D-dimer as an indicator of prognosis in SARS-CoV-2 infection: a systematic review

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulates pro-thrombotic changes. This, combined with its tropism for endothelium and lung structures, may explain its association with thrombotic events, reduction of pulmonary gas exchange, acute respiratory distress syndrome (ARDS) and a composite end-point (intensive care unit, invasive ventilation, death). This study aims to highlight the correlation between elevated D-dimer (an indirect thrombosis marker) and the increased rate of poor prognosis-associated conditions, and to introduce D-dimer-labelled anticoagulant administration as a potentially useful tool to prevent complications and positively influence coronavirus disease 2019 (COVID-19) course. Methods: An online database search (PubMed, Google Scholar, Scopus, Web of Science and Cochrane) was performed between 13 March and 10 April 2020. The most relevant keywords were "D-dimer", "SARS-CoV-2", "COVID-19", "thrombosis" and "ARDS". Selection was independently conducted by three reviewers. References and previews of accepted articles were evaluated. Data inclusion/extraction inaccuracy was limited by the work of three reviewers. Selection bias reduction was addressed by thoughtfully designing the search protocol. Quality assessment was performed with the Newcastle-Ottawa Scale. The systematic review protocol was not registered because we anticipated the very limited available evidence on the topic and due to the urgency of the study. Results: 16 studies were evaluated. Good-quality criteria were reached in 13 out of 16 studies. D-dimer was increased and significantly higher in COVID-19 patients compared with healthy controls, in COVID-19 patients with severe disease or a composite end-point compared with non-severe disease, in ARDS compared with non-ARDS patients and in deceased ARDS patients compared with ARDS patients who survived (all p<0.001). COVID-19 patients treated with anticoagulants demonstrated lower mortality compared with those not treated (p=0.017). Conclusions: Correlations exist between COVID-19 infection, severe elevation of D-dimer levels, and increase in the rate of complications and composite end-point. The appropriateness of early and continuous D-dimer monitoring and labelled anticoagulation as management tools for COVID-19 disease deserves accurate investigation, to prevent complications and reduce interventions.