Influence of smoking history on the evolution of hospitalized in COVID-19 positive patients: Results from the SEMI-COVID-19 registry.

Introduction: Smoking can play a key role in SARS-CoV-2 infection and in the course of the disease. Previous studies have conflicting or inconclusive results on the prevalence of smoking and the severity of the coronavirus disease (COVID-19). Methods: Observational, multicenter, retrospective cohort study of 14,260 patients admitted for COVID-19 in Spanish hospitals between February and September 2020. Their clinical characteristics were recorded and the patients were classified into a smoking group (active or former smokers) or a non-smoking group (never smokers). The patients were followed up to one month after discharge. Differences between groups were analysed. A multivariate logistic regression and Kapplan Meier curves analysed the relationship between smoking and in-hospital mortality. Results: The median age was 68.6 (55.8-79.1) years, with 57.7% of males. Smoking patients were older (69.9 (59.6-78.0 years)), more frequently male (80.3%) and with higher Charlson index (4 (2-6)) than non-smoking patients. Smoking patients presented a worse evolution, with a higher rate of admission to the intensive care unit (ICU) (10.4 vs. 8.1%), higher in-hospital mortality (22.5 vs. 16.4%) and readmission at one month (5.8 vs. 4.0%) than in non-smoking patients. After multivariate analysis, smoking remained associated with these events. Conclusions: Active or past smoking is an independent predictor of poor prognosis in patients with COVID-19. It is associated with higher ICU admissions and in-hospital mortality.

Introducción: El tabaquismo puede tener un papel importante en la infección por SARS-CoV-2 y en el curso de la enfermedad. Los estudios previos muestran resultados contradictorios o no concluyentes sobre la prevalencia de fumar y la severidad en la enfermedad por coronavirus (COVID-19). Material y métodos: Estudio de cohortes observacional, multicéntrico y retrospectivo de 14.260 pacientes que ingresaron por COVID-19 en hospitales españoles desde febrero a septiembre de 2020. Se registraron sus características clínicas y se clasificaron en el grupo con tabaquismo si tabaquismo activo o previo o en el grupo sin tabaquismo si nunca habían fumado. Se realizó un seguimiento hasta un mes después del alta. Se analizaron las diferencias entre grupos. La relación entre tabaquismo y mortalidad intrahospitalaria se valoró mediante una regresión logística multivariante y curvas de Kapplan Meier. Resultados: La mediana de edad fue 68,6 (55,8­79,1) años, con un 57,7% de varones. El grupo con tabaquismo presentó mayor edad (69,9 (59,6­78,0 años)), predominio masculino (80,3%) y mayor índice de Charlson (4 (2−6)). La evolución fue peor en estos pacientes, con una mayor tasa de ingreso en UCI (10,4 vs 8,1%), mayor mortalidad intrahospitalaria (22,5 vs 16,4%) y reingreso al mes (5,8 vs 4,0%) que el grupo sin tabaquismo. Tras el análisis multivariante, el tabaquismo permanecía asociado a estos eventos. Conclusiones: El tabaquismo de forma activa o pasada es un factor predictor independiente de mal pronóstico en los pacientes con COVID-19, estando asociada a mayor probabilidad de ingreso en UCI y a mayor mortalidad intrahospitalaria.

Influence of smoking history on the progression of hospitalised COVID-19 positive patients: results from the SEMI-COVID-19 registry Influencia de la historia de tabaquismo en la evolución de la hospitalización en pacientes COVID-19 positivos: datos del registro SEMI-COVID-19

Introduction Smoking can play a key role in SARS-CoV-2 infection and in the course of the disease. Previous studies have conflicting or inconclusive results on the prevalence of smoking and the severity of the coronavirus disease (COVID-19). Methods Observational, multicenter, retrospective cohort study of 14,260 patients admitted for COVID-19 in Spanish hospitals between February and September 2020. Their clinical characteristics were recorded and the patients were classified into a smoking group (active or former smokers) or a non-smoking group (never smokers). The patients were followed up to one month after discharge. Differences between groups were analyzed. A multivariate logistic regression and Kapplan Meier curves analyzed the relationship between smoking and in-hospital mortality. Results The median age was 68.6 (55.8-79.1) years, with 57.7% of males. Smoking patients were older (69.9 (59.6-78.0 years)), more frequently male (80.3%) and with higher Charlson index (4 (2-6)) than non-smoking patients. Smoking patients presented a worse evolution, with a higher rate of admission to the intensive care unit (ICU) (10.4 vs 8.1%), higher in-hospital mortality (22.5 vs 16.4%) and readmission at one month (5.8 vs 4.0%) than in non-smoking patients. After multivariate analysis, smoking remained associated with these events. Conclusions Active or past smoking is an independent predictor of poor prognosis in patients with COVID-19. It is associated with higher ICU admissions and in-hospital mortality.

Remdesivir in Very Old Patients (≥80 Years) Hospitalized with COVID-19: Real World Data from the SEMI-COVID-19 Registry.

(1) Background: Large cohort studies of patients with COVID-19 treated with remdesivir have reported improved clinical outcomes, but data on older patients are scarce. Objective: This work aims to assess the potential benefit of remdesivir in unvaccinated very old patients hospitalized with COVID-19; (2) Methods: This is a retrospective analysis of patients ≥ 80 years hospitalized in Spain between 15 July and 31 December 2020 (SEMI-COVID-19 Registry). Differences in 30-day all-cause mortality were adjusted using a multivariable regression analysis. (3) Results: Of the 4331 patients admitted, 1312 (30.3%) were ≥80 years. Very old patients treated with remdesivir (n: 140, 10.7%) had a lower mortality rate than those not treated with remdesivir (OR (95% CI): 0.45 (0.29-0.69)). After multivariable adjustment by age, sex, and variables associated with lower mortality (place of COVID-19 acquisition; degree of dependence; comorbidities; dementia; duration of symptoms; admission qSOFA; chest X-ray; D-dimer; and treatment with corticosteroids, tocilizumab, beta-lactams, macrolides, and high-flow nasal canula oxygen), the use of remdesivir remained associated with a lower 30-day all-cause mortality rate (adjusted OR (95% CI): 0.40 (0.22-0.61) (p < 0.001)). (4) Conclusions: Remdesivir may reduce mortality in very old patients hospitalized with COVID-19.

Clusters of inflammation in COVID-19: descriptive analysis and prognosis on more than 15,000 patients from the Spanish SEMI-COVID-19 Registry.

Uncontrolled inflammation following COVID-19 infection is an important characteristic of the most seriously ill patients. The present study aims to describe the clusters of inflammation in COVID-19 and to analyze their prognostic role. This is a retrospective observational study including 15,691 patients with a high degree of inflammation. They were included in the Spanish SEMI-COVID-19 registry from March 1, 2020 to May 1, 2021. The primary outcome was in-hospital mortality. Hierarchical cluster analysis identified 7 clusters. C1 is characterized by lymphopenia, C2 by elevated ferritin, and C3 by elevated LDH. C4 is characterized by lymphopenia plus elevated CRP and LDH and frequently also ferritin. C5 is defined by elevated CRP, and C6 by elevated ferritin and D-dimer, and frequently also elevated CRP and LDH. Finally, C7 is characterized by an elevated D-dimer. The clusters with the highest in-hospital mortality were C4, C6, and C7 (17.4% vs. 18% vs. 15.6% vs. 36.8% vs. 17.5% vs. 39.3% vs. 26.4%). Inflammation clusters were found as independent factors for in-hospital mortality. In detail and, having cluster C1 as reference, the model revealed a worse prognosis for all other clusters: C2 (OR = 1.30, p = 0.001), C3 (OR = 1.14, p = 0.178), C4 (OR = 2.28, p < 0.001), C5 (OR = 1.07, p = 0.479), C6 (OR = 2.29, p < 0.001), and C7 (OR = 1.28, p = 0.001). We identified 7 groups based on the presence of lymphopenia, elevated CRP, LDH, ferritin, and D-dimer at the time of hospital admission for COVID-19. Clusters C4 (lymphopenia + LDH + CRP), C6 (ferritin + D-dimer), and C7 (D-dimer) had the worst prognosis in terms of in-hospital mortality.

Influence of chronic use of corticosteroids and calcineurin inhibitors on COVID-19 clinical outcomes: analysis of a nationwide registry.

OBJECTIVES: The aim of this study was to analyze whether subgroups of immunosuppressive (IS) medications conferred different outcomes in COVID-19. METHODS: The study involved a multicenter retrospective cohort of consecutive immunosuppressed patients (ISPs) hospitalized with COVID-19 from March to July, 2020. The primary outcome was in-hospital mortality. A propensity score-matched (PSM) model comparing ISP and non-ISP was planned, as well as specific PSM models comparing individual IS medications associated with mortality. RESULTS: Out of 16 647 patients, 868 (5.2%) were on chronic IS therapy prior to admission and were considered ISPs. In the PSM model, ISPs had greater in-hospital mortality (OR 1.25, 95% CI 0.99-1.62), which was related to a worse outcome associated with chronic corticoids (OR 1.89, 95% CI 1.43-2.49). Other IS drugs had no repercussions with regard to mortality risk (including calcineurin inhibitors (CNI); OR 1.19, 95% CI 0.65-2.20). In the pre-planned specific PSM model involving patients on chronic IS treatment before admission, corticosteroids were associated with an increased risk of mortality (OR 2.34, 95% CI 1.43-3.82). CONCLUSIONS: Chronic IS therapies comprise a heterogeneous group of drugs with different risk profiles for severe COVID-19 and death. Chronic systemic corticosteroid therapy is associated with increased mortality. On the contrary, CNI and other IS treatments prior to admission do not seem to convey different outcomes.

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.

INFLUENCIA DE LA HISTORIA DE TABAQUISMO EN LA EVOLUCIÓN DE LA HOSPITALIZACIÓN EN PACIENTES COVID-19 POSITIVOS: DATOS DEL REGISTRO SEMI-COVID-19 INFLUENCE OF SMOKING HISTORY ON THE EVOLUTION OF HOSPITALIZED IN COVID-19 POSITIVE PATIENTS: RESULTS FROM THE SEMI-COVID-19 REGISTRY

Introducción: El tabaquismo puede tener un papel importante en la infección por SARS-CoV-2 y en el curso de la enfermedad. Los estudios previos muestran resultados contradictorios o no concluyentes sobre la prevalencia de fumar y la severidad en la enfermedad por coronavirus (COVID-19). Material y métodos: Estudio de cohortes observacional, multicéntrico y retrospectivo de 14.260 pacientes que ingresaron por COVID-19 en hospitales españoles desde febrero a septiembre de 2020. Se registraron sus características clínicas y se clasificaron en el grupo con tabaquismo si tabaquismo activo o previo o en el grupo sin tabaquismo si nunca habían fumado. Se realizó un seguimiento hasta un mes después del alta. Se analizaron las diferencias entre grupos. La relación entre tabaquismo y mortalidad intrahospitalaria se valoró mediante una regresión logística multivariante y curvas de Kapplan Meier. Resultados: La mediana de edad fue 68,6 (55,8-79,1) años, con un 57,7% de varones. El grupo con tabaquismo presentó mayor edad (69,9 (59,6-78,0 años)), predominio masculino (80,3%) y mayor índice de Charlson (4 (2-6)). La evolución fue peor en estos pacientes, con una mayor tasa de ingreso en UCI (10,4 vs 8,1%), mayor mortalidad intrahospitalaria (22,5 vs 16,4%) y reingreso al mes (5,8 vs 4,0%) que el grupo sin tabaquismo. Tras el análisis multivariante, el tabaquismo permanecía asociado a estos eventos. Conclusiones: El tabaquismo de forma activa o pasada es un factor predictor independiente de mal pronóstico en los pacientes con COVID-19, estando asociada a mayor probabilidad de ingreso en UCI y a mayor mortalidad intrahospitalaria.

Incidence of venous thromboembolism in patients with non-hematological cancer admitted for COVID-19 at a third-level hospital in Madrid.

An increased risk of venous thromboembolism (VTE) in hospitalized patients with COVID-19 has been reported. We aimed to describe the incidence rate of VTE on patients with non-hematological cancer who required hospitalization due to COVID-19 at our center. In this prospective study, non-hematological cancer patients hospitalized for confirmed COVID-19 at our institution from 1st March to 30th April 2020, were evaluated daily for VTE complications during their hospital stay, and after discharge until 30th June 2020. Furthermore, Doppler ultrasound of lower limbs was routinely performed in asymptomatic patients based on D-dimer levels and current active cancer therapy. The primary outcome of this study was the cumulative incidence of VTE. Secondary outcomes were the cumulative incidence of bleeding and mortality. A total of 58 hospitalized non-hematological cancer patients and confirmed COVID-19 were identified. Median follow-up since initial symptoms of COVID-19 was 91 days (IQR 19-104). Pulmonary embolism was diagnosed in three (5%) patients. Symptomatic catheter-related deep vein thrombosis (DVT) was observed in one patient. Doppler ultrasound of lower limbs was done in 11 asymptomatic patients, showing distal DVT in two of them (18%). The cumulative incidence of VTE on day 14 after admission was 10%, without new VTE events after hospital discharge and up to 90 days follow-up. No bleeding complication was observed. Seventeen patients (29%) died in the first 14 days after COVID-19 diagnosis. Four patients died after discharge due to malignancy progression. The cumulative incidence of VTE in non-hematological cancer patients under active treatment was 10% at day 14 after admission, with no further new events in the following 12 weeks.

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.

Clinical Characteristics and Prognosis of COPD Patients Hospitalized with SARS-CoV-2.

Objective: To describe the characteristics and prognosis of patients with COPD admitted to the hospital due to SARS-CoV-2 infection. Methods: The SEMI-COVID registry is an ongoing retrospective cohort comprising consecutive COVID-19 patients hospitalized in Spain since the beginning of the pandemic in March 2020. Data on demographics, clinical characteristics, comorbidities, laboratory tests, radiology, treatment, and progress are collected. Patients with COPD were selected and compared to patients without COPD. Factors associated with a poor prognosis were analyzed. Results: Of the 10,420 patients included in the SEMI-COVID registry as of May 21, 2020, 746 (7.16%) had a diagnosis of COPD. Patients with COPD are older than those without COPD (77 years vs 68 years) and more frequently male. They have more comorbidities (hypertension, hyperlipidemia, diabetes mellitus, atrial fibrillation, heart failure, ischemic heart disease, peripheral vascular disease, kidney failure) and a higher Charlson Comorbidity Index (2 vs 1, p<0.001). The mortality rate in COPD patients was 38.3% compared to 19.2% in patients without COPD (p<0.001). Male sex, a history of hypertension, heart failure, moderate-severe chronic kidney disease, presence of cerebrovascular disease with sequelae, degenerative neurological disease, dementia, functional dependence, and a higher Charlson Comorbidity Index have been associated with increased mortality due to COVID-19 in COPD patients. Survival was higher among patients with COPD who were treated with hydroxychloroquine (87.1% vs 74.9%, p<0.001) and with macrolides (57.9% vs 50%, p<0.037). Neither prone positioning nor non-invasive mechanical ventilation, high-flow nasal cannula, or invasive mechanical ventilation were associated with a better prognosis. Conclusion: COPD patients admitted to the hospital with SARS-CoV-2 infection have more severe disease and a worse prognosis than non-COPD patients.

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.