Clinical Profile and Determinants of Mortality in Patients with Interstitial Lung Disease Admitted for COVID-19.

BACKGROUND: Concern has risen about the effects of COVID-19 in interstitial lung disease (ILD) patients. The aim of our study was to determine clinical characteristics and prognostic factors of ILD patients admitted for COVID-19. METHODS: Ancillary analysis of an international, multicenter COVID-19 registry (HOPE: Health Outcome Predictive Evaluation) was performed. The subgroup of ILD patients was selected and compared with the rest of the cohort. RESULTS: A total of 114 patients with ILDs were evaluated. Mean ± SD age was 72.4 ± 13.6 years, and 65.8% were men. ILD patients were older, had more comorbidities, received more home oxygen therapy and more frequently had respiratory failure upon admission than non-ILD patients (all p < 0.05). In laboratory findings, ILD patients more frequently had elevated LDH, C-reactive protein, and D-dimer levels (all p < 0.05). A multivariate analysis showed that chronic kidney disease and respiratory insufficiency on admission were predictors of ventilatory support, and that older age, kidney disease and elevated LDH were predictors of death. CONCLUSIONS: Our data show that ILD patients admitted for COVID-19 are older, have more comorbidities, more frequently require ventilatory support and have higher mortality than those without ILDs. Older age, kidney disease and LDH were independent predictors of mortality in this population.

Post-COVID-19 syndrome and diabetes mellitus: a propensity-matched analysis of the International HOPE-II COVID-19 Registry.

Background: Diabetes mellitus (DM) is one of the most frequent comorbidities in patients suffering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with a higher rate of severe course of coronavirus disease (COVID-19). However, data about post-COVID-19 syndrome (PCS) in patients with DM are limited. Methods: This multicenter, propensity score-matched study compared long-term follow-up data about cardiovascular, neuropsychiatric, respiratory, gastrointestinal, and other symptoms in 8,719 patients with DM to those without DM. The 1:1 propensity score matching (PSM) according to age and sex resulted in 1,548 matched pairs. Results: Diabetics and nondiabetics had a mean age of 72.6 ± 12.7 years old. At follow-up, cardiovascular symptoms such as dyspnea and increased resting heart rate occurred less in patients with DM (13.2% vs. 16.4%; p = 0.01) than those without DM (2.8% vs. 5.6%; p = 0.05), respectively. The incidence of newly diagnosed arterial hypertension was slightly lower in DM patients as compared to non-DM patients (0.5% vs. 1.6%; p = 0.18). Abnormal spirometry was observed more in patients with DM than those without DM (18.8% vs. 13; p = 0.24). Paranoia was diagnosed more frequently in patients with DM than in non-DM patients at follow-up time (4% vs. 1.2%; p = 0.009). The incidence of newly diagnosed renal insufficiency was higher in patients suffering from DM as compared to patients without DM (4.8% vs. 2.6%; p = 0.09). The rate of readmission was comparable in patients with and without DM (19.7% vs. 18.3%; p = 0.61). The reinfection rate with COVID-19 was comparable in both groups (2.9% in diabetics vs. 2.3% in nondiabetics; p = 0.55). Long-term mortality was higher in DM patients than in non-DM patients (33.9% vs. 29.1%; p = 0.005). Conclusions: The mortality rate was higher in patients with DM type II as compared to those without DM. Readmission and reinfection rates with COVID-19 were comparable in both groups. The incidence of cardiovascular symptoms was higher in patients without DM.

[Management and impact of interventions to reduce COVID-19 cases in Costa RicaGestão e impacto das medidas de intervenção para reduzir os casos de COVID-19 na Costa Rica]. / Gestión e impacto de las medidas de intervención para la reducción de casos por COVID-19 en Costa Rica.

Objective: Assess the impact of interventions introduced in Costa Rica during 2020 and 2021 to control the COVID-19 pandemic. Methods: A Bayesian Poisson regression model was used, incorporating control or intervention measures as independent variables in the changes in reported case numbers per epidemiological week. Results: The results showed the relative and combined impact of containment policies and measures on the reduction of cases: mainly vehicular traffic restrictions, use of masks, and implementation of health guidelines and protocols. Evidence of impact was optimized and made available for decision-making by the country's health and emergency authorities. Several iterations were generated for constant monitoring of variations in impact at four different moments in the pandemic's spread. Conclusion: The simultaneous implementation of different mitigation measures in Costa Rica has been a driving force in reducing the number of COVID-19 cases.

Objetivo: Avaliar o impacto das intervenções realizadas na Costa Rica durante 2020 e 2021 para o controle da pandemia de COVID-19. Método: Foi utilizado um modelo Bayesiano de regressão de Poisson que incorporou as medidas de controle ou intervenção como variáveis independentes sobre a variação do número de casos por semana epidemiológica. Resultados: Os resultados evidenciaram o efeito relativo e conjunto que as políticas ou medidas de contenção tiveram na redução de casos, principalmente as restrições a veículos, o uso de máscaras e a implementação de diretrizes e protocolos de saúde. As evidências dos efeitos foram otimizadas e disponibilizadas às autoridades sanitárias e de emergência do país para auxiliar na tomada de decisão. Diversas iterações foram geradas para o monitoramento constante da variação nos efeitos em quatro momentos distintos do avanço da pandemia. Conclusão: A aplicação simultânea de diferentes medidas de mitigação na Costa Rica tem sido um agente promotor da diminuição de casos de COVID-19.

Post-COVID-19 Symptoms and Heart Disease: Incidence, Prognostic Factors, Outcomes and Vaccination: Results from a Multi-Center International Prospective Registry (HOPE 2).

BACKGROUND: Heart disease is linked to worse acute outcomes after coronavirus disease 2019 (COVID-19), although long-term outcomes and prognostic factor data are lacking. We aim to characterize the outcomes and the impact of underlying heart diseases after surviving COVID-19 hospitalization. METHODS: We conducted an analysis of the prospective registry HOPE-2 (Health Outcome Predictive Evaluation for COVID-19-2, NCT04778020). We selected patients discharged alive and considered the primary end-point all-cause mortality during follow-up. As secondary main end-points, we included any readmission or any post-COVID-19 symptom. Clinical features and follow-up events are compared between those with and without cardiovascular disease. Factors with p < 0.05 in the univariate analysis were entered into the multivariate analysis to determine independent prognostic factors. RESULTS: HOPE-2 closed on 31 December 2021, with 9299 patients hospitalized with COVID-19, and 1805 died during this acute phase. Finally, 7014 patients with heart disease data were included in the present analysis, from 56 centers in 8 countries. Heart disease (+) patients were older (73 vs. 58 years old), more frequently male (63 vs. 56%), had more comorbidities than their counterparts, and suffered more frequently from post-COVID-19 complications and higher mortality (OR heart disease: 2.63, 95% CI: 1.81-3.84). Vaccination was found to be an independent protector factor (HR all-cause death: 0.09; 95% CI: 0.04-0.19). CONCLUSIONS: After surviving the acute phase, patients with underlying heart disease continue to present a more complex clinical profile and worse outcomes including increased mortality. The COVID-19 vaccine could benefit survival in patients with heart disease during follow-up.

Aspirin Therapy on Prophylactic Anticoagulation for Patients Hospitalized With COVID-19: A Propensity Score-Matched Cohort Analysis of the HOPE-COVID-19 Registry.

Background COVID-19 is an infectious illness, featured by an increased risk of thromboembolism. However, no standard antithrombotic therapy is currently recommended for patients hospitalized with COVID-19. The aim of this study was to evaluate safety and efficacy of additional therapy with aspirin over prophylactic anticoagulation (PAC) in patients hospitalized with COVID-19 and its impact on survival. Methods and Results A total of 8168 patients hospitalized for COVID-19 were enrolled in a multicenter-international prospective registry (HOPE COVID-19). Clinical data and in-hospital complications, including mortality, were recorded. Study population included patients treated with PAC or with PAC and aspirin. A comparison of clinical outcomes between patients treated with PAC versus PAC and aspirin was performed using an adjusted analysis with propensity score matching. Of 7824 patients with complete data, 360 (4.6%) received PAC and aspirin and 2949 (37.6%) PAC. Propensity-score matching yielded 298 patients from each group. In the propensity score-matched population, cumulative incidence of in-hospital mortality was lower in patients treated with PAC and aspirin versus PAC (15% versus 21%, Log Rank P=0.01). At multivariable analysis in propensity matched population of patients with COVID-19, including age, sex, hypertension, diabetes, kidney failure, and invasive ventilation, aspirin treatment was associated with lower risk of in-hospital mortality (hazard ratio [HR], 0.62; [95% CI 0.42-0.92], P=0.018). Conclusions Combination PAC and aspirin was associated with lower mortality risk among patients hospitalized with COVID-19 in a propensity score matched population compared to PAC alone.

Chronic Oral Anticoagulation Therapy and Prognosis of Patients Admitted to Hospital for COVID-19: Insights from the HOPE COVID-19 Registry.

Background: Most evidence regarding anticoagulation and COVID-19 refers to the hospitalization setting, but the role of oral anticoagulation (OAC) before hospital admission has not been well explored. We compared clinical outcomes and short-term prognosis between patients with and without prior OAC therapy who were hospitalized for COVID-19. Methods: Analysis of the whole cohort of the HOPE COVID-19 Registry which included patients discharged (deceased or alive) after hospital admission for COVID-19 in 9 countries. All-cause mortality was the primary endpoint. Study outcomes were compared after adjusting variables using propensity score matching (PSM) analyses. Results: 7698 patients were suitable for the present analysis (675 (8.8%) on OAC at admission: 427 (5.6%) on VKAs and 248 (3.2%) on DOACs). After PSM, 1276 patients were analyzed (638 with OAC; 638 without OAC), without significant differences regarding the risk of thromboembolic events (OR 1.11, 95% CI 0.59-2.08). The risk of clinically relevant bleeding (OR 3.04, 95% CI 1.92-4.83), as well as the risk of mortality (HR 1.22, 95% CI 1.01-1.47; log-rank p value = 0.041), was significantly increased in previous OAC users. Amongst patients on prior OAC only, there were no differences in the risk of clinically relevant bleeding, thromboembolic events, or mortality when comparing previous VKA or DOAC users, after PSM. Conclusion: Hospitalized COVID-19 patients on prior OAC therapy had a higher risk of mortality and worse clinical outcomes compared to patients without prior OAC therapy, even after adjusting for comorbidities using a PSM. There were no differences in clinical outcomes in patients previously taking VKAs or DOACs. This trial is registered with NCT04334291/EUPAS34399.

[Atrial fibrillation in patients with COVID-19. Usefulness of the CHA2DS2-VASc score: an analysis of the international HOPE COVID-19 registry]. / Fibrilación auricular en pacientes con COVID-19. Utilidad de la puntuación CHA2DS2-VASc: un análisis del registro internacional HOPE COVID-19.

INTRODUCTION AND OBJECTIVES: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2. Atrial fibrillation (AF) is common in acute situations, where it is associated with more complications and higher mortality. METHODS: Analysis of the international HOPE registry (NCT04334291). The objective was to assess the prognostic information of AF in COVID-19 patients. A multivariate analysis and propensity score matching were performed to assess the relationship between AF and mortality. We also evaluated the impact on mortality and embolic events of the CHA2DS2-VASc score in these patients. RESULTS: Among 6217 patients enrolled in the HOPE registry, 250 had AF (4.5%). AF patients had a higher prevalence of cardiovascular risk factors and comorbidities. After propensity score matching, these differences were attenuated. Despite this, patients with AF had a higher incidence of in-hospital complications such as heart failure (19.3% vs 11.6%, P = .021) and respiratory insufficiency (75.9% vs 62.3%, P = .002), as well as a higher 60-day mortality rate (43.4% vs 30.9%, P = .005). On multivariate analysis, AF was independently associated with higher 60-day mortality (hazard ratio, 1.234; 95%CI, 1.003-1.519). CHA2DS2-VASc score acceptably predicts 60-day mortality in COVID-19 patients (area ROC, 0.748; 95%CI, 0.733-0.764), but not its embolic risk (area ROC, 0.411; 95%CI, 0.147-0.675). CONCLUSIONS: AF in COVID-19 patients is associated with a higher number of complications and 60-day mortality. The CHA2DS2-VASc score may be a good risk marker in COVID patients but does not predict their embolic risk.

Thalassaemia is paradoxically associated with a reduced risk of in-hospital complications and mortality in COVID-19: Data from an international registry.

Although numerous patient-specific co-factors have been shown to be associated with worse outcomes in COVID-19, the prognostic value of thalassaemic syndromes in COVID-19 patients remains poorly understood. We studied the outcomes of 137 COVID-19 patients with a history of transfusion-dependent thalassaemia (TDT) and transfusion independent thalassaemia (TIT) extracted from a large international cohort and compared them with the outcomes from a matched cohort of COVID-19 patients with no history of thalassaemia. The mean age of thalassaemia 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. 40% of thalassaemia 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 an intensive care unit for CPAP therapy or intubation) and all-cause mortality was significantly lower in the thalassaemia group compared to the matched cohort with no history of thalassaemia. Amongst thalassaemia patients in general, the TIT 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 TIT 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 thalassaemia (either TDT or TIT) was found to be independently associated with reduced all-cause mortality. The presence of thalassaemia in COVID-19 patients was independently associated with lower in-hospital, all-cause mortality and few in-hospital complications in our study. The pathophysiology of this is unclear and needs to be studied in vitro and in animal models.

Sepsis of Patients Infected by SARS-CoV-2: Real-World Experience From the International HOPE-COVID-19-Registry and Validation of HOPE Sepsis Score.

Background: Patients with sepsis with a concomitant coronavirus (COVID-19) infection are related to a high morbidity and mortality rate. We investigated a large cohort of patients with sepsis with a concomitant COVID-19, and we developed a risk score for the estimation of sepsis risk in COVID-19. Methods: We conducted a sub-analysis from the international Health Outcome Predictive Evaluation Registry for COVID-19 (HOPE-COVID-19-Registry, NCT04334291). Out of 5,837 patients with COVID-19, 624 patients were diagnosed with sepsis according to the Sepsis-3 International Consensus. Results: In multivariable analysis, the following risk factors were identified as independent predictors for developing sepsis: current smoking, tachypnoea (>22 breath per minute), hemoptysis, peripheral oxygen saturation (SpO2) <92%, blood pressure (BP) (systolic BP <90 mmHg and diastolic BP <60 mmHg), Glasgow Coma Scale (GCS) <15, elevated procalcitonin (PCT), elevated troponin I (TnI), and elevated creatinine >1.5 mg/dl. By assigning odds ratio (OR) 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%); and high-risk-group (58.3-100%). A score of 1 was assigned to current smoking, tachypnoea, decreased SpO2, decreased BP, decreased GCS, elevated PCT, TnI, and creatinine, whereas a score of 2 was assigned to hemoptysis. Conclusions: The HOPE Sepsis Score including nine parameters is useful in identifying high-risk COVID-19 patients to develop sepsis. Sepsis in COVID-19 is associated with a high mortality rate.

Predictors of poor prognosis in healthy, young, individuals with SARS-CoV-2 infections.

OBJECTIVES: To identify predictors of poor prognosis in previously healthy young individuals admitted to hospital with coronavirus disease 2019 (COVID-19). METHODS: We studied a cohort of patients hospitalized with COVID-19. All patients without co-morbidities, without usual treatments and ≤65 years old were selected from an international registry (HOPE-COVID-19, NCT04334291). We focused on baseline variables-symptoms and signs at admission-to analyse risk factors for poor prognosis. The primary end point was a composite of major adverse clinical events during hospitalization including mortality, mechanical ventilation, high-flow nasal oxygen therapy, prone, sepsis, systemic inflammatory response syndrome and embolic events. RESULTS: Overall, 773 healthy young patients were included. The primary composite end point was observed in 29% (225/773) and the overall mortality rate was 3.6% (28/773). In the combined event group, 75% (168/225) of patients were men and the mean age was 49 (±11) years, whereas in the non-combined event group, the prevalence of male gender was 43% (238/548) and the mean age was 42 (±13) years (p < 0.001 for both). On admission, respiratory insufficiency and cough were described in 51.4% (114/222) and 76% (170/223) of patients, respectively, in the combined event group, versus 7.9% (42/533) and 56% (302/543) of patients in the other group (p < 0.001 for both). The strongest independent predictor for the combined end point was desaturation (Spo2 <92%) (OR 5.40; 95% CI 3.34-8.75; p < 0.001), followed by tachypnoea (OR 3.17; 95% CI 1.93-5.21; p < 0.001), male gender (OR 3.01; 95% CI 1.96-4.61; p < 0.001) and pulmonary infiltrates on chest X-ray at admission (OR 2.21; 95% CI 1.18-4.16; p 0.014). CONCLUSIONS: Major adverse clinical events were unexpectedly high considering the baseline characteristics of the cohort. Signs of respiratory compromise at admission and male gender, were predictive for poor prognosis among young healthy patients hospitalized with COVID-19.

COVID-19 and the impact of arterial hypertension-An analysis of the international HOPE COVID-19 Registry (Italy-Spain-Germany).

BACKGROUND: A systematic analysis of concomitant arterial hypertension in COVID-19 patients and the impact of angiotensin-converting-enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARBs) have not been studied in a large multicentre cohort yet. We conducted a subanalysis from the international HOPE Registry (https://hopeprojectmd.com, NCT04334291) comparing COVID-19 in presence and absence of arterial hypertension. MATERIALS AND METHODS: Out of 5837 COVID-19 patients, 2850 (48.8%) patients had the diagnosis arterial hypertension. 1978/2813 (70.3%) patients were already treated with ACEI or ARBs. The clinical outcome of the present subanalysis included all-cause mortality over 40 days of follow-up. RESULTS: Patients with arterial hypertension suffered significantly more from different complications including respiratory insufficiency (60.8% vs 39.5%), heart failure (9.9% vs 3.1%), acute kidney injury (25.3% vs 7.3%), pneumonia (90.6% vs 86%), sepsis (14.7% vs 7.5%), and bleeding events (3.6% vs 1.6%). The mortality rate was 29.6% in patients with concomitant arterial hypertension and 11.3% without arterial hypertension (P < .001). Invasive and non-invasive respiratory supports were significantly more required in presence of arterial hypertension as compared without it. In the multivariate cox regression analysis, while age≥65, benzodiazepine, antidepressant at admission, elevated LDH or creatinine, respiratory insufficiency and sepsis might be a positive independent predictors of mortality, antiviral drugs, interferon treatment, ACEI or ARBs at discharge or oral anticoagulation at discharge might be an independent negative predictor of the mortality. CONCLUSIONS: The mortality rate and in-hospital complications might be increased in COVID-19 patients with a concomitant history of arterial hypertension. The history of ACEI or ARBs treatments does not seem to impact the outcome of these patients.

Modelado estadístico para la gestión de los primeros tres meses de la COVID-19 en Costa Rica

El papel del modelado estadístico en la gestión de emergencias es fundamental para perfilar o apoyar las decisiones en torno a la atención de los eventos. En 2020 con el surgimiento de la pandemia por coronavirus, los países rápidamente se prepararon para la atención del comportamiento de contagio y el impacto que tendría en la salud pública. En Costa Rica, un equipo de especialistas preparó estudios sobre el comportamiento de la curva de contagio y su efecto en la ocupación de camas hospitalarias durante los primeros tres meses de la presencia de la epidemia. Los estudios se basaron en la estimación de modelos estadísticos de crecimiento exponencial y logístico, los cuales proporcionaron los pronósticos del número de casos diarios y acumulados. La predicción de casos permitió alimentar un modelo de simulación para la proyección de demanda de camas hospitalarias por pacientes de la COVID-19. Los análisis se basaron en los datos aportados por el Ministerio de Salud en torno a los casos confirmados por coronavirus desde la aparición del primer caso en Costa Rica. Se estimaron cuatro modelos: logístico, Richards, Gompertz y exponencial, los cuales generaron la predicción de casos diarios. También se estimó el número de reproducibilidad mediante estadística bayesiana para cuantificar la transmisibilidad del virus. Los resultados permitieron anticipar el comportamiento inicial del virus en Costa Rica y el potencial efecto de las medidas de contención que se adopta-ron a partir de la declaratoria de emergencia nacional. JEL: C15 Métodos de simulación estadísticaAlternate abstract: The role of statistical modeling in emergency management is essential to shape or sup-port decisions regarding the care of events. In 2020 with coronavirus pandemic, countries quickly braced themselves for attention to contagious behavior and the impact it would have on public health. In Costa Rica, a team of specialists prepared studies on the behavior of the contagion curve and its effect on the occupation of hospital beds during the first three months of the epidemic. The studies were based on statistical model estimation of exponential and logistic growth, which provided forecasts of the daily and accumulated case numbers. The prediction of cases allowed feeding a simulation model for the projection of demand for hospital beds by patients with COVID-19. The analysis were based on data provided by the Ministry of Health regarding confirmed cases of coronavirus since the appearance of the first case in Costa Rica. Four models were estimated: logistic, Richards, Gompertz and Exponential, which generated daily case predictions. The reproducibility number was also estimated using Bayesian statistics to quantify the virus transmissibility. The results made it possible to anticipate the initial behavior of the virus in Costa Rica and the potential effect of the containment measures adopted after the declaration of national emergency. JEL: C15 Statistical simulation methods: general.Alternate abstract: O papel da modelagem estatística na gestão de emergências é fundamental para delinear ou apoiar as decisões em torno da resposta aos eventos. Em 2020, com o surgimento da pandemia do coronavírus, os países rapidamente se prepararam para responder ao com-portamento de contágio e para o impacto que provocaria sobre a saúde pública. Na Costa Rica, uma equipe de especialistas preparou estudos sobre o comportamento da curva de contágio e seu efeito sobre a ocupação de leitos hospitalares durante os primeiros três meses da epidemia. Os estudos se basearam na estimativa de modelos estatísticos de crescimento exponencial e logístico, os quais proporcionaram prognósticos quanto ao número de casos diários e acumulados. A predição de casos permitiu alimentar um modelo de simulação para a projeção da demanda de leitos hospitalares por pacientes com COVID-19. As análises se basearam em dados fornecidos pelo Ministério de Saúde em relação aos casos confirmados de coronavírus a partir do aparecimento do primeiro caso na Costa Rica. Estimaram-se quatro modelos: logístico, Richards, Gompertz e exponencial, os quais geraram a estimativa de casos diários. Estimou-se também o número de reprodutibilidade por meio da estatística bayesiana de forma a quantificar a transmissibi-lidade do vírus. Os resultados permitiram antecipar o comportamento inicial do vírus na Costa Rica e o potencial efeito das medidas de contenção adotadas a partir da declaração de emergência nacional. JEL: C15 Métodos de simulação estatística.

Impact of smoking on COVID-19 outcomes: a HOPE Registry subanalysis.

BACKGROUND: Smoking has been associated with poorer outcomes in relation to COVID-19. Smokers have higher risk of mortality and have a more severe clinical course. There is paucity of data available on this issue, and a definitive link between smoking and COVID-19 prognosis has yet to be established. METHODS: We included 5224 patients with COVID-19 with an available smoking history in a multicentre international registry Health Outcome Predictive Evaluation for COVID-19 (NCT04334291). Patients were included following an in-hospital admission with a COVID-19 diagnosis. We analysed the outcomes of patients with a current or prior history of smoking compared with the non-smoking group. The primary endpoint was all-cause in-hospital death. RESULTS: Finally, 5224 patients with COVID-19 with available smoking status were analysed. A total of 3983 (67.9%) patients were non-smokers, 934 (15.9%) were former smokers and 307 (5.2%) were active smokers. The median age was 66 years (IQR 52.0-77.0) and 58.6% were male. The most frequent comorbidities were hypertension (48.5%) and dyslipidaemia (33.0%). A relevant lung disease was present in 19.4%. In-hospital complications such sepsis (23.6%) and embolic events (4.3%) occurred more frequently in the smoker group (p<0.001 for both). All cause-death was higher among smokers (active or former smokers) compared with non-smokers (27.6 vs 18.4%, p<0.001). Following a multivariate analysis, current smoking was considered as an independent predictor of mortality (OR 1.77, 95% CI 1.11 to 2.82, p=0.017) and a combined endpoint of severe disease (OR 1.68, 95% CI 1.16 to 2.43, p=0.006). CONCLUSION: Smoking has a negative prognostic impact on patients hospitalised with COVID-19.

Gender Differences in the Presentation and Outcomes of Hospitalized Patients With COVID-19.

Gender-related differences in COVID-19 clinical presentation, disease progression, and mortality have not been adequately explored. We analyzed the clinical profile, presentation, treatments, and outcomes of patients according to gender in the HOPE-COVID-19 International Registry. Among 2,798 enrolled patients, 1,111 were women (39.7%). Male patients had a higher prevalence of cardiovascular risk factors and more comorbidities at baseline. After propensity score matching, 876 men and 876 women were selected. Male patients more often reported fever, whereas female patients more often reported vomiting, diarrhea, and hyposmia/anosmia. Laboratory tests in men presented alterations consistent with a more severe COVID-19 infection (eg, significantly higher C-reactive protein, troponin, transaminases, lymphocytopenia, thrombocytopenia, and ferritin). Systemic inflammatory response syndrome, bilateral pneumonia, respiratory insufficiency, and renal failure were significantly more frequent in men. Men more often required pronation, corticosteroids, and tocilizumab administration. A significantly higher 30-day mortality was observed in men vs women (23.4% vs 19.2%; P = .039). Trial Numbers: NCT04334291/EUPAS34399.

Anticoagulation Therapy in Patients With Coronavirus Disease 2019: Results From a Multicenter International Prospective Registry (Health Outcome Predictive Evaluation for Corona Virus Disease 2019 [HOPE-COVID19]).

OBJECTIVES: No standard therapy, including anticoagulation regimens, is currently recommended for coronavirus disease 2019. Aim of this study was to evaluate the efficacy of anticoagulation in coronavirus disease 2019 hospitalized patients and its impact on survival. DESIGN: Multicenter international prospective registry (Health Outcome Predictive Evaluation for Corona Virus Disease 2019). SETTING: Hospitalized patients with coronavirus disease 2019. PATIENTS: Five thousand eight hundred thirty-eight consecutive coronavirus disease 2019 patients. INTERVENTIONS: Anticoagulation therapy, including prophylactic and therapeutic regimens, was obtained for each patient. MEASUREMENTS AND MAIN RESULTS: Five thousand four hundred eighty patients (94%) did not receive any anticoagulation before hospitalization. Two-thousand six-hundred one patients (44%) during hospitalization received anticoagulation therapy and it was not associated with better survival rate (81% vs 81%; p = 0.94) but with higher risk of bleeding (2.7% vs 1.8%; p = 0.03). Among patients admitted with respiratory failure (49%, n = 2,859, including 391 and 583 patients requiring invasive and noninvasive ventilation, respectively), anticoagulation started during hospitalization was associated with lower mortality rates (32% vs 42%; p < 0.01) and nonsignificant higher risk of bleeding (3.4% vs 2.7%; p = 0.3). Anticoagulation therapy was associated with lower mortality rates in patients treated with invasive ventilation (53% vs 64%; p = 0.05) without increased rates of bleeding (9% vs 8%; p = 0.88) but not in those with noninvasive ventilation (35% vs 38%; p = 0.40). At multivariate Cox' analysis mortality relative risk with anticoagulation was 0.58 (95% CI, 0.49-0.67) in patients admitted with respiratory failure, 0.50 (95% CI, 0.49-0.67) in those requiring invasive ventilation, 0.72 (95% CI, 0.51-1.01) in noninvasive ventilation. CONCLUSIONS: Anticoagulation therapy in general population with coronavirus disease 2019 was not associated with better survival rates but with higher bleeding risk. Better results were observed in patients admitted with respiratory failure and requiring invasive ventilation.

Renin-angiotensin system inhibitors effect before and during hospitalization in COVID-19 outcomes: Final analysis of the international HOPE COVID-19 (Health Outcome Predictive Evaluation for COVID-19) registry.

BACKGROUND: The use of Renin-Angiotensin system inhibitors (RASi) in patients with coronavirus disease 2019 (COVID-19) has been questioned because both share a target receptor site. METHODS: HOPE-COVID-19 (NCT04334291) is an international investigator-initiated registry. Patients are eligible when discharged after an in-hospital stay with COVID-19, dead or alive. Here, we analyze the impact of previous and continued in-hospital treatment with RASi in all-cause mortality and the development of in-stay complications. RESULTS: We included 6503 patients, over 18 years, from Spain and Italy with data on their RASi status. Of those, 36.8% were receiving any RASi before admission. RASi patients were older, more frequently male, with more comorbidities and frailer. Their probability of death and ICU admission was higher. However, after adjustment, these differences disappeared. Regarding RASi in-hospital use, those who continued the treatment were younger, with balanced comorbidities but with less severe COVID19. Raw mortality and secondary events were less frequent in RASi. After adjustment, patients receiving RASi still presented significantly better outcomes, with less mortality, ICU admissions, respiratory insufficiency, need for mechanical ventilation or prone, sepsis, SIRS and renal failure (p<0.05 for all). However, we did not find differences regarding the hospital use of RASi and the development of heart failure. CONCLUSION: RASi historic use, at admission, is not related to an adjusted worse prognosis in hospitalized COVID-19 patients, although it points out a high-risk population. In this setting, the in-hospital prescription of RASi is associated with improved survival and fewer short-term complications.

Non-invasive ventilation for SARS-CoV-2 acute respiratory failure: a subanalysis from the HOPE COVID-19 registry.

BACKGROUND: The COVID-19 pandemic has seriously challenged worldwide healthcare systems and limited intensive care facilities, leading to physicians considering the use of non-invasive ventilation (NIV) for managing SARS-CoV-2-related acute respiratory failure (ARF). METHODS: We conducted an interim analysis of the international, multicentre HOPE COVID-19 registry including patients admitted for a confirmed or highly suspected SARS-CoV-2 infection until 18 April 2020. Those treated with NIV were considered. The primary endpoint was a composite of death or need for intubation. The components of the composite endpoint were the secondary outcomes. Unadjusted and adjusted predictors of the primary endpoint within those initially treated with NIV were investigated. RESULTS: 1933 patients who were included in the registry during the study period had data on oxygen support type. Among them, 390 patients (20%) were treated with NIV. Compared with those receiving other non-invasive oxygen strategy, patients receiving NIV showed significantly worse clinical and laboratory signs of ARF at presentation. Of the 390 patients treated with NIV, 173 patients (44.4%) met the composite endpoint. In-hospital death was the main determinant (147, 37.7%), while 62 patients (15.9%) needed invasive ventilation. Those requiring invasive ventilation had the lowest survival rate (41.9%). After adjustment, age (adjusted OR (adj(OR)) for 5-year increase: 1.37, 95% CI 1.15 to 1.63, p<0.001), hypertension (adj(OR) 2.95, 95% CI 1.14 to 7.61, p=0.03), room air O2 saturation <92% at presentation (adj(OR) 3.05, 95% CI 1.28 to 7.28, p=0.01), lymphocytopenia (adj(OR) 3.55, 95% CI 1.16 to 10.85, p=0.03) and in-hospital use of antibiotic therapy (adj(OR) 4.91, 95% CI 1.69 to 14.26, p=0.003) were independently associated with the composite endpoint. CONCLUSION: NIV was used in a significant proportion of patients within our cohort, and more than half of these patients survived without the need for intubation. NIV may represent a viable strategy particularly in case of overcrowded and limited intensive care resources, but prompt identification of failure is mandatory to avoid harm. Further studies are required to better clarify our hypothesis. TRIAL REGISTRATION NUMBERS: NCT04334291/EUPAS34399.

Does there exist an obesity paradox in COVID-19? Insights of the international HOPE-COVID-19-registry.

BACKGROUND: Obesity has been described as a protective factor in cardiovascular and other diseases being expressed as 'obesity paradox'. However, the impact of obesity on clinical outcomes including mortality in COVID-19 has been poorly systematically investigated until now. We aimed to compare clinical outcomes among COVID-19 patients divided into three groups according to the body mass index (BMI). METHODS: We retrospectively collected data up to May 31st, 2020. 3635 patients were divided into three groups of BMI (<25 kg/m2; n = 1110, 25-30 kg/m2; n = 1464, and >30 kg/m2; n = 1061). Demographic, in-hospital complications, and predictors for mortality, respiratory insufficiency, and sepsis were analyzed. RESULTS: The rate of respiratory insufficiency was more recorded in BMI 25-30 kg/m2 as compared to BMI < 25 kg/m2 (22.8% vs. 41.8%; p < 0.001), and in BMI > 30 kg/m2 than BMI < 25 kg/m2, respectively (22.8% vs. 35.4%; p < 0.001). Sepsis was more observed in BMI 25-30 kg/m2 and BMI > 30 kg/m2 as compared to BMI < 25 kg/m2, respectively (25.1% vs. 42.5%; p = 0.02) and (25.1% vs. 32.5%; p = 0.006). The mortality rate was higher in BMI 25-30 kg/m2 and BMI > 30 kg/m2 as compared to BMI < 25 kg/m2, respectively (27.2% vs. 39.2%; p = 0.31) (27.2% vs. 33.5%; p = 0.004). In the Cox multivariate analysis for mortality, BMI < 25 kg/m2 and BMI > 30 kg/m2 did not impact the mortality rate (HR 1.15, 95% CI: 0.889-1.508; p = 0.27) (HR 1.15, 95% CI: 0.893-1.479; p = 0.27). In multivariate logistic regression analyses for respiratory insufficiency and sepsis, BMI < 25 kg/m2 is determined as an independent predictor for reduction of respiratory insufficiency (OR 0.73, 95% CI: 0.538-1.004; p = 0.05). CONCLUSIONS: HOPE COVID-19-Registry revealed no evidence of obesity paradox in patients with COVID-19. However, Obesity was associated with a higher rate of respiratory insufficiency and sepsis but was not determined as an independent predictor for a high mortality.

Clinical profile and predictors of in-hospital mortality among older patients hospitalised for COVID-19.

BACKGROUND: the coronavirus disease 2019 (COVID-19) is characterized by poor outcomes and mortality, particularly in older patients. METHODS: post hoc analysis of the international, multicentre, 'real-world' HOPE COVID-19 registry. All patients aged ≥65 years hospitalised for COVID-19 were selected. Epidemiological, clinical, analytical and outcome data were obtained. A comparative study between two age subgroups, 65-74 and ≥75 years, was performed. The primary endpoint was all cause in-hospital mortality. RESULTS: about, 1,520 patients aged ≥65 years (60.3% male, median age of 76 [IQR 71-83] years) were included. Comorbidities such as hypertension (69.2%), dyslipidaemia (48.6%), cardiovascular diseases (any chronic heart disease in 38.4% and cerebrovascular disease in 12.5%), and chronic lung disease (25.3%) were prevalent, and 49.6% were on ACEI/ARBs. Patients aged 75 years and older suffered more in-hospital complications (respiratory failure, heart failure, renal failure, sepsis) and a significantly higher mortality (18.4 vs. 48.2%, P < 0.001), but fewer admissions to intensive care units (11.2 vs. 4.8%). In the overall cohort, multivariable analysis demonstrated age ≥75 (OR 3.54), chronic kidney disease (OR 3.36), dementia (OR 8.06), peripheral oxygen saturation at admission <92% (OR 5.85), severe lymphopenia (<500/mm3) (OR 3.36) and qSOFA (Quick Sequential Organ Failure Assessment Score) >1 (OR 8.31) to be independent predictors of mortality. CONCLUSION: patients aged ≥65 years hospitalised for COVID-19 had high rates of in-hospital complications and mortality, especially among patients 75 years or older. Age ≥75 years, dementia, peripheral oxygen saturation <92%, severe lymphopenia and qSOFA scale >1 were independent predictors of mortality in this population.

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.

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 in 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.