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2.
Inflamm Res ; 72(4): 875-878, 2023 Apr.
Article in English | MEDLINE | ID: covidwho-2315746

ABSTRACT

BACKGROUND: Hypereosinophilic dermatitis (HED) is a subtype of hypereosinophilic syndrome (HES). Glucocorticoids are preferred for treatment but carry substantial side effect profiles. Symptoms of HED may recur after systemic glucocorticoid tapering. As an interleukin-4 receptor (IL-4Rα) monoclonal antibody targeting interleukin-4 (IL-4) and interleukin-13 (IL-13), dupilumab might be an efficacious adjuvant therapy for HED. METHOD: We report a young male diagnosed with HED who suffered from erythematous papules with pruritus for over five years. Once reducing the dosage of glucocorticoid was, his skin lesions relapsed. RESULTS: After using dupilumab, the patient's condition significantly improved with the glucocorticoid dosing decreased successfully. CONCLUSION: In conclusion, we report a new application of dupilumab in HED patients, especially with difficulties in reducing the glucocorticoid dose.


Subject(s)
Dermatitis, Atopic , Glucocorticoids , Humans , Male , Glucocorticoids/therapeutic use , Dermatitis, Atopic/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal/therapeutic use , Interleukin-13 , Treatment Outcome
3.
BMC Infect Dis ; 23(1): 290, 2023 May 05.
Article in English | MEDLINE | ID: covidwho-2315408

ABSTRACT

OBJECTIVE: The preferred agent of glucocorticoids in the treatment of patients with severe COVID-19 is still controversial. This study aimed to compare the efficacy and safety of methylprednisolone and dexamethasone in the treatment of patients with severe COVID-19. METHODS: By searching the electronic literature database including PubMed, Cochrane Central Register of Controlled Trials, and Web of Science, the clinical studies comparing methylprednisolone and dexamethasone in the treatment of severe COVID-19 were selected according to the inclusion criteria and exclusion criteria. Relevant data were extracted and literature quality was assessed. The primary outcome was short-term mortality. The secondary outcomes were the rates of ICU admission and mechanical ventilation, PaO2/FiO2 ratio, plasma levels of C-reactive protein (CRP), ferritin, and neutrophil/lymphocyte ratio, hospital stay, and the incidence of severe adverse events. Statistical pooling applied the fixed or random effects model and reported as risk ratio (RR) or mean difference (MD) with the corresponding 95% confidence interval (CI). Meta-analysis was performed using Review Manager 5.1.0. RESULTS: Twelve clinical studies were eligible, including three randomized controlled trials (RCTs) and nine non-RCTs. A total of 2506 patients with COVID-19 were analyzed, of which 1242 (49.6%) received methylprednisolone and 1264 (50.4%) received dexamethasone treatment. In general, the heterogeneity across studies was significant, and the equivalent doses of methylprednisolone were higher than that of dexamethasone. Our meta-analysis showed that methylprednisolone treatment in severe COVID-19 patients was related to significantly reduced plasma ferritin and neutrophil/lymphocyte ratio compared with dexamethasone, and that no significant difference in other clinical outcomes between the two groups was found. However, subgroup analyses of RCTs demonstrated that methylprednisolone treatment was associated with reduced short-term mortality, and decreased CRP level compared with dexamethasone. Moreover, subgroup analyses observed that severe COVID-19 patients treated with a moderate dose (2 mg/kg/day) of methylprednisolone were related to a better prognosis than those treated with dexamethasone. CONCLUSIONS: This study showed that compared with dexamethasone, methylprednisolone could reduce the systemic inflammatory response in severe COVID-19, and its effect was equivalent to that of dexamethasone on other clinical outcomes. It should be noted that the equivalent dose of methylprednisolone used was higher. Based on the evidence of subgroup analyses of RCTs, methylprednisolone, preferably at a moderate dose, has an advantage over dexamethasone in the treatment of patients with severe COVID-19.


Subject(s)
COVID-19 , Glucocorticoids , Humans , Glucocorticoids/therapeutic use , Methylprednisolone/therapeutic use , COVID-19 Drug Treatment , Dexamethasone/therapeutic use
4.
BMJ Case Rep ; 16(5)2023 May 16.
Article in English | MEDLINE | ID: covidwho-2315176

ABSTRACT

Organising pneumonia after a mild COVID-19 infection has been increasingly reported and poses a diagnostic challenge to physicians especially in immunocompromised patients. We report a patient with a background of lymphoma in remission on rituximab who presented with prolonged and persistent fever after recovering from a mild COVID-19 infection. The initial workup showed bilateral lower zone lung consolidation; however, the infective and autoimmune workup were unremarkable. Subsequently, a bronchoscopy with transbronchial lung biopsy confirmed the diagnosis of organising pneumonia. A tapering glucocorticoid regimen was commenced with prompt resolution of the patient's clinical symptoms, and subsequent resolution of biochemical markers and radiological lung changes 3 months later. This case highlights the importance of early recognition of the diagnosis of organising pneumonia in immunocompromised populations after a mild COVID-19 infection as it shows promising response to glucocorticoid therapy.


Subject(s)
COVID-19 , Organizing Pneumonia , Pneumonia , Humans , COVID-19/pathology , Glucocorticoids/therapeutic use , Pneumonia/drug therapy , Lung/pathology , Immunocompromised Host
6.
Front Endocrinol (Lausanne) ; 13: 1031188, 2022.
Article in English | MEDLINE | ID: covidwho-2311206

ABSTRACT

COVID-19 often results in generalized inflammation and affects various organs and systems. Endocrine research focused on the possible sequelae of COVID-19, with special interest given to the thyroid gland. Clinical problems such as thyroid function in non-thyroidal illness (NTI), autoimmune thyroiditis, and COVID-19-related subacute thyroiditis (SAT) quickly gained wide coverage. Thyrotoxicosis of various origins leads to the release of peripheral thyroid hormones and thyroglobulin (TG), the main glycoprotein contained within the thyroid follicular lumen. In our study, we evaluated TG levels in COVID-19-positive patients and investigated the possible relationships between TG, thyroid function tests (TFTs), and inflammatory markers. Our approach included separate subanalyses of patients who received and those who did not receive glucocorticoids (GCs). In the entire population studied, the concentration of TG tended to decrease with time (p<0.001; p1,2 = 0.025, p1,3 = 0.001, p2,3 = 0.003), and this pattern was especially clear among patients treated with GCs (p<0.001; p1,2=<0.001; p1,3=<0.001; p 2,3=<0.001). The concentration of TG differed significantly between patients treated and those not treated with GC at the second and third time points of observation (p=0.033 and p=0.001, consecutively). TG concentration did not differ between the patients with normal and abnormal TFTs. The correlations between TG, TFTs, and inflammatory markers were very limited. 19 patients had elevated TG levels, but a TFT pattern suggestive of thyrotoxicosis was not common in this group. There were no statistically significant differences between patients who met and those who did not meet the predefined combined primary endpoint.


Subject(s)
COVID-19 , Thyroglobulin , Humans , Thyroid Function Tests , Glucocorticoids/therapeutic use , COVID-19/complications , Thyroid Gland
7.
Arthritis Rheumatol ; 75(5): 664-672, 2023 05.
Article in English | MEDLINE | ID: covidwho-2291189

ABSTRACT

OBJECTIVE: Hyperinflammation (HI) that develops in week 2 of COVID-19 contributes to a worse outcome. Because week 2 laboratory findings can be relatively mild, the available criteria for classification of hemophagocytic lymphohistiocytosis or macrophage activation syndrome are not helpful. METHODS: Our study included a discovery cohort of patients from Turkey with symptomatic COVID-19 who were followed up while hospitalized during the initial wave and a replication cohort of hospitalized patients from a later period, all of whom required oxygen support and received glucocorticoids. Diagnosis of HI was made by an expert panel; most patients with COVID-19-associated HI (HIC) received tocilizumab or anakinra. Clinical and laboratory data from start day of treatment with tocilizumab or anakinra in HIC patients were compared with the data from day 5-6 in patients without HIC. Values maximizing the sensitivity and specificity of each parameter were calculated to determine criteria items. RESULTS: The discovery cohort included 685 patients, and the replication cohort included 156 patients, with 150 and 61 patients receiving treatment for HI, respectively. Mortality rate in HI patients in the discovery cohort (23.3%) was higher than the rate in patients without HI (3.7%) and the rate in patients in the overall replication cohort (10.3%). The 12-item criteria that we developed for HIC showed that a score of 35 provided 85.3% sensitivity and 81.7% specificity for identification of HIC. In the replication cohort, the same criteria resulted in 90.0% sensitivity for HIC; however, lower specificity values were observed because of the inclusion of milder cases of HIC responding only to glucocorticoids. CONCLUSION: The use of the 12-item criteria for HIC can better define patients with HIC with reasonable sensitivity and specificity and enables an earlier treatment start.


Subject(s)
COVID-19 , Humans , Interleukin 1 Receptor Antagonist Protein/therapeutic use , SARS-CoV-2 , Pandemics , Glucocorticoids/therapeutic use
8.
BMC Ophthalmol ; 23(1): 113, 2023 Mar 21.
Article in English | MEDLINE | ID: covidwho-2298726

ABSTRACT

BACKGROUND: Vogt‒Koyanagi‒Harada (VKH) disease is a multifactorial systemic autoimmune disorder against melanocytes that is characterized by panuveitis. Familial occurrence of VKH disease is rare. Here, we report two cases of a father and his son with characteristic manifestations of VKH disease. CASE PRESENTATION: A 53-year-old male with typical clinical symptoms of VKH disease was referred to Tangshan Eye Hospital. Examination showed the presence of ciliochoroidal effusion and exudative retinal detachment in both eyes. The patient was given intravenous methylprednisolone 120 mg for 2 days and intravenous methylprednisolone 80 mg for 1 day followed by 48 mg (1 mg/kg/day) oral methylprednisolone daily, accompanied by oral azathioprine 50 mg daily. Cycloplegic agent (0.5% tropicamide three times daily [TID]) was added. The patient was free of symptoms and recurrence within more than 1-year-follow-up period, the best corrected visual acuity (BVCA) was increased and maintained in both eyes with complete resolution of subretinal fluid. One year and nine months later, case 2 (his son) also presented with the typical clinical symptoms of VKH disease at 29 years of age. The son also recovered from VKH disease after routine and standard treatment. CONCLUSIONS: To the best of our knowledge, this is the first VKH disease case report of a father-son relationship. Although genetic factors have been demonstrated to be involved in the pathogenesis of VKH disease, the different inheritance modes of VKH patients need to be further explored and studied.


Subject(s)
Glucocorticoids , Methylprednisolone , Uveomeningoencephalitic Syndrome , Humans , Male , Middle Aged , Fathers , Glucocorticoids/therapeutic use , Methylprednisolone/therapeutic use , Nuclear Family , Uveomeningoencephalitic Syndrome/diagnosis , Uveomeningoencephalitic Syndrome/drug therapy , Uveomeningoencephalitic Syndrome/complications , Adult , Visual Acuity , Treatment Outcome
9.
Lancet ; 401(10381): 1001-1010, 2023 03 25.
Article in English | MEDLINE | ID: covidwho-2300365

ABSTRACT

BACKGROUND: Baricitinib is an oral selective inhibitor of Janus kinase 1 and 2 approved for the treatment of rheumatoid arthritis, atopic dermatitis, and alopecia areata. In a 24-week phase 2 study in patients with systemic lupus erythematosus (SLE), baricitinib 4 mg significantly improved SLE disease activity compared with placebo. The objective of this trial was to evaluate the efficacy and safety of baricitinib in patients with active SLE in a 52-week phase 3 study. METHODS: In a multicentre, double-blind, randomised, placebo-controlled, parallel-group, phase 3 study, SLE-BRAVE-I, patients (aged ≥18 years) with active SLE receiving stable background therapy were randomly assigned 1:1:1 to baricitinib 4 mg, 2 mg, or placebo once daily for 52 weeks with standard of care. Glucocorticoid tapering was encouraged but not required per protocol. The primary endpoint was the proportion of patients reaching an SLE Responder Index (SRI)-4 response at week 52 in the baricitinib 4 mg treatment group compared with placebo. The primary endpoint was assessed by logistic regression analysis with baseline disease activity, baseline corticosteroid dose, region, and treatment group in the model. Efficacy analyses were done on a modified intention-to-treat population, comprising all participants who were randomly assigned and received at least one dose of investigational product. Safety analyses were done on all randomly assigned participants who received at least one dose of investigational product and who did not discontinue from the study for the reason of lost to follow-up at the first post-baseline visit. This study is registered with ClinicalTrials.gov, NCT03616912. FINDINGS: 760 participants were randomly assigned and received at least one dose of baricitinib 4 mg (n=252), baricitinib 2 mg (n=255), or placebo (n=253). A significantly greater proportion of participants who received baricitinib 4 mg (142 [57%]; odds ratio 1·57 [95% CI 1·09 to 2·27]; difference with placebo 10·8 [2·0 to 19·6]; p=0·016), but not baricitinib 2 mg (126 [50%]; 1·14 [0·79 to 1·65]; 3·9 [-4·9 to 12·6]; p=0·47), reached SRI-4 response compared with placebo (116 [46%]). There were no significant differences between the proportions of participants in either baricitinib group reaching any of the major secondary endpoints compared with placebo, including glucocorticoid tapering and time to first severe flare. 26 (10%) participants receiving baricitinib 4 mg had serious adverse events, 24 (9%) participants receiving baricitinib 2 mg, and 18 (7%) participants receiving placebo. The safety profile of baricitinib in participants with SLE was consistent with the known baricitinib safety profile. INTERPRETATION: The primary endpoint in this study was met for the 4 mg baricitinib group. However, key secondary endpoints were not. No new safety signals were observed. FUNDING: Eli Lilly and Company.


Subject(s)
Arthritis, Rheumatoid , Lupus Erythematosus, Systemic , Humans , Adolescent , Adult , Glucocorticoids/therapeutic use , Lupus Erythematosus, Systemic/drug therapy , Arthritis, Rheumatoid/drug therapy , Double-Blind Method , Treatment Outcome
10.
J Investig Med ; 70(8): 1662-1680, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2291209

ABSTRACT

Each year, hundreds of millions of individuals are affected by respiratory disease leading to approximately 4 million deaths. Most respiratory pathologies involve substantially dysregulated immune processes that either fail to resolve the underlying process or actively exacerbate the disease. Therefore, clinicians have long considered immune-modulating corticosteroids (CSs), particularly glucocorticoids (GCs), as a critical tool for management of a wide spectrum of respiratory conditions. However, the complex interplay between effectiveness, risks and side effects can lead to different results, depending on the disease in consideration. In this comprehensive review, we present a summary of the bench and the bedside evidence regarding GC treatment in a spectrum of respiratory illnesses. We first describe here the experimental evidence of GC effects in the distal airways and/or parenchyma, both in vitro and in disease-specific animal studies, then we evaluate the recent clinical evidence regarding GC treatment in over 20 respiratory pathologies. Overall, CS remain a critical tool in the management of respiratory illness, but their benefits are dependent on the underlying pathology and should be weighed against patient-specific risks.


Subject(s)
Glucocorticoids , Animals , Glucocorticoids/therapeutic use
11.
Eur Arch Otorhinolaryngol ; 280(8): 3515-3528, 2023 Aug.
Article in English | MEDLINE | ID: covidwho-2299917

ABSTRACT

INTRODUCTION: COVID-19 can result in an extensive range of extrapulmonary, and neurological signs and symptoms such as olfactory and/or taste dysfunction, and otologic symptoms. The aim of this study was to investigate the hearing loss manifestation from COVID-19. METHODS: The goal of this umbrella review was to examine hearing loss associated with COVID-19 disease. English literature published until October 15, 2022 in online databases including PubMed, Scopus, Web of Science, and Embase was considered for this purpose. Eligibility of the articles for subsequent data extraction was evaluated in a two-step selection process with consideration to an inclusion/exclusion criterion. This review followed the PRISMA protocol and the Amstar-2 checklist for quality assessment. RESULTS: A total of four treatment strategies were used by different studies which included oral corticosteroids, intratympanic corticosteroids, combined oral and intratympanic corticosteroids, and hyperbaric oxygen therapy. Five studies investigated corticosteroid use in the forms of oral or intratympanic injection; four studies reported (complete or partial) hearing improvements after steroid treatment, while one study stated no significant improvement in hearing function. One study reported that oral corticosteroid monotherapy alone was not effective, while vestibular symptoms were ameliorated by a combination of oral prednisone, intratympanic dexamethasone injection, and hydroxychloroquine. CONCLUSION: The findings suggest that despite being one of the rare complications of COVID-19, hearing loss can impact a patient's quality of life. The most common type reported was sensorineural hearing loss, which can be diagnosed with variable techniques.


Subject(s)
COVID-19 , Deafness , Hearing Loss, Sensorineural , Hearing Loss, Sudden , Humans , Hearing Loss, Sudden/diagnosis , Quality of Life , COVID-19/complications , Hearing Loss, Sensorineural/diagnosis , Adrenal Cortex Hormones/therapeutic use , Injection, Intratympanic , Treatment Outcome , Dexamethasone/therapeutic use , Glucocorticoids/therapeutic use
12.
Curr Opin Pulm Med ; 29(3): 215-222, 2023 05 01.
Article in English | MEDLINE | ID: covidwho-2283832

ABSTRACT

PURPOSE OF REVIEW: Three years after the emergence of coronavirus disease 2019 (COVID-19), many studies have examined the association between asthma and COVID-related morbidity and mortality, with most showing that asthma does not increase risk. However, the U.S. Centers for Disease Control (CDC) currently suggests that patients with severe asthma may, nonetheless, be particularly vulnerable to COVID-19-related morbidity. RECENT FINDINGS: With respect to poor COVID-19 outcomes, our search yielded nine studies that quantified associations with severe asthma, seven that considered use of monoclonal antibodies (mAB), and 14 that considered inhaled corticosteroids (ICS) use. mAb and ICS use have been used as measures of severe asthma in several studies. Severe asthma was significantly associated with poor COVID-19 outcomes. The results for mAb and ICS were mixed. SUMMARY: An increased risk of poor COVID-19 outcomes in patients with severe asthma is possible. However, these studies remain sparse and suffer from several methodological limitations that hinder their interpretation. Additional evidence is needed to provide clear, cogent guidance for health agencies seeking to inform patients with asthma about potential risks due to COVID-19.


Subject(s)
Anti-Asthmatic Agents , Asthma , COVID-19 , Humans , Administration, Inhalation , Anti-Asthmatic Agents/therapeutic use , Asthma/complications , Asthma/drug therapy , Asthma/epidemiology , COVID-19/complications , COVID-19/epidemiology , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use , Antibodies, Monoclonal/therapeutic use , Patient Acuity , Risk Factors , Outcome Assessment, Health Care
13.
Eur J Endocrinol ; 188(2)2023 Feb 14.
Article in English | MEDLINE | ID: covidwho-2275134

ABSTRACT

OBJECTIVE: Autoimmune Addison's disease (AAD) entails a chronic adrenal insufficiency and is associated with an increased risk of severe infections. It is, however, unknown how patients with AAD were affected by the coronavirus disease 2019 (COVID-19) pandemic of 2020-2021. This study was aimed at investigating the incidence of COVID-19 in patients with AAD in Sweden, the self-adjustment of medications during the disease, impact on social aspects, and treatment during hospitalization. Additionally, we investigated if there were any possible risk factors for infection and hospitalization. DESIGN AND METHODS: Questionnaires were sent out from April to October 2021 to 813 adult patients with AAD in the Swedish Addison Registry. The questionnaires included 55 questions inquiring about COVID-19 sickness, hospital care, medications, and comorbidities, focusing on the pre-vaccine phase. RESULTS: Among the 615 included patients with AAD, COVID-19 was reported in 17% of which 8.5% required hospital care. Glucocorticoid treatment in hospitalized patients varied. For outpatients, 85% increased their glucocorticoid dosage during sickness. Older age (P = .002) and hypertension (P = .014) were associated with an increased risk of hospital care, while younger age (P < .001) and less worry about infection (P = .030) were correlated with a higher risk of COVID-19. CONCLUSIONS: In the largest study to date examining AAD during the COVID-19 pandemic, we observed that although one-fifth of the cohort contracted COVID-19, few patients required hospital care. A majority of the patients applied general recommended sick rules despite reporting limited communication with healthcare during the pandemic.


Subject(s)
Addison Disease , COVID-19 , Self-Management , Adult , Humans , Addison Disease/epidemiology , Addison Disease/complications , Retrospective Studies , Sweden/epidemiology , Pandemics , Glucocorticoids/therapeutic use , COVID-19/epidemiology , COVID-19/complications
14.
BMC Pulm Med ; 23(1): 92, 2023 Mar 21.
Article in English | MEDLINE | ID: covidwho-2269006

ABSTRACT

OBJECTIVE: We aimed to identify new classes in acute respiratory distress syndrome (ARDS) using physiological and clinical variables and to explore heterogeneity in the effects of glucocorticoid therapy between classes. METHODS: Using the Medical Information Mart for Intensive Care-IV database, we identified patients with ARDS. Potential profile analysis was used to identify classes with physiological and clinical data as delineating variables. Baseline characteristics and clinical outcomes were compared between classes. The effect of glucocorticoid treatment was explored by stratifying by class and glucocorticoid treatment. RESULTS: From 2008 to 2019, 1104 patients with ARDS were enrolled in the study. The 2-class potential analysis model had the best fit (P < 0.0001), with 78% of patients falling into class 1 and 22% into class 2. Additional classes did not improve the model fit. Patients in class 2 had higher anion gap, lactate, creatinine, and glucose levels and lower residual base, blood pressure, and bicarbonate compared with class 1. In-hospital mortality and 28-day mortality were significantly higher among patients in class 2 than those in class 1 (P < 0.001). Heterogeneity of glucocorticoid treatment was observed, stratified by class and treatment, with no significant effect in class 1 (P = 0.496), increased mortality in class 2 (P = 0.001), and a significant interaction (P = 0.0381). In class 2, 28-day survival was significantly lower with glucocorticoid treatment compared with no hormone treatment (P = 0.001). CONCLUSION: We used clinical and physiological variables to identify two classes of non-COVID-19-associated ARDS with different baseline characteristics and clinical outcomes. The response to glucocorticoid therapy varied among different classes of patients.


Subject(s)
Glucocorticoids , Respiratory Distress Syndrome , Humans , Glucocorticoids/therapeutic use , Retrospective Studies , Respiratory Distress Syndrome/therapy , Hospital Mortality
15.
Endocrinol Metab (Seoul) ; 38(2): 253-259, 2023 04.
Article in English | MEDLINE | ID: covidwho-2267341

ABSTRACT

BACKGRUOUND: The severity of coronavirus disease 2019 (COVID-19) among patients with long-term glucocorticoid treatment (LTGT) has not been established. We aimed to evaluate the association between LTGT and COVID-19 prognosis. METHODS: A Korean nationwide cohort database of COVID-19 patients between January 2019 and September 2021 was used. LTGT was defined as exposure to at least 150 mg of prednisolone (≥5 mg/day and ≥30 days) or equivalent glucocorticoids 180 days before COVID-19 infection. The outcome measurements were mortality, hospitalization, intensive care unit (ICU) admission, length of stay, and mechanical ventilation. RESULTS: Among confirmed patients with COVID-19, the LTGT group (n=12,794) was older and had a higher proportion of comorbidities than the control (n=359,013). The LTGT group showed higher in-hospital, 30-day, and 90-day mortality rates than the control (14.0% vs. 2.3%, 5.9% vs. 1.1%, and 9.9% vs. 1.8%, respectively; all P<0.001). Except for the hospitalization rate, the length of stay, ICU admission, and mechanical ventilation proportions were significantly higher in the LTGT group than in the control (all P<0.001). Overall mortality was higher in the LTGT group than in the control group, and the significance remained in the fully adjusted model (odds ratio [OR], 5.75; 95% confidence interval [CI], 5.31 to 6.23) (adjusted OR, 1.82; 95% CI, 1.67 to 2.00). The LTGT group showed a higher mortality rate than the control within the same comorbidity score category. CONCLUSION: Long-term exposure to glucocorticoids increased the mortality and severity of COVID-19. Prevention and early proactive measures are inevitable in the high-risk LTGT group with many comorbidities.


Subject(s)
COVID-19 , Humans , Cohort Studies , Glucocorticoids/therapeutic use , Hospitalization , Republic of Korea/epidemiology
16.
Crit Care ; 27(1): 112, 2023 03 16.
Article in English | MEDLINE | ID: covidwho-2264356

ABSTRACT

BACKGROUND: The use of glucocorticoids has given contradictory results for treating acute respiratory distress syndrome (ARDS). The use of intravenous Interferon beta (IFN ß) for the treatment of ARDS was recently tested in a phase III ARDS trial (INTEREST), in which more than half of the patients simultaneously received glucocorticoids. Trial results showed deleterious effects of glucocorticoids when administered together with IFN ß, and therefore, we aimed at finding the reason behind this. METHODS: We first sequenced the genes encoding the IFN α/ß receptor of the patients, who participated in the INTEREST study (ClinicalTrials.gov Identifier:  NCT02622724 , November 24, 2015) in which the patients were randomized to receive an intravenous injection of IFN ß-1a (144 patients) or placebo (152 patients). Genetic background was analyzed against clinical outcome, concomitant medication, and pro-inflammatory cytokine levels. Thereafter, we tested the influence of the genetic background on IFN α/ß receptor expression in lung organ cultures and whether, it has any effect on transcription factors STAT1 and STAT2 involved in IFN signaling. RESULTS: We found a novel disease association of a SNP rs9984273, which is situated in the interferon α/ß receptor subunit 2 (IFNAR2) gene in an area corresponding to a binding motif of the glucocorticoid receptor (GR). The minor allele of SNP rs9984273 associates with higher IFNAR expression, more rapid decrease of IFN γ and interleukin-6 (IL-6) levels and better outcome in IFN ß treated patients with ARDS, while the major allele associates with a poor outcome especially under concomitant IFN ß and glucocorticoid treatment. Moreover, the minor allele of rs9984273 associates with a less severe form of coronavirus diseases (COVID-19) according to the COVID-19 Host Genetics Initiative database. CONCLUSIONS: The distribution of this SNP within clinical study arms may explain the contradictory results of multiple ARDS studies and outcomes in COVID-19 concerning type I IFN signaling and glucocorticoids.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Humans , Glucocorticoids/pharmacology , Glucocorticoids/therapeutic use , COVID-19/genetics , Interferon-beta/pharmacology , Interferon-beta/therapeutic use , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/genetics , Interferon-alpha
17.
J Int Med Res ; 51(2): 3000605221149292, 2023 Feb.
Article in English | MEDLINE | ID: covidwho-2254525

ABSTRACT

OBJECTIVE: We aimed to investigate the clinical effects of intravenous glucocorticoid (GC) therapy for severe COVID-19 pneumonia. METHODS: Seventy-two patients hospitalized with severe COVID-19 pneumonia who were discharged or died between 5 January 2020 and 3 March 2020 at Huangshi Infectious Disease Hospital were included. Patients were divided into a treatment group (GC group) and non-treatment group (non-GC group) according to whether they had received GCs within 7 days of hospital admission. RESULTS: There was no significant difference between groups for Acute Physiology and Chronic Health Evaluation (APACHE) II score and 28-day survival rate. The rate of invasive mechanical ventilation was higher in the GC group than in the non-GC group. On day 7 after admission, the GC group had shorter fever duration and higher white blood cell count than the non-GC group. In subgroup analysis by age and severity, there was no significant difference in 28-day survival rate and other indicators. Compared with those in the non-GC group, patients in the GC group more frequently required admission to the intensive care unit. CONCLUSION: In the present study, we found no significant improvement in patients with severe COVID-19 pneumonia treated with GCs within 7 days of admission.


Subject(s)
COVID-19 , Humans , Glucocorticoids/therapeutic use , Critical Illness/therapy , Intensive Care Units , Hospitalization , Retrospective Studies
18.
Am J Health Behav ; 47(1): 182-193, 2023 02 28.
Article in English | MEDLINE | ID: covidwho-2252870

ABSTRACT

Objective: The objective of this research was to determine the impact of glucocorticoid treatment on preventing scarring of lung parenchyma in COVID-19 patients by considering their health behavior. Methods: A sample of 65 Turkish patients who had pneumonia and were hospitalized between March/December 2020 were included in this research. The data for this research was collected after the consent of the hospital. The structural equation model approach was used in data analysis and empirical findings. Results: The research identified that the patients with appropriate health behavior were satisfied with their clinical treatment of scarring of lung parenchyma by the method of glucocorticoid treatment. The research also identified that the patient's health behavior was a significant indicator to improve their perception of the clinical treatment. Conclusion: This study has reliable theoretical implications that are significantly important in the literature because of the nature and uniqueness of the findings. However, this research also has some practical implications related to the patient's lungs mostly infected by COVID-19. Furthermore, the findings of this research can be generalized in a significant way because the respondents of this research belonged to a diverse population.


Subject(s)
COVID-19 , Humans , Glucocorticoids/therapeutic use , SARS-CoV-2 , Cicatrix , Lung/diagnostic imaging
19.
Front Endocrinol (Lausanne) ; 13: 1042119, 2022.
Article in English | MEDLINE | ID: covidwho-2287777

ABSTRACT

Objective: To determine self-reported incidence and potential risk factors for COVID-19 in patients with adrenal insufficiency (AI). Methods: A 27-item AI survey was developed for AI and COVID-19 status, vetted by specialists and patients, and distributed via social media, websites, and advocacy groups. Participation was voluntary and anonymous. Data were collected from September 20th, 2020 until December 31st, 2020. Results: Respondents (n=1291) with self-reported glucocorticoid treatment for AI, completed the survey, with 456 who reported having symptoms and were screened for COVID-19 during 2020; 40 tested positive (+ve), representing an 8.8% incidence. Of the COVID-19+ve, 31 were female (78%), with mean age of 39.9 years. COVID-19 among AI patients occurred most commonly in those aged 40-59 years (n=17; 42.5%); mean time since AI diagnosis was 13.5 years (range 0.2-42.0 years). Pulmonary disease, congenital adrenal hyperplasia, and higher maintenance doses of glucocorticoids were significantly associated with +ve COVID-19 (p=0.04, p=0.01, and p=0.001, respectively. In respondents the cumulative incidence of COVID-19+ve during 2020 was 3.1%; greater than the 1.03% worldwide-incidence reported by WHO, by December 31st, 2020. There was a 3-fold (95% CI 2.16-3.98) greater relative risk (RR) of COVID-19 infection and a 23.8- fold (95% CI 20.7-31.2) RR of hospitalization in patients with AI, compared with the global population. Conclusion: A markedly raised RR of COVID-19 and hospitalization in respondents reporting chronic AI was detected. We found that a diagnosis of congenital adrenal hyperplasia, age>40 years, male gender, pulmonary disease, and higher maintenance doses of glucocorticoids were associated with greatest risk.


Subject(s)
Adrenal Hyperplasia, Congenital , Adrenal Insufficiency , COVID-19 , Humans , Female , Male , Adult , COVID-19/complications , COVID-19/epidemiology , Glucocorticoids/therapeutic use , Hospitalization , Self Report , Adrenal Insufficiency/epidemiology , Adrenal Insufficiency/etiology
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