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The Incidence of Pulmonary Embolism in Hospitalized Non-ICU Patients with COVID-19 during the First Wave: A Multicenter Retrospective Cohort Study in the Netherlands
Abstract
Introduction:
During the first COVID-19 outbreak in 2020 in the Netherlands, the incidence of pulmonary embolism (PE) appeared to be high in COVID-19 patients admitted to the intensive care unit (ICU). This study was performed to evaluate the incidence of PE during hospital stay in COVID-19 patients not admitted to the ICU.
Methods:
Data were retrospectively collected from 8 hospitals in the Netherlands. Patients admitted between February 27, 2020, and July 31, 2020, were included. Data extracted comprised clinical characteristics, medication use, first onset of COVID-19-related symptoms, admission date due to COVID-19, and date of PE diagnosis. Only polymerase chain reaction (PCR)-positive patients were included. All PEs were diagnosed with computed tomography pulmonary angiography (CTPA).
Results:
Data from 1,852 patients who were admitted to the hospital ward were collected. Forty patients (2.2%) were diagnosed with PE within 28 days following hospital admission. The median time to PE since admission was 4.5 days (IQR 0.0-9.0). In all 40 patients, PE was diagnosed within the first 2 weeks after hospital admission and for 22 (55%) patients within 2 weeks after onset of symptoms. Patient characteristics, pre-existing comorbidities, anticoagulant use, and laboratory parameters at admission were not related to the development of PE.
Conclusion:
In this retrospective multicenter cohort study of 1,852 COVID-19 patients only admitted to the non-ICU wards, the incidence of CTPA-confirmed PE was 2.2% during the first 4 weeks after onset of symptoms and occurred exclusively within 2 weeks after hospital admission.
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Objective
Develop and validate models that predict mortality of patients diagnosed with COVID-19 admitted to the hospital.
Design
Retrospective cohort study.
Setting
A multicentre cohort across 10 Dutch hospitals including patients from 27 February to 8 June 2020.
Participants
SARS-CoV-2 positive patients (age ≥18) admitted to the hospital.
Main outcome measures
21-day all-cause mortality evaluated by the area under the receiver operator curve (AUC), sensitivity, specificity, positive predictive value and negative predictive value. The predictive value of age was explored by comparison with age-based rules used in practice and by excluding age from the analysis.
Results
2273 patients were included, of whom 516 had died or discharged to palliative care within 21 days after admission. Five feature sets, including premorbid, clinical presentation and laboratory and radiology values, were derived from 80 features. Additionally, an Analysis of Variance (ANOVA)-based data-driven feature selection selected the 10 features with the highest F values: age, number of home medications, urea nitrogen, lactate dehydrogenase, albumin, oxygen saturation (%), oxygen saturation is measured on room air, oxygen saturation is measured on oxygen therapy, blood gas pH and history of chronic cardiac disease. A linear logistic regression and non-linear tree-based gradient boosting algorithm fitted the data with an AUC of 0.81 (95% CI 0.77 to 0.85) and 0.82 (0.79 to 0.85), respectively, using the 10 selected features. Both models outperformed age-based decision rules used in practice (AUC of 0.69, 0.65 to 0.74 for age >70). Furthermore, performance remained stable when excluding age as predictor (AUC of 0.78, 0.75 to 0.81).
Conclusion
Both models showed good performance and had better test characteristics than age-based decision rules, using 10 admission features readily available in Dutch hospitals. The models hold promise to aid decision-making during a hospital bed shortage.
Objectives
Early in the coronavirus 2019 (COVID-19) pandemic, a high frequency of pulmonary embolism was identified. This audit aims to assess the frequency and severity of pulmonary embolism in 2020 compared to 2019.
Methods
In this retrospective audit, we compared computed tomography pulmonary angiography (CTPA) frequency and pulmonary embolism severity in April and May 2020, compared to 2019. Pulmonary embolism severity was assessed with the Modified Miller score and the presence of right heart strain was assessed. Demographic information and 30-day mortality was identified from electronic health records.
Results
In April 2020, there was a 17% reduction in the number of CTPA performed and an increase in the proportion identifying pulmonary embolism (26%, n = 68/265 vs 15%, n = 47/320, p < 0.001), compared to April 2019. Patients with pulmonary embolism in 2020 had more comorbidities (p = 0.026), but similar age and sex compared to 2019. There was no difference in pulmonary embolism severity in 2020 compared to 2019, but there was an increased frequency of right heart strain in May 2020 (29 vs 12%, p = 0.029). Amongst 18 patients with COVID-19 and pulmonary embolism, there was a larger proportion of males and an increased 30 day mortality (28% vs 6%, p = 0.008).
Conclusion
During the COVID-19 pandemic, there was a reduction in the number of CTPA scans performed and an increase in the frequency of CTPA scans positive for pulmonary embolism. Patients with both COVID-19 and pulmonary embolism had an increased risk of 30-day mortality compared to those without COVID-19.
Advances in knowledge
During the COVID-19 pandemic, the number of CTPA performed decreased and the proportion of positive CTPA increased. Patients with both pulmonary embolism and COVID-19 had worse outcomes compared to those with pulmonary embolism alone.
Introduction
Acute respiratory illnesses from COVID19 infection are increasing globally. Reports from earlier in the pandemic suggested that patients hospitalized for COVID19 are at particularly high risk for pulmonary embolism (PE). To estimate the incidences of PE during hospitalization for COVID19, we performed a rigorous systematic review of published literature.
Methods
We searched for case series, cohort studies and clinical trials from December 1, 2019 to July 13, 2020 that reported the incidence of PE among consecutive patients who were hospitalized for COVID19 in ICUs and in non-ICU hospital wards. To reflect the general population of hospitalized COVID19 patients, we excluded studies in which subject enrollment was linked to the clinical suspicion for venous thromboembolism (VTE).
Results
Fifty-seven studies were included in the analysis. The combined random effects estimate of PE incidence among all hospitalized COVID19 patients was 7.1% (95% CI: 5.2%, 9.1%). Studies with larger sample sizes reported significantly lower PE incidences than smaller studies (r ² = 0.161, p = 0.036). The PE incidence among studies that included 400 or more patients was 3.0% (95% CI: 1.7%, 4.6%). Among COVID19 patients admitted to ICUs, the combined estimated PE incidence was 13.7% (95% CI: 8.0%, 20.6%). The incidence of ICU-related PE also decreased as the study sample sizes increased. The single largest COVID19 ICU study (n = 2215) disclosed a PE incidence of 2.3% (95% CI: 1.7%, 3.0%).
Conclusion
PE incidences among hospitalized COVID19 patients are much lower than has been previously postulated based on smaller, often biased study reports. The incidence of “microthrombosis,” leading to occlusion of microscopic blood vessels, remains unknown.
Although SARS-CoV-2 is considered a lung-tropic virus, severe COVID-19 is not just a viral pulmonary infection, clinically it is a multi-organ pathology with major coagulation abnormalities and thromboembolism events. Recently, antiphospholipid (aPL) antibodies were found increased in a large number of COVID-19 patients. Elevated aPL have been well documented in antiphospholipid syndrome (APS), a systemic autoimmune disorder characterized by recurrent venous or arterial thrombosis and/or obstetrical morbidity. Among treatment regimen of APS, hydroxychloroquine (HCQ) is one of the molecules proposed in the primary prevention of thrombosis and obstetrical morbidity in those patients. Due to its antithrombotic properties documented in APS therapy, HCQ could be considered a good candidate for the prevention of thrombotic events in COVID-19 patients in association with anticoagulant and its repurposing deserves further evaluation.
Background
COVID-19 is diagnosed via detection of SARS-CoV-2 RNA using real time reverse-transcriptase polymerase chain reaction (rtRT-PCR). Performance of many SARS-CoV-2 rtRT-PCR assays is not entirely known due to the lack of a gold standard. We sought to evaluate the false negative rate (FNR) and sensitivity of our laboratory-developed SARS-CoV-2 rtRT-PCR targeting the envelope (E) and RNA-dependent RNA-polymerase (RdRp) genes.
Methods
SARS-CoV-2 rtRT-PCR results at the Public Health Laboratory (Alberta, Canada) from January 21 to April 18, 2020 were reviewed to identify patients with an initial negative rtRT-PCR followed by a positive result on repeat testing within 14 days (defined as discordant results). Negative samples from these discordant specimens were re-tested using three alternate rtRT-PCR assays (targeting the E gene and N1/N2 regions of the nucleocapsid genes) to assess for false negative (FN) results.
Results
During the time period specified, 95,919 patients (100,001 samples) were tested for SARS-CoV-2. Of these, 49 patients were found to have discordant results including 49 positive and 52 negative swabs. Repeat testing of 52 negative swabs found five FNs (from five separate patients). Assuming 100% specificity of the diagnostic assay, the FNR and sensitivity in this group of patients with discordant testing was 9.3% (95% CI 1.5–17.0%) and 90.7% (95% CI 82.6–98.9%) respectively.
Conclusions
Studies to understand the FNR of routinely used assays are important to confirm adequate clinical performance. In this study, most FN results were due to low amounts of SARS-CoV-2 virus concentrations in patients with multiple specimens collected during different stages of infection. Post-test clinical evaluation of each patient is advised to ensure that rtRT-PCR results are not the only factor in excluding COVID-19.
Background
A false-negative case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is defined as a person with suspected infection and an initial negative result by reverse transcription-polymerase chain reaction (RT-PCR) test, with a positive result on a subsequent test. False-negative cases have important implications for isolation and risk of transmission of infected people and for the management of coronavirus disease 2019 (COVID-19). We aimed to review and critically appraise evidence about the rate of RT-PCR false-negatives at initial testing for COVID-19.
Methods
We searched MEDLINE, EMBASE, LILACS, as well as COVID-19 repositories, including the EPPI-Centre living systematic map of evidence about COVID-19 and the Coronavirus Open Access Project living evidence database. Two authors independently screened and selected studies according to the eligibility criteria and collected data from the included studies. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We calculated the proportion of false-negative test results using a multilevel mixed-effect logistic regression model. The certainty of the evidence about false-negative cases was rated using the GRADE approach for tests and strategies. All information in this article is current up to July 17, 2020.
Results
We included 34 studies enrolling 12,057 COVID-19 confirmed cases. All studies were affected by several risks of bias and applicability concerns. The pooled estimate of false-negative proportion was highly affected by unexplained heterogeneity (tau-squared = 1.39; 90% prediction interval from 0.02 to 0.54). The certainty of the evidence was judged as very low due to the risk of bias, indirectness, and inconsistency issues.
Conclusions
There is substantial and largely unexplained heterogeneity in the proportion of false-negative RT-PCR results. The collected evidence has several limitations, including risk of bias issues, high heterogeneity, and concerns about its applicability. Nonetheless, our findings reinforce the need for repeated testing in patients with suspicion of SARS-Cov-2 infection given that up to 54% of COVID-19 patients may have an initial false-negative RT-PCR (very low certainty of evidence).
Systematic review registration
Protocol available on the OSF website: https://tinyurl.com/vvbgqya .
Background
The risk of pulmonary embolism (PE) in patients with Coronavirus Disease 2019 (COVID-19) is recognized. The prevalence of PE in patients with respiratory deterioration at the Emergency Department (ED), the regular ward, and the Intensive Care Unit (ICU) are not well-established.
Objectives
We aimed to investigate how often PE was present in individuals with COVID-19 and respiratory deterioration in different settings, and whether or not disease severity as measured by CT-severity score (CTSS) was related to the occurrence of PE.
Patients/methods
Between April 6th and May 3rd, we enrolled 60 consecutive adult patients with confirmed COVID-19 from the ED, regular ward and ICU who met the pre-specified criteria for respiratory deterioration.
Results
A total of 24 (24/60: 40% (95% CI: 28–54%)) patients were diagnosed with PE, of whom 6 were in the ED (6/23: 26% (95% CI: 10–46%)), 8 in the regular ward (8/24: 33% (95% CI: 16–55%)), and 10 in the ICU (10/13: 77% (95% CI: 46–95%)). CTSS (per unit) was not associated with the occurrence of PE (age and sex-adjusted OR 1.06 (95%CI 0.98–1.15)).
Conclusion
The number of PE diagnosis among patients with COVID-19 and respiratory deterioration was high; 26% in the ED, 33% in the regular ward and 77% in the ICU respectively. In our cohort CTSS was not associated with the occurrence of PE. Based on the high number of patients diagnosed with PE among those scanned we recommend a low threshold for performing computed tomography angiography in patients with COVID-19 and respiratory deterioration.
Importance
The coronavirus disease 2019 (COVID-19) pandemic, due to the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease. This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19.
Observations
SARS-CoV-2 is spread primarily via respiratory droplets during close face-to-face contact. Infection can be spread by asymptomatic, presymptomatic, and symptomatic carriers. The average time from exposure to symptom onset is 5 days, and 97.5% of people who develop symptoms do so within 11.5 days. The most common symptoms are fever, dry cough, and shortness of breath. Radiographic and laboratory abnormalities, such as lymphopenia and elevated lactate dehydrogenase, are common, but nonspecific. Diagnosis is made by detection of SARS-CoV-2 via reverse transcription polymerase chain reaction testing, although false-negative test results may occur in up to 20% to 67% of patients; however, this is dependent on the quality and timing of testing. Manifestations of COVID-19 include asymptomatic carriers and fulminant disease characterized by sepsis and acute respiratory failure. Approximately 5% of patients with COVID-19, and 20% of those hospitalized, experience severe symptoms necessitating intensive care. More than 75% of patients hospitalized with COVID-19 require supplemental oxygen. Treatment for individuals with COVID-19 includes best practices for supportive management of acute hypoxic respiratory failure. Emerging data indicate that dexamethasone therapy reduces 28-day mortality in patients requiring supplemental oxygen compared with usual care (21.6% vs 24.6%; age-adjusted rate ratio, 0.83 [95% CI, 0.74-0.92]) and that remdesivir improves time to recovery (hospital discharge or no supplemental oxygen requirement) from 15 to 11 days. In a randomized trial of 103 patients with COVID-19, convalescent plasma did not shorten time to recovery. Ongoing trials are testing antiviral therapies, immune modulators, and anticoagulants. The case-fatality rate for COVID-19 varies markedly by age, ranging from 0.3 deaths per 1000 cases among patients aged 5 to 17 years to 304.9 deaths per 1000 cases among patients aged 85 years or older in the US. Among patients hospitalized in the intensive care unit, the case fatality is up to 40%. At least 120 SARS-CoV-2 vaccines are under development. Until an effective vaccine is available, the primary methods to reduce spread are face masks, social distancing, and contact tracing. Monoclonal antibodies and hyperimmune globulin may provide additional preventive strategies.
Conclusions and Relevance
As of July 1, 2020, more than 10 million people worldwide had been infected with SARS-CoV-2. Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.
The pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is having serious consequences on health and the economy worldwide. All evidence-based treatment strategies need to be considered to combat this new virus. Drugs need to be considered on scientific grounds of efficacy, safety and cost. Chloroquine (CQ) and hydroxychloroquine (HCQ) are old drugs used in the treatment of malaria; in addition, their antiviral properties have been previously studied, including in coronaviruses, where evidence of efficacy has been found. The safety of CQ and HCQ has been studied for over 50 years. In the current race against time triggered by the SARS-CoV-2 pandemic, the search for new antivirals is very important. However, consideration should be given to old drugs with known anti-coronavirus activity, such as CQ and HCQ; these could be integrated into current treatment strategies while novel treatments are awaited, also in light of the fact that they display an anticoagulant effect that facilitates the activity of low MW heparin, aimed at preventing ARDS-associated thrombotic events.
The safety of CQ and HCQ has been studied for over 50 years, however, recently published data raise concerns for cardiac toxicity of CQ/HCQ in patients with COVID-19. The review that we here provide also reexamines the real information provided by some of the published alarming reports although concluding that cardiac toxicity should in any case be stringently monitored with patients with CQ/HCQ.
Background:
Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients.
Methods:
We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death.
Results:
The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission.
Conclusions:
During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.).
Background:
The incidence of pulmonary embolism has been increasing, but its case-fatality rate is decreasing, suggesting a lesser severity of illness. The clinical importance of patients with pulmonary embolism isolated to the subsegmental vessels is unknown.
Objective:
To determine the rate of recurrent venous thromboembolism in patients with subsegmental pulmonary embolism managed without anticoagulation.
Design:
Multicenter prospective cohort study. (ClinicalTrials.gov: NCT01455818).
Setting:
Eighteen sites between February 2011 and February 2021.
Patients:
Patients with isolated subsegmental pulmonary embolism.
Intervention:
At diagnosis, patients underwent bilateral lower-extremity venous ultrasonography, which was repeated 1 week later if results were negative. Patients without deep venous thrombosis did not receive anticoagulant therapy.
Measurements:
The primary outcome was recurrent venous thromboembolism during the 90-day follow-up period.
Results:
Recruitment was stopped prematurely because the predefined stopping rule was met after 292 of a projected 300 patients were enrolled. Of the 266 patients included in the primary analysis, the primary outcome occurred in 8 patients, for a cumulative incidence of 3.1% (95% CI, 1.6% to 6.1%) over the 90-day follow-up. The incidence of recurrent venous thromboembolism was 2.1% (CI, 0.8% to 5.5%) and 5.7% (CI, 2.2% to 14.4%) over the 90-day follow-up in patients with single and multiple isolated subsegmental pulmonary embolism, respectively. No patients had a fatal recurrent pulmonary embolism.
Limitation:
The study was restricted to patients with low-risk subsegmental pulmonary embolism.
Conclusion:
Overall, patients with subsegmental pulmonary embolism who did not have proximal deep venous thrombosis had a higher-than-expected rate of recurrent venous thromboembolism.
Primary funding source:
Heart and Stroke Foundation of Canada and French Ministry of Health Programme Hospitalier de Recherche Clinique.
Background
The reported incidence of venous thromboembolism (VTE) in COVID-19 patients varies widely depending on patient populations sampled and has been predominately studied in hospitalized patients. The goal of this study was to assess the evolving burden of COVID-19 and the timing of associated VTE events in a systems-wide cohort.
Methods
COVID-19 PCR positive hospitalized and non-hospitalized patients ≥18 years of age tested between 1/1/2020 through 12/31/2020 were retrospectively analyzed using electronic medical records from multiple states across the Mayo Clinic enterprise.
Radiology reports within 90 days before and after confirmed COVID-19 diagnosis were examined for VTE outcomes using validated Natural Language Processing (NLP) algorithms.
Results
A 29-fold increased rate of VTE compared to the pre-COVID-19 period was noted during the first week following the first positive COVID-19 test (RR: 29.39; 95% CI 21.77-40.03). The rate of VTE steadily decreased and returned to baseline by the 6th week. Among 366 VTE events, most occurred during (n = 243, 66.3%) or after (n = 111, 30.3%) initial hospitalization. Only 11 VTE events were identified in patients who did not require hospitalization (3.0% of total VTE events). VTE and mortality increased with advancing age with a pronounced increased each decade in older patients.
Conclusion
We observed a profoundly increased risk of VTE within the first week after positive testing for COVID-19 that returned to baseline levels after 6 weeks. VTE events occurred almost exclusively in patients who were hospitalized, with the majority of VTE events identified within the first days of hospitalization.
Aims
We investigated the incidence, risk factors, clinical characteristics, and outcomes of pulmonary embolism (PE) in patients with COVID-19 attending emergency departments (EDs), before hospitalization.
Methods and Results
We retrospectively reviewed all COVID-19 patients diagnosed with PE in 62 Spanish EDs (20% of Spanish EDs, case group) during the first COVID-19 outbreak. COVID-19 patients without PE and non-COVID-19 patients with PE were included as control groups. Adjusted comparisons for baseline characteristics, acute episode characteristics, and outcomes were made between cases and randomly selected controls (1:1 ratio). We identified 368 PE in 74 814 patients with COVID-19 attending EDs (4.92‰). The standardized incidence of PE in the COVID-19 population resulted in 310 per 100 000 person-years, significantly higher than that observed in the non-COVID-19 population [35 per 100 000 person-years; odds ratio (OR) 8.95 for PE in the COVID-19 population, 95% confidence interval (CI) 8.51–9.41]. Several characteristics in COVID-19 patients were independently associated with PE, the strongest being D-dimer >1000 ng/mL, and chest pain (direct association) and chronic heart failure (inverse association). COVID-19 patients with PE differed from non-COVID-19 patients with PE in 16 characteristics, most directly related to COVID-19 infection; remarkably, D-dimer >1000 ng/mL, leg swelling/pain, and PE risk factors were significantly less present. PE in COVID-19 patients affected smaller pulmonary arteries than in non-COVID-19 patients, although right ventricular dysfunction was similar in both groups. In-hospital mortality in cases (16.0%) was similar to COVID-19 patients without PE (16.6%; OR 0.96, 95% CI 0.65–1.42; and 11.4% in a subgroup of COVID-19 patients with PE ruled out by scanner, OR 1.48, 95% CI 0.97–2.27), but higher than in non-COVID-19 patients with PE (6.5%; OR 2.74, 95% CI 1.66–4.51). Adjustment for differences in baseline and acute episode characteristics and sensitivity analysis reported very similar associations.
Conclusions
PE in COVID-19 patients at ED presentation is unusual (about 0.5%), but incidence is approximately ninefold higher than in the general (non-COVID-19) population. Moreover, risk factors and leg symptoms are less frequent, D-dimer increase is lower and emboli involve smaller pulmonary arteries. While PE probably does not increase the mortality of COVID-19 patients, mortality is higher in COVID-19 than in non-COVID-19 patients with PE.
Background
Many studies confirmed an association between COVID-19 and venous thromboembolism (VTE). Whether the risk of VTE significantly differed between COVID-19 cohorts and non-COVID-19 cohorts with similar disease severity remains unknown.
Objectives
The aim of this systematic review with meta-analysis was to compare the rate of VTE between COVID-19 and non-COVID-19 cohorts with similar disease severity.
Methods
A systematic literature search (MEDLINE, Embase and Google Scholar) was conducted from January 1, 2020 to March 31, 2021 to identify studies reporting VTE in COVID-19. Relative risks (RR) were estimated for the effect measure with 95% confidence intervals.
Results
Seven studies (41,768 patients) evaluated VTE in COVID-19 cohorts compared to non-COVID-19 cohorts. The overall risk of VTE (RR 1.18; 95%CI 0.79–1.77; p = 0.42; I² = 54%), pulmonary embolism (RR 1.25; 95%CI 0.77–2.03; p = 0.36; I² = 52%) and deep venous thrombosis (RR 0.92; 95%CI 0.52–1.65; p = 0.78; I² = 0%) did not significantly differ between COVID-19 and non-COVID-19 cohorts. However, subgroup analyses suggested an increased risk of VTE amongst CODID-19 versus non COVID-19 cohorts when only patients hospitalized within the intensive care unit (ICU) were considered (RR 3.10; 95%CI 1.54–6.23), which was not observed in cohorts of predominantly non-ICU patients (RR 0.95; 95%CI 0.81–1.11) (Pinteraction = 0.001).
Conclusion
There was no signal for a difference in VTE in COVID-19 cohorts compared to non-COVID-19 cohorts, except for the subgroup of patients hospitalized in the ICU. These results should be viewed as exploratory and further studies are needed to confirm these results.
Background
While pulmonary embolism (PE) appears to be a major issue in Covid-19, data remain sparse.
Purpose
We aimed to describe the risk factors and baseline characteristics of patients with PE in a large cohort of Covid-19 patients.
Methods
In a retrospective multicentric observational study, we included consecutive hospitalised patients for Covid-19. Patients without computed tomography pulmonary angiography (CTPA)-proven PE diagnosis, those who were directly admitted to an intensive care unit (ICU), and those still hospitalised without PE experience were excluded.
Results
Among 1240 patients (58.1% men, mean age 64 ± 17 years), 103 (8.3%) patients had PE confirmed by CTPA. The ICU transfer requirement and mechanical ventilation requirement were significantly higher in the PE group (P < 0.001 and P < 0.001, respectively). In an univariable analysis, traditional venous thromboembolic risk factors were not associated with PE (P > 0.05), while patients under therapeutic-dose anticoagulation before hospitalisation or prophylaxis-dose anticoagulation introduced during hospitalisation had lower PE occurrence (OR 0.40, 95%CI(0.14-0.91); P = 0.04 and OR 0.11, 95%CI(0.06-0.18); P < 0.001, respectively). In a multivariable analysis, the following variables (also statistically significant in univariable analysis) were associated with PE: male gender (OR 1.03, 95%CI(1.003-1.069); P = 0.04), anticoagulation with prophylaxis-dose (OR 0.83, 95%CI(0.79-0.85), P < 0.001) or therapeutic-dose (OR 0.87, 95%CI(0.82-0.92), P < 0.001), C-reactive protein (OR 1.03, 95%CI(1.01-1.04), P = 0.001) and time from symptom onset to hospitalisation (OR 1.02, 95%CI(1.006-1.038), P = 0.002) (Table 1).
Conclusion
Pulmonary embolism risk factors in Covid-19 context do not include traditional thromboembolic risk factors but rather independent clinical and biological findings at admission, including a major contribution to inflammation.
Background
Systemic coagulation activation and thrombotic complications are frequent among critically ill patients with COVID-19. Limited data are available in non-intensive care unit (ICU) patients.
Purpose
To determine the incidence, risk factors and prognosis of venous thromboembolism (VTE) in non-ICU COVID-19 patients.
Methods
We studied consecutive COVID-19 patients admitted to general ward at Strasbourg Hospital, France (25.02.2020–19.04.2020). The primary outcome was any VTE complication. The secondary outcome was the composite of death or transfer to ICU.
Results
Among the 289 patients included (62.2 ± 17.0 years, 59.2% male), VTE occurred in 49 (17.0%). Padua prediction score for VTE was similar between VTE and non-VTE patients. VTE imaging tests were performed in 100 (34.6%) patients and VTE diagnosed in median 7 (3–11) days after admission. On-admission, time from symptom onset to admission (OR 1.07, CI 95% [1.00–1.16], P = 0.045), Improve score (OR 1.37, [1.02–1.83], P = 0.032), leukocyte count (OR 1.16, [1.06–1.27], P = 0.001) and lack of thromboprophylaxis (OR 27.85, CI 95% [9.35–82.95], P < 0.001) were independent predictors of VTE. The incidence of the composite of death or ICU transfer was 31.0% and more frequent among patients with VTE (47.9% vs. 27.9%, P = 0.01). Fever (OR 5.37, CI 95% [1.44–19.97], P = 0.012), VTE (OR 3.44, CI 95% [1.63–7.25], P = 0.001), lymphopenia (OR 0.32, 95% CI [0.15–0.71]; P = 0.005) and extent of COVID-19 evaluated by chest CT severity (OR 1.56, 95% CI [1.12–2.16]; P = 0.007) were independently associated with in-hospital death or transfer to ICU (Table 1, Fig. 1).
Conclusions
The 17.0% incidence of VTE in non-ICU patients with COVID-19 was associated with worse outcomes. Given the high incidence of VTE in ward patients, there is an urgent need to investigate the optimal anticoagulation regimen.
Background. Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19.
Methods. We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to an university hospital in Milan, Italy (13.02.2020-10.04.2020). The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI). Secondary outcome was overt disseminated intravascular coagulation (DIC).
Results. We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]). Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward. Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%-11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward). Half of the thromboembolic events were diagnosed within 24 hours of hospital admission. Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%). Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA). The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively. Overt DIC was present in 8 (2.2%) patients.
Conclusions. The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 hours of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.
Background:
Since 3 months ago, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan, China, and spread rapidly around the world. Severe novel coronavirus pneumonia (NCP) patients have abnormal blood coagulation function, but their venous thromboembolism(VTE) prevalence is still rarely mentioned.
Objectives:
To determine the incidence of VTE in patients with severe NCP.
Methods:
In this study, 81 severe NCP patients in the Intensive Care Unit (ICU) of Union Hospital (Wuhan, China) were enrolled. The results of conventional coagulation parameters and lower limb vein ultrasonography of these patients were retrospectively collected and analyzed.
Results:
The incidence of VTE in these patients was 25%(20/81), of which 8 patients with VTE events died. VTE group was different from non-VTE group in age, lymphocytes counts, activated partial thromboplastin time (APTT), D-dimer, etc. If 1.5 µg/mL was used as the D-dimer cut-off value to predicting VTE, the sensitivity was 85.0%, the specificity was 88.5% and the negative predictive value (NPV) was 94.7%.
Conclusions:
The incidence of VTE in patients with severe NCP is 25% (20/81), which may be related to poor prognosis. The significant increase of D-dimer in severe NCP patients is a good index for identifying high-risk groups of VTE.
Background
Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.
Methods
In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.
Findings
191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/L (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days.
Interpretation
The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/L could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
Funding
Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
Prophylaxis of venous thromboembolism (VTE) in hospitalized medical patients is largely underused. We sought to assess the value of a simple risk assessment model (RAM) for the identification of patients at risk of VTE.
In a prospective cohort study, 1180 consecutive patients admitted to a department of internal medicine in a 2-year period were classified as having a high or low risk of VTE according to a predefined RAM. They were followed-up for up to 90 days to assess the occurrence of symptomatic VTE complications. The primary study outcome was to assess the adjusted hazard ratio (HR) of VTE in high-risk patients who had adequate in-hospital thromboprophylaxis in comparison with those who did not, and that of VTE in the latter group in comparison with low-risk patients.
Four hundred and sixty-nine patients (39.7%) were labelled as having a high risk of thrombosis. VTE developed in four of the 186 (2.2%) who received thromboprophylaxis, and in 31 of the 283 (11.0%) who did not (HR of VTE, 0.13; 95% CI, 0.04-0.40). VTE developed also in two of the 711 (0.3%) low-risk patients (HR of VTE in high-risk patients without prophylaxis as compared with low-risk patients, 32.0; 95% CI, 4.1-251.0). Bleeding occurred in three of the 186 (1.6%) high-risk patients who had thromboprophylaxis.
Our RAM can help discriminate between medical patients at high and low risk of VTE. The adoption of adequate thromboprophylaxis in high-risk patients during hospitalization leads to longstanding protection against thromboembolic events with a low risk of bleeding.
Strengthening the reporting of observational studies in epidemiology (STROBE): explanation and elaboration
- JP Vandenbroucke
- E von Elm
- DG Altman
- PC Gøtzsche
- CD Mulrow
- SJ Pocock