key: cord-0971645-2b0wyjw9
authors: Safari, Saeed; Mehrani, Mehdi; Yousefifard, Mahmoud
title: Pulmonary Thromboembolism as a Potential Cause of Clinical Deterioration in COVID-19 Patients; a Commentary
date: 2020-04-19
journal: Arch Acad Emerg Med
DOI: nan
sha: 843c32f662ec2b15bee48be3bd6c6c5a753c9675
doc_id: 971645
cord_uid: 2b0wyjw9

Although the findings of some studies have been indicative of the direct relationship between the severity of clinical findings and imaging, reports have been published regarding inconsistency of clinical findings with imaging and laboratory evidence. Physicians treating these patients frequently report cases in which patients, sometimes in the recovery phase and despite improvements in imaging indices, suddenly deteriorate and in some instances suddenly expire. This letter aimed to draw attention to the role of pulmonary thromboembolism as a potential and possible cause of clinical deterioration in covid-19 patients.

More than three months has passed from identification of the first case of pneumonia due to SARS-CoV-2 virus in China and it has subsequently spread to countries around the world. With publication of clinical, imaging, and laboratory findings of COVID-19 patients, our information on the behavior of the virus in the human body has increased. Although the findings of some studies have been indicative of the direct relationship between the severity of clinical findings and imaging (1), reports have been published regarding inconsistency of clinical findings with imaging and laboratory evidence (2, 3) . For example, a study on more than 1000 patients with COVID-19 in China has shown that about 18% of non-severe cases and 3% of severe cases had no abnormal finding in radiography and computed tomography (CT) scan (4). In addition, significant and notable reports among the lab- * Corresponding Author: Mahmood Yousefifard; Physiology Research Center, School of Medicine, Iran University of Medical Sciences, Hemmat highway, Tehran, Iran; Email: yousefifard.m@iums.ac.ir; Tel: +982186704771 oratory findings include thrombocytopenia, disturbances in coagulation profile [Prothrombin Time (PT), Partial Thromboplastin Time (PTT)], increase in D-dimer, and fibrin/fibrinogen degradation products (FDP). In a study on 94 patients, whose COVID-19 was confirmed using RT-PCR, Huan Han et al. showed that the serum levels of D-dimer, FDP, and fibrinogen (FIB) in these patients were higher than healthy individuals. They showed that D-dimer and FDP levels significantly and directly correlated with the severity of the disease and suggested D-dimer and FDP monitoring for early detection of severe cases (5) . Another study in China, which had evaluated about 300 patients, reported increased D-dimer levels in more than 35% of the studied patients. Based on the findings of this study, Ddimer levels were significantly higher in patients with more severe presentation of the disease (0.96 versus 0.35 mg/L; p < 0.001) (6) . Findings of a study in Suzhou, China, has shown that fibrinogen level has increased in more than 65% of those with pneumonia due to COVID-19 and the interesting part is that at the level of 4.8 gr/L, the sensitivity of fibrinogen in differentiation of severe patients has been reported to be 100% (7) . By studying 192 patients with COVID-19, Zhou et al. in-troduced D-dimer levels over 1 µg/mL as a predictor of poor outcome, which can aid physicians in detecting more severe patients in the initial stages (8) . In addition to the mentioned findings, physicians treating these patients frequently report cases in which patients, sometimes in the recovery phase and despite improvements in imaging indices, suddenly deteriorate and in some instances suddenly expire (9) . Putting all the pieces of this puzzle together (thrombocytopenia, high serum D-dimer, inconsistency between clinical and imaging findings, and clinical deterioration of patients) a possible explanation for the afore-mentioned cases, from a clinical point of view, might be the formation of thrombosis. In this regard, a study revealed that CT angiography results of 25 patients with D-dimer levels higher than 6 Îijg/mL in China indicated pulmonary embolism in ten (40%) patients (10) . In this study, the emboli were found to be centralized in the small branches of pulmonary artery. Additionally, using CT angiography, Yuanliang Xie et al. confirmed and reported the presence of pulmonary embolism in two COVID-19 patients who had deteriorated (11) . Histopathologic findings of pulmonary biopsy of critical patients with COVID-19 pneumonia indicated small vessels hyperplasia, vessel wall thickening, lumen stenosis, occlusion, and micro-thrombosis formation. The blood vessels of alveolar septum were congested, edematous and widened, with modest infiltration of monocytes and lymphocytes, which could be additional evidence for confirmation of this hypothesis (12, 13) . A study on confirmed COVID-19 cases admitted to ICU reported a 31% prevalence of vascular thrombosis, which was most frequently (81%) seen in pulmonary vessels (14) . It should be noted that micro-emboli are generally undetectable in CT angiography. Therefore, worsening of respiratory condition in hospitalized patients should raise high suspicion to thrombosis formation as a potential cause of clinical deterioration. As a preliminary suggestion, it might be better to strongly consider performing pulmonary CT angiography for patients with disturbances in coagulation parameters, high D-dimer, pleuritic chest pain (reported in about 2% of patients) (15) , inconsistency of dyspnea with imaging findings, as well as those whose clinical symptoms worsen and deteriorate during treatment. We should also add anticoagulant agents to the treatment cocktail of high-risk patients such as old, obese, pregnant, and intubated cases, as well as those with other risk factors of thromboembolism.

None.

All the authors met the standard criteria of authorship based on recommendations of the international committee of medical journal editors.

Saeed Safari: 0000-0002-7407-1739 Mahmoud Yousefifard: 0000-0001-5181-4985

Not applicable.

The authors declare that there is no conflict of interest.

Chest CT findings in patients with corona virus disease 2019 and its relationship with clinical features

Chest CT findings in coronavirus disease-19 (COVID-19): relationship to duration of infection

Correlation of chest CT and RT-PCR testing in coronavirus disease 2019 (COVID-19) in China: a report of 1014 cases

Clinical Characteristics of Coronavirus Disease 2019 in China

Prominent changes in blood coagulation of patients with SARS-CoV-2 infection

COVID-19 in a Designated Infectious Diseases HospitalOutside Hubei Province

Clinical Characteristics and Laboratory Indicator Analysis of 69 COVID-19 Pneumonia Patients in Suzhou

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Pathological findings of COVID-19 associated with acute respiratory distress syndrome

Findings of Acute Pulmonary Embolism in COVID-19 Patients

COVID-19 Complicated by Acute Pulmonary Embolism

Clinical pathology of critical patient with novel coronavirus pneumonia (COVID-19)

A pathological report of three COVID-19 cases by minimally invasive autopsies

Incidence of thrombotic complications in critically ill ICU patients with COVID-19

Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study