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 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.

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.

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.

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.

Atrial fibrillation in patients with COVID-19. Usefulness of the CHA2DS2-VASc score: an analysis of the international HOPE COVID-19 registry.

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.

Underlying heart diseases and acute COVID-19 outcomes.

BACKGROUND: The presence of any underlying heart condition could influence outcomes during the coronavirus disease 2019 (COVID-19). METHODS: The registry HOPE-COVID-19 (Health Outcome Predictive Evaluation for COVID-19, NCT04334291) is an international ambispective study, enrolling COVID-19 patients discharged from hospital, dead or alive. RESULTS: HOPE enrolled 2798 patients from 35 centers in 7 countries. Median age was 67 years (IQR: 53.0-78.0), and most were male (59.5%). A relevant heart disease was present in 682 (24%) cases. These were older, more frequently male, with higher overall burden of cardiovascular risk factors (hypertension, dyslipidemia, diabetes mellitus, smoking habit, obesity) and other comorbidities such renal failure, lung, cerebrovascular disease and oncologic antecedents (p < 0.01, for all). The heart cohort received more corticoids (28.9% vs. 20.4%, p < 0.001), antibiotics, but less hydroxychloroquine, antivirals or tocilizumab. Considering the epidemiologic profile, a previous heart condition was independently related with shortterm mortality in the Cox multivariate analysis (1.62; 95% CI 1.29-2.03; p < 0.001). Moreover, heart patients needed more respiratory, circulatory support, and presented more in-hospital events, such heart failure, renal failure, respiratory insufficiency, sepsis, systemic infammatory response syndrome and clinically relevant bleedings (all, p < 0.001), and mortality (39.7% vs. 15.5%; p < 0.001). CONCLUSIONS: An underlying heart disease is an adverse prognostic factor for patients suffering COVID-19. Its presence could be related with different clinical drug management and would benefit from maintaining treatment with angiotensin converting enzyme inhibitors or angiotensin receptor blockers during in-hospital stay.

Mortality risk assessment in Spain and Italy, insights of the HOPE COVID-19 registry.

Recently the coronavirus disease (COVID-19) outbreak has been declared a pandemic. Despite its aggressive extension and significant morbidity and mortality, risk factors are poorly characterized outside China. We designed a registry, HOPE COVID-19 (NCT04334291), assessing data of 1021 patients discharged (dead or alive) after COVID-19, from 23 hospitals in 4 countries, between 8 February and 1 April. The primary end-point was all-cause mortality aiming to produce a mortality risk score calculator. The median age was 68 years (IQR 52-79), and 59.5% were male. Most frequent comorbidities were hypertension (46.8%) and dyslipidemia (35.8%). A relevant heart or lung disease were depicted in 20%. And renal, neurological, or oncological disease, respectively, were detected in nearly 10%. Most common symptoms were fever, cough, and dyspnea at admission. 311 patients died and 710 were discharged alive. In the death-multivariate analysis, raised as most relevant: age, hypertension, obesity, renal insufficiency, any immunosuppressive disease, 02 saturation < 92% and an elevated C reactive protein (AUC = 0.87; Hosmer-Lemeshow test, p > 0.999; bootstrap-optimist: 0.0018). We provide a simple clinical score to estimate probability of death, dividing patients in four grades (I-IV) of increasing probability. Hydroxychloroquine (79.2%) and antivirals (67.6%) were the specific drugs most commonly used. After a propensity score adjustment, the results suggested a slight improvement in mortality rates (adjusted-ORhydroxychloroquine 0.88; 95% CI 0.81-0.91, p = 0.005; adjusted-ORantiviral 0.94; 95% CI 0.87-1.01; p = 0.115). COVID-19 produces important mortality, mostly in patients with comorbidities with respiratory symptoms. Hydroxychloroquine could be associated with survival benefit, but this data need to be confirmed with further trials. Trial Registration: NCT04334291/EUPAS34399.

Impact of renal function on admission in COVID-19 patients: an analysis of the international HOPE COVID-19 (Health Outcome Predictive Evaluation for COVID 19) Registry.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite its international aggressive extension, with a significant morbidity and mortality, the impact of renal function on its prognosis is uncertain. METHODS: Analysis from the international HOPE-Registry (NCT04334291). The objective was to evaluate the association between kidney failure severity on admission with the mortality of patients with SARS-CoV-2 infection. Patients were categorized in 3 groups according to the estimated glomerular filtration rate on admission (eGFR > 60 mL/min/1.73 m2, eGFR 30-60 mL/min/1.73 m2 and eGFR < 30 mL/min/1.73 m2). RESULTS: 758 patients were included: mean age was 66 ± 18 years, and 58.6% of patient were male. Only 8.5% of patients had a history of chronic kidney disease (CKD); however, 30% of patients had kidney dysfunction upon admission (eGFR < 60 mL/min/1.73 m2). These patients received less frequently pharmacological treatment with hydroxychloroquine or antivirals and had a greater number of complications such as sepsis (11.9% vs 26.4% vs 40.8%, p < 0.001) and respiratory failure (35.4% vs 72.2% vs 62.0%, p < 0.001) as well as a higher in-hospital mortality rate (eGFR > 60 vs eGFR 30-60 vs and eGFR < 30, 18.4% vs 56.5% vs 65.5%, p < 0.001). In multivariate analysis: age, hypertension, renal function, 02 saturation < 92% and lactate dehydrogenase elevation on admission independently predicted all-cause mortality. CONCLUSIONS: Renal failure on admission in patients with SARS-CoV-2 infection is frequent and is associated with a greater number of complications and in-hospital mortality. Our data comes from a multicenter registry and therefore does not allow to have a precise mortality risk assessment. More studies are needed to confirm these findings.