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1.
Clin Infect Dis ; 75(1): e403-e409, 2022 08 24.
Article in English | MEDLINE | ID: covidwho-2188484

ABSTRACT

BACKGROUND: Remdesivir is an antiviral used to treat coronavirus disease 2019 (COVID-19), which improves some clinical outcomes. Dexamethasone has been shown to be effective in reducing mortality. It has been hypothesized that combination of these two drugs can improve mortality. We evaluated the effect of combination on mortality of COVID-19 patients requiring O2 therapy. METHODS: A prospective quasi-experimental study, including two independent, sequential controlled cohorts, one received remdesivir-dexamethasone and the other dexamethasone alone, was designed. All COVID-19 patients requiring supplemental O2 therapy were enrolled consecutively. The sample size to power mortality was a priori calculated. The primary endpoints were 30-day mortality and viral clearance differences. Secondary endpoints were differences in hospitalization times, improvement in respiratory failure (PO2/FiO2) and inflammatory indices (fibrinogen, CRP, neutrophil/lymphocyte ratio, D-Dimer). Kaplan-Meier curves and the log-rank test were used to evaluate significant differences in mortality between groups. RESULTS: In total, 151 COVID-19 patients were enrolled (remdesivir/dexamethasone group, 76, and dexamethasone alone, 75). No differences in demographic, clinical, and laboratory characteristics were observed between the 2 groups at baseline. Faster viral clearance occurred in the remdesivir/dexamethasone group compared to dexamethasone alone (median 6 vs 16 days; P < .001). The 30-day mortality in the remdesivir/dexamethasone group was 1.3%, whereas in dexamethasone alone was 16% (P < .005). In the remdesivir/dexamethasone group compared to dexamethasone alone there was a reduction in hospitalization days (P < .0001) and a faster improvement in both respiratory function and inflammatory markers. CONCLUSIONS: Remdesivir/dexamethasone treatment is associated with significant reduction in mortality, length of hospitalization, and faster SARS-CoV-2 clearance, compared to dexamethasone alone.


Subject(s)
COVID-19 , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents , COVID-19/drug therapy , Dexamethasone/therapeutic use , Humans , Prospective Studies , SARS-CoV-2
2.
Front Immunol ; 13: 1021928, 2022.
Article in English | MEDLINE | ID: covidwho-2123417

ABSTRACT

ACE2 and TMPRSS2 are crucial for SARS-CoV-2 entry into the cell. Although ACE2 facilitates viral entry, its loss leads to promoting the devastating clinical symptoms of COVID-19 disease. Thus, enhanced ACE2/TMPRSS2 expression is likely to increase predisposition of target cells to SARS-CoV-2 infection. However, little evidence existed about the biological kinetics of these two enzymes and whether dexamethasone treatment modulates their expression. Here, we show that the expression of ACE2 at the protein and mRNA levels was significantly higher in the lung and heart tissues of neonatal compared to adult mice. However, the expression of TMPRSS2 was developmentally regulated. Our results may introduce a novel concept for the reduced susceptibility of the young to SARS-CoV-2 infection. Moreover, ACE2 expression but not TMPRSS2 was upregulated in adult female lungs compared to their male counterparts. Interestingly, the ACE2 and TMPRSS2 expressions were upregulated by dexamethasone treatment in the lung and heart tissues in both neonatal and adult mice. Furthermore, our findings provide a novel mechanism for the observed differential therapeutic effects of dexamethasone in COVID-19 patients. As such, dexamethasone exhibits different therapeutic effects depending on the disease stage. This was supported by increased ACE2/TMPRSS2 expression and subsequently enhanced infection of normal human bronchial epithelial cells (NHBE) and Vero E6 cells with SARS-CoV-2 once pre-treated with dexamethasone. Therefore, our results suggest that individuals who take dexamethasone for other clinical conditions may become more prone to SARS-CoV-2 infection.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Humans , Male , Female , Mice , Animals , Angiotensin-Converting Enzyme 2/genetics , COVID-19/drug therapy , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , SARS-CoV-2 , Dexamethasone/pharmacology , Dexamethasone/therapeutic use , Serine Endopeptidases/genetics
3.
Medicine (Baltimore) ; 101(45): e31681, 2022 Nov 11.
Article in English | MEDLINE | ID: covidwho-2115809

ABSTRACT

This study aimed to evaluate the efficacy of early antiviral treatment in preventing clinical deterioration in asymptomatic or mildly symptomatic severe acute respiratory syndrome coronavirus 2 infected (COVID-19) patients in home isolation and to share our experiences with the ambulatory management of nonsevere COVID-19 patients. This retrospective study included mild COVID-19 adult patients confirmed by real-time reverse transcription-polymerase chain reaction. They received care via an ambulatory management strategy between July 2021 and November 2021. Demographic data, clinical progression, and outcomes were collected. Both descriptive and inferential statistics were performed to illustrate the cohort's characteristic and outcomes of the study. Univariable and multivariable logistic regression models were employed to investigate the associations between clinical factors and disease progression. A total of 1940 patients in the Siriraj home isolation system met the inclusion criteria. Their mean age was 42.1 ±â€…14.9 years, with 14.2% older than 60 years, 54.3% female, and 7.1% with a body weight ≥ 90 kg. Only 115 patients (5.9%) had deterioration of clinical symptoms. Two-thirds of these could be managed at home by dexamethasone treatment under physician supervision; however, 38 of the 115 patients (2.0% of the study cohort) needed hospitalization. Early favipiravir outpatient treatment (≤ 5 days from onset of symptoms) in nonsevere COVID-19 patients was significantly associated with a lower rate of symptom deterioration than late favipiravir treatment (50 [4.6%] vs 65 [7.5%] patients, respectively; P = .008; odds ratio 1.669; 95% confidence interval, 1.141-2.441). The unfavorable prognostic factors for symptom deterioration were advanced age, body weight ≥ 90 kg, unvaccinated status, higher reverse transcription-polymerase chain reaction cycle threshold, and late favipiravir treatment. The early delivery of essential treatment, including antiviral and supervisory dexamethasone, to ambulatory nonsevere COVID-19 patients yielded favorable outcomes during the COVID-19 pandemic in Thailand.


Subject(s)
COVID-19 , Influenza, Human , Adult , Humans , Female , Middle Aged , Male , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Pandemics , Retrospective Studies , Body Weight , Dexamethasone/therapeutic use
4.
Ann Intern Med ; 175(10): JC115, 2022 10.
Article in English | MEDLINE | ID: covidwho-2110760

ABSTRACT

SOURCE CITATION: Wolfe CR, Tomashek KM, Patterson TF, et al. Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial. Lancet Respir Med. 2022;10:888-99. 35617986.


Subject(s)
COVID-19 , Adenosine Monophosphate/analogs & derivatives , Adult , Alanine/analogs & derivatives , Azetidines , COVID-19/drug therapy , Dexamethasone/therapeutic use , Double-Blind Method , Humans , Purines , Pyrazoles , Sulfonamides
5.
Respir Res ; 23(1): 303, 2022 Nov 05.
Article in English | MEDLINE | ID: covidwho-2108781

ABSTRACT

Blood levels of the soluble receptor for advanced glycation end-products (sRAGE) are acutely elevated during the host inflammatory response to infection and predict mortality in COVID-19. However, the prognostic performance of this biomarker in the context of treatments to reduce inflammation is unclear. In this study we investigated the association between sRAGE and mortality in dexamethasone-treated COVID-19 patients. We studied 89 SARS-CoV-2 positive subjects and 22 controls attending the emergency department of a University Teaching Hospital during the second wave of COVID-19 and measured sRAGE at admission. In positive individuals sRAGE increased with disease severity and correlated with the National Early Warning Score 2 (Pearson's r = 0.56, p < 0.001). Fourteen out of 72 patients treated with dexamethasone died during 28 days of follow-up. Survival rates were significantly lower in patients with high sRAGE (> 3532 pg/mL) than in those with low sRAGE (p = 0.01). Higher sRAGE levels were associated with an increased risk of death after adjustment for relevant covariates. In contrast, IL-6 did not predict mortality in these patients. These results demonstrate that sRAGE remains an independent predictor of mortality among COVID-19 patients treated with dexamethasone. Determination of sRAGE could be useful for the clinical management of this patient population.


Subject(s)
COVID-19 , Humans , Receptor for Advanced Glycation End Products , COVID-19/drug therapy , SARS-CoV-2 , Biomarkers , Dexamethasone/therapeutic use , Glycation End Products, Advanced
6.
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
7.
Endocr Pract ; 28(10): 1100-1106, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2061131

ABSTRACT

OBJECTIVE: Since January 2020, the highly contagious novel coronavirus SARS-CoV-2 has caused a global pandemic. Severe COVID-19 leads to a massive release of proinflammatory mediators, leading to diffuse damage to the lung parenchyma, and the development of acute respiratory distress syndrome. Treatment with the highly potent glucocorticoid (GC) dexamethasone was found to be effective in reducing mortality in severely affected patients. METHODS: To review the effects of glucocorticoids in the context of COVID-19 we performed a literature search in the PubMed database using the terms COVID-19 and glucocorticoid treatment. We identified 1429 article publications related to COVID-19 and glucocorticoid published from 1.1.2020 to the present including 238 review articles and 36 Randomized Controlled Trials. From these studies, we retrieved 13 Randomized Controlled Trials and 86 review articles that were relevant to our review topics. We focused on the recent literature dealing with glucocorticoid metabolism in critically ill patients and investigating the effects of glucocorticoid therapy on the immune system in COVID-19 patients with severe lung injury. RESULTS: In our review, we have discussed the regulation of the hypothalamic-pituitary-adrenal axis in patients with critical illness, selection of a specific GC for critical illness-related GC insufficiency, and recent studies that investigated hypothalamic-pituitary-adrenal dysfunction in patients with COVID-19. We have also addressed the specific activation of the immune system with chronic endogenous glucocorticoid excess, as seen in patients with Cushing syndrome, and, finally, we have discussed immune activation due to coronavirus infection and the possible mechanisms leading to improved outcomes in patients with COVID-19 treated with GCs. CONCLUSION: For clinical endocrinologists prescribing GCs for their patients, a precise understanding of both the molecular- and cellular-level mechanisms of endogenous and exogenous GCs is imperative, including timing of administration, dosage, duration of treatment, and specific formulations of GCs.


Subject(s)
COVID-19 , Glucocorticoids , COVID-19/drug therapy , Critical Illness , Dexamethasone/therapeutic use , Glucocorticoids/pharmacology , Glucocorticoids/therapeutic use , Humans , Hypothalamo-Hypophyseal System , Pituitary-Adrenal System , SARS-CoV-2
8.
PLoS One ; 17(10): e0275217, 2022.
Article in English | MEDLINE | ID: covidwho-2054365

ABSTRACT

BACKGROUND: Dexamethasone 6 mg daily for 10 days is the recommended treatment for patients with severe or critical coronavirus disease 2019 (COVID-19). The evidence on the benefit of high-dose dexamethasone is limited. The goal of this study was to assess the effects of 6 mg daily vs. 20 mg daily of dexamethasone in hospitalized patients with COVID-19 pneumonia. METHODS: We conducted a single-center, randomized, clinical trial involving hospitalized patients with COVID-19 pneumonia. Participants were randomized 1:1 to dexamethasone 6 mg daily or dexamethasone 20 mg daily, and were stratified by the WHO-Ordinal Scale for Clinical Improvement (OSCI). The primary outcome was clinical improvement equal to or greater than 2 points by OSCI on day 28. Secondary outcomes were 28-day mortality, intensive care unit-free days, and ventilator-free days on day 28. RESULTS: Of the 107 patients who enrolled and completed the follow up, 55 patients enrolled in the low-dose group and 52 patients enrolled in the high-dose group. Treatment with dexamethasone 20 mg daily compared with dexamethasone 6 mg daily did not result in better clinical improvement based on OSCI on day 28 (71.2% vs. 78.2%; odds ratio, 1.45 [0.55-3.86]; p = 0.403). For participants who required high-flow oxygen or noninvasive ventilation at randomization, the 6-mg group had better survival than the 20-mg group on day 28 (100% vs. 57.1%; p = 0.025). Although more participants in the 6-mg group received immune modulators (40% vs. 21.2%; p = 0.035), 50% of death cases in the 20-mg group who required high-flow oxygen or noninvasive ventilation at randomization received immune modulators. CONCLUSIONS: Dexamethasone 20 mg daily did not result in better clinical outcome improvement, and was probably associated with higher 28-day mortality in patients on high-flow oxygen or noninvasive ventilation, compared with dexamethasone 6 mg daily. TRIAL REGISTRATION: Clinialtrials.gov number, NCT04707534, registered January 13, 2021.


Subject(s)
COVID-19 , COVID-19/drug therapy , Dexamethasone/therapeutic use , Humans , Oxygen , SARS-CoV-2
10.
Clin Drug Investig ; 42(11): 949-964, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2048650

ABSTRACT

BACKGROUND: Unprotected and fragile elderly people in nursing homes experienced the highest mortality rates during the initial coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE: Our aim was to study the role of two oral anti-inflammatory drugs, colchicine and prednisone, in elderly patients with COVID-19 in geriatric centers. METHODS: A phase II/III, randomized, controlled, multicenter clinical trial was performed in a geriatric population comparing the efficacy and safety of an oral combination of prednisone (60 mg/day for 3 days) and colchicine (at loading doses of 1-1.5 mg/day for 3 days, followed by 0.5 mg/day for 11 days) with the standard treatment, based on intravenous dexamethasone. Primary endpoints assessed the efficacy in reducing death or the modified endpoint death/therapeutic failure to the study drugs over a 28-day period, while secondary endpoints included safety, laboratory changes, and additional therapies used. RESULTS: Fifty-four patients (35 female/19 male) were enrolled, 25 (46.3%) of whom were allocated to the experimental arm and 29 (53.7%) to the control arm. At day 28, no differences in deaths were observed. The combination of mortality or therapeutic failure occurred in 12 (45.13%) patients receiving dexamethasone and 6 (28.13%) patients receiving colchicine/prednisone, resulting in a reduction of risk difference (RD) of - 17% (p = 0.17), with an average reduction of 39% (risk ratio [RR] 0.61) in patients receiving colchicine/prednisone (p = 0.25). Control patients received higher amounts of additional glucocorticoids (p = 0.0095) over a longer time frame (p = 0.0003). Colchicine/prednisone significantly reduced ferritin levels at day 14, as well as D-dimer and lactate dehydrogenase (LDH) levels at day 28. Adverse events were similar in both groups. CONCLUSIONS: The combination colchicine/prednisone compared with intravenous dexamethasone has shown a remarkable trend to increase disease survival over a 28-day period in elderly patients requiring oxygen therapy in geriatric centers, without safety issues. CLINICAL TRIAL REGISTRY: Clinical Trials Registration Number: NCT04492358.


Subject(s)
COVID-19 , Humans , Male , Female , Aged , COVID-19/drug therapy , Prednisone/adverse effects , Colchicine/adverse effects , SARS-CoV-2 , Dexamethasone/therapeutic use , Treatment Outcome
11.
Farm Hosp ; 46(3): 166-172, 2022 May 04.
Article in English | MEDLINE | ID: covidwho-2044834

ABSTRACT

OBJECTIVE: One year after the declaration of the SARS-CoV-2 pandemic, only  dexamethasone has clearly shown a reduction in mortality for COVID-19  hospitalized patients. For interleukin-6 inhibitors, results are variable and  nclear. The objective was to review and analyze the effect of tocilizumab and  sarilumab on survival in this setting. METHOD: The PRISMA statements were fulfilled for the systematic review. A  systematic search in Medline, Embase and medRxiv was conducted to identify  randomized controlled trials with tocilizumab or sarilumab in hospitalized  patients with COVID-19. Mortality data from non-critical and critical patients  were extracted. A random-effects (DerSimonian-Laird) meta-analysis was  performed for both subgroups and the whole population using MAVIS software  v. 1.1.3. Similarity and homogeneity among trials were assessed. RESULTS: Twenty-five and 23 articles were identified in Medline and Embase,  respectively, five were trials with tocilizumab and/or sarilumab; two more were  identified at medRxiv. Seven randomized clinical trials fulfilled the  inclusion criteria. Another trial was pre-published and included post-hoc. The  meta-analysis, with eight randomized clinical trials and 6,340 patients, showed  a benefit on mortality for interleukin-6  heterogeneity (I2 = 7%), but  a low similarity among studies. The results showed no differences among  critical and non-critical patients. A sensitivity analysis excluding non-similar or  heterogeneous studies showed different results, without benefit and with low  precision of the result in non-critical patients. CONCLUSIONS: A benefit in mortality for interleukine-6 inhibitors was found, but  with important differences among the scenarios analyzed in the clinical  trials. Positive results are mainly caused by two randomized clinical trials which  are similar in concomitant use of steroids and veryhigh mortality in  critical patents. Sarilumab was poorly represented in the meta-analysis.  Nevertheless, an association between the benefit and the critical/non-critical  condition was not found. More randomized clinical trials, mainly focused in  atients at high mortality risk, are needed to confirm the benefit of interleukine- 6 inhibitors for COVID-19. Sarilumab was underrepresented in the meta- analysis.


OBJETIVO: Un año después de la declaración de la pandemia por SARS­CoV-2,  solo dexametasona había mostrado claramente una reducción de la mortalidad  en pacientes hospitalizados por COVID-19. Los resultados de los inhibidores de  interleucina 6 son diversos y poco claros. El objetivo de este trabajo es  revisar y analizar el efecto de tocilizumab y sarilumab sobre la supervivencia  de los pacientes en este escenario.Método: La revisión sistemática siguió las recomendaciones de PRISMA. Se  realizó una búsqueda sistemática en Medline, Embase y medRxiv para identificar ensayos controlados aleatorizados con tocilizumab o sarilumab  en pacientes hospitalizados con COVID-19. Se recopilaron los datos de mortalidad de pacientes críticos y no críticos y se llevó a cabo un metaanálisis de efectos aleatorios (Der Simonian-Laird) para ambos  subgrupos y para toda la población, usando el software MAVIS v. 1.1.3. La similitud y homogeneidad entre los ensayos fue evaluada. RESULTADOS: Se identificaron 25 y 23 artículos en Medline y Embase, respectivamente; cinco eran ensayos con tocilizumab y/o sarilumab;  se identificaron dos más en medRxiv. En total, siete ensayos clínicos  aleatorizados cumplieron los criterios de inclusión. Posteriormente, se  prepublicó otro ensayo que cumplía los criterios de inclusión y se incorporó al  análisis. El metaanálisis, con ocho ensayos clínicos aleatorizados y 6.340  pacientes, mostró un beneficio sobre la mortalidad para los inhibidores de  interleucina-6 (hazard ratio 0,85; intervalo de confianza al 95% 0,74-0,99),  con baja heterogeneidad (I2 = 7%), pero reducida similitud entre los estudios.  Los resultados no mostraron diferencias entre pacientes críticos y no  críticos. Un análisis de sensibilidad excluyendo estudios heterogéneos o no  similares mostró resultados diferentes, sin beneficio y con baja precisión del  resultado en pacientes no críticos. CONCLUSIONES: Se encontró un beneficio en la mortalidad de los inhibidores de  la interleucina 6, pero con importantes diferencias entre los escenarios analizados en los ensayos clínicos. Los resultados positivos se  eben principalmente a dos ensayos que son similares en el uso concomitante  de esteroides y una mortalidad muy alta en pacientes críticos. Sarilumab estuvo escasamente representado en el metaanálisis. Sin embargo, el metaanálisis por subescenarios no encontró una relación entre  el beneficio y la condición de pacientes críticos/no críticos. Se necesitan más ensayos clínicos aleatorizados, principalmente enfocados en  pacientes con alto riesgo de mortalidad, para confirmar el beneficio de los  inhibidores de interleucina-6 en COVID-19.


Subject(s)
COVID-19 , COVID-19/drug therapy , Dexamethasone/therapeutic use , Humans , Interleukin-6 , Pandemics , SARS-CoV-2
12.
PLoS One ; 17(9): e0267815, 2022.
Article in English | MEDLINE | ID: covidwho-2043198

ABSTRACT

OBJECTIVE: To describe differences by race and ethnicity in treatment patterns among hospitalized COVID-19 patients in the US from March-August 2020. METHODS: Among patients in de-identified Optum electronic health record data hospitalized with COVID-19 (March-August 2020), we estimated odds ratios of receiving COVID-19 treatments of interest (azithromycin, dexamethasone, hydroxychloroquine, remdesivir, and other steroids) at hospital admission, by race and ethnicity, after adjusting for key covariates of interest. RESULTS: After adjusting for key covariates, Black/African American patients were less likely to receive dexamethasone (adj. OR [95% CI]: 0.83 [0.71, 0.96]) and more likely to receive other steroids corticosteroids (adj. OR [95% CI]: 2.13 [1.90, 2.39]), relative to White patients. Hispanic/Latino patients were less likely to receive dexamethasone than Not Hispanic/Latino patients (adj. OR [95% CI]: 0.69 [0.58, 0.82]). CONCLUSIONS: Our findings suggest that COVID-19 treatments patients received in Optum varied by race and ethnicity after adjustment for other possible explanatory factors. In the face of rapidly evolving treatment landscapes, policies are needed to ensure equitable access to novel and repurposed therapeutics to avoid disparities in care by race and ethnicity.


Subject(s)
COVID-19 , Pandemics , Azithromycin/therapeutic use , COVID-19/drug therapy , COVID-19/epidemiology , Dexamethasone/therapeutic use , Ethnicity , Humans , Hydroxychloroquine/therapeutic use , SARS-CoV-2 , United States , Whites
13.
Medicine (Baltimore) ; 101(38): e30474, 2022 Sep 23.
Article in English | MEDLINE | ID: covidwho-2042654

ABSTRACT

Although some studies have reported prognostic factors for coronavirus disease 2019 (COVID-19), they were conducted before standard treatment with remdesivir and dexamethasone was implemented. This retrospective, observational study was conducted to evaluate various prognostic factors in patients with COVID-19 pneumonia receiving standard treatment with remdesivir and dexamethasone. Of 99 patients with COVID-19 pneumonia, 68 (68.7%) died within 30 days of hospitalization. The mean age was 71.3 years. Remdesivir and dexamethasone were administered to 80 (80.8%) and 84 (84.8%) patients, respectively. Early antibiotic treatment was administered to 70 patients (70.7%) within 5 days of hospitalization. Dexamethasone (79.4% vs 96.8%, P = .033) was more frequently administered in the survived group, whereas early antibiotics (60.3% vs 93.5%, P = .001) were less frequently administered. In the multivariate analysis, a high National Early Warning Score (NEWS; odds ratio [OR] 1.272), high Charlson Comorbidity Index (CCI; OR 1.441), and dyspnea (OR 4.033) were independent risk factors for 30-day mortality. There was no significant difference in age, sex, and vaccination doses between the survived and fatal groups. Lymphopenia, monocytopenia and high levels of C-reactive protein (CRP)/lactate dehydrogenase (LDH) reflected poor prognosis. NEWS, CCI, and dyspnea were predictors of 30-day mortality in patients with COVID-19 pneumonia. Early antibiotic use did not lower the 30-day mortality risk.


Subject(s)
COVID-19 , Pneumonia , Adenosine Monophosphate/analogs & derivatives , Aged , Alanine/analogs & derivatives , Anti-Bacterial Agents/therapeutic use , C-Reactive Protein/metabolism , COVID-19/drug therapy , Dexamethasone/therapeutic use , Dyspnea , Humans , Lactate Dehydrogenases , Prognosis , Retrospective Studies , SARS-CoV-2
15.
Int J Infect Dis ; 122: 659-664, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-2015434

ABSTRACT

OBJECTIVE: In this study, we aimed to compare the effects of intravenous dexamethasone and methylprednisolone on the treatment of inpatients with COVID-19. METHODS: In this randomized clinical trial, 143 patients under 80 years of age with moderate to severe COVID-19 were enrolled and randomly assigned to two groups: dexamethasone (8 mg/day) and methylprednisolone (60 mg/day in two divided doses). The primary outcome was the length of hospital stay. The secondary outcomes included: duration of oxygen therapy, absolute leukocyte and lymphocyte count, hypokalemia, hyperglycemia, intensive care unit admission, and mortality in the two groups for 28 days. Data were analyzed by SPSS version 26 using t-test, chi-square, and analysis of variance. RESULTS: The duration of hospitalization was significantly (P <0.001) shorter in the dexamethasone group than in the methylprednisolone group (8 [95% confidence interval [CI]:6-10] and 11 [95% CI: 7-14], respectively). In addition, the duration of oxygen therapy in the dexamethasone group (7 [95% CI: 5-9]) was significantly (P <0.001) shorter than in the methylprednisolone group (10 [95% CI: 5.5-14]). The mortality rate was 17.1% (95% CI: 8.1-26.1) in the dexamethasone group and 12.3% (95% CI: 4.6-20.0) in the methylprednisolone group, which was not statistically significant (P = 0.46). CONCLUSION: Results showed better effectiveness of 8 mg/day dexamethasone compared with 60 mg/day methylprednisolone based on the shorter hospital stay, which can be considered in the therapeutic protocol of COVID-19. TRIAL REGISTRATION: IRCT20210223050466N1.


Subject(s)
COVID-19 , COVID-19/drug therapy , Dexamethasone/therapeutic use , Humans , Methylprednisolone/therapeutic use , Oxygen , SARS-CoV-2
16.
Future Microbiol ; 17: 1217-1229, 2022 10.
Article in English | MEDLINE | ID: covidwho-2009815

ABSTRACT

Aim: Our main objectives were to compare the effects of Rejuveinix (RJX), dexamethasone (DEX) and their combination on the severity of sepsis and survival outcome in an animal model of fatal sepsis. Methods: We used the LPS plus D-galactosamine mouse model of sepsis to compare the anti-inflammatory activities of RJX, dexamethasone and a combination of RJX plus DEX. Additionally, we examined the clinical feasibility and tolerability of combining RJX with DEX in COVID-19 patients in a clinical phase I study. Data were analyzed using standard methods. Results & conclusion: RJX exhibited potent anti-inflammatory activity in the murine sepsis model. The combination of RJX plus DEX was more effective than either agent alone, decreased the inflammatory cytokine responses and associated organ damage, and improved the survival outcome in mice. In the phase I clinical study, RJX plus DEX was well tolerated by COVID-19 patients.


Subject(s)
Anti-Inflammatory Agents , COVID-19 , Sepsis , Animals , Anti-Inflammatory Agents/therapeutic use , Ascorbic Acid , COVID-19/drug therapy , Dexamethasone/therapeutic use , Disease Models, Animal , Drug Combinations , Magnesium Sulfate , Mice , Niacinamide , Pantothenic Acid , Pyridoxine , Riboflavin , Sepsis/drug therapy , Thiamine
17.
PLoS One ; 17(8): e0271807, 2022.
Article in English | MEDLINE | ID: covidwho-1993479

ABSTRACT

INTRODUCTION: The aim of this study was to determine the efficacy of early tocilizumab treatment for hospitalized patients with COVID-19 disease. METHODS: Open-label randomized phase II clinical trial investigating tocilizumab in patients with proven COVID-19 admitted to the general ward and in need of supplemental oxygen. The primary endpoint of the study was 30-day mortality with a prespecified 2-sided significance level of α = 0.10. A post-hoc analysis was performed for a combined endpoint of mechanical ventilation or death at 30 days. Secondary objectives included comparing the duration of hospital stay, ICU admittance and duration of ICU stay and the duration of mechanical ventilation. RESULTS: A total of 354 patients (67% men; median age 66 years) were enrolled of whom 88% received dexamethasone. Thirty-day mortality was 19% (95% CI 14%-26%) in the standard arm versus 12% (95% CI: 8%-18%) in the tocilizumab arm, hazard ratio (HR) = 0.62 (90% CI 0.39-0.98; p = 0.086). 17% of patients were admitted to the ICU in each arm (p = 0.89). The median stay in the ICU was 14 days (IQR 9-28) in the standard arm versus 9 days (IQR 5-14) in the tocilizumab arm (p = 0.014). Mechanical ventilation or death at thirty days was 31% (95% CI 24%-38%) in the standard arm versus 21% (95% CI 16%-28%) in the tocilizumab arm, HR = 0.65 (95% CI 0.42-0.98; p = 0.042). CONCLUSIONS: This randomized phase II study supports efficacy for tocilizumab when given early in the disease course in hospitalized patients who need oxygen support, especially when concomitantly treated with dexamethasone. TRIAL REGISTRATION: https://www.trialregister.nl/trial/8504.


Subject(s)
COVID-19 , Aged , Antibodies, Monoclonal, Humanized , COVID-19/drug therapy , Dexamethasone/therapeutic use , Female , Humans , Male , Oxygen , Respiration, Artificial , SARS-CoV-2 , Treatment Outcome
18.
Int J Obes (Lond) ; 46(11): 2000-2005, 2022 11.
Article in English | MEDLINE | ID: covidwho-1991549

ABSTRACT

OBJECTIVE: A fixed 6 mg dexamethasone dose for 10 days is the standard treatment for all hospitalised COVID-19 patients who require supplemental oxygen. Yet, the pharmacokinetic properties of dexamethasone can lead to diminishing systemic dexamethasone exposure with increasing body mass index (BMI). The present study examines whether this translates to overweight and obesity being associated with worse clinical outcomes, defined as ICU admission or in hospital death, in COVID-19 patients treated with fixed-dose dexamethasone. METHODS: We conducted a single centre retrospective cohort study in COVID-19 patients who were admitted to a non-ICU ward and were treated with dexamethasone (6 mg once daily for a maximum of ten days) between June 2020 and January 2021. Univariable and multivariable logistic regression analyses were conducted to assess the association between BMI-categories and an unfavourable clinical course (ICU admission and/or in hospital death). Analyses were adjusted for age, comorbidities, inflammatory status, and oxygen requirement at admission. For reference, similar analyses were repeated in a cohort of patients hospitalised before dexamethasone was introduced (March 2020 through May 2020). RESULTS: In patients treated with dexamethasone (n = 385) an unfavourable clinical course was most prevalent in patients with normal weight (BMI < 25) compared to patients with overweight (BMI 25-30) and patients with obesity (BMI ≥ 30) with percentages of 33, 26 and 21% respectively. In multivariable analyses, there was no association between BMI-category and an unfavourable clinical course (respectively with aORs of 0.81 (0.43-1.53) and 0.61 (0.30-1.27) with normal weight as reference). In the reference cohort (n = 249) the opposite was observed with an unfavourable clinical course being most prevalent in patients with overweight (39% vs 28%; aOR 2.17 (0.99-4.76)). In both cohorts, CRP level at admission was higher and lymphocyte count was lower in patients with normal weight compared to patients with obesity. CONCLUSIONS: Overweight and obesity are not associated with an unfavourable clinical course in COVID-19 patients admitted to a non-ICU ward and treated with 6 mg dexamethasone once daily.


Subject(s)
COVID-19 , Overweight , Humans , Overweight/complications , Overweight/drug therapy , Overweight/epidemiology , COVID-19/complications , COVID-19/drug therapy , Hospital Mortality , Retrospective Studies , Obesity/complications , Obesity/drug therapy , Obesity/epidemiology , Body Mass Index , Dexamethasone/therapeutic use , Oxygen
19.
Rev Med Interne ; 43(11): 673-676, 2022 Nov.
Article in French | MEDLINE | ID: covidwho-1991254

ABSTRACT

Systemic immunoglobulin light-chain (AL) amyloidosis is characterized by deposition of amyloid fibrils of light chains produced by clonal CD38+plasma cells, resulting in organ dysfunction. Cardiac involvement has a major prognostic value. Antiplasma cell chemotherapy reduces the synthesis of immunoglobulin light chains (precursors of amyloid deposits). We describe a case of AL amyloidosis in a 95-year-old patient. Our patient responded poorly to treatment with rituximab, cyclophosphamide-bortezomib-dexamethasone, and rituximab-bendamustine. Finally, the anti-CD38 antibody daratumumab was associated with the best hematologic responsiveness without significant adverse effects. In conclusion, our case suggests that daratumumab is an effective and well-tolerated alternative to chemotherapy in the treatment af AL amyloidosis in very elderly patients.


Subject(s)
Immunoglobulin Light-chain Amyloidosis , Humans , Aged , Aged, 80 and over , Immunoglobulin Light-chain Amyloidosis/complications , Immunoglobulin Light-chain Amyloidosis/diagnosis , Immunoglobulin Light-chain Amyloidosis/drug therapy , Rituximab/therapeutic use , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal/adverse effects , Immunoglobulin Light Chains , Cyclophosphamide/therapeutic use , Dexamethasone/therapeutic use
20.
Adv Ther ; 39(10): 4723-4741, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1990786

ABSTRACT

INTRODUCTION: To compare the mortality of hospitalized patients with COVID-19 between those that required supplemental oxygen and received dexamethasone with a comparable set of patients who did not receive dexamethasone. METHODS: We utilized the Premier Health Database to identify hospitalized adult patients with COVID-19 from July 1, 2020-January 31, 2021. Index date was when patients first initiated oxygen therapy. The primary endpoint was in-hospital mortality for patients receiving dexamethasone versus those not receiving dexamethasone 1-day pre- to 1-day post-index period. Secondary endpoints included 28-day mortality, time to in-hospital mortality, progression to invasive mechanical ventilation or death, time to discharge, and proportion discharged alive by day 28. Twenty-three models using weighting, matching, stratification, and regression were deployed through the concept of frequentist model average (FMA) to estimate the effect of dexamethasone on all-cause mortality up to the 28-day hospitalization period. RESULTS: A total of 1,208,881 patients with COVID-19 were screened; as an inpatient 255,216 used oxygen, and 251,536 were included in the analysis. In the dexamethasone group, odds of in-hospital mortality were higher than those of the comparator (FMA: odds ratio [OR] 1.15, 95% CI 1.08, 1.22). Using a best fit model, OR for in-hospital mortality was non-significant for the dexamethasone group compared with the comparator (OR 1.02, 95% CI 0.92, 1.14). Dexamethasone treatment was associated with poorer outcomes versus the comparator group across the majority of secondary endpoints, except for number of days in hospital, which was lower in the dexamethasone group versus the comparator group (mean difference - 2.14, 95% CI - 2.43, - 1.47). CONCLUSIONS: Hospitalized adult patients with COVID-19 who required supplemental oxygen and received dexamethasone did not have a survival benefit versus similar patients not receiving dexamethasone. The dexamethasone group was not associated with favorable responses for outcomes such as progression to death or mechanical ventilation and time to in-hospital death.


Subject(s)
COVID-19 , Adult , COVID-19/drug therapy , Dexamethasone/therapeutic use , Hospital Mortality , Humans , Inpatients , Oxygen , SARS-CoV-2 , United States
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