The association between D-dimer levels and thromboembolism, worsening severity, and mortality among hospitalized adults with COVID-19

Objective@#To assess the association between D-dimer and clinical outcomes in adults with COVID-19. @*Methods@#We reviewed published articles and preprints from MEDLINE, Cochrane Library, Cornell Open Access Publication (COAP), MedRxiv, and BioRxiv databases. We included cohort studies on the association between D-dimer and the outcomes of thromboembolism, mortality, and worsening severity among hospitalized adults with COVID-19. @*Results@#We found 25 observational studies on the association between D-dimer and the outcomes of thromboembolism, mortality, or worsening severity. There was an increased risk of thromboembolism (OR 5.61 [95% CI 3.97, 7.94]) with higher D-dimer levels across different COVID-19 severities. D-dimer levels are associated with higher in-hospital mortality (OR 5.57 [95% CI 2.74, 11.31]) and worsening severity manifesting as critical illness (OR 1.91 [95% CI 1.05, 3.48] to 2.58 [95% CI 1.57, 4.24]), disease progression (HR 2.846 [95% CI 2.10, 3.85]), or need for mechanical ventilation (HR 3.28 [95% CI 1.07, 10.10]). However, some methodological flaws, such as incomplete laboratory or follow-up data and concern on varied D-dimer cut-offs and definitions of worsening disease, raise some uncertainty in the widespread use of D-dimer as a prognostic marker. @*Conclusion@#A higher D-dimer value is associated with worse clinical outcomes among hospitalized adults with COVID-19 and may be a useful prognostic indicator.

The use of prognostic prediction models for mortality or clinical deterioration among hospitalized and non-hospitalized adults with COVID-19: A systematic review

Objective@#To assess the performance of prognostic models in predicting mortality or clinical deterioration among patients with COVID-19, both hospitalized and non-hospitalized @*Methods@#We conducted a systematic review of the literature until March 8, 2021. We included models for the prediction of mortality or clinical deterioration in COVID-19 with external validation. We used the Prediction model Risk Of Bias ASsessment Tool (PROBAST) and the GRADEpro Guideline Development Tool (GDT) to assess the evidence obtained. @*Results@#We reviewed 33 cohort studies. Two studies had a low risk of bias, four unclear risks, and 27 with a high risk of bias due to participant selection and analysis. For the outcome of mortality, the QCOVID model had excellent prediction with high certainty of evidence but was specific for use in England. The COVID Outcome Prediction in the Emergency Department (COPE) model, the 4C Mortality Score, the Age, BUN, number of comorbidities, CRP, SpO2/FiO2 ratio, platelet count, heart rate (ABC2-SPH) risk score, the Confusion Urea Respiration Blood Pressure (CURB-65) severity score, the Rapid Emergency Medicine Score (REMS), and the Risk Stratification in the Emergency Department in Acutely Ill Older Patients (RISE UP) score had fair to good prediction of death among inpatients, while the quick Sepsis-related Organ Failure Assessment (qSOFA) score had poor to fair prediction. The certainty of evidence for these models was very low to low. For the outcome of clinical deterioration, the 4C Deterioration Score had fair prediction, the National Early Warning Score 2 (NEWS2) score poor to good, and the Modified Early Warning Score (MEWS) had poor prediction. The certainty of evidence for these three models was also very low to low. None of these models had been validated in the Philippine setting. @*Conclusion@#The QCOVID, COPE, ABC2-SPH, 4C, CURB-65, REMS, RISE-UP models for prediction of mortality and the 4C Deterioration and NEWS2 models for prediction of clinical deterioration are potentially useful but need to be validated among patients with COVID-19 of varying severity in the Philippine setting.

Should anticoagulation be used in the treatment of severe COVID-19?

Background@#The progression of COVID-19 to its acute (pneumonia) phase occurs during the 7th to 14th day of illness. During this highly inflammatory phase, a proportion of patients with severe COVID-19 develop a hypercoagulable state associated with poor prognosis. Hence, anticoagulation is seen as a potentially beneficial intervention due to its antithrombotic effect, anti-inflammatory function, and anti-viral properties. @*Objective@#This review aims to determine the efficacy and safety of anticoagulation in severe COVID-19. @*Methods@#A rapid review was done on April 11, 2020 and updated on April 23, 2020. PubMed, MEDLINE, and medRxiv.org were searched. The review included studies on the association between the use of anticoagulants on top of other interventions, and disease progression and/or mortality among adults >18 years old with severe COVID-19 infection, as well as studies on patients with disseminated intravascular coagulopathy (DIC) of sepsis investigating bleeding complications with anticoagulant use. Four ongoing registered clinical trials on anticoagulants for COVID-19 were also found. @*Results@#Current evidence shows that the use of low-molecular weight heparin (LMWH) in COVID-19 is associated with the following: (1) improved surrogate markers for disease progression (increase in lymphocyte & platelet counts and decrease in D-dimer, fibrinogen degradation products, and IL-6); and (2) reduced 28-day mortality in high risk patients. Studies on DIC related to bacterial sepsis did not show significant increase in bleeding complications with anticoagulation. @*Conclusion@#The use of anticoagulants appears to be beneficial for severe COVID-19 due to a reduction in 28-day mortality and improvement in inflammatory and coagulation markers. However, these findings come from low-quality studies, and confirmation of the effect is needed through randomized controlled trials.

Should laboratory markers be used for early prediction of severe and possibly fatal COVID-19?

Key Findings@#Several laboratory tests are found to be associated with disease severity and mortality in COVID-19, and may be used to prognosticate patients and guide management. • Around 20% of COVID-19 patients develop severe illness that may require intensive care and lead to fatal complications. This necessitates prioritization of patients requiring urgent medical care before disease progression. • Certain laboratory markers (biomarkers) may reflect the processes involved in the clinical deterioration of infected patients. Hence, their use in the identification of patients at high risk of progression to severe disease or death has been investigated. • Current available evidence shows that the following laboratory abnormalities in a person with COVID-19, especially when found early during hospitalization, are associated with severe or critical disease or mortality: 1. Markers of organ dysfunction a. Reduced oxygen saturation b. Elevated lactic dehydrogenase (LDH) c. Elevated blood urea nitrogen (BUN) or serum creatinine d. Elevated cardiac troponin (cTnI) e. Elevated direct bilirubin, reduced albumin f. High radiographic score or CT severity score, or consolidation on CT scan 2. Marker of abnormal coagulation – D-dimer 3. Markers of immune dysfunction a. Elevated IL-6 b. Elevated C-reactive protein (CRP) c. Elevated neutrophils d. Reduced lymphocyte percentage e. Reduced CD4+ T lymphocytes 4. Secondary bacterial infection – Elevated procalcitonin • Proposed prediction models utilizing these markers, however, need further validation before they can be recommended for routine clinical use.

Clinical profile and outcomes of Filipino Lupus patients with Myocarditis in a tertiary hospital

Introduction@#Myocarditis is a rare but serious complication of systemic lupus erythematosus (SLE). Existing literature on adult Filipino SLE patients with myocarditis is limited. This study aims to determine clinical characteristics and outcomes of myocarditis in Filipino patients with lupus.@*Methods@#Review of medical records (between 2015 and 2017) of eight adult patients with lupus myocarditis in a tertiary government hospital was done. Clinical features, electrographic and echocardiographic findings, management, and outcomes were described.@*Results@#All patients were females with a mean lupus duration of 10 months at the time myocarditis was diagnosed. Half of them had severe lupus activity, mostly with concomitant hematologic activity (100%) and nephritis (75%). Echocardiography showed wall motion abnormalities in all patients, with 63% having global hypokinesia and 75% having moderate to severe hypokinesia of the left ventricular wall. Treatment included methylprednisolone pulse therapy (88%) and high-dose steroids (13%). One patient died from cardiogenic and septic shock prior to receiving MPPT. Most patients (75%) were clinically improved at the time of discharge.@*Conclusion@#Filipino patients with lupus typically present with myocarditis early in the course of the disease, with high disease activity and concomitant hematologic activity and nephritis. Outcomes are generally favorable with early immunosuppressive therapy.