Effect of EARLY administration of DEXamethasone in patients with COVID-19 pneumonia without acute hypoxemic respiratory failure and risk of development of acute respiratory distress syndrome (EARLY-DEX COVID-19): study protocol for a randomized controlled trial (preprint)

BackgroundCorticosteroids are one of the few drugs that have shown a reduction in mortality in coronavirus disease 2019 (COVID-19). In the RECOVERY trial, the use of dexamethasone reduced 28-day mortality compared to standard care in hospitalized patients with suspected or confirmed COVID-19 requiring supplemental oxygen or invasive mechanical ventilation. No benefit in patients not requiring respiratory support at randomization was observed. However, we believe that the use of corticosteroids in patients with COVID-19 pneumonia might not be subject to a decision based solely on oxygen needs. Evidence has shown that 30% of COVID-19 patients with mild symptoms at presentation will progress to acute respiratory distress syndrome (ARDS), particularly patients in whom laboratory inflammatory biomarkers associated with COVID-19 disease progression are detected. We postulated that dexamethasone treatment in hospitalized patients with COVID-19 pneumonia without additional oxygen requirements and at risk of progressing to severe disease might lead to a decrease in the development of ARDS, and thereby reduce death.Methods/designThis is a multicenter, randomized, controlled, parallel, open-label trial testing dexamethasone in 252 adult patients with COVID-19 pneumonia who do not require supplementary oxygen on admission, but are at risk factors for development ARDS. Risk for development ARDS is defined as levels of lactate dehydrogenase >245 U/L, C-reactive protein >100 mg/L, and lymphocyte count of <0.80 × 109/L. Eligible patients will be randomly assigned to receive either dexamethasone or standard of care. Patients in the dexamethasone group will receive an intravenous dose of 6 mg once daily from day 1 to day 3, followed by an oral dose of 6 mg once daily from day 4 to day 7. The primary outcome is a composite of development of moderate ARDS and all-cause mortality during the 30-day period following enrollment.DiscussionIf our hypothesis is correct, the results of this study will provide additional insights about the management and progression of this specific subpopulation of patients with COVID-19 pneumonia without additional oxygen requirements and at risk of progressing to severe disease.Trial registrationClinicalTrials.gov NCT04836780. Registered on 8 April 2021 as EARLY-DEX COVID-19.

Thalassemia Is Paradoxically Associated with a Reduced Risk of In-Hospital Complications and Mortality in COVID-19: Data from an International Registry (preprint)

Background: Although numerous patient specific co-factors have been shown to be associated with worse outcomes in COVID-19, the prognostic value of thalasemic syndromes in COVID-19 patients remains poorly understood.Aims: We studied the outcomes of 137 COVID-19 patients with a history of Transfusion Dependent Thalassemia (TDT) and non-Transfusion Dependent Thalassemia (NTDT) extracted from a large international cohort and compared them with the outcomes from a matched cohort of COVID-19 patients with no history of thalasemia.Results: The mean age of thalassemia patients included in our study was 41±16 years (48.9% male). Almost 81% of these patients suffered from TDT requiring blood transfusions on a regular basis. 38.7% of patients were blood group O. Cardiac iron overload was documented in 6.8% of study patients, whereas liver iron overload was documented in 35% of study patients. 25% of thalassemia patients had a history of splenectomy. 27.7% of study patients required hospitalization due to COVID-19 infection. Amongst the hospitalized patients, one patient died (0.7%) and one patient required intubation. Continuous positive airway pressure (CPAP) was required in almost 5% of study patients. After adjustment for age-, sex- and other known risk factors (cardiac disease, kidney disease and pulmonary disease), the rate of in-hospital complications (supplemental oxygen use, admission to the an intensive care unit for CPAP therapy or intubation) and all-cause mortality was significantly lower in the thalassemia group compared to the matched cohort with no history of thalassemia. Amongst thalassemia patients in general, the NTDT group exhibited a higher rate of hospitalization compared to the TDT group (p=0.001). In addition, the rate of complications such as acute kidney injury and need for supplemental oxygen was significantly higher in the NTDT group compared to the TDT group. In the multivariable logistic regression analysis, age and history of heart or kidney disease were all found to be independent risk factors for increased in-hospital, all-cause mortality, whereas the presence of thalassemia (either TDT or NTDT) was found to be independently associated with reduced all-cause mortality.Conclusions: The presence of thalassemia in COVID-19 patients was independently associated with lower in-hospital, all-cause mortality and few in-hospital complications in in our study. The pathophysiology of this is unclear and needs to be studied in vitro and in animal models.Trial Registration for sources of data extraction: NCT: 04334291, 04746066Funding Statement: This study was funded by a non-conditioned grant from FUNDACIÓN INTERHOSPITALARIA PARA LA INVESTIGACIÓN CARDIOVASCULAR, FIC. (Madrid, Spain). This nonprofit institution had no role in the study design, the collection, analysis and interpretation of data, the writing of the report, or the decision to submit the paper for publication.Declaration of Interests: The authors declare no conflicts of interest.Ethics Approval Statement: The study was approved by the Ethics Committees in all of the centers involved (Banjarmasin, Bari, Cagliari, Catania, Ferrara, Gela, Genoa, Getafe, Guadalajara, Legan, Madrid, Mannheim, Milan, Monza, Naples, Olbia, Padua, Pavia, Ragusa, Rome, Salerno, Turin, Valladolid and Verona).

Sepsis of Patients Infected by SARS-CoV-2: Real-World Experience from the International HOPE-COVID-19-Registry and Validation of HOPE Sepsis Score (preprint)

Background: Sepsis patients with a concomitant Coronavirus (COVID-19) infection are related to a high morbidity and mortality rate. We investigated a large cohort of sepsis patients with a concomitant COVID-19 to determine clinical characteristics, laboratory and radiological findings, and predictors of mortality. We developed a risk score for the estimation of sepsis risk in patients with COVID-19.Methods: In the present study, we conducted a sub-analysis from the international Health Outcome Predictive Evaluation Registry for COVID-19 (HOPE-COVID-19-Registry). Out of 5,837 patients with COVID-19, 624 patients were diagnosed with sepsis according to the Sepsis-3 International Consensus.Findings: In multivariable analysis, the following risk factors were identified as independent predictors for developing sepsis: current smoking, tachypnoea (>22 breath per minute), haemoptysis, peripheral oxygen saturation (SpO2) < 92%, blood pressure (BP) (systolic BP< 90mmHg and diastolic BP <60mmHg), Glasgow coma scale (GCS) <15, elevated procalcitonin (PCT), elevated troponin I (TnI), and elevated Creatinine > 1.5 mg/dl. By assigning odds ratio weighted points to these variables, the following three risk categories were defined to develop sepsis during admission: low-risk group (probability of sepsis 3.1-11.8%); intermediate-risk group (24.8-53.8%); high-risk-group (58.3-100%). A score of 1 was assigned to current smoking, tachypnoea, decreased SpO2, decreased blood pressure, decreased GCS, elevated PCT, TnI, and creatinine, whereas a score of 2 was assigned to haemoptysis.Interpretation: The HOPE Sepsis Score including 9 parameters is useful in identifying high-risk COVID-19 patients to develop sepsis. Sepsis in COVID-19 is associated with a high mortality rate.Funding Statement: Non-conditioned grant (FUNDACIÓN INTERHOSPITALARIA PARA LA INVESTIGACIÓN CARDIOVASCULAR, FIC. Madrid, Spain)Declaration of Interests: We declare no competing interests.Ethics Approval Statement: The study was approved by the Ethics Committee in all involved centres.

COVID-19 anosmia and gustatory symptoms as a prognosis factor: a subanalysis of the HOPE COVID-19 (Health Outcome Predictive Evaluation for COVID-19) Registry (preprint)

Olfactory and gustatory dysfunctions (OGD) are a frequent symptom of Coronavirus disease 2019 (COVID-19). It has been proposed that the neuroinvasive potential of the novel SARS-CoV-2 could be due to olfactory bulb invasion, conversely studies suggest it could be a good prognostic factor. The aim of the current study was to investigate the prognosis value of OGD in COVID-19.These symptoms were recorded on admission from a cohort study of 5868 patients with confirmed or highly suspected COVID-19 infection included in the multicenter international HOPE Registry (NCT04334291).There was statistical relation in multivariate analysis for OGD in gender, more frequent in female 12.41% vs 8.67% in male, related to age, more frequent under 65 years, presence of hypertension, dyslipidemia, diabetes, smoke, renal insufficiency, lung, heart, cancer and neurological disease. We did not find statistical differences in pregnant (p=0.505), patient suffering cognitive (p=0.484), liver (p=0.1) or immune disease (p=0.32). There was inverse relation (protective) between OGD and prone positioning (0.005) and death (<0.0001), but no with ICU (0.165) or mechanical ventilation (0.292). On univariable logistic regression OGD was found to be inversely related to death in COVID-19 patients. The Odds Ratio was 0.26 (0.15-0.44) (p<0.001) and Z was -5.05.The presence of anosmia is fundamental in the diagnosis of SARS.CoV-2 infection, but also could be important when classifying patients and in therapeutic decisions. Even more knowing that it is an early symptom of the disease. Knowing that other situations as being Afro-American or Latino-American, Hypertension, renal insufficiency, or increase of C-reactive protein (CRP) imply a worse prognosis we can make a clinical score to estimate the vital prognosis of the patient.The exact pathogenesis of SARS-CoV-2 that causes olfactory and gustative disorders remains unknown but seems related to the prognosis. This point is fundamental, insomuch as could be a plausible way to find a treatment.