Systemic Corticosteroids in Patients with Bronchial Asthma: A Real-Life Study.

OBJECTIVES: The objective of the present study was to determine the use of systemic corti-costeroids (SCs) in patients with bronchial asthma using big data analysis. METHODS: We performed an observational, retrospective, noninterventional study based on secondary data captured from free text in the electronic health records. This study was per-formed based on data from the regional health service of Castille-La Mancha (SESCAM), Spain. We performed the analysis using big data and artificial intelligence via Savana® Manager version 3.0. RESULTS: During the study period, 103 667 patients were diagnosed with and treated for asthma at different care levels. The search was restricted to patients aged 10 to 90 years (mean age, 43.5 [95%CI, 43.4-43.7] years). Of these, 59.8% were women. SCs were taken for treatment of asthma by 58 745 patients at some point during the study period. These patients were older, with a higher prevalence of hypertension, dyslipidemia, diabetes, ob-esity, depression, and hiatus hernia. SCs are used frequently in the general population with asthma (31.4% in 2015 and 39.6% in 2019). SCs were prescribed mainly in primary care (59%), allergy (13%) and pulmonology (20%). The frequency of prescription of SCs had a direct impact on the main associated adverse effects. CONCLUSION: In clinical practice, SCs are frequently prescribed to patients with asthma, especially in primary care. Use of SCs is associated with a greater number of adverse events. It is necessary to implement measures to reduce prescription of SCs to patients with asthma, especially in primary care.

COVID-19 Advanced Care.

The coronavirus disease 2019 (COVID-19) pandemic, related to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial burden in public health due to an enormous increase in hospitalizations for pneumonia with the multiorgan disease. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care, and ongoing trials are testing the efficacy of antiviral therapies, immune modulators and anticoagulants in the prevention of disease progression and complications, while monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies. Consensus suggestions can standardize care, thereby improving outcomes and facilitating future research. This review discusses current evidence regarding the pharmacotherapy of COVID-19.

New-onset hyperglycaemia and prolonged systemic corticosteroids therapy in mild COVID-19 patients as major risk factors for invasive mucormycosis: a preliminary study.

Background and Purpose: Rapid surge of invasive mucormycosis has surprised the Indian healthcare system amidst the coronavirus disease-19 (COVID-19) pandemic. Hence, there is an urgent need to find the risk factors for the sudden rise in cases of invasive mucormycosis among COVID-19 patients. This study aimed to find crucial risk factors for the sudden surge of invasive mucormycosis in India. Materials and Methods: This case-control study included 77 cases of COVID-19 associated mucormycosis (CAM) who matched the controls (45 controls) in terms of age , gender, and COVID-19 disease severity. The control group included subjects that matched controls without mucormycosis confirmed by reverse transcription-polymerase chain reaction at our tertiary care center during April-May 2021. Probable predisposing factors, such as duration of diabetes mellitus (DM), history of recent hospitalization, duration of hospital stay, mode of the received oxygen supplementation, and use of steroids, zinc, vitamin c, and any other specific drugs were collected and compared between the two groups. Moreover, the laboratory parameters, like glycated hemoglobin (HbA1c), highly sensitive C-reactive protein (hs-CRP), and erythrocyte sedimentation rate (ESR) were analyzed to find out the significant association with CAM. Results: DM (Odds ratio=7.7, 95% CI 3.30-18.12; P=<0.0001) and high glycated hemoglobin level (HbA1c>7.5 gm %) (odds ratio=6.2, 95% CI 1.4-26.7; P=0.014) were significant risk factors for the development of invasive mucormycosis among the COVID-19 cases. A higher number of mild COVID-19 cases developed CAM, compared to the moderate to severe cases (59.7% vs 40.3%). Use of systemic corticosteroids (odd ratio=5 with 95% CI 1.5-16.9; P=0.007) was found to be a risk factor for invasive mucormycosis only in mild COVID-19 cases. Use of oxygen, zinc, and vitamin C supplementation, and proprietary medicine did not lead to a significant risk of invasive mucormycosis in cases, compared to controls. Cases with invasive mucormycosis had a higher level of inflammatory markers (hs-CRP and ESR, P=<0.001 and 0.002, respectively), compared to the controls. Conclusion: Uncontrolled and new-onset DM and the use of systemic corticosteroids in mild cases were significantly associated with a higher risk of invasive mucormycosis in COVID-19 cases. There should be a strong recommendation against the use of systemic corticosteroids in mild COVID-19 cases.

Phase II Clinical Trial of Combination Therapy with Favipiravir and Methylprednisolone for COVID-19 with Non-Critical Respiratory Failure.

INTRODUCTION: The administration of systemic corticosteroids is a key strategy for improving COVID-19 outcomes. However, evidence is lacking on combination therapies of antiviral agents and systemic corticosteroids. The objective of this study was to investigate the efficacy and safety of the combination therapy of favipiravir and methylprednisolone in preventing respiratory failure progression in patients with COVID-19 and non-critical respiratory failure. METHODS: We conducted a multicenter, open-label, single-arm phase II study. The patients received favipiravir 3600 mg on the first day, followed by 1600 mg for a total of 10-14 days. Methylprednisolone was administered intravenously at 1 mg/ideal body weight (IBW)/day from days 1 to 5, followed by 0.5 mg/IBW/day from days 6 to 10 if clinically indicated. The primary endpoint was the proportion of patients requiring mechanical ventilation (MV) (including noninvasive positive pressure ventilation) or those who met the criteria for tracheal intubation within 14 days of the study treatment initiation (MVCTI-14). RESULTS: Sixty-nine patients were enrolled and underwent the study treatment. Of them, the MVCTI-14 proportion was 29.2% (90% confidence interval 20.1-39.9, p = 0.200). The proportion of patients who required MV or who died within 30 days was 26.2%, and 30-day mortality was 4.9%. The most significant risk factor for MVCTI-14 was a smoking history (odds ratio 4.1, 95% confidence interval 1.2-14.2). The most common grade 3-4 treatment-related adverse event was hyperglycemia, which was observed in 21.7%. CONCLUSION: The MVCTI-14 proportion did not reach a favorable level in the clinical trial setting with the threshold of 35%. However, the proportion of MV or death within 30 days was 26.6%, which might be close to the findings (28.1%) of the RECOVERY trial, which showed the efficacy of dexamethasone for patients with COVID-19 and non-critical respiratory failure. Further evaluation of this combination therapy is needed. CLINICAL TRIAL REGISTRATION: Japan Registry of Clinical Trials (jRCT) identifier jRCTs041200025.

COVID-19 risk and outcomes in adult asthmatic patients treated with biologics or systemic corticosteroids: Nationwide real-world evidence.

BACKGROUND: Managing severe asthma during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is challenging, particularly due to safety concerns regarding the use of systemic corticosteroids and biologics. OBJECTIVES: We sought to determine the association between biologics or systemic corticosteroids use and PCR positivity for SARS-CoV-2 and coronavirus disease 2019 (COVID-19) outcomes among asthmatic patients. METHODS: We used the computerized database of Clalit Health Services, the largest health care provider in Israel, to identify all asthmatic adult patients who underwent PCR testing for SARS-CoV-2, between March 1, 2020, and December 7, 2020. A cohort approach was used to assess the association between biologics use and steroids treatment and COVID-19 severity and 90-day mortality. RESULTS: Overall, 8,242 of 80,602 tested asthmatic patients had positive PCR testing result for SARS-CoV-2. Both biologics and systemic corticosteroids were not associated with increased risk of SARS-CoV-2 infection. Multivariate analyses revealed that biologics were not associated with a significantly increased risk of moderate to severe COVID-19, nor with the composite end point of moderate to severe COVID-19 or all-cause mortality within 90 days. Chronic systemic corticosteroid use was associated with significantly increased risk of all tested outcome. Recent (within the previous 120 days) systemic corticosteroid use, but not former use, was significantly associated with increased risk of both moderate to severe COVID-19 and the composite of moderate to severe COVID-19 or all-cause mortality. CONCLUSIONS: Biologics approved for asthma and systemic corticosteroids are not associated with increased risk of SARS-CoV-2 infection. In contrast, systemic corticosteroids are an independent risk factor for worst COVID-19 severity and all-cause mortality. Our findings underscore the risk of recent or current exposure to systemic corticosteroids in asthmatic patients infected with SARS-CoV-2.

Mucormycosis and COVID-19: An epidemic within a pandemic in India.

IMPORTANCE: Coronavirus disease (COVID-19) causes an immunosuppressed state and increases risk of secondary infections like mucormycosis. We evaluated clinical features, predisposing factors, diagnosis and outcomes for mucormycosis among patients with COVID-19 infection. METHODS: This prospective, observational, multi-centre study included 47 consecutive patients with mucormycosis, diagnosed during their course of COVID-19 illness, between January 3 and March 27, 2021. Data regarding demography, underlying medical conditions, COVID-19 illness and treatment were collected. Clinical presentations of mucormycosis, imaging and biochemical characteristics and outcome were recorded. RESULTS: Of the 2567 COVID-19 patients admitted to 3 tertiary centres, 47 (1.8%) were diagnosed with mucormycosis. Mean age was 55 ± 12.8years, and majority suffered from diabetes mellitus (n = 36, 76.6%). Most were not COVID-19 vaccinated (n = 31, 66.0%) and majority (n = 43, 91.5%) had developed moderate-to-severe pneumonia, while 20 (42.6%) required invasive ventilation. All patients had received corticosteroids and broad-spectrum antibiotics while most (n = 37, 78.7%) received at least one anti-viral medication. Mean time elapsed from COVID-19 diagnosis to mucormycosis was 12.1 ± 4.6days. Eleven (23.4%) subjects succumbed to their disease, mostly (n = 8, 72.7%) within 7 days of diagnosis. Among the patients who died, 10 (90.9%) had pre-existing diabetes mellitus, only 2 (18.2%) had received just one vaccine dose and all developed moderate-to-severe pneumonia, requiring oxygen supplementation and mechanical ventilation. CONCLUSIONS: Mucormycosis can occur among COVID-19 patients, especially with poor glycaemic control, widespread and injudicious use of corticosteroids and broad-spectrum antibiotics, and invasive ventilation. Owing to the high mortality, high index of suspicion is required to ensure timely diagnosis and appropriate treatment in high-risk populations.

Efficacy of Intratympanic Glucocorticoid Steroid Administration Therapy as an Initial Treatment for Idiopathic Sudden Sensorineural Hearing Loss During the COVID-19 Pandemic.

OBJECTIVE: Systemic administration of glucocorticoid steroids is the most common initial treatment for idiopathic sudden sensorineural hearing loss (ISSNHL); however, due to the prevalence of coronavirus disease, the indications for this treatment must be carefully determined. The aim of this study was to investigate the efficacy of intratympanic steroid therapy as an initial treatment for idiopathic SSNHL. METHODS: Sixty-eight patients with idiopathic ISSNHL who were treated with intravenous or intratympanic steroids were included in this study. Patients were retrospectively evaluated regarding preoperative grade, type of additional treatment, outcome of treatment, and side effects of each treatment. RESULTS: In 46 cases, patients received intravenous steroid therapy as the initial treatment, while 22 patients received intratympanic steroid therapy; 10 patients underwent salvage treatment due to inadequate improvement of symptoms. Regarding additional treatment, intravenous steroid monotherapy was used in 37 patients. The outcomes were similar after both treatments; 16 (43%) and 11 (52%) patients treated exclusively with intravenous and intratympanic steroids, respectively, were completely cured. There were no significant differences in the effects between the 2 treatments, indicating that they were almost equally effective. The side effects observed in patients treated with intravenous steroid therapy were increased blood pressure, acute gastric mucosal disorder, and insomnia. None of these side effects were observed in any of the patients treated with intratympanic steroids; however, 1 case of perforation of the tympanic membrane occurred due to the procedure. CONCLUSION: There were no significant differences in posttreatment outcomes between patients treated with either intratympanic or intravenous steroids. The therapeutic effects were comparable, and no severe side effects were observed; therefore, intratympanic steroid therapy may be considered useful as an initial treatment for ISSNHL in the context of widespread coronavirus disease.

Impact of previous exposure to systemic corticosteroids on unfavorable outcome in patients hospitalized for COVID-19.

BACKGROUND: The impact of prior exposure to systemic corticosteroids on COVID-19 severity in patients hospitalized for a SARS-CoV-2 pneumonia is not known. The present study was designed to answer to this question. METHODS: The population study was the Covid-Clinic-Toul cohort which records data about all hospitalized patients with a positive reverse transcriptase polymerase chain reaction for a SARS-CoV-2 infection at Toulouse University hospital, France. Exposure to systemic corticosteroids was assessed at hospital admission. A propensity score (PS) according to corticosteroid exposure was calculated including comorbidities, clinical, radiological and biological variables that impact COVID-19 severity. The primary outcome was composite, including admission to intensive care unit, need of mechanical ventilation and death occurring during the 14 days after hospital admission. Logistic regression models adjusted for the PS (overlap weighting) provided odds ratios (ORs) and their 95% confidence intervals (95% CIs). RESULTS: Overall, 253 patients were included in the study. Median age was 64 years, 140 patients (59.6%) were men and 218 (86.2%) had at least one comorbidity. Seventeen patients (6.7%) were exposed to corticosteroids before hospital admission. Chronic inflammatory disease (n = 8) was the most frequent indication. One hundred and twenty patients (47.4%) met the composite outcome. In the crude model, the OR of previous exposure to systemic corticosteroids was 1.64; 95% CI: 0.60-4.44. In the adjusted model, it was 1.09 (95% CI: 0.65-1.83). CONCLUSION: Overall, this study provide some evidences for an absence of an increased risk of unfavorable outcome with previous exposure to corticosteroids in the general setting of patients hospitalized for COVID-19.

Risk Factors for Invasive Pulmonary Aspergillosis in Critically Ill Patients With Coronavirus Disease 2019-Induced Acute Respiratory Distress Syndrome.

Severe coronavirus disease 2019 pneumonia can lead to acute respiratory distress syndrome. Recently, several publications reported on coronavirus disease 2019-associated pulmonary aspergillosis. However, risk factors remain unclear. We retrospectively collected all the cases of coronavirus disease 2019 acute respiratory distress syndrome patients (n = 46) admitted to our 34-bed ICU between March 24, 2020, and May 25, 2020, and identified six patients that met the diagnosis of invasive pulmonary aspergillosis according to previously established definitions. This population exhibited higher severity scores at admission and less hospital discharge compared with noninvasive pulmonary aspergillosis patients. Chronic obstructive pulmonary disease, malnutrition, and systemic corticosteroid use were identified as risk factors for invasive pulmonary aspergillosis in coronavirus disease 2019-induced acute respiratory distress syndrome patients. Coronavirus disease 2019-associated pulmonary aspergillosis may be a serious concern regarding corticosteroids use to control the inflammatory response of coronavirus disease 2019-induced acute respiratory distress syndrome.

Systemic Corticosteroids and Mortality in Severe and Critical COVID-19 Patients in Wuhan, China.

BACKGROUND: Systemic corticosteroids are now recommended in many treatment guidelines, although supporting evidence is limited to 1 randomized controlled clinical trial (RECOVERY). OBJECTIVE: To identify whether corticosteroids were beneficial to COVID-19 patients. METHODS: A total of 1514 severe and 249 critical hospitalized COVID-19 patients from 2 medical centers in Wuhan, China. Multivariable Cox models, Cox model with time-varying exposure and propensity score analysis (inverse-probability-of-treatment-weighting [IPTW] and propensity score matching [PSM]) were used to estimate the association of corticosteroid use with risk of in-hospital mortality in severe and critical cases. RESULTS: Corticosteroids were administered in 531 (35.1%) severe and 159 (63.9%) critical patients. Compared to the non-corticosteroid group, systemic corticosteroid use was not associated with beneficial effect in reducing in-hospital mortality in either severe cases (HR = 1.77; 95% CI, 1.08-2.89; P = 0.023), or critical cases (HR = 2.07; 95% CI, 1.08-3.98; P = 0.028). Findings were similar in time-varying Cox analysis. For patients with severe COVID-19 at admission, corticosteroid use was not associated with improved or harmful outcome in either PSM or IPTW analysis. For critical COVID-19 patients at admission, results were consistent with multivariable Cox model analysis. CONCLUSION: Corticosteroid use was not associated with beneficial effect in reducing in-hospital mortality for severe or critical cases in Wuhan. Absence of the beneficial effect in our study in contrast to that observed in the RECOVERY clinical trial may be due to biases in observational data, in particular prescription by indication bias, differences in clinical characteristics of patients, choice of corticosteroid used, timing of initiation of treatment, and duration of treatment.