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1.
Lancet Respir Med ; 2022 May 23.
Article in English | MEDLINE | ID: covidwho-1864689

ABSTRACT

BACKGROUND: Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19. METHODS: In this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (≥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (≤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults ≥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (≤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168. FINDINGS: Between Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58·3 years (SD 14·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87·0% [95% CI 83·7 to 89·6] in the baricitinib plus remdesivir plus placebo group and 87·6% [84·2 to 90·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0·6 [95% CI -3·6 to 4·8]; p=0·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1·01 (95% CI 0·80 to 1·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·5% [1·6 to 13·3]; p=0·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6·0% [2·8 to 9·3]; p=0·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·7% [1·8 to 13·4]; p=0·012). INTERPRETATION: In hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered. FUNDING: National Institute of Allergy and Infectious Diseases.

2.
Int J Obes (Lond) ; 46(4): 866-873, 2022 04.
Article in English | MEDLINE | ID: covidwho-1635369

ABSTRACT

BACKGROUND: Increased adiposity and visceral obesity have been linked to adverse COVID-19 outcomes. The amount of epicardial adipose tissue (EAT) may have relevant implications given its proximity to the heart and lungs. Here, we explored the role of EAT in increasing the risk for COVID-19 adverse outcomes. METHODS: We included 748 patients with COVID-19 attending a reference center in Mexico City. EAT thickness, sub-thoracic and extra-pericardial fat were measured using thoracic CT scans. We explored the association of each thoracic adipose tissue compartment with COVID-19 mortality and severe COVID-19 (defined as mortality and need for invasive mechanical ventilation), according to the presence or absence of obesity. Mediation analyses evaluated the role of EAT in facilitating the effect of age, body mass index and cardiac troponin levels with COVID-19 outcomes. RESULTS: EAT thickness was associated with increased risk of COVID-19 mortality (HR 1.18, 95% CI 1.01-1.39) independent of age, gender, comorbid conditions and BMI. Increased EAT was associated with lower SpO2 and PaFi index and higher levels of cardiac troponins, D-dimer, fibrinogen, C-reactive protein, and 4 C severity score, independent of obesity. EAT mediated 13.1% (95% CI 3.67-28.0%) and 5.1% (95% CI 0.19-14.0%) of the effect of age and 19.4% (95% CI 4.67-63.0%) and 12.8% (95% CI 0.03-46.0%) of the effect of BMI on requirement for intubation and mortality, respectively. EAT also mediated the effect of increased cardiac troponins on myocardial infarction during COVID-19. CONCLUSION: EAT is an independent risk factor for severe COVID-19 and mortality independent of obesity. EAT partly mediates the effect of age and BMI and increased cardiac troponins on adverse COVID-19 outcomes.


Subject(s)
COVID-19 , Adipose Tissue/diagnostic imaging , Adipose Tissue/metabolism , Adiposity , Adult , Body Mass Index , Humans , Pericardium/diagnostic imaging , Pericardium/metabolism , Young Adult
4.
Open forum infectious diseases ; 8(Suppl 1):S264-S264, 2021.
Article in English | EuropePMC | ID: covidwho-1563907

ABSTRACT

Background Invasive fungal infections (IFI) are emergent complications in SARS-CoV-2 infection. We aimed to describe the epidemiology, characteristics and outcome of IFI during the pandemic. Methods Between March 2020 and April 2021, patients admitted to the Intensive Care Unit (ICU) in a COVID-19 center in Mexico City who developed IFI were included. COVID-19 associated pulmonary aspergillosis (CAPA) was defined according to the ECMM/ISHAM criteria. Demographic and clinical data were obtained from the electronic medical record. Descriptive analysis was made. The study was approved by the Institutional Review Board. Results Sixty-seven (67/743, 9%) patients with COVID-19 developed IFI during ICU stay, of which 37 (55%) had CAPA, 24 (36%) had Invasive Candidiasis (IC), 3 Cryptococcosis and 3 pulmonary Mucormycosis. The median age was 57.5 (IQR 48-68) and 46 (69%) were male. Thirty-six (54%) had obesity and 20 (30%) type 2 diabetes. Sixty-two received COVID-19 directed therapy: 48/67 (72%) steroids, 4/67 (6%) tocilizumab and 8/67 (12%) were included in clinical trials. Among 24 patients with IC, 13 (54%) were fluconazole-resistant C. parapsilosis, 11 (46%) C. albicans and 2 C. glabrata. Twenty-two received antifungal treatment, 20 with echinocandins and 2 fluconazole. Among 37 CAPA, 8 (22%) were probable and 29 (78%) possible. Serum galactomannan was positive in 8 (22%), 33 respiratory cultures grew Aspergillus (31 tracheal aspirates and 2 bronchoalveolar lavage). Aspergillus fumigatus was the most frequent isolate in 18/33 (55%). Chest CT showed ground glass opacities in 21 (57%). Most received voriconazole (26/37, 70%). The median time from ICU admission to IFI was 9.5 (IQR 3-14) days. The median ICU and hospital stay length were 30 days (IQR 16-41) and 40 days (IQR 23-49), respectively. In-hospital mortality was 48%. The incidence rate of IC was higher early in the pandemic, due to Infection Control breaches, while higher CAPA incidence may have occurred later due to ventilation system gaps (Figure 1). Bi-monthly Invasive Fungal Infection incidence rate/100 ICU admissions. Conclusion We found 9% incidence of IFIs in critically-ill COVID-19 patients with high mortality. The majority received steroids, had obesity and had a prolonged hospital stay. Most had possible CAPA. An outbreak of fluconazole-resistant C. parapsilosis was found. Disclosures All Authors: No reported disclosures

5.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-296213

ABSTRACT

ABSTRACT INTRODUCTION Coronavirus disease (COVID-19) is a global pandemic. Vitamin D (25-OHD) deficiency has been associated with susceptibility to infectious disease. In this study, the association between COVID-19 outcomes and 25-OHD levels in patients attending a COVID-19 reference center in Mexico City are examined. METHODS Consecutive patients with confirmed COVID-19 were evaluated. All patients underwent clinical evaluation (including outcomes), laboratory measurements (including 25-OHD) and a thoracic computerized tomography (including the measurement of epicardial fat thickness). Low vitamin D was defined as levels <20ng/mL (<50nmol/L) and severely low (or deficient) 25-OHD as a level ≤12ng/mL (<30nmol/L) RESULTS Of the 551 patients included, low 25-OHD levels were present in 45.6% and severely low levels in 10.9%. Severely low 25-OHD levels were associated with mortality (HR 2.11, 95%CI 1.24-3.58, p=0.006) but not with critical COVID-19 (OR 0.97, 95%CI 0.94-0.99, p=0.042), adjusted for age, sex, body-mass index and epicardial fat. Using model-based causal mediation analyses the increased risk of COVID-19 mortality conferred by 25-OHD levels was partly mediated by its effect on D-dimer and cardiac ultrasensitive troponins. Notably, increased risk of COVID-19 mortality conferred by low vitamin D levels was independent of BMI and epicardial fat. CONCLUSION Vitamin D deficiency (≤12ng/mL or <30nmol/L), is independently associated with COVID-19 mortality after adjustment for visceral fat (epicardial fat thickness). Low 25-OHD may contribute to a pro-inflammatory and pro-thrombotic state, increasing the risk for adverse COVID-19 outcomes.

6.
PLoS One ; 15(12): e0244051, 2020.
Article in English | MEDLINE | ID: covidwho-978947

ABSTRACT

BACKGROUND: During the COVID-19 pandemic, risk stratification has been used to decide patient eligibility for inpatient, critical and domiciliary care. Here, we sought to validate the MSL-COVID-19 score, originally developed to predict COVID-19 mortality in Mexicans. Also, an adaptation of the formula is proposed for the prediction of COVID-19 severity in a triage setting (Nutri-CoV). METHODS: We included patients evaluated from March 16th to August 17th, 2020 at the Instituto Nacional de Ciencias Médicas y Nutrición, defining severe COVID-19 as a composite of death, ICU admission or requirement for intubation (n = 3,007). We validated MSL-COVID-19 for prediction of mortality and severe disease. Using Elastic Net Cox regression, we trained (n = 1,831) and validated (n = 1,176) a model for prediction of severe COVID-19 using MSL-COVID-19 along with clinical assessments obtained at a triage setting. RESULTS: The variables included in MSL-COVID-19 are: pneumonia, early onset type 2 diabetes, age > 65 years, chronic kidney disease, any form of immunosuppression, COPD, obesity, diabetes, and age <40 years. MSL-COVID-19 had good performance to predict COVID-19 mortality (c-statistic = 0.722, 95%CI 0.690-0.753) and severity (c-statistic = 0.777, 95%CI 0.753-0.801). The Nutri-CoV score includes the MSL-COVID-19 plus respiratory rate, and pulse oximetry. This tool had better performance in both training (c-statistic = 0.797, 95%CI 0.765-0.826) and validation cohorts (c-statistic = 0.772, 95%CI 0.0.745-0.800) compared to other severity scores. CONCLUSIONS: MSL-COVID-19 predicts inpatient COVID-19 lethality. The Nutri-CoV score is an adaptation of MSL-COVID-19 to be used in a triage environment. Both scores have been deployed as web-based tools for clinical use in a triage setting.


Subject(s)
COVID-19/pathology , Severity of Illness Index , Adult , Aged , Area Under Curve , Body Mass Index , COVID-19/mortality , COVID-19/virology , Female , Hospital Mortality , Humans , Intensive Care Units , Kaplan-Meier Estimate , Male , Middle Aged , ROC Curve , Respiratory Rate , Risk Assessment , SARS-CoV-2/isolation & purification , Triage
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