Pulmonary thromboembolism in critical ill COVID-19 patients

Abstract

•COVID-19 in critically ill patients causes death not only from pneumonia but also from multiple organ injuries.•In critically ill COVID-19 patients with pneumonia, pulmonary thromboembolism may be considered.•In critically ill COVID-19 patients, contrast-enhanced computed tomography of the chest is mandatory to assess parenchymal patterns and to diagnose pulmonary thromboembolism. The outbreak of novel coronavirus disease 2019 (COVID-19) in the city of Wuhan, Hubei Province, China, was declared a pandemic by the World Health Organization (WHO) on March 21, 2020. Since then, this outbreak has forced the scientific community to consider two fundamental aspects: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, does not only cause pneumonia, and the death of many critically ill patients is caused by multiple organ failure (involving the heart, liver, kidneys, blood, and immune system) (Wang et al., 2020Wang T. Du Z. Zhu F. et al.Comorbidities and multi-organ injuries in the treatment of COVID-19.Thelancet. 2020; 395 (21 march): 10228Abstract Full Text Full Text PDF Scopus (426) Google Scholar). Therefore, attention should be paid to potential multiorgan injury, and its prevention should be part of the treatment of COVID-19, especially in critically ill patients (Wang et al., 2020Wang T. Du Z. Zhu F. et al.Comorbidities and multi-organ injuries in the treatment of COVID-19.Thelancet. 2020; 395 (21 march): 10228Abstract Full Text Full Text PDF Scopus (426) Google Scholar). Since the first report of COVID-19 pneumonia by Zhu et al. (Zhu et al., 2020Zhu N. Zhang D. Wang W. et al.A novel coronavirus from patients with pneumonia in China, 2019.N Engl J Med. 2020; 382: 727-733Crossref PubMed Scopus (17888) Google Scholar), several studies have been published highlighting the role of chest computed tomography (CT) in detecting typical and atypical parenchymal patterns and in assessing the evolution over time of COVID-19 pneumonia (Chung et al., 2020Chung M. Bernheim A. Mei X. et al.CT imaging features of 2019 novel coronavirus (2019- nCoV).Radiology. 2020; 295: 202-207Crossref PubMed Scopus (1884) Google Scholar, Pan et al., 2020Pan F. Ye T. Sun P. et al.Time course of lung changes on chest CT during recovery from 2019 novel coronavirus (COVID-19) pneumonia.Radiology. 2020; (Published February 1, 2020. Accessed February 13, 2020): 200370https://doi.org/10.1148/radiol.2020200370Crossref PubMed Scopus (1811) Google Scholar). Other findings include enlarged subsegmental pulmonary vessels in 59–89% of COVID-19 pneumonia cases (Bai et al., 2020Bai H.X. Hsieh B. Xiong Z. et al.Performance of radiologists in differentiating COVID-19 from viral pneumonia on chest CT.Radiology. 2020; (doi: 0.1148/radiol.2020200823): 200823Crossref PubMed Scopus (799) Google Scholar, Caruso et al., 2020Caruso D. Zerunian M. Polici M. et al.Chest CT features of COVID -19 in Rome, Italy.Radiology. 2020; : 201237https://doi.org/10.1148/radiol.2020201237Crossref PubMed Scopus (416) Google Scholar), which could be related to pro-inflammatory factors or hyperaemia (Ye et al., 2020Ye Z. Zhang Y. Wang Y. et al.Chest CT manifestations of new coronavirus disease 2019 (COVID-19): a pictorial review.Eur Radiol. 2020; https://doi.org/10.1007/s00330-020-06801-0Crossref Scopus (852) Google Scholar, Li et al., 2003Li W. Moore M.J. Vasilieva N. et al.Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus.Nature. 2003; 426: 450-454Crossref PubMed Scopus (4413) Google Scholar). Pulmonary thromboembolism has been reported on CT in patients with COVID-19 pneumonia with high D-dimer levels (Danzi et al., 2020Danzi G.B. Loffi M. Galeazzi G. Gherbesi E. Acute pulmonary embolism and COVID-19 pneumonia: a random association?.Eur Heart J. 2020; (Mar 30. pii: ehaa254)Crossref PubMed Scopus (456) Google Scholar, Xie et al., 2020Xie Y. Wang X. Yang P. Zhang S. COVID-19 Complicated by Acute Pulmonary Embolism Radiology.Cardiothoracic Imaging. 2020; 2 (Online:Mar 16)Google Scholar), and in COVID-19 patients with normal D-dimer levels, without strong predisposing risk factors for venous thromboembolism (VTE) (Chen et al., 2020Chen J. et al.Findings of Acute Pulmonary Embolism in COVID-19 Patients.Lancet. 2020; Google Scholar). At the moment it is unclear whether hospitalized patients with COVID-19 have a greater risk of VTE than other patients who have chest infections and elevated D-dimer values (Darzi et al., 2020 Feb 24Darzi A.J. Karam S.G. Charide R. et al.Prognostic factors for VTE and Bleeding in Hospitalized Medical Patients: a systematic review and meta-analysis.Blood. 2020 Feb 24; (pii: blood.2019003603.)https://doi.org/10.1182/blood.2019003603Crossref PubMed Scopus (4) Google Scholar). Critically ill patients are likely to be at increased risk of VTE, especially if they become immobilized on critical care. However, the risk of VTE must be assessed in all patients admitted to the hospital, and prevention should be administered to all high-risk patients according to international guidance on thromboprophylaxis (Anderson et al., 2019Anderson D. Morgano G.P. Bennett C. et al.American Society of Hematology 2019 guidelines for management of venous thromboembolism: prevention of venous thromboembolism in surgical hospitalized patients.Blood Adv. 2019; 3: 3898-3944Crossref PubMed Scopus (260) Google Scholar). Lee et al. (Lee et al., 2020Lee A, deSancho M, Pai M et al. COVID-19 and Pulmonary embolism: frequentlyasked questions. Americam Society of haematology, COVID- resources. Update 10 april 2020.Google Scholar) performed an observational study and suggested that up to 5–10% of patients with COVID-19 who require mechanical ventilation have acute pulmonary embolism and/or deep venous thrombosis. Coronavirus causes direct endothelial cell injury to the microvessels, with subsequent release of damaged endothelial cells into the bloodstream (Zhang et al., 2020 MarZhang W. Zhao Y. Zhang F. et al.The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The experience of clinical immunologists from China.Clin Immunol. 2020 Mar; 25: 108393Crossref Scopus (917) Google Scholar). Patients with severe COVID-19 are often immobile and present with an acute inflammatory state that leads to hypercoagulability. Therefore pulmonary thromboembolism may be considered in COVID-19 patients with sudden onset of oxygenation deterioration, respiratory distress, and reduced blood pressure. This might be supported by the altered D-dimer values, and although it is true that D-dimer is a non-specific acute-phase reactant, elevated D-dimer values have been used to identify those severe COVID-19 patients at increased risk of VTE (Spyropoulos et al., 2020 Mar 13Spyropoulos A.C. Lipardi C. Xu J. et al.Modified IMPROVE VTE Risk Score and Elevated D-Dimer Identify a High Venous Thromboembolism Risk in Acutely Ill Medical Population for Extended Thromboprophylaxis.TH Open. 2020 Mar 13; 4: e59-e65https://doi.org/10.1055/s-0040-1705137Crossref PubMed Google Scholar). CT plays a critical role in identifying the pathological pulmonary changes observed in severe and critical COVID-19 patients (An et al., 2020An P. Ye Y. Chen M. Chen Y. Fan W. Wang Y. Management strategy of novel coronavirus (COVID-19) pneumonia in the radiology department: a Chinese experience.Diagn Interv Radiol. 2020; https://doi.org/10.5152/dir.2020.2016Crossref Google Scholar). Contrast-enhanced CT of the chest is mandatory to assess parenchymal patterns and their evolution over time. Moreover, CT allows the diagnosis of pulmonary thromboembolism, a common finding in severe COVID-19, guiding correct treatment after a careful evaluation of the patient's pre-existing comorbidities. In COVID-19, which is associated with a high morbidity and mortality rate, largely due to respiratory failure, a pathophysiological role of pulmonary embolism and the usefulness of contrast-enhanced CT in diagnosis may be considered. Funding source: None. Ethical approval: Approval was not required. Conflict of interest: No conflict of interest to declare. Writing manuscript: MS, SS. Editing manuscript: MS, SS, IP, GBS, FL. Literature research: IP, GBS, FL.

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