key: cord-0789635-z67n67na
authors: Kanso, Mohamad; Cardi, Thomas; Marzak, Halim; Schatz, Alexandre; Faucher, Loïc; Grunebaum, Lélia; Morel, Olivier; Jesel, Laurence
title: Delayed pulmonary embolism after COVID-19 pneumonia: a case report
date: 2020-11-24
journal: Eur Heart J Case Rep
DOI: 10.1093/ehjcr/ytaa449
sha: c55812ef4107d290ad19bf8e84a3d1f34c2dc9b5
doc_id: 789635
cord_uid: z67n67na

BACKGROUND : Since the onset of the COVID-19 pandemic, several cardiovascular manifestations have been described. Among them, venous thromboembolism (VTE) seems to be one of the most frequent, particularly in intensive care unit patients. We report two cases of COVID-19 patients developing acute pulmonary embolism (PE) after discharge from a first hospitalization for pneumonia of moderate severity. CASE SUMMARY : Two patients with positive RT-PCR test were initially hospitalized for non-severe COVID-19. Both received standard thromboprophylaxis during the index hospitalization and had no strong predisposing risk factors for VTE. Few days after discharge, they were both readmitted for worsening dyspnoea due to PE. One patient was positive for lupus anticoagulant. DISCUSSION : Worsening respiratory status in COVID-19 patients must encourage physicians to search for PE since SARS-CoV-2 infection may act as a precipitant risk factor for VTE. Patients may thus require more aggressive and longer thromboprophylaxis after COVID-19 related hospitalization.

On 11 March 2020, The World Health Organization (WHO) declared the onset of the COVID-19 pandemic; the disease caused by the novel coronavirus, SARS-CoV-2.

Since then, several reports have been published on the cardiovascular implications of this emerging disease. 1 Among them, venous thromboembolism (VTE) appears to be a frequent complication 2 particularly in patients hospitalized for severe acute respiratory distress syndrome. 3, 4 In this observation, we report two cases of COVID-19 male patients developing acute pulmonary embolism (PE) Learning points • A deterioration in respiratory status in COVID-19 patients associated with increased D-dimer level must encourage physicians to search for pulmonary embolism.

• COVID-19 patients may require more aggressive and longer thromboprophylaxis after hospital admission since SARS-CoV-2 could be a precipitant factor for venous thromboembolism. after a first hospitalization for pneumonia of moderate severity. To the best of our knowledge, no cases of pulmonary embolism (PE) occurring secondly after a first hospitalization for COVID-19 non-severe infection have been described yet.

Case presentations Patient 1 Patient 1, aged 68, with history of heavy smoking (60 pack-year) and hypercholesterolaemia presented with polypnoea (22 cycle/min) and low oxygen saturation in room air of 88% after 3 days of fever and myalgia. Physical examination demonstrated coarse crackles in both lower lung fields. Reverse transcription-polymerase chain reaction (RT-PCR) testing on nasopharyngeal swab was positive for SARS-Cov-2. A low-dose computed tomography (CT) scan on the first admission showed peripheral ground-glass opacifications with underlying centrilobular emphysema lesions with an extension of COVID lesions estimated to 10-25% of lung parenchyma ( Figure 1A) . The baseline electrocardiogram (ECG) was normal. A modest lymphopenia was present [750/mm 3 , referential range (RR) 1000-4000/mm 3 ] with increased values of C-reactive protein (CRP) (41 mg/L, RR < 4 mg/L) and D-dimer (1040 mg/L, RR < 500 mg/L). Brain natriuretic peptide (BNP) and troponin I levels were normal. Lupus anticoagulant (LA) testing was negative. The arterial blood gas on nasal cannula 8 L/min showed PaO2 60 mmHg, PCO2 37 mmHg, and SaO2 90%. Based on these findings, treatments with low molecular weight heparin (LMWH), enoxaparin 40 mg once a day, ceftriaxone, and hydroxycholoroquine were started. The following day, oxygen flow was increased to 15 L/min and delivered on a non-rebreather mask. After 8 days, the clinical status improved, and the patient was discharged home after progressive oxygen weaning.

Forty-eight hours after discharge, he presented with rapidly worsening dyspnoea and severe hypoxaemia. D-dimer level was high (>20 000 mg/L), and Troponin I and BNP remained normal. A second chest CT evidenced worsening infectious lesions ( Figure 1B) with an extension of 30% and filling defects in the right pulmonary artery and its right superior lobe divisions diagnostic for pulmonary embolism ( Figure 1C ). Unfractionated heparin was then started and switched after 48 h to LMWH twice a day. A second LA testing was positive. Vitamin K antagonist treatment with warfarin was initiated. A second LA test was planned after 3 months to decide whether anticoagulation should be discontinued or not. The patient was advised to consult his cardiologist one month after discharge.

Patient 2, aged 62, was referred for dyspnoea after 5 days of fever, dry cough, and myalgia. He had a history of dilated cardiomyopathy with mildly reduced ejection fraction (42%) and several cardiovascular risk factors (smoking, hypertension, type 2 diabetes mellitus, and hypercholesterolaemia). The physical examination did not demonstrate any abnormalities on admission. No crackles had been detected on lung auscultation. RT-PCR testing on nasopharyngeal swab was positive for SARS-Cov-2. A low-dose CT scan was initially normal (Figure 2A) . The baseline ECG showed sinus tachycardia. Creactive protein was mildly increased (peak value of 20 mg/L) with no leucocytosis. No troponin, BNP, or D-dimer tests were performed during the index hospitalization. Despite subnormal arterial blood gas on room air on admission (PaO2 of 73 mmHg, PCO2 of 42 mmHg, SO2 of 95%), the patient received low flow nasal oxygen (1 L/min) for 2 days. Enoxaparin 40 mg once a day during the hospital stay of 5 days was the sole treatment.

Four days after discharge, he was referred for a worsened dyspnoea (New York Heart Association III). A second CT scan showed multiple subpleural ground-glass opacifications and a filling defect diagnostic for pulmonary embolism in the left inferior lobe ( Figure 2B 

We describe two cases of COVID-19 patients presenting with posthospital discharge acute pulmonary embolism despite adequate thromboprophylaxis in a non-intensive care unit setting. Despite the absence of major predisposing risk factors for venous thromboembolism (VTE), the administration of a weight-adjusted thromboprophylaxis during hospitalization and the absence of severe inflammatory syndrome, PE occurred and was associated with a worsening of CT lung injuries. In one case, LA could be evidenced by questioning about the correct anticoagulant treatment and its duration. To the best of our knowledge, no reports of acute pulmonary embolism (PE) after discharge from the hospital have been described yet in non-intensive care unit patients.

The novel Coronavirus Disease outbreak is a global public health challenge. Since the first cases of SARS-CoV-2 were detected in Wuhan, China, 5 more than 2 500 000 confirmed cases and 175 000 deaths have been documented worldwide. 6 COVID-19-induced interstitial pneumonia leading potentially to acute respiratory distress syndrome (ARDS) and multi-organ failure is in the spotlight of all medical teams as it often triggers transfer of patients in intensive care units. Recently, it has been evidenced that SARS-CoV-2 could predispose patients to increased thrombotic disease in the venous and arterial circulations. 7 Severe inflammation, hypoxia, endothelial dysfunction, platelet activation and stasis particularly in intensive care unit patients could explain this pro-thrombotic state. Very recently, in a ARDS population, 16.7% of PE were diagnosed and 88.7% of those patients had positive LA. 4 Llitjos et al. observed that the systematic screening by complete duplex ultrasound in 26 intensive care unit patients showed a peripheral VTE prevalence of 67%. 8 Interestingly, in the two cases described here, thrombotic events occurred 13-14 days from the onset of COVID-19 symptoms, at home after a first non-intensive care unit hospitalization and in patients clinically recovered.

There were no clinical signs of severe pneumonia, fever nor major inflammatory syndrome when PE occurred. Interestingly, both patients evidenced an increased extension of the peripheral groundglass opacifications when PE was diagnosed despite a clear clinical improvement before discharge. Thromboprophylaxis during first hospital stay was effective but stopped after discharge. Several reports confirmed that attention should be paid to venous thromboembolism prophylaxis in COVID patients during hospitalization 9 but no recommendations existed regarding routine post-hospital discharge thromboprophylaxis, recommended agent and/or duration.

Our case report suggests the potential role of SARS-CoV-2 as a major precipitant factor for VTE. Some acute viral infections are known to be associated with LA which are often transient, but can persist and lead to thromboembolic complications by various mechanisms including the release of membrane microparticles and the exposure of pro-thrombotic phospholipids. 10 Although the significance of these antibodies is not well established yet, COVID-19-induced LA could favour the highly frequent thrombo-embolic events in this population and should be systematically tested. COVID-19 patients may thus require longer and more aggressive VTE prophylaxis after discharge. The type of anticoagulant treatment after pulmonary embolism may be adapted according to the presence of COVID-19induced LA, taking into consideration that oral direct anticoagulants are contraindicated in case of LA in the general population.

Since COVID-19 patients are at high risk of developing PE, a sudden deterioration in respiratory status associated with high level of D-dimers must draw attention to progressive radiographic deterioration on CT and/or pulmonary embolism occurrence.

Dr Mohamad Kanso is a cardiologist in Strasbourg University Hospital, Strasbourg, France. He graduated from the Cardiovascular Medicine, University of Strasbourg, in 2018 and is actually training in interventional electrophysiology.

Supplementary material is available at European Heart Journal -Case Reports online.

Slide sets: A fully edited slide set detailing this case and suitable for local presentation is available online as Supplementary data.

The author/s confirm that written consent for submission and publication of this case report including images and associated text has been obtained from the patients in line with COPE guidance.

Cardiovascular considerations for patients, health care workers, and health systems during the coronavirus disease 2019 (COVID-19) pandemic

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

Pulmonary embolism in COVID-19 patients: awareness of an increased prevalence

High risk of thrombosis in patients in severe SARS-CoV-2 infection: a multicenter prospective cohort study

A novel coronavirus from patients with pneumonia in China

Coronavirus disease 2019 (COVID-19) Situation Report -94

COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up

High incidence of venous thromboembolic events in anticoagulated severe COVID-19 patients

Attention should be paid to venous thromboembolism prophylaxis in the management of COVID-19

Risk of developing antiphospholipid antibodies following viral infection: a systematic review and meta-analysis

Conflict of interest: none declared.Funding: This work was supported by GERCA (Groupe pour l'Enseignement, la prévention et la Recheche Cardiologique en Alsace).