Predicting critical illness on initial diagnosis of COVID-19 based on easily obtained clinical variables: development and validation of the PRIORITY model

Objectives: We aimed to develop and validate a prediction model, based on clinical history and examination findings on initial diagnosis of coronavirus disease 2019 (COVID-19), to identify patients at risk of critical outcomes. Methods: We used data from the SEMI-COVID-19 Registry, a cohort of consecutive patients hospitalized for COVID-19 from 132 centres in Spain (23rd March to 21st May 2020). For the development cohort, tertiary referral hospitals were selected, while the validation cohort included smaller hospitals. The primary outcome was a composite of in-hospital death, mechanical ventilation, or admission to intensive care unit. Clinical signs and symptoms, demographics, and medical history ascertained at presentation were screened using least absolute shrinkage and selection operator, and logistic regression was used to construct the predictive model. Results: There were 10 433 patients, 7850 in the development cohort (primary outcome 25.1%, 1967/7850) and 2583 in the validation cohort (outcome 27.0%, 698/2583). The PRIORITY model included: age, dependency, cardiovascular disease, chronic kidney disease, dyspnoea, tachypnoea, confusion, systolic blood pressure, and SpO2 ≤93% or oxygen requirement. The model showed high discrimination for critical illness in both the development (C-statistic 0.823; 95% confidence interval (CI) 0.813, 0.834) and validation (C-statistic 0.794; 95%CI 0.775, 0.813) cohorts. A freely available web-based calculator was developed based on this model (https://www.evidencio.com/models/show/2344). Conclusions: The PRIORITY model, based on easily obtained clinical information, had good discrimination and generalizability for identifying COVID-19 patients at risk of critical outcomes.No funding was received for this work

C-Reactive Protein and Serum Albumin Ratio: A Feasible Prognostic Marker in Hospitalized Patients with COVID-19

Background: C-reactive protein (CRP) and albumin are inflammatory markers. We analyzed the prognostic capacity of serum albumin (SA) and CRP for an outcome comprising mortality, length of stay, ICU admission, and non-invasive mechanical ventilation in hospitalized COVID-19 patients. (2) Methods: We conducted a retrospective cohort study based on the Spanish national SEMI-COVID-19 Registry. Two multivariate logistic models were adjusted for SA, CRP, and their combination. Training and testing samples were used to validate the models. (3) Results: The outcome was present in 41.1% of the 3471 participants, who had lower SA (mean [SD], 3.5 [0.6] g/dL vs. 3.8 [0.5] g/dL; p < 0.001) and higher CRP (108.9 [96.5] mg/L vs. 70.6 [70.3] mg/L; p < 0.001). In the adjusted multivariate model, both were associated with poorer evolution: SA, OR 0.674 (95% CI, 0.551-0.826; p < 0.001); CRP, OR 1.002 (95% CI, 1.001-1.004; p = 0.003). The CRP/SA model had a similar predictive capacity (honest AUC, 0.8135 [0.7865-0.8405]), with a continuously increasing risk and cutoff value of 25 showing the highest predictive capacity (OR, 1.470; 95% CI, 1.188-1.819; p < 0.001). (4) Conclusions: SA and CRP are good independent predictors of patients hospitalized with COVID-19. For the CRP/SA ratio value, 25 is the cutoff for poor clinical course

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 &lt;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 &lt; 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 &gt;1.0 µg/ml treated with prophylactic dose (p &lt; 0.0001), 28.8% for pDd for patients with pDd &gt;2.0 µg/ml treated with intermediate dose (p = 0.0001), and 31.3% for those with pDd &gt;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. © 2021, Society of General Internal Medicine

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

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

Use of glucocorticoids megadoses in SARS-CoV-2 infection in a spanish registry: SEMI-COVID-19

Objective To describe the impact of different doses of corticosteroids on the evolution of patients with COVID-19 pneumonia, based on the potential benefit of the non-genomic mechanism of these drugs at higher doses. Methods Observational study using data collected from the SEMI-COVID-19 Registry. We evaluated the epidemiological, radiological and analytical scenario between patients treated with megadoses therapy of corticosteroids vs low-dose of corticosteroids and the development of complications. The primary endpoint was all-cause in-hospital mortality according to use of corticosteroids megadoses. Results Of a total of 14,921 patients, corticosteroids were used in 5,262 (35.3%). Of them, 2,216 (46%) specifically received megadoses. Age was a factor that differed between those who received megadoses therapy versus those who did not in a significant manner (69 years [IQR 59-79] vs 73 years [IQR 61-83]; p < .001). Radiological and analytical findings showed a higher use of megadoses therapy among patients with an interstitial infiltrate and elevated inflammatory markers associated with COVID-19. In the univariate study it appears that steroid use is associated with increased mortality (OR 2.07 95% CI 1.91-2.24 p < .001) and megadose use with increased survival (OR 0.84 95% CI 0.75-0.96, p 0.011), but when adjusting for possible confounding factors, it is observed that the use of megadoses is also associated with higher mortality (OR 1.54, 95% CI 1.32-1.80; p < .001). There is no difference between megadoses and low-dose (p.298). Although, there are differences in the use of megadoses versus low-dose in terms of complications, mainly infectious, with fewer pneumonias and sepsis in the megadoses group (OR 0.82 95% CI 0.71-0.95; p < .001 and OR 0.80 95% CI 0.65-0.97; p < .001) respectively. Conclusion There is no difference in mortality with megadoses versus low-dose, but there is a lower incidence of infectious complications with glucocorticoid megadoses

Gender-Based Differences by Age Range in Patients Hospitalized with COVID-19: A Spanish Observational Cohort Study

There is some evidence that male gender could have a negative impact on the prognosis and severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The aim of the present study was to compare the characteristics of coronavirus disease 2019 (COVID-19) between hospitalized men and women with confirmed SARS-CoV-2 infection. This multicenter, retrospective, observational study is based on the SEMI-COVID-19 Registry. We analyzed the differences between men and women for a wide variety of demographic, clinical, and treatment variables, and the sex distribution of the reported COVID-19 deaths, as well as intensive care unit (ICU) admission by age subgroups. This work analyzed 12,063 patients (56.8% men). The women in our study were older than the men, on average (67.9 vs. 65.7 years; p < 001). Bilateral condensation was more frequent among men than women (31.8% vs. 29.9%; p = 0.007). The men needed non-invasive and invasive mechanical ventilation more frequently (5.6% vs. 3.6%, p < 0.001, and 7.9% vs. 4.8%, p < 0.001, respectively). The most prevalent complication was acute respiratory distress syndrome, with severe cases in 19.9% of men (p < 0.001). In men, intensive care unit admission was more frequent (10% vs. 6.1%; p < 0.001) and the mortality rate was higher (23.1% vs. 18.9%; p < 0.001). Regarding mortality, the differences by gender were statistically significant in the age groups from 55 years to 89 years of age. A multivariate analysis showed that female sex was significantly and independently associated with a lower risk of mortality in our study. Male sex appears to be related to worse progress in COVID-19 patients and is an independent prognostic factor for mortality. In order to fully understand its prognostic impact, other factors associated with sex must be considered

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

Mortality and other adverse outcomes in patients with type 2 diabetes mellitus admitted for COVID-19 in association with glucose-lowering drugs: a nationwide cohort study

Background: Limited evidence exists on the role of glucose-lowering drugs in patients with COVID-19. Our main objective was to examine the association between in-hospital death and each routine at-home glucose-lowering drug both individually and in combination with metformin in patients with type 2 diabetes mellitus admitted for COVID-19. We also evaluated their association with the composite outcome of the need for ICU admission, invasive and non-invasive mechanical ventilation, or in-hospital death as well as on the development of in-hospital complications and a long-time hospital stay. Methods: We selected all patients with type 2 diabetes mellitus in the Spanish Society of Internal Medicine's registry of COVID-19 patients (SEMI-COVID-19 Registry). It is an ongoing, observational, multicenter, nationwide cohort of patients admitted for COVID-19 in Spain from March 1, 2020. Each glucose-lowering drug user was matched with a user of other glucose-lowering drugs in a 1:1 manner by propensity scores. In order to assess the adequacy of propensity score matching, we used the standardized mean difference found in patient characteristics after matching. There was considered to be a significant imbalance in the group if a standardized mean difference > 10% was found. To evaluate the association between treatment and study outcomes, both conditional logit and mixed effect logistic regressions were used when the sample size was ≥ 100. Results: A total of 2666 patients were found in the SEMI-COVID-19 Registry, 1297 on glucose-lowering drugs in monotherapy and 465 in combination with metformin. After propensity matching, 249 patients on metformin, 105 on dipeptidyl peptidase-4 inhibitors, 129 on insulin, 127 on metformin/dipeptidyl peptidase-4 inhibitors, 34 on metformin/sodium-glucose cotransporter 2 inhibitor, and 67 on metformin/insulin were selected. No at-home glucose-lowering drugs showed a significant association with in-hospital death; the composite outcome of the need of intensive care unit admission, mechanical ventilation, or in-hospital death; in-hospital complications; or long-time hospital stays. Conclusions: In patients with type 2 diabetes mellitus admitted for COVID-19, at-home glucose-lowering drugs showed no significant association with mortality and adverse outcomes. Given the close relationship between diabetes and COVID-19 and the limited evidence on the role of glucose-lowering drugs, prospective studies are needed

Ethnicity and Clinical Outcomes in Patients Hospitalized for COVID-19 in Spain: Results from the Multicenter SEMI-COVID-19 Registry

Background: This work aims to analyze clinical outcomes according to ethnic groups in patients hospitalized for COVID-19 in Spain. (2) Methods: This nationwide, retrospective, multicenter, observational study analyzed hospitalized patients with confirmed COVID-19 in 150 Spanish hospitals (SEMI-COVID-19 Registry) from 1 March 2020 to 31 December 2021. Clinical outcomes were assessed according to ethnicity (Latin Americans, Sub-Saharan Africans, Asians, North Africans, Europeans). The outcomes were in-hospital mortality (IHM), intensive care unit (ICU) admission, and the use of invasive mechanical ventilation (IMV). Associations between ethnic groups and clinical outcomes adjusted for patient characteristics and baseline Charlson Comorbidity Index values and wave were evaluated using logistic regression. (3) Results: Of 23,953 patients (median age 69.5 years, 42.9% women), 7.0% were Latin American, 1.2% were North African, 0.5% were Asian, 0.5% were Sub-Saharan African, and 89.7% were European. Ethnic minority patients were significantly younger than European patients (median (IQR) age 49.1 (40.5-58.9) to 57.1 (44.1-67.1) vs. 71.5 (59.5-81.4) years, p < 0.001). The unadjusted IHM was higher in European (21.6%) versus North African (11.4%), Asian (10.9%), Latin American (7.1%), and Sub-Saharan African (3.2%) patients. After further adjustment, the IHM was lower in Sub-Saharan African (OR 0.28 (0.10-0.79), p = 0.017) versus European patients, while ICU admission rates were higher in Latin American and North African versus European patients (OR (95%CI) 1.37 (1.17-1.60), p < 0.001) and (OR (95%CI) 1.74 (1.26-2.41), p < 0.001). Moreover, Latin American patients were 39% more likely than European patients to use IMV (OR (95%CI) 1.43 (1.21-1.71), p < 0.001). (4) Conclusion: The adjusted IHM was similar in all groups except for Sub-Saharan Africans, who had lower IHM. Latin American patients were admitted to the ICU and required IMV more often

Mortality and other adverse outcomes in patients with type 2 diabetes mellitus admitted for COVID-19 in association with glucose-lowering drugs: a nationwide cohort study

Background: Limited evidence exists on the role of glucose-lowering drugs in patients with COVID-19. Our main objective was to examine the association between in-hospital death and each routine at-home glucose-lowering drug both individually and in combination with metformin in patients with type 2 diabetes mellitus admitted for COVID-19. We also evaluated their association with the composite outcome of the need for ICU admission, invasive and non-invasive mechanical ventilation, or in-hospital death as well as on the development of in-hospital complications and a long-time hospital stay. Methods: We selected all patients with type 2 diabetes mellitus in the Spanish Society of Internal Medicine’s registry of COVID-19 patients (SEMI-COVID-19 Registry). It is an ongoing, observational, multicenter, nationwide cohort of patients admitted for COVID-19 in Spain from March 1, 2020. Each glucose-lowering drug user was matched with a user of other glucose-lowering drugs in a 1:1 manner by propensity scores. In order to assess the adequacy of propensity score matching, we used the standardized mean difference found in patient characteristics after matching. There was considered to be a significant imbalance in the group if a standardized mean difference > 10% was found. To evaluate the association between treatment and study outcomes, both conditional logit and mixed effect logistic regressions were used when the sample size was ≥ 100. Results: A total of 2666 patients were found in the SEMI-COVID-19 Registry, 1297 on glucose-lowering drugs in monotherapy and 465 in combination with metformin. After propensity matching, 249 patients on metformin, 105 on dipeptidyl peptidase-4 inhibitors, 129 on insulin, 127 on metformin/dipeptidyl peptidase-4 inhibitors, 34 on metformin/sodium-glucose cotransporter 2 inhibitor, and 67 on metformin/insulin were selected. No at-home glucose-lowering drugs showed a significant association with in-hospital death; the composite outcome of the need of intensive care unit admission, mechanical ventilation, or in-hospital death; in-hospital complications; or long-time hospital stays. Conclusions: In patients with type 2 diabetes mellitus admitted for COVID-19, at-home glucose-lowering drugs showed no significant association with mortality and adverse outcomes. Given the close relationship between diabetes and COVID-19 and the limited evidence on the role of glucose-lowering drugs, prospective studies are needed