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1.
Front Immunol ; 13: 881259, 2022.
Article in English | MEDLINE | ID: covidwho-2141875

ABSTRACT

Critical respiratory manifestations of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are rare in children, and little is known about how immunocompromised children respond to the infection. We report a case of a 4-year-old boy with activated PI3K delta syndrome type 2 (APDS2) with a protracted and severe COVID-19 course with both inflammatory and acute respiratory features. He was treated with remdesivir, nitazoxanide, high-dose corticosteroids, and tocilizumab and made a full recovery. We propose that remdesivir may be used in combination with nitazoxanide to improve viral clearance and reduce the chance of resistance in treating acute SARS-CoV-2 infection.


Subject(s)
COVID-19 , Immunologic Deficiency Syndromes , Adrenal Cortex Hormones , Child , Child, Preschool , Humans , Immunocompromised Host , Male , SARS-CoV-2
2.
BMC Infect Dis ; 22(1): 891, 2022 Nov 28.
Article in English | MEDLINE | ID: covidwho-2139180

ABSTRACT

BACKGROUND: The impact of corticosteroids on patients with severe coronavirus disease 2019 (COVID-19)/chronic hepatitis B virus (HBV) co-infection is currently unknown. We aimed to investigate the association of corticosteroids on these patients. METHODS: This retrospective multicenter study screened 5447 confirmed COVID-19 patients hospitalized between Jan 1, 2020 to Apr 18, 2020 in seven centers in China, where the prevalence of chronic HBV infection is moderate to high. Severe patients who had chronic HBV and acute SARS-cov-2 infection were potentially eligible. The diagnosis of chronic HBV infection was based on positive testing for hepatitis B surface antigen (HBsAg) or HBV DNA during hospitalization and a medical history of chronic HBV infection. Severe patients (meeting one of following criteria: respiratory rate > 30 breaths/min; severe respiratory distress; or SpO2 ≤ 93% on room air; or oxygen index < 300 mmHg) with COVID-19/HBV co-infection were identified. The bias of confounding variables on corticosteroids effects was minimized using multivariable logistic regression model and inverse probability of treatment weighting (IPTW) based on propensity score. RESULTS: The prevalence of HBV co-infection in COVID-19 patients was 4.1%. There were 105 patients with severe COVID-19/HBV co-infections (median age 62 years, 57.1% male). Fifty-five patients received corticosteroid treatment and 50 patients did not. In the multivariable analysis, corticosteroid therapy (OR, 6.32, 95% CI 1.17-34.24, P = 0.033) was identified as an independent risk factor for 28-day mortality. With IPTW analysis, corticosteroid treatment was associated with delayed SARS-CoV-2 viral RNA clearance (OR, 2.95, 95% CI 1.63-5.32, P < 0.001), increased risk of 28-day and in-hospital mortality (OR, 4.90, 95% CI 1.68-14.28, P = 0.004; OR, 5.64, 95% CI 1.95-16.30, P = 0.001, respectively), and acute liver injury (OR, 4.50, 95% CI 2.57-7.85, P < 0.001). Methylprednisolone dose per day and cumulative dose in non-survivors were significantly higher than in survivors. CONCLUSIONS: In patients with severe COVID-19/HBV co-infection, corticosteroid treatment may be associated with increased risk of 28-day and in-hospital mortality.


Subject(s)
COVID-19 , Coinfection , Hepatitis B, Chronic , Hepatitis B , Humans , Male , Middle Aged , Female , SARS-CoV-2 , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/drug therapy , COVID-19/drug therapy , Coinfection/drug therapy , Coinfection/epidemiology , Hepatitis B virus , Adrenal Cortex Hormones/therapeutic use , Hepatitis B Surface Antigens
4.
J Immigr Minor Health ; 24(6): 1431-1434, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2128926

ABSTRACT

The aim of this study is to highlight the potentially fatal risk of Strongyloidiasis Hyperinfection Syndrome for hospitalized immigrant patients with moderate to severe COVID-19 disease and undiagnosed Strongyloidiasis. We reviewed electronic medical records of immigrants from 2010 to 2022 and extracted the number of patients with eosinophilia, strongyloidiasis and COVID-19 infection, outpatient and hospitalized. While 885 outpatients were diagnosed with eosinophilia, only 356 (40.2%) were tested for strongyloidiasis and 160 (44.9%) yielded a reactive serology. COVID-19 infection was reported in 6,412 patients. 1135 (17.7%) of these patients sought hospital care. Patients with undiagnosed strongyloidiasis are at risk for a potentially fatal parasitosis if treated with systemic corticosteroids for COVID-19. This supports clinical guidelines in hospital settings for those with severe COVID-19. Strongyloidiasis should be considered by taking a thorough travel or migration history and testing before giving immunosuppressive drugs.


Subject(s)
COVID-19 , Eosinophilia , Strongyloides stercoralis , Strongyloidiasis , Transients and Migrants , Animals , Humans , Strongyloidiasis/drug therapy , Strongyloidiasis/diagnosis , Adrenal Cortex Hormones/therapeutic use
5.
Int J Mol Sci ; 23(21)2022 Oct 24.
Article in English | MEDLINE | ID: covidwho-2118692

ABSTRACT

Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder with an unknown cause characterized by high-spiking fever, lymphadenopathy, hepatosplenomegaly, hyperferritinemia, and leukocytosis. The clinical course can be divided into three significant patterns, each with a different prognosis: Self-limited or monophasic, intermittent or polycyclic systemic, and chronic articular. Two criteria sets have been validated. The Yamaguchi criteria are the most generally used, although the Fautrel criteria offer the benefit of adding ferritin and glycosylated ferritin values. AOSD's pathogenesis is not yet completely understood. Chemokines and pro-inflammatory cytokines, including interferon (IFN)-γ, tumor necrosis factor α (TNFα), interleukin (IL)-1, IL-6, IL-8, and IL-18, play a crucial role in the progression of illness, resulting in the development of innovative targeted therapeutics. There are no treatment guidelines for AOSD due to its rarity, absence of controlled research, and lack of a standard definition for remission and therapy objectives. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids (CS), and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) are used in AOSD treatment. Biological therapy, including IL-1, IL-6, IL-18, and IL-17 inhibitors, as well as TNFα or Janus-kinases (JAKs) inhibitors, is administered to patients who do not react to CS and csDMARDs or achieve an inadequate response.


Subject(s)
Antirheumatic Agents , Still's Disease, Adult-Onset , Adult , Humans , Still's Disease, Adult-Onset/diagnosis , Still's Disease, Adult-Onset/drug therapy , Interleukin-18 , Tumor Necrosis Factor-alpha/therapeutic use , Interleukin-6 , Antirheumatic Agents/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Interleukin-1/therapeutic use
6.
Cochrane Database Syst Rev ; 11: CD014963, 2022 11 17.
Article in English | MEDLINE | ID: covidwho-2117992

ABSTRACT

BACKGROUND: Systemic corticosteroids are used to treat people with COVID-19 because they counter hyper-inflammation. Existing evidence syntheses suggest a slight benefit on mortality. Nonetheless, size of effect, optimal therapy regimen, and selection of patients who are likely to benefit most are factors that remain to be evaluated. OBJECTIVES: To assess whether and at which doses systemic corticosteroids are effective and safe in the treatment of people with COVID-19, to explore equity-related aspects in subgroup analyses, and to keep up to date with the evolving evidence base using a living systematic review approach. SEARCH METHODS: We searched the Cochrane COVID-19 Study Register (which includes PubMed, Embase, CENTRAL, ClinicalTrials.gov, WHO ICTRP, and medRxiv), Web of Science (Science Citation Index, Emerging Citation Index), and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies to 6 January 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that evaluated systemic corticosteroids for people with COVID-19. We included any type or dose of systemic corticosteroids and the following comparisons: systemic corticosteroids plus standard care versus standard care, different types, doses and timings (early versus late) of corticosteroids. We excluded corticosteroids in combination with other active substances versus standard care, topical or inhaled corticosteroids, and corticosteroids for long-COVID treatment. DATA COLLECTION AND ANALYSIS: We followed standard Cochrane methodology. To assess the risk of bias in included studies, we used the Cochrane 'Risk of bias' 2 tool for RCTs. We rated the certainty of the evidence using the GRADE approach for the following outcomes: all-cause mortality up to 30 and 120 days, discharged alive (clinical improvement), new need for invasive mechanical ventilation or death (clinical worsening), serious adverse events, adverse events, hospital-acquired infections, and invasive fungal infections. MAIN RESULTS: We included 16 RCTs in 9549 participants, of whom 8271 (87%) originated from high-income countries. A total of 4532 participants were randomised to corticosteroid arms and the majority received dexamethasone (n = 3766). These studies included participants mostly older than 50 years and male. We also identified 42 ongoing and 23 completed studies lacking published results or relevant information on the study design. Hospitalised individuals with a confirmed or suspected diagnosis of symptomatic COVID-19 Systemic corticosteroids plus standard care versus standard care plus/minus placebo We included 11 RCTs (8019 participants), one of which did not report any of our pre-specified outcomes and thus our analyses included outcome data from 10 studies. Systemic corticosteroids plus standard care compared to standard care probably reduce all-cause mortality (up to 30 days) slightly (risk ratio (RR) 0.90, 95% confidence interval (CI) 0.84 to 0.97; 7898 participants; estimated absolute effect: 274 deaths per 1000 people not receiving systemic corticosteroids compared to 246 deaths per 1000 people receiving the intervention (95% CI 230 to 265 per 1000 people); moderate-certainty evidence). The evidence is very uncertain about the effect on all-cause mortality (up to 120 days) (RR 0.74, 95% CI 0.23 to 2.34; 485 participants). The chance of clinical improvement (discharged alive at day 28) may slightly increase (RR 1.07, 95% CI 1.03 to 1.11; 6786 participants; low-certainty evidence) while the risk of clinical worsening (new need for invasive mechanical ventilation or death) may slightly decrease (RR 0.92, 95% CI 0.84 to 1.01; 5586 participants; low-certainty evidence). For serious adverse events (two RCTs, 678 participants), adverse events (three RCTs, 447 participants), hospital-acquired infections (four RCTs, 598 participants), and invasive fungal infections (one study, 64 participants), we did not perform any analyses beyond the presentation of descriptive statistics due to very low-certainty evidence (high risk of bias, heterogeneous definitions, and underreporting). Different types, dosages or timing of systemic corticosteroids We identified one RCT (86 participants) comparing methylprednisolone to dexamethasone, thus the evidence is very uncertain about the effect of methylprednisolone on all-cause mortality (up to 30 days) (RR 0.51, 95% CI 0.24 to 1.07; 86 participants). None of the other outcomes of interest were reported in this study. We included four RCTs (1383 participants) comparing high-dose dexamethasone (12 mg or higher) to low-dose dexamethasone (6 mg to 8 mg). High-dose dexamethasone compared to low-dose dexamethasone may reduce all-cause mortality (up to 30 days) (RR 0.87, 95% CI 0.73 to 1.04; 1269 participants; low-certainty evidence), but the evidence is very uncertain about the effect of high-dose dexamethasone on all-cause mortality (up to 120 days) (RR 0.93, 95% CI 0.79 to 1.08; 1383 participants) and it may have little or no impact on clinical improvement (discharged alive at 28 days) (RR 0.98, 95% CI 0.89 to 1.09; 200 participants; low-certainty evidence). Studies did not report data on clinical worsening (new need for invasive mechanical ventilation or death). For serious adverse events, adverse events, hospital-acquired infections, and invasive fungal infections, we did not perform analyses beyond the presentation of descriptive statistics due to very low-certainty evidence. We could not identify studies for comparisons of different timing and systemic corticosteroids versus other active substances. Equity-related subgroup analyses We conducted the following subgroup analyses to explore equity-related factors: sex, age (< 70 years; ≥ 70 years), ethnicity (Black, Asian or other versus White versus unknown) and place of residence (high-income versus low- and middle-income countries). Except for age and ethnicity, no evidence for differences could be identified. For all-cause mortality up to 30 days, participants younger than 70 years seemed to benefit from systemic corticosteroids in comparison to those aged 70 years and older. The few participants from a Black, Asian, or other minority ethnic group showed a larger estimated effect than the many White participants. Outpatients with asymptomatic or mild disease There are no studies published in populations with asymptomatic infection or mild disease. AUTHORS' CONCLUSIONS: Systemic corticosteroids probably slightly reduce all-cause mortality up to 30 days in people hospitalised because of symptomatic COVID-19, while the evidence is very uncertain about the effect on all-cause mortality up to 120 days. For younger people (under 70 years of age) there was a potential advantage, as well as for Black, Asian, or people of a minority ethnic group; further subgroup analyses showed no relevant effects. Evidence related to the most effective type, dose, or timing of systemic corticosteroids remains immature. Currently, there is no evidence on asymptomatic or mild disease (non-hospitalised participants). Due to the low to very low certainty of the current evidence, we cannot assess safety adequately to rule out harmful effects of the treatment, therefore there is an urgent need for good-quality safety data. Findings of equity-related subgroup analyses should be interpreted with caution because of their explorative nature, low precision, and missing data. We identified 42 ongoing and 23 completed studies lacking published results or relevant information on the study design, suggesting there may be possible changes of the effect estimates and certainty of the evidence in the future.


Subject(s)
COVID-19 , Invasive Fungal Infections , Humans , Aged , Aged, 80 and over , COVID-19/drug therapy , Adrenal Cortex Hormones/adverse effects , Methylprednisolone , Dexamethasone/adverse effects , Randomized Controlled Trials as Topic
7.
PLoS One ; 17(11): e0276848, 2022.
Article in English | MEDLINE | ID: covidwho-2119483

ABSTRACT

INTRODUCTION: Management of severe COVID-19 patients with persistent respiratory failure after acute phase treatment is not only challenging, but evidence for treatment is scarce, despite some authors reporting favourable clinical responses to corticosteroid therapy in histologically proven secondary organising pneumonia (OP). This study aimed to report the course of the disease, radiological pattern and clinical outcomes of severe COVID-19 patients with persistent respiratory failure. METHODS: This was a retrospective cohort study of severe COVID-19 patients who were admitted to a single tertiary centre from 1 January 2021 to 30 June 2021. The clinical data of the patients during admission and clinic follow-up, including radiological images, were traced using electronic medical records. RESULTS: In our cohort, the mortality rate for those with severe COVID-19 was 23.1% (173/749). Among the survivors, 46.2% (266/576) had persistent respiratory failure (PRF) after 14 days of illness. Of them, 70.3% (187/266) were followed up, and 68% (128/187) received oral corticosteroid (prednisolone) maintenance treatment. OP pattern made up the majority (81%) of the radiological pattern with a mean severity CT score of 10 (SD±3). The mean prednisolone dose was 0.68mg/kg/day with a mean treatment duration of 47 days (SD±18). About one-third of patients (67/187) had respiratory symptoms at 4 weeks (SD±3). Among 78.1% (146/187) who had a repeated CXR during follow-up, only 12 patients (8.2%, SD±3) had radiological improvement of less than 50% at 6 weeks (SD±3), with 2 of them later diagnosed as pulmonary tuberculosis. Functional assessments, such as the 6-minute walk test and the spirometry, were only performed in 52.4% and 15.5% of the patients, respectively. CONCLUSION: Almost half of the patients with severe COVID-19 had PRF, with a predominant radiological OP pattern. More than two-thirds of the PRF patients required prolonged oral corticosteroid treatment. Familiarising clinicians with the disease course, radiological patterns, and potential outcomes of this group of patients may better equip them to manage their patients.


Subject(s)
COVID-19 , Pneumonia , Respiratory Insufficiency , Humans , COVID-19/complications , Retrospective Studies , Malaysia/epidemiology , Respiratory Insufficiency/complications , Pneumonia/complications , Adrenal Cortex Hormones/therapeutic use , Cohort Studies , Prednisolone/therapeutic use
8.
Respir Res ; 23(1): 301, 2022 Nov 04.
Article in English | MEDLINE | ID: covidwho-2108780

ABSTRACT

PURPOSE: Acute respiratory distress syndrome (ARDS) is an acute and critical disease among children and adults, and previous studies have shown that the administration of corticosteroids remains controversial. Therefore, a meta-analysis of randomized controlled trials (RCTs) was performed to evaluate the safety and efficacy of corticosteroids. METHODS: The RCTs investigating the safety and efficacy of corticosteroids in ARDS were searched from electronic databases (Embase, Medline, and the Cochrane Central Register of Controlled Trials). The primary outcome was 28-day mortality. Heterogeneity was assessed using the Chi square test and I2 with the inspection level of 0.1 and 50%, respectively. RESULTS: Fourteen RCTs (n = 1607) were included for analysis. Corticosteroids were found to reduce the risk of death in patients with ARDS (relative risk (RR) = 0.78, 95% confidence interval (CI): 0.70-0.87; P < 0.01). Moreover, no significant adverse events were observed, compared to placebo or standard support therapy. Further subgroup analysis showed that variables, such as adults (RR = 0.78; 95% CI: 0.70-0.88; P < 0.01), non-COVID-19 (RR = 0.71; 95% CI: 0.62-0.83; P < 0.01), methylprednisolone (RR = 0.70; 95% CI: 0.56-0.88; P < 0.01), and hydrocortisone (RR = 0.79; 95% CI: 0.63-0.98; P = 0.03) were associated with 28-day mortality among patients who used corticosteroids. However, no association was found, regarding children (RR = 0.21; 95% CI: 0.01-4.10; P = 0.30). CONCLUSION: The use of corticosteroids is an effective approach to reduce the risk of death in ARDS patients. However, this effect is associated with age, non-COVID-19 diseases, and methylprednisolone and hydrocortisone use. Therefore, evidence suggests patients with age ≥ 18 years and non-COVID-19 should be encouraged during the corticosteroid treatment. However, due to substantial differences in the use of corticosteroids among these studies, questions still remain regarding the dosage, optimal corticosteroid agent, and treatment duration in patients with ARDS.


Subject(s)
Hydrocortisone , Respiratory Distress Syndrome , Child , Adult , Humans , Adolescent , Hydrocortisone/therapeutic use , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/drug therapy , Adrenal Cortex Hormones/adverse effects , Methylprednisolone/adverse effects , Randomized Controlled Trials as Topic
9.
Aging Clin Exp Res ; 34(10): 2585-2590, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2104161

ABSTRACT

Corticosteroids lower mortality in hospitalized patients with COVID-19 pneumonia requiring oxygen support. In this observational retrospective study (September 2020-June 2021), we explored the association between receiving home corticosteroids without oxygen supply and 30-day mortality in hospitalized patients with COVID-19 pneumonia. Among a total of 794 COVID-19 pneumonia patients, 763 were included into the study (males 68%; mean age 65 ±12 years), of whom 197 (26%) received home corticosteroids (mean daily prednisone equivalent-dose 40 mg ± 12 mg; range 10-50 mg; median 50 mg; IQR 25-50 mg; for 4 days). The overall 30-day mortality of the study population was 12%. The risk of death-adjusted for age, comorbidities, administration of remdesivir and respiratory failure severity-was lower (HR 0.405; p = 0.024) in patients receiving home corticosteroids. After stratifying the study population by age categories, home corticosteroids were associated with an adjusted decrease in mortality risk in patients > 77 years (HR 0.346; p = 0.040). Home corticosteroids may lower the 30-day mortality in elderly COVID-19 patients.


Subject(s)
COVID-19 , Male , Humans , Aged , COVID-19/drug therapy , SARS-CoV-2 , Outpatients , Retrospective Studies , Adrenal Cortex Hormones/therapeutic use , Oxygen , Steroids
10.
Ann Intern Med ; 173(2): JC3, 2020 07 21.
Article in English | MEDLINE | ID: covidwho-2103352

ABSTRACT

SOURCE CITATION: Ye Z, Rochwerg B, Wang Y, et al. Treatment of patients with nonsevere and severe coronavirus disease 2019: an evidence-based guideline. CMAJ. 2020;192:E536-45. 32350002.


Subject(s)
Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Adrenal Cortex Hormones/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus , COVID-19 , Coronavirus Infections/immunology , Humans , Immunization, Passive/methods , Pandemics , Plasma , Pneumonia, Viral/immunology , SARS-CoV-2 , Severity of Illness Index
11.
Eur Respir Rev ; 31(166)2022 Dec 31.
Article in English | MEDLINE | ID: covidwho-2098296

ABSTRACT

BACKGROUND: The Joint Committee on Vaccination and Immunisation in the United Kingdom requested an evidence synthesis to investigate the relationship between asthma and coronavirus disease 2019 (COVID-19) outcomes. OBJECTIVE: We conducted a systematic review and meta-analysis to summarise evidence on the risk of severe COVID-19 outcomes in people with uncontrolled asthma or markers of asthma severity. METHODS: High-dose inhaled corticosteroids (ICS) or oral corticosteroids (OCS) were used as markers of asthma severity, following international or national asthma guidelines. Risk of bias was assessed using Joanna Briggs Institute tools. Adjusted point estimates were extracted for random-effects meta-analyses and subgroup analyses. RESULTS: After screening, 12 studies (11 in adults and one in children) met the eligibility criteria. Adults using high-dose ICS or OCS had a pooled adjusted hazard ratio (aHR) of 1.33 (95% CI 1.06-1.67, I2=0%) for hospitalisation and an aHR of 1.22 (95% CI 0.90-1.65, I2=70%) for mortality for COVID-19. We found insufficient evidence for associations between markers on COVID-19 mortality in the subgroup analyses. CONCLUSIONS: Adults with severe asthma are at increased risk of COVID-19 hospitalisation compared to nonusers. Our analysis highlighted the dearth of studies in children with asthma investigating serious COVID-19 outcomes.


Subject(s)
Anti-Asthmatic Agents , Asthma , COVID-19 , Adult , Child , Humans , Anti-Asthmatic Agents/adverse effects , Administration, Inhalation , Asthma/diagnosis , Asthma/drug therapy , Asthma/epidemiology , Adrenal Cortex Hormones/therapeutic use
13.
Ter Arkh ; 94(4): 497-502, 2022 May 26.
Article in Russian | MEDLINE | ID: covidwho-2091496

ABSTRACT

Treatment of patients with long-term persistent symptoms after COVID-19 is an urgent problem for clinicians around the world. One of the most significant manifestations of post-COVID-19 syndrome is organizing pneumonia that is usually treat with corticosteroids. The paper presents a clinical case of typical course of post-COVID-19 organizing pneumonia in a patient without previous lung disease. Risk factors, diagnostic methods and treatment options in this group of patients are also discuss.


Subject(s)
COVID-19 , Pneumonia , Humans , COVID-19/diagnosis , Lung/diagnostic imaging , Pneumonia/diagnosis , Pneumonia/drug therapy , Pneumonia/etiology , Adrenal Cortex Hormones/therapeutic use
15.
Am J Rhinol Allergy ; 36(6): 733-740, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2084686

ABSTRACT

BACKGROUND: The efficacy of topical corticosteroids is limited in chronic rhinosinusitis (CRS) due to rapid clearance from the nasal cavity and insufficient drug delivery to inflamed sinonasal passages. LYR-210 is an implantable corticosteroid matrix designed to provide up to 24 weeks of treatment to patients with CRS by locally delivering mometasone furoate (MF) to the sinonasal mucosa. In a randomized, controlled, dose-ranging LANTERN study, LYR-210 (7500 µg) achieved clinically relevant improvement in CRS cardinal symptom composite scores, the 22-item Sinonasal Outcome Test (SNOT-22), ethmoid opacification, and the need for rescue treatment at 24 weeks. OBJECTIVE: As the plasma MF concentrations of LYR-210 (2500 µg) and LYR-210 (7500 µg) were evaluated at weeks 4, 12, and 24 in the LANTERN study (data on file at Lyra Therapeutics, Inc.), this study aims to characterize the pharmacokinetic profiles of both doses of LYR-210 at earlier timepoints post-placement in patients with CRS. METHODS: Twenty-four surgically naïve adult patients with CRS were enrolled in an open-label, multicenter study and underwent in-office bilateral administration of LYR-210 (2500 µg) (n = 12 patients) or LYR-210 (7500 µg) (n = 12 patients) into the middle meatus. Plasma MF concentrations were determined pre-placement and 1-h post-placement (day 1), and on days 2, 3, 7, 14, 21, 28, 42, and 56 by liquid chromatography-tandem mass spectrometry. RESULTS: Both LYR-210 doses were well-tolerated with no serious adverse events. Systemic MF levels were dose-dependent and lower than reported values of other respiratory MF products. Plasma MF concentrations showed steady drug release from LYR-210 (2500 µg) and LYR-210 (7500 µg) that persisted through day 56. CONCLUSION: LYR-210 achieved dose-dependent, continuous local MF delivery at a steady rate with low systemic exposure for months.


Subject(s)
Pregnadienediols , Sinusitis , Adrenal Cortex Hormones/therapeutic use , Adult , Chronic Disease , Drug Liberation , Humans , Mometasone Furoate/therapeutic use , Pharmaceutical Preparations , Pregnadienediols/adverse effects , Pregnadienediols/pharmacokinetics , Sinusitis/drug therapy , Treatment Outcome
16.
Eur Rev Med Pharmacol Sci ; 26(19): 7297-7304, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2081434

ABSTRACT

OBJECTIVE: Pneumonia and hyperinflammatory state related to COVID-19 infection are fatal clinical conditions without definite treatment modalities. Interleukin-6 and Interleukin-1 targeted therapies have been proposed as treatment options. This study was conducted to investigate the efficacy of anakinra and tocilizumab added to corticosteroids in patients with COVID-19-associated pneumonia and hyper-inflammatory syndrome in our tertiary clinical center. PATIENTS AND METHODS: Patients with COVID-19-associated pneumonia and hyperinflammatory state who did not respond to initial treatments, including corticosteroids, were included in the study. The patients' electronic records were reviewed retrospectively and recorded according to a standardized data table. Univariate and multivariate regression analyses were used to identify risk factors associated with intubation. RESULTS: 388 patients were included in the study. 197 patients were intubated and most of them died (n=194/197, 98%). 67 patients received tocilizumab, and 97 patients received anakinra. Anakinra [OR: 0.440, 95% CI=0.244-0.794, p=0.006] and tocilizumab [OR: 0.491, 95% CI=0.256-0.943, p=0.033] were both associated with a decreased risk for intubation. However, having a neutrophil/lymphocyte ratio ≥ 10 [OR: 2.035, 95% CI=1.143-3.623, p=0.016], serum lactate dehydrogenase (LDH) level ≥ 400 [OR: 3.160, 95% CI=1.937-5.156, p<0.001] and age ≥ 50 [OR: 4.048, 95% CI=2.037-8.043, p < 0.001] was associated with an increased risk for intubation. CONCLUSIONS: Both anakinra and tocilizumab, added to initial standard COVID-19 treatments (including glucocorticoids) reduced the need for intubation in patients with COVID-19-associated severe pneumonia and hyperinflammatory syndrome. Given the high mortality rate of intubated patients with COVID-19, both treatments may have added benefits on mortality.


Subject(s)
COVID-19 , Humans , COVID-19/drug therapy , SARS-CoV-2 , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Interleukin-6 , Retrospective Studies , Treatment Outcome , Adrenal Cortex Hormones/therapeutic use , Interleukin-1 , Lactate Dehydrogenases
17.
Travel Med Infect Dis ; 50: 102472, 2022.
Article in English | MEDLINE | ID: covidwho-2069733

ABSTRACT

BACKGROUND: To explore the association between the use of prehospital medications and the development of fatal outcomes in patients who required hospitalization due to coronavirus disease-2019 (COVID-19). METHODS: This retrospective cohort study included adult patients who were hospitalized due to COVID-19. Demographic, clinical, and laboratory data, prehospital medication history, and fatal outcome development (use of high-flow oxygen therapy, intensive care unit [ICU] admission, or mortality) were extracted from the medical records of patients who were admitted due to COVID-19 to the Carlos Seguín Escobedo National Hospital of Arequipa, Peru during July to September 2021, the period after the second wave of COVID-19 cases in Peru. Survival was analyzed using the Cox proportional hazards model, and crude hazard ratios and adjusted hazard ratios (aHR) with their respective 95% confidence intervals (95% CI) were calculated. RESULTS: A total of 192 patients were evaluated, of whom 62% were males and 46.9% did not require oxygen support at admission. Additionally, 64.6% used nonsteroidal anti-inflammatory drugs, 35.4% used corticosteroids, 28.1% used macrolides or ceftriaxone, 24.5% used ivermectin, and 21.9% used warfarin before hospitalization. Of the patients, 30.2% developed a fatal outcome during follow-up. The multivariate analysis revealed that prehospital corticosteroid use was independently associated with the fatal outcome due to COVID-19 with an aHR = 5.29 (95%CI: 1.63-17.2). CONCLUSION: Prehospital corticosteroid use was associated with a 5-fold increased risk of fatal outcome development.


Subject(s)
COVID-19 , Emergency Medical Services , Adult , Male , Humans , Female , COVID-19/drug therapy , SARS-CoV-2 , Retrospective Studies , Peru/epidemiology , Hospitalization , Cohort Studies , Hospitals , Adrenal Cortex Hormones , Referral and Consultation , Oxygen
18.
J Infect Dev Ctries ; 16(9): 1424-1431, 2022 09 30.
Article in English | MEDLINE | ID: covidwho-2066669

ABSTRACT

INTRODUCTION: The aim of the study was to determine the survival probability of critically ill patients with COVID-19 infection who needed mechanical ventilation and to determine the efficacy of Tocilizumab use. METHODOLOGY: The study was designed as a retrospective analysis of consecutive patients older than 18 years, treated in an intensive care unit. The criteria for admission to the intensive care unit was severe respiratory failure requiring mechanical ventilation. All patients received corticosteroid therapy (methylprednisolone 1-2 mg/kg). Tocilizumab was used at a dose of 8 mg/kg in patients with a severe form of the disease (onset, or developed ARDS), followed by cytokine storm (IL-6 ≥ 40 ng/L and CRP ≥ 50 mg/L). RESULTS: 88 patients were included in the study. Intrahospital mortality was 48.86%. No statistically significant difference was observed between patients with and without tocilizumab therapy. In the group of patients in whom this therapy was applied, the values of intrahospital survival were 45.7%, while in the group without this therapy the probability of intrahospital survival was only 0.93%. The probability of survival in the group with noninvasive mechanical ventilation (NIV) was 94.7%, while in the group with invasive mechanical ventilation (IMV) 0.78%. The duration of symptoms before hospitalization (RR-1.088 CI 1.025-1.155, p < 0.05), as well as the duration of IMV (RR-0.906 CI 0.841-0.976, p < 0.05), were shown to be an independent predictor of poor outcome. CONCLUSIONS: The mortality of patients with the most severe form of respiratory failure caused by COVID-19 infection remains high. Independent predictors of poor outcomes were needed for invasive mechanical ventilation and the duration of symptoms before hospitalization or late initiation of appropriate therapy.


Subject(s)
COVID-19 , Respiratory Insufficiency , Adrenal Cortex Hormones , COVID-19/drug therapy , COVID-19/mortality , Critical Illness , Humans , Interleukin-6 , Methylprednisolone , Respiratory Insufficiency/therapy , Retrospective Studies
19.
J Infect Dev Ctries ; 16(9): 1390-1397, 2022 09 30.
Article in English | MEDLINE | ID: covidwho-2066663

ABSTRACT

INTRODUCTION: Using steroids to manage hospitalised coronavirus disease 2019 (COVID-19) patients caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection has been shown to reduce the need for mechanical ventilation and mortality. To date, low-dose dexamethasone and methylprednisolone corticosteroids have been effective in reducing the infection's progress in hospitalised patients. However, it is unknown if high dosages of corticosteroids can achieve a better clinical outcome. This study aims to compare the clinical outcomes of hospitalised COVID-19 patients who are given a 10-day low-dose corticosteroid treatment (IV 2 mg/kg/day methylprednisolone loading dose (LD) then 0.25 mg/kg four times a day (q.i.d.)) with patients given a 10-day high-dose corticosteroid treatment (IV 20 mg dexamethasone once daily (o.d.) or a 1.5 mg/kg prednisolone tablet o.d.). METHODOLOGY: Retrospective data on hospitalised COVID-19 patients were collected for this study, and the primary outcome measure was the patients' clinical status based on the World Health Organization's (WHO) Ordinal Scale for Clinical Improvement (OSCI) on Day-5 and Day-10 post-steroid. RESULTS: The results demonstrated that using steroids significantly improved patients' clinical outcomes from a WHO OSCI level of 4 (0.1) on Day-1 to 2.6 (2.5) on Day-5 (p < 0.001). There was no significant difference in clinical outcome between low-dose and high-dose corticosteroid treatment on Day-5 (H = 2.15; p = 0.34) and Day-10 (H = 1.12; p = 0.58). CONCLUSIONS: This study concludes that using low-dose corticosteroids is recommended for hospitalised COVID-19 patients to ensure clinical outcomes are optimised.


Subject(s)
COVID-19 , Adrenal Cortex Hormones/therapeutic use , COVID-19/drug therapy , Dexamethasone/therapeutic use , Humans , Malaysia , Methylprednisolone/therapeutic use , RNA, Viral , Retrospective Studies , SARS-CoV-2
20.
Medicina (Kaunas) ; 58(10)2022 Sep 27.
Article in English | MEDLINE | ID: covidwho-2066240

ABSTRACT

Aseptic abscess syndrome (AAS) is a rare, potentially life-threatening disorder, with numerous features of neutrophilic dermatoses. The main symptoms include aseptic abscess-like collections in internal organs (spleen, liver, lungs), lack of microbes (bacteria, viruses, or parasites) after an exhaustive search, ineffectiveness of antibiotics, and high sensitivity to corticosteroid therapy. AAS is characterized by the development of deep, inflammatory abscesses and systemic symptoms (weight loss, abdominal pain, fever, and leukocytosis). They may be associated with inflammatory bowel disease (IBD) and autoimmune diseases. The patient in this study is a 67-year-old man, suffering from rheumatoid arthritis (RA), with numerous purulent abscesses in the mediastinum, within the subcutaneous tissue above the extension surfaces of the joints, and on the dorsum of the hands. The lesions are accompanied by bone destruction. The patient was treated with prednisone 40 mg and adalimumab, which resulted in a quick reduction of inflammatory markers and clinical improvement, as well as the healing and absorption of abscesses. Despite COVID-19 infection, treatment with remdesivir, prednisone, and adalimumab was continued, with the complete resolution of the lesions. AAS is difficult to recognize, so practitioners have to be aware of this condition, especially in patients with RA.


Subject(s)
Arthritis, Rheumatoid , COVID-19 , Male , Humans , Aged , Abscess/complications , Abscess/drug therapy , Prednisone/therapeutic use , Adalimumab , COVID-19/complications , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/drug therapy , Syndrome , Anti-Bacterial Agents/therapeutic use , Adrenal Cortex Hormones
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