Clinical prediction model for pulmonary thrombosis diagnosis in hospitalized patients with SARS-CoV-2 infection.

Background and Aim: We aimed to develop a clinical prediction model for pulmonary thrombosis (PT) diagnosis in hospitalized COVID-19 patients. Methods: Non-intensive care unit hospitalized COVID-19 patients who underwent a computed tomography pulmonary angiogram (CTPA) for suspected PT were included in the study. Demographic, clinical, analytical, and radiological variables as potential factors associated with the presence of PT were selected. Multivariable Cox regression analysis to develop a score for estimating the pre-test probability of PT was performed. The score was internally validated by bootstrap analysis. Results: Among the 271 patients who underwent a CTPA, 132 patients (48.7%) had PT. Heart rate >100 bpm (OR = 4.63 [95% CI: 2.30-9.34]; P < 0.001), respiratory rate >22 bpm (OR = 5.21 [95% CI: 2.00-13.54]; P < 0.001), RALE score ≥4 (OR = 3.24 [95% CI: 1.66-6.32]; P < 0.001), C-reactive protein (CRP) >100 mg/L (OR = 2.10 [95% CI: 0.95-4.63]; P = 0.067), and D-dimer >3.000 ng/mL (OR = 6.86 [95% CI: 3.54-13.28]; P < 0.001) at the time of suspected PT were independent predictors of thrombosis. Using these variables, we constructed a nomogram (CRP, Heart rate, D-dimer, RALE score, and respiratory rate [CHEDDAR score]) for estimating the pre-test probability of PT. The score showed a high predictive accuracy (area under the receiver-operating characteristics curve = 0.877; 95% CI: 0.83-0.92). A score lower than 182 points on the nomogram confers a low probability for PT with a negative predictive value of 92%. Conclusions: CHEDDAR score can be used to estimate the pre-test probability of PT in hospitalized COVID-19 patients outside the intensive care unit. Relevance for Patients: Developing a new clinical prediction model for PT diagnosis in COVID-19 may help in the triage of patients, and limit unnecessary exposure to radiation and the risk of nephrotoxicity due to iodinated contrast.

Prevalence of thrombosis in patients with cancer and SARS-CoV-2 infection.

BACKGROUND: Covid-19 infection and cancer are associated with an increased risk of thrombotic events. The aim of our study is to analyze the cumulative incidence of thrombosis in oncological patients with Covid-19 and detect differences with the non-cancer Covid-19 population. METHODS: We retrospectively reviewed 1127 medical records of all admitted patients to ward of the Hospital Universitario Infanta Leonor (Madrid, Spain), including 86 patients with active cancer between March 5th, 2020 to May 3rd, 2020. We analyzed cumulative incidence of thrombosis and risk factors associated to the cancer patient's cohort. RESULTS: We diagnosed 10 thrombotic events in 8 oncological patients with a cumulative incidence of 9.3%. A statistically significant association was found regarding thrombosis and history of obesity (p=0.009). No differences related to cumulative incidence of thrombosis between both groups were detected (9.8% vs 5.80%) in our hospital (p=0.25). CONCLUSION: No significant differences were observed in the cumulative incidence of thrombosis in the two study groups. The thrombotic effect of Covid-19 is not as evident in cancer patients and does not seem to be added to its prothrombotic activity.

[Utility of probability scores for the diagnosis of pulmonary embolism in patients with SARS-CoV-2 infection: a systematic review]. / Utilidad de las escalas de predicción diagnósticas de embolia de pulmón en pacientes con infección por SARS-CoV-2: una revisión sistemática.

BACKGROUND AND OBJECTIVE: Clinical prediction models determine the pre-test probability of pulmonary embolism (PE) and assess the need for tests for these patients. Coronavirus infection is associated with a greater risk of PE, increasing its severity and conferring a worse prognosis. The pathogenesis of PE appears to be different in patients with and without SARS-CoV-2 infection. This systematic review aims to discover the utility of probability models developed for PE in patients with COVID-19 by reviewing the available literature. METHODS: A literature search on the PubMed, Scopus, and EMBASE databases was carried out. All studies that reported data on the use of clinical prediction models for PE in patients with COVID-19 were included. Study quality was assessed using the Newcastle-Ottawa scale for non-randomized studies. RESULTS: Thirteen studies that evaluated five prediction models (Wells score, Geneva score, YEARS algorithm, and PERC and PEGeD clinical decision rules) were included. The different scales were used in 1,187 patients with COVID-19. Overall, the models showed limited predictive ability. The two-level Wells score with low (or unlikely) clinical probability in combination with a D-dimer level <3000 ng/mL or a normal bedside lung ultrasound showed an adequate correlation for ruling out PE. CONCLUSIONS: Our systematic review suggests that the clinical prediction models available for PE that were developed in the general population are not applicable to patients with COVID-19. Therefore, their use is in clinical practice as the only diagnostic screening tool is not recommended. New clinical probability models for PE that are validated in these patients are needed.

Efficacy and Safety of Tinzaparin in Prophylactic, Intermediate and Therapeutic Doses in Non-Critically Ill Patients Hospitalized with COVID-19: The PROTHROMCOVID Randomized Controlled Trial.

Hospitalized patients with COVID-19 are at increased risk of thrombosis, acute respiratory distress syndrome and death. The optimal dosage of thromboprophylaxis is unknown. The aim was to evaluate the efficacy and safety of tinzaparin in prophylactic, intermediate, and therapeutic doses in non-critical patients admitted for COVID-19 pneumonia. PROTHROMCOVID is a randomized, unblinded, controlled, multicenter trial enrolling non-critical, hospitalized adult patients with COVID-19 pneumonia. Patients were randomized to prophylactic (4500 IU), intermediate (100 IU/kg), or therapeutic (175 IU/kg) groups. All tinzaparin doses were administered once daily during hospitalization, followed by 7 days of prophylactic tinzaparin at discharge. The primary efficacy outcome was a composite endpoint of symptomatic systemic thrombotic events, need for invasive or non-invasive mechanical ventilation, or death within 30 days. The main safety outcome was major bleeding at 30 days. Of the 311 subjects randomized, 300 were included in the prespecified interim analysis (mean [SD] age, 56.7 [14.6] years; males, 182 [60.7%]). The composite endpoint at 30 days from randomization occurred in 58 patients (19.3%) of the total population; 19 (17.1 %) in the prophylactic group, 20 (22.1%) in the intermediate group, and 19 (18.5%) in the therapeutic dose group (p = 0.72). No major bleeding event was reported; non-major bleeding was observed in 3.7% of patients, with no intergroup differences. Due to these results and the futility analysis, the trial was stopped. In non-critically ill COVID-19 patients, intermediate or full-dose tinzaparin compared to standard prophylactic doses did not appear to affect the risk of thrombotic event, non-invasive ventilation, or mechanical ventilation or death. Trial RegistrationClinicalTrials.gov Identifier (NCT04730856). Edura-CT registration number: 2020-004279-42.

Prevalence of thrombosis in patients with cancer and SARS-CoV-2 infection Prevalencia de trombosis en pacientes con cáncer e infección por SARS-CoV-2

Background Covid-19 infection and cancer are associated with an increased risk of thrombotic events. The aim of our study is to analyze the cumulative incidence of thrombosis in oncological patients with Covid-19 and detect differences with the non-cancer Covid-19 population. Methods We retrospectively reviewed 1127 medical records of all admitted patients to ward of the Hospital Universitario Infanta Leonor (Madrid, Spain), including 86 patients with active cancer between March 5th, 2020 to May 3rd, 2020. We analyzed cumulative incidence of thrombosis and risk factors associated to the cancer patient's cohort. Results We diagnosed 10 thrombotic events in 8 oncological patients with a cumulative incidence of 9.3%. A statistically significant association was found regarding thrombosis and history of obesity (p = 0.009). No differences related to cumulative incidence of thrombosis between both groups were detected (9.8% vs 5.80%) in our hospital (p = 0.25). Conclusion No significant differences were observed in the cumulative incidence of thrombosis in the two study groups. The thrombotic effect of Covid-19 is not as evident in cancer patients and does not seem to be added to its prothrombotic activity.

Prevalence of thrombosis in patients with cancer and SARS-CoV-2 infection.

Background: Covid-19 infection and cancer are associated with an increased risk of thrombotic events. The aim of our study is to analyze the cumulative incidence of thrombosis in oncological patients with Covid-19 and detect differences with the non-cancer Covid-19 population. Methods: We retrospectively reviewed 1127 medical records of all admitted patients to ward of the Hospital Universitario Infanta Leonor (Madrid, Spain), including 86 patients with active cancer between March 5th, 2020 to May 3rd, 2020. We analyzed cumulative incidence of thrombosis and risk factors associated to the cancer patient's cohort. Results: We diagnosed 10 thrombotic events in 8 oncological patients with a cumulative incidence of 9.3%. A statistically significant association was found regarding thrombosis and history of obesity (p = 0.009). No differences related to cumulative incidence of thrombosis between both groups were detected (9.8% vs 5.80%) in our hospital (p = 0.25). Conclusion: No significant differences were observed in the cumulative incidence of thrombosis in the two study groups. The thrombotic effect of Covid-19 is not as evident in cancer patients and does not seem to be added to its prothrombotic activity.

Antecedentes: La infección por COVID-19 y el cáncer se asocian a mayor riesgo de eventos trombóticos. El objetivo de nuestro estudio es analizar la incidencia acumulada de trombosis en pacientes oncológicos con COVID-19 y detectar diferencias con la población sin cáncer y COVID-19. Métodos: Revisamos retrospectivamente 1.127 historias clínicas de los pacientes ingresados en del Hospital Infanta Leonor (Madrid, España), incluyendo 86 pacientes con cáncer activo entre el 5 de marzo y el 3 de mayo de 2020. Se analizó la incidencia acumulada de trombosis y los factores de riesgo asociados a la cohorte de pacientes con cáncer. Resultados: Diagnosticamos 10 eventos trombóticos en 8 pacientes oncológicos, con una incidencia acumulada del 9,3%. Se encontró una asociación estadísticamente significativa entre trombosis y obesidad (p = 0,009). No se detectaron diferencias relacionadas con la incidencia acumulada de trombosis entre ambos grupos (9,8%vs. 5,80%, p = 0,25). Conclusión: No se observaron diferencias significativas en la incidencia acumulada de trombosis en los 2 grupos de estudio. El efecto trombótico de la COVID-19 no es tan evidente en los pacientes con cáncer y no parece sumarse a su actividad protrombótica.

Utilidad de las escalas de predicción diagnósticas de embolia de pulmón en pacientes con infección por SARS-CoV-2: una revisión sistemática Utility of probability scores for the diagnosis of pulmonary embolism in patients with SARS-CoV-2 infection: a systematic review

Antecedentes y objetivo: Las escalas de predicción clínica para embolia de pulmón (EP) determinan la probabilidad pretest y valoran la necesidad de las pruebas para estos pacientes. La infección por coronavirus se asocia a un mayor riesgo de EP aumentando su gravedad y confiriendo un peor pronóstico. La patogénesis de la EP parece ser diferente en pacientes con y sin infección por SARS-CoV-2. Esta revisión sistemática pretende conocer, revisando la bibliografía disponible, la utilidad de los modelos predictivos desarrollados para EP en pacientes con COVID-19. Métodos: Se realizó una búsqueda bibliográfica en las bases de datos de PubMed, Scopus y EMBASE, incluyendo todos los estudios que comunican datos relacionados con la aplicación de escalas de predicción clínica para EP en pacientes con COVID-19. La calidad de los estudios se evaluó con la escala Newcastle-Ottawa para estudios no aleatorizados. Resultados: Se incluyeron 13 estudios de cohortes que evaluaron cinco modelos predictivos (escala de Wells, puntuación de Ginebra, algoritmo YEARS y las reglas de decisión clínica PERC y PEGeD). Las diversas escalas se aplicaron en 1.187 pacientes con COVID-19. En general, los modelos tuvieron una capacidad predictiva limitada. La escala de Wells de dos categorías con probabilidad clínica baja (o improbable) en combinación con un dímero D <3000 ng/mL o con una ecografía pulmonar a pie de cama normal mostraron una adecuada correlación para excluir la EP. Conclusión: Nuestra revisión sistemática sugiere que las escalas de predicción disponibles para EP desarrolladas en población general no son aplicables a los pacientes con COVID-19 por lo que, de momento, no se recomienda su uso en la práctica clínica como única herramienta de cribado diagnóstico. Se necesitan nuevas escalas de probabilidad clínica para EP validadas en estos pacientes.

Increased Incidence of In-Hospital Ischemic Stroke During SARS-CoV-2 Outbreak: A Single-Center Study.

BACKGROUND: Meta-analyses of observational studies report a 1.1-1.7% pooled risk of stroke among patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requiring hospitalization, but consultations for stroke and reperfusion procedures have decreased during the outbreak that occurred during the first half of the year 2020. It is still unclear whether a true increase in the risk of stroke exists among patients with coronavirus disease 2019 (COVID-19). In-hospital ischemic stroke (IHIS) complicated the 0.04-0.06% of all admissions in the pre-COVID-19 era, but its incidence has not been assessed among inpatients with COVID-19. We aimed to compare IHIS incidence among patients with SARS-CoV-2 infection with that of inpatients with non-COVID-19 illnesses from the same outbreak period and from previous periods. METHODS: This historical cohort study belongs to the COVID-19@Vallecas cohort. The incidence of IHIS was estimated for patients with SARS-CoV-2 hospitalized during March-April 2020 [COVID-19 cohort (CC)], for patients with non-COVID-19 medical illness hospitalized during the same outbreak period [2020 non-COVID-19 cohort (20NCC)], and for inpatients with non-COVID-19 illness admitted during March-April of the years 2016-2019 [historical non-COVID-19 cohort (HNCC)]. Unadjusted risk of IHIS was compared between the three cohorts, and adjusted incidence rate ratio (IRR) of IHIS between cohorts was obtained by means of Poisson regression. RESULTS: Overall, 8126 inpatients were included in this study. Patients in the CC were younger and more commonly men than those from the HNCC and 20NCC. Absolute risk of IHIS was 0.05% for HNCC, 0.23% for 20NCC, and 0.36% for CC, (p = 0.004 for HNCC vs. CC). Cumulative incidence for IHIS by day nine after admission, with death as a competing risk, was 0.09% for HNCC, 0.23% for 20NCC, and 0.50% for CC. In an adjusted Poisson regression model with sex, age, needing of intensive care unit admission, and cohort (HNCC as reference) as covariates, COVID-19 was an independent predictor for IHIS (IRR 6.76, 95% confidence interval 1.66-27.54, p = 0.01). A nonsignificant increase in the risk of IHIS was observed for the 20NCC (IRR 5.62, 95% confidence interval 0.93-33.9, p = 0.06). CONCLUSIONS: SARS-CoV-2 outbreak was associated with an increase in the incidence of IHIS when compared with inpatients from a historical cohort. Viral infection itself may be related to the increased risk of IHIS among patients with COVID-19, but in view of our results from the 20NCC, it is likely that other factors, such as hospital saturation and overwhelming of health systems, may have played a role in the increased frequency of IHIS.

Impact of Systemic Corticosteroids on Mortality in Older Adults With Critical COVID-19 Pneumonia.

BACKGROUND: The most susceptible population group to critical and fatal coronavirus disease 2019 (COVID-19) is older adults. In severe acute respiratory syndrome coronavirus 2 infection, the host immune response is thought to play a key role in the pathophysiological effects of lung damage. Therefore, corticosteroid therapy could modulate inflammation-mediated pulmonary injury and thereby reduce progression to severe respiratory failure and death. The aim of this study was to analyze the safety and clinical efficacy of corticosteroid therapy in older adults with severe COVID-19 pneumonia. METHOD: We reviewed the clinical records of confirmed COVID-19 patients aged 75 years or older admitted to our hospital over a 3-month period (March 1-May 31, 2020). A total of 143 patients were included in the study cohort. From 2 April, 2020, in accordance with World Health Organization guidance on COVID-19, our hospital protocol added corticosteroid for COVID-19 treatment. We compared in-hospital mortality among patients with critical COVID-19 who received corticosteroids therapy and those who did not. RESULTS: In total, 88 patients (61.5%) were treated with corticosteroids, and 55 patients (38.4%) were not. Both groups were similar in baseline characteristics. The median age was 85 years (interquartile range: 82-89), and 61.5% (88/143) were male. In-hospital mortality was lower in the corticosteroid group (68.2%) compared with patients in the noncorticosteroid group (81.8%). Treatment with corticosteroids was an independent survival factor (hazard ratio: 0.61; 95% CI: 0.41-0.93; p = .006). CONCLUSIONS: In critically ill older adults with COVID-19 pneumonia, the use of corticosteroid treatment resulted in lower mortality without severe adverse events.

Systemic thrombosis in a large cohort of COVID-19 patients despite thromboprophylaxis: A retrospective study.

BACKGROUND: Incidence of thrombotic events associated to Coronavirus disease-2019 (COVID-19) is difficult to assess and reported rates differ significantly. Optimal thromboprophylaxis is unclear. OBJECTIVES: We aimed to analyze the characteristics of patients with a confirmed thrombotic complication including inflammatory and hemostatic parameters, compare patients affected by arterial vs venous events and examine differences between survivors and non-survivors. We reviewed compliance with thromboprophylaxis and explored how the implementation of a severity-adjusted protocol could have influenced outcome. METHODS: Single-cohort retrospective study of COVID-19 patients admitted, from March 3 to May 3 2020, to the Infanta Leonor University Hospital in Madrid, epicenter of the Spanish outbreak. RESULTS: Among 1127 patients, 80 thrombotic events were diagnosed in 69 patients (6.1% of the entire cohort). Forty-three patients (62%) suffered venous thromboembolism, 18 (26%) arterial episodes and 6 (9%) concurrent venous and arterial thrombosis. Most patients (90%) with a confirmed thrombotic complication where under low-molecular-weight heparin treatment. Overt disseminated intravascular coagulation (DIC) was rare. Initial ISTH DIC score and pre-event CRP were significantly higher among non-survivors. In multivariate analysis, arterial localization was an independent predictor of mortality (OR = 18, 95% CI: 2.4-142, p < .05). CONCLUSIONS: Despite quasi-universal thromboprophylaxis, COVID-19 lead to a myriad of arterial and venous thrombotic events. Considering the subgroup of patients with thrombotic episodes, arterial events appeared earlier in the course of disease and conferred very poor prognosis, and an ISTH DIC score ≥ 3 at presentation was identified as a potential predictor of mortality. Severity-adjusted thromboprophylaxis seemed to decrease the number of events and could have influenced mortality. Randomized controlled trials are eagerly awaited.

Incidence of Deep Venous Thrombosis in Patients With COVID-19 and Pulmonary Embolism: Compression Ultrasound COVID Study.

OBJECTIVES: Several reports had observed a high risk of pulmonary embolism (PE) in patients with coronavirus disease 2019 (COVID-19), most of them in the intensive care unit. Reported findings indicate that a direct viral-mediated hyperinflammatory response leads to local thromboinflammation. According to those findings, the incidence of deep venous thrombosis (DVT) in patients with COVID-19 and PE should be low. The objective of this study was to evaluate the incidence of DVT in patients with COVID-19 who developed PE. METHODS: In this prospective observational study, consecutive patients hospitalized in the internal medicine ward with a diagnosis of COVID-19 who developed PE were screened for DVT in the lower extremities with complete compression ultrasound. RESULTS: The study comprised 26 patients. Fifteen patients (57.7%) were male. The median age was 60 years (interquartile range, 54-73 years). Compression ultrasound findings were positive for DVT in 2 patients (7.7%; 95% confidence interval, 3.6%-11.7%). Patients with DVT had central and bilateral PE. In both, venous thromboembolism was diagnosed in the emergency department, so they did not receive previous prophylactic therapy with low-molecular-weight heparin. Patients without DVT had higher median d-dimer levels: 25,688 µg/dL (interquartile range, 80,000-1210 µg/dL) versus 5310 µg/dL (P < .05). CONCLUSIONS: Our study showed a low incidence of DVT in a cohort of patients with COVID-19 and PE. This observation suggests that PE in these patients could be produced mainly by a local thromboinflammatory syndrome induced by severe acute respiratory syndrome coronavirus 2 infection and not by a thromboembolic event.

Aortic thrombus in patients with severe COVID-19: review of three cases.

Coronavirus disease 2019 (COVID-19) could predispose to both venous and arterial thromboembolism, in an exaggerated immune response to the virus, especially in severe patients. Even though aortic clots are a rare entity, the pro-coagulant nature of COVID-19 is associated with thrombosis in atypical locations and should be considered in patients with severe abnormalities in coagulation parameters. We describe a series of three cases of aortic thrombi diagnosed by computerized tomography (CT) angiography in patients with confirmed SARS-CoV-2 infection.