Differences in clinical features and mortality in very old unvaccinated patients (≥ 80 years) hospitalized with COVID-19 during the first and successive waves from the multicenter SEMI-COVID-19 Registry (Spain).

BACKGROUND: Old age is one of the most important risk factors for severe COVID-19. Few studies have analyzed changes in the clinical characteristics and prognosis of COVID-19 among older adults before the availability of vaccines. This work analyzes differences in clinical features and mortality in unvaccinated very old adults during the first and successive COVID-19 waves in Spain. METHODS: This nationwide, multicenter, retrospective cohort study analyzes unvaccinated patients ≥ 80 years hospitalized for COVID-19 in 150 Spanish hospitals (SEMI-COVID-19 Registry). Patients were classified according to whether they were admitted in the first wave (March 1-June 30, 2020) or successive waves (July 1-December 31, 2020). The endpoint was all-cause in-hospital mortality, expressed as the case fatality rate (CFR). RESULTS: Of the 21,461 patients hospitalized with COVID-19, 5,953 (27.7%) were ≥ 80 years (mean age [IQR]: 85.6 [82.3-89.2] years). Of them, 4,545 (76.3%) were admitted during the first wave and 1,408 (23.7%) during successive waves. Patients hospitalized in successive waves were older, had a greater Charlson Comorbidity Index and dependency, less cough and fever, and met fewer severity criteria at admission (qSOFA index, PO2/FiO2 ratio, inflammatory parameters). Significant differences were observed in treatments used in the first (greater use of antimalarials, lopinavir, and macrolides) and successive waves (greater use of corticosteroids, tocilizumab and remdesivir). In-hospital complications, especially acute respiratory distress syndrome and pneumonia, were less frequent in patients hospitalized in successive waves, except for heart failure. The CFR was significantly higher in the first wave (44.1% vs. 33.3%; -10.8%; p < 0.001) and was higher among patients ≥ 95 years (54.4% vs. 38.5%; -15.9%; p < 0.001). After adjustments to the model, the probability of death was 33% lower in successive waves (OR: 0.67; 95% CI: 0.57-0.79). CONCLUSIONS: Mortality declined significantly between the first and successive waves in very old unvaccinated patients hospitalized with COVID-19 in Spain. This decline could be explained by a greater availability of hospital resources and more effective treatments as the pandemic progressed, although other factors such as changes in SARS-CoV-2 virulence cannot be ruled out.

The importance of association of comorbidities on COVID-19 outcomes: a machine learning approach.

BACKGROUND: The individual influence of a variety of comorbidities on COVID-19 patient outcomes has already been analyzed in previous works in an isolated way. We aim to determine if different associations of diseases influence the outcomes of inpatients with COVID-19. METHODS: Retrospective cohort multicenter study based on clinical practice. Data were taken from the SEMI-COVID-19 Registry, which includes most consecutive patients with confirmed COVID-19 hospitalized and discharged in Spain. Two machine learning algorithms were applied in order to classify comorbidities and patients (Random Forest -RF algorithm, and Gaussian mixed model by clustering -GMM-). The primary endpoint was a composite of either, all-cause death or intensive care unit admission during the period of hospitalization. The sample was randomly divided into training and test sets to determine the most important comorbidities related to the primary endpoint, grow several clusters with these comorbidities based on discriminant analysis and GMM, and compare these clusters. RESULTS: A total of 16,455 inpatients (57.4% women and 42.6% men) were analyzed. According to the RF algorithm, the most important comorbidities were heart failure/atrial fibrillation (HF/AF), vascular diseases, and neurodegenerative diseases. There were six clusters: three included patients who met the primary endpoint (clusters 4, 5, and 6) and three included patients who did not (clusters 1, 2, and 3). Patients with HF/AF, vascular diseases, and neurodegenerative diseases were distributed among clusters 3, 4 and 5. Patients in cluster 5 also had kidney, liver, and acid peptic diseases as well as a chronic obstructive pulmonary disease; it was the cluster with the worst prognosis. CONCLUSION: The interplay of several comorbidities may affect the outcome and complications of inpatients with COVID-19.

Estimation of Admission D-dimer Cut-off Value to Predict Venous Thrombotic Events in Hospitalized COVID-19 Patients: Analysis of the SEMI-COVID-19 Registry.

BACKGROUND: Venous thrombotic events (VTE) are frequent in COVID-19, and elevated plasma D-dimer (pDd) and dyspnea are common in both entities. OBJECTIVE: To determine the admission pDd cut-off value associated with in-hospital VTE in patients with COVID-19. METHODS: Multicenter, retrospective study analyzing the at-admission pDd cut-off value to predict VTE and anticoagulation intensity along hospitalization due to COVID-19. RESULTS: Among 9386 patients, 2.2% had VTE: 1.6% pulmonary embolism (PE), 0.4% deep vein thrombosis (DVT), and 0.2% both. Those with VTE had a higher prevalence of tachypnea (42.9% vs. 31.1%; p = 0.0005), basal O2 saturation <93% (45.4% vs. 33.1%; p = 0.0003), higher at admission pDd (median [IQR]: 1.4 [0.6-5.5] vs. 0.6 [0.4-1.2] µg/ml; p < 0.0001) and platelet count (median [IQR]: 208 [158-289] vs. 189 [148-245] platelets × 109/L; p = 0.0013). A pDd cut-off of 1.1 µg/ml showed specificity 72%, sensitivity 49%, positive predictive value (PPV) 4%, and negative predictive value (NPV) 99% for in-hospital VTE. A cut-off value of 4.7 µg/ml showed specificity of 95%, sensitivity of 27%, PPV of 9%, and NPV of 98%. Overall mortality was proportional to pDd value, with the lowest incidence for each pDd category depending on anticoagulation intensity: 26.3% for those with pDd >1.0 µg/ml treated with prophylactic dose (p < 0.0001), 28.8% for pDd for patients with pDd >2.0 µg/ml treated with intermediate dose (p = 0.0001), and 31.3% for those with pDd >3.0 µg/ml and full anticoagulation (p = 0.0183). CONCLUSIONS: In hospitalized patients with COVID-19, a pDd value greater than 3.0 µg/ml can be considered to screen VTE and to consider full-dose anticoagulation.

Prior Treatment with Statins is Associated with Improved Outcomes of Patients with COVID-19: Data from the SEMI-COVID-19 Registry.

BACKGROUND: The impact of statins on COVID-19 outcomes is important given the high prevalence of their use among individuals at risk for severe COVID-19. Our aim is to assess whether patients receiving chronic statin treatment who are hospitalized with COVID-19 have reduced in-hospital mortality if statin therapy is maintained during hospitalization. METHODS: This work is a cross-sectional, observational, retrospective multicenter study that analyzed 2921 patients who required hospital admission at 150 Spanish centers included in the nationwide SEMI-COVID-19 Network. We compared the clinical characteristics and COVID-19 disease outcomes between patients receiving chronic statin therapy who maintained this therapy during hospitalization versus those who did not. Propensity score matching was used to match each statin user whose therapy was maintained during hospitalization to a statin user whose therapy was withdrawn during hospitalization. RESULTS: After propensity score matching, continuation of statin therapy was associated with lower all-cause mortality (OR 0.67, 0.54-0.83, p < 0.001); lower incidence of acute kidney injury (AKI) (OR 0.76,0.6-0.97, p = 0.025), acute respiratory distress syndrome (ARDS) (OR 0.78, 0.69- 0.89, p < 0.001), and sepsis (4.82% vs 9.85%, p = 0.008); and less need for invasive mechanical ventilation (IMV) (5.35% vs 8.57, p < 0.001) compared to patients whose statin therapy was withdrawn during hospitalization. CONCLUSIONS: Patients previously treated with statins who are hospitalized for COVID-19 and maintain statin therapy during hospitalization have a lower mortality rate than those in whom therapy is withdrawn. In addition, statin therapy was associated with a decreased probability that patients with COVID-19 will develop AKI, ARDS, or sepsis and decreases the need for IMV.

Healthcare workers hospitalized due to COVID-19 have no higher risk of death than general population. Data from the Spanish SEMI-COVID-19 Registry.

AIM: To determine whether healthcare workers (HCW) hospitalized in Spain due to COVID-19 have a worse prognosis than non-healthcare workers (NHCW). METHODS: Observational cohort study based on the SEMI-COVID-19 Registry, a nationwide registry that collects sociodemographic, clinical, laboratory, and treatment data on patients hospitalised with COVID-19 in Spain. Patients aged 20-65 years were selected. A multivariate logistic regression model was performed to identify factors associated with mortality. RESULTS: As of 22 May 2020, 4393 patients were included, of whom 419 (9.5%) were HCW. Median (interquartile range) age of HCW was 52 (15) years and 62.4% were women. Prevalence of comorbidities and severe radiological findings upon admission were less frequent in HCW. There were no difference in need of respiratory support and admission to intensive care unit, but occurrence of sepsis and in-hospital mortality was lower in HCW (1.7% vs. 3.9%; p = 0.024 and 0.7% vs. 4.8%; p<0.001 respectively). Age, male sex and comorbidity, were independently associated with higher in-hospital mortality and healthcare working with lower mortality (OR 0.211, 95%CI 0.067-0.667, p = 0.008). 30-days survival was higher in HCW (0.968 vs. 0.851 p<0.001). CONCLUSIONS: Hospitalized COVID-19 HCW had fewer comorbidities and a better prognosis than NHCW. Our results suggest that professional exposure to COVID-19 in HCW does not carry more clinical severity nor mortality.

Impact of Arterial Stiffness on All-Cause Mortality in Patients Hospitalized With COVID-19 in Spain.

Older age and cardiovascular comorbidities are well-known risk factors for all-cause mortality in patients with coronavirus disease 2019 (COVID-19). Hypertension and age are the 2 principal determinants of arterial stiffness (AS). This study aimed to estimate AS in patients with COVID-19 requiring hospitalization and analyze its association with all-cause in-hospital mortality. This observational, retrospective, multicenter cohort study analyzed 12 170 patients admitted to 150 Spanish centers included in the SEMI-COVID-19 Network. We compared AS, defined as pulse pressure ≥60 mm Hg, and clinical characteristics between survivors and nonsurvivors. Mean age was 67.5 (±16.1) years and 42.5% were women. Overall, 2606 (21.4%) subjects died. Admission systolic blood pressure (BP) <120 and ≥140 mm Hg was a predictor of higher all-cause mortality (23.5% and 22.8%, respectively, P<0.001), compared with systolic BP between 120 and 140 mm Hg (18.6%). The 4379 patients with AS (36.0%) were older and had higher systolic and lower diastolic BP. Multivariate analysis showed that AS and systolic BP <120 mm Hg significantly and independently predicted all-cause in-hospital mortality (adjusted odds ratio [ORadj]: 1.27, P=0.0001; ORadj: 1.48, P=0.0001, respectively) after adjusting for sex (males, ORadj: 1.6, P=0.0001), age tertiles (second and third tertiles, ORadj: 2.0 and 4.7, P=0.0001), Charlson Comorbidity Index (second and third tertiles, ORadj: 4.8 and 8.6, P=0.0001), heart failure, and previous and in-hospital antihypertensive treatment. Our data show that AS and admission systolic BP <120 mm Hg had independent prognostic value for all-cause mortality in patients with COVID-19 requiring hospitalization.

The Prognostic Value of Eosinophil Recovery in COVID-19: A Multicentre, Retrospective Cohort Study on Patients Hospitalised in Spanish Hospitals.

OBJECTIVES: A decrease in blood cell counts, especially lymphocytes and eosinophils, has been described in patients with serious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), but there is no knowledge of their potential role of the recovery in these patients' prognosis. This article aims to analyse the effect of blood cell depletion and blood cell recovery on mortality due to COVID-19. DESIGN: This work was a retrospective, multicentre cohort study of 9644 hospitalised patients with confirmed COVID-19 from the Spanish Society of Internal Medicine's SEMI-COVID-19 Registry. SETTING: This study examined patients hospitalised in 147 hospitals throughout Spain. PARTICIPANTS: This work analysed 9644 patients (57.12% male) out of a cohort of 12,826 patients ≥18 years of age hospitalised with COVID-19 in Spain included in the SEMI-COVID-19 Registry as of 29 May 2020. MAIN OUTCOME MEASURES: The main outcome measure of this work is the effect of blood cell depletion and blood cell recovery on mortality due to COVID-19. Univariate analysis was performed to determine possible predictors of death, and then multivariate analysis was carried out to control for potential confounders. RESULTS: An increase in the eosinophil count on the seventh day of hospitalisation was associated with a better prognosis, including lower mortality rates (5.2% vs. 22.6% in non-recoverers, OR 0.234; 95% CI, 0.154 to 0.354) and lower complication rates, especially regarding the development of acute respiratory distress syndrome (8% vs. 20.1%, p = 0.000) and ICU admission (5.4% vs. 10.8%, p = 0.000). Lymphocyte recovery was found to have no effect on prognosis. Treatment with inhaled or systemic glucocorticoids was not found to be a confounding factor. CONCLUSION: Eosinophil recovery in patients with COVID-19 who required hospitalisation had an independent prognostic value for all-cause mortality and a milder course.

Admission hyperglycaemia as a predictor of mortality in patients hospitalized with COVID-19 regardless of diabetes status: data from the Spanish SEMI-COVID-19 Registry.

BACKGROUND: Hyperglycaemia has emerged as an important risk factor for death in coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the association between blood glucose (BG) levels and in-hospital mortality in non-critically patients hospitalized with COVID-19. METHODS: This is a retrospective multi-centre study involving patients hospitalized in Spain. Patients were categorized into three groups according to admission BG levels: <140 mg/dL, 140-180 mg/dL and >180 mg/dL. The primary endpoint was all-cause in-hospital mortality. RESULTS: Of the 11,312 patients, only 2128 (18.9%) had diabetes and 2289 (20.4%) died during hospitalization. The in-hospital mortality rates were 15.7% (<140 mg/dL), 33.7% (140-180 mg) and 41.1% (>180 mg/dL), p<.001. The cumulative probability of mortality was significantly higher in patients with hyperglycaemia compared to patients with normoglycaemia (log rank, p<.001), independently of pre-existing diabetes. Hyperglycaemia (after adjusting for age, diabetes, hypertension and other confounding factors) was an independent risk factor of mortality (BG >180 mg/dL: HR 1.50; 95% confidence interval (CI): 1.31-1.73) (BG 140-180 mg/dL; HR 1.48; 95%CI: 1.29-1.70). Hyperglycaemia was also associated with requirement for mechanical ventilation, intensive care unit (ICU) admission and mortality. CONCLUSIONS: Admission hyperglycaemia is a strong predictor of all-cause mortality in non-critically hospitalized COVID-19 patients regardless of prior history of diabetes. KEY MESSAGE Admission hyperglycaemia is a stronger and independent risk factor for mortality in COVID-19. Screening for hyperglycaemia, in patients without diabetes, and early treatment of hyperglycaemia should be mandatory in the management of patients hospitalized with COVID-19. Admission hyperglycaemia should not be overlooked in all patients regardless prior history of diabetes.