in patients treated with invasive ventilation (53% vs 64%; p = 0.05) without increased rates of bleeding (9% vs 8%; p = 0.88) but not in those with noninvasive ventilation (35% vs 38%; p = 0.40). At multivariate Cox' analysis mortality relative risk with anticoagulation was 0.58 (95% CI, 0.49-0.67) in patients admitted with respiratory failure, 0.50 (95% CI, 0.49-0.67) in those requiring invasive ventilation, 0.72 (95% CI, 0.51-1.01) in noninvasive ventilation. CONCLUSIONS: Anticoagulation therapy in general population with coronavirus disease 2019 was not associated with better survival rates but with higher bleeding risk. Better results were observed in patients admitted with respiratory failure and requiring invasive ventilation.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/drug therapy , Outcome Assessment, Health Care , Registries , COVID-19/mortality , Case-Control Studies , Correlation of Data , Cross-Cultural Comparison , Hemorrhage/chemically induced , Hemorrhage/mortality , Hospitalization , Humans , Multicenter Studies as Topic , Prospective Studies , Respiration, Artificial , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/mortality , Risk , Survival Rate , Treatment Outcome
17.
Diabetes Obes Metab ; 23(4): 886-896, 2021 04.
Article in English | MEDLINE | ID: covidwho-1171152

ABSTRACT

AIMS: Coronavirus disease 2019 (COVID-19) is caused by a novel severe acute respiratory syndrome coronavirus 2. It can lead to multiorgan failure, including respiratory and cardiovascular decompensation, and kidney injury, with significant associated morbidity and mortality, particularly in patients with underlying metabolic, cardiovascular, respiratory or kidney disease. Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, has shown significant cardio- and renoprotective benefits in patients with type 2 diabetes (with and without atherosclerotic cardiovascular disease), heart failure and chronic kidney disease, and may provide similar organ protection in high-risk patients with COVID-19. MATERIALS AND METHODS: DARE-19 (NCT04350593) is an investigator-initiated, collaborative, international, multicentre, randomized, double-blind, placebo-controlled study testing the dual hypotheses that dapagliflozin can reduce the incidence of cardiovascular, kidney and/or respiratory complications or all-cause mortality, or improve clinical recovery, in adult patients hospitalized with COVID-19 but not critically ill on admission. Eligible patients will have ≥1 cardiometabolic risk factor for COVID-19 complications. Patients will be randomized 1:1 to dapagliflozin 10 mg or placebo. Primary efficacy endpoints are time to development of new or worsened organ dysfunction during index hospitalization, or all-cause mortality, and the hierarchical composite endpoint of change in clinical status through day 30 of treatment. Safety of dapagliflozin in individuals with COVID-19 will be assessed. CONCLUSIONS: DARE-19 will evaluate whether dapagliflozin can prevent COVID-19-related complications and all-cause mortality, or improve clinical recovery, and assess the safety profile of dapagliflozin in this patient population. Currently, DARE-19 is the first large randomized controlled trial investigating use of sodium-glucose cotransporter 2 inhibitors in patients with COVID-19.


Subject(s)
Benzhydryl Compounds/therapeutic use , COVID-19/drug therapy , Cardiovascular Diseases/prevention & control , Glucosides/therapeutic use , Kidney Diseases/prevention & control , Mortality , Respiratory Insufficiency/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Atherosclerosis/epidemiology , COVID-19/complications , COVID-19/epidemiology , Cardiometabolic Risk Factors , Cardiovascular Diseases/etiology , Cause of Death , Comorbidity , Diabetes Mellitus, Type 2/epidemiology , Disease Progression , Double-Blind Method , Heart Failure/epidemiology , Humans , Hypertension/epidemiology , Kidney Diseases/etiology , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Renal Insufficiency, Chronic/epidemiology , Respiratory Insufficiency/etiology , SARS-CoV-2 , Treatment Outcome
18.
Ann Intern Med ; 174(2): JC16, 2021 02.
Article in English | MEDLINE | ID: covidwho-1110694

ABSTRACT

SOURCE CITATION: Stone JH, Frigault MJ, Serling-Boyd NJ, et al. Efficacy of tocilizumab in patients hospitalized with Covid-19. N Engl J Med. 2020;383:2333-44. 33085857.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , Respiratory Insufficiency/drug therapy , Adult , Aged , Aged, 80 and over , COVID-19/mortality , Female , Humans , Male , Middle Aged , Multicenter Studies as Topic , Randomized Controlled Trials as Topic , Respiratory Insufficiency/mortality , Respiratory Insufficiency/virology , SARS-CoV-2
19.
Pan Afr Med J ; 35(Suppl 2): 130, 2020.
Article in English | MEDLINE | ID: covidwho-1106476

ABSTRACT

The COVID-19 pandemic has strained health care systems beyond capacity resulting in many people not having access to life-sustaining measures even in well-resourced countries. Palliative and end-of-life care are therefore essential to alleviate suffering and ensure a continuum of care for patients unlikely to survive. This is challenging in sub-Saharan Africa where lack of trained teams on basic palliative care and reduced access to opioids limit implementation of palliative and end-of-life care. At the same time, health care providers have to cope with local cultural conceptions of death and absence of advance care directives.


Subject(s)
Betacoronavirus , Coronavirus Infections/therapy , Palliative Care/organization & administration , Pandemics , Pneumonia, Viral/therapy , Terminal Care/organization & administration , Advance Directives , Africa South of the Sahara/epidemiology , Analgesics, Opioid/supply & distribution , Analgesics, Opioid/therapeutic use , Attitude to Death , COVID-19 , Communication Barriers , Continuity of Patient Care , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/psychology , Culture , Health Services Accessibility , Humans , Palliative Care/psychology , Pneumonia, Viral/epidemiology , Pneumonia, Viral/psychology , Professional-Patient Relations , Respiratory Insufficiency/drug therapy , Respiratory Insufficiency/etiology , Respiratory Insufficiency/mortality , SARS-CoV-2 , Social Stigma , Terminal Care/psychology
20.
Intern Med ; 60(4): 639-643, 2021 Feb 15.
Article in English | MEDLINE | ID: covidwho-1082267

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has become an urgent global health issue. An older age and underlying conditions, such as diabetes, have been reported as risk factors, but whether or not autoimmune diseases increase the risk remains unknown. An 85-year-old man with Sjögren's syndrome developed a severe COVID-19 infection that required oxygen supplementation. After discussing the goals of care with him and his wife, off-label tocilizumab was given concomitantly, resulting in a rapid improvement in his symptoms and respiratory failure. This patient represents a supplementary case confirming the efficacy and safety of tocilizumab for COVID-19 in elderly patients with autoimmune diseases.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/complications , Off-Label Use , Respiratory Distress Syndrome/drug therapy , Sjogren's Syndrome/complications , Adrenal Cortex Hormones/therapeutic use , Aged, 80 and over , Anti-Inflammatory Agents/therapeutic use , COVID-19/immunology , Cytokine Release Syndrome , Drug Therapy, Combination , Dyspnea/etiology , Humans , Male , Pandemics , Respiratory Distress Syndrome/etiology , Respiratory Insufficiency/drug therapy , SARS-CoV-2
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