Background

SARS-CoV-2 induces the coronavirus disease, COVID-19, first reported in China and later becoming a pandemic. It produces a respiratory and systemic clinical syndrome with varying extent of pneumonia, lung damage, hypercoagulable state and multiorgan failure with death in severe cases.1 2

Acute lower limb ischaemia has been reported by various workers and can broadly be categorised into two groups. The first type is the ‘COVID-19 toe’ wherein distal acral ‘chilblain-like’ features are seen, and the second type is the large artery thrombosis, with resultant risk of gangrene, amputation and possible fatal outcomes.3–5 Management of moderate and severe COVID-19 includes use of anticoagulants, including heparin (usually low molecular weight heparin), as per national guidelines.6 Despite use of such medications, ischaemic events have still been reported.7

Surgical embolectomy, the standard of care, may not be feasible in some cases due to the severity of lung disease. Endovascular approaches are less morbid,8 which may provide a better chance at treatment in such cases of severe lung disease.

Case presentation

A 75-year-old man, a surgeon by profession, presented with dry cough, fever and loose stools for 7 days, progressively increasing respiratory distress for the past 3 days. He had no significant antecedent medical or surgical history. He was found to be SARS-CoV-2 positive on a real-time reverse transcription PCR test at admission. He had oxygen saturation (SpO₂) of 87%, heart rate of 102 beats/min and temperature of 101.8°F.

Baseline investigations

On admission, he had pre-renal azotaemia, which improved rapidly in the next 48 hours. Blood investigation results are summarised in table 1.

A CT examination of the chest showed extensive ground glass opacification of both lungs with some areas of consolidation, bronchiectasis, and thickened lobular and interlobular septae (figure 1). A two-dimensional echo examination and ECG were normal.

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Figure 1

(A) Initial frontal chest radiograph after admission showing extensive opacification of both lungs, a central line is inserted in the right internal jugular vein. (B) High-resolution CT (HRCT) scan of chest, coronal reformatted view, at admission, showing extensive ground glass opacification of nearly entire lung volume on either sides with some areas of consolidation, ectasia of airways and thickening of the interlobular and intralobular septae. (C) Clinical photograph at initial reporting, showing discolouration of the toes of right foot. (D) Axial image of CT angiography (CTA) showing calcified plaque in the right common iliac artery (dashed black arrow) with hypodense thrombus in the lumen (solid black arrow), minimal lumen opacification is seen anteriorly (solid white arrow). (E) CTA of the lower limbs, maximum intensity projection image showing non-visualisation of the posterior tibial and distal half of the anterior tibial artery and partial opacification of the peroneal artery, possibly via collaterals. (F) Digital subtraction angiography (DSA) image showing occlusion of the tibioperoneal trunk (TPT) from origin, ATA occlusion has progressed further higher up, some filling of peroneal artery via collaterals. (G) DSA image at leg level showing the filling of the mid part of the peroneal artery with occlusion distally, a long thin collateral is coming down and opacifying a small length of the posterior tibial artery around the ankle level. (H) Aspiration catheter lodged in the TPT (dashed white arrow), with a guidewire passed through it; (solid black arrow) multiple passes of the catheter was done in all the three vessels. (I) Angioplasty balloon in the distal ATA (dashed black arrows); angioplasty of all the three arteries was done at various levels. (J) Final DSA image at knee showing opening of the TPT (black arrowhead) and the ATA (white arrowhead). (K) DSA image at leg level showing patent PTA in entire length (dashed black arrow), peroneal (thick dashed white arrow) and ATA (thin dashed white arrow) are seen upto distal leg. (L) A sample of the retrieved material, appearing bright white. (M) Histopathology section showing thrombus composed of fibrinous material, haemorrhage and inflammatory cells (H&E stain, ×400 magnification). (N) Progressively increasing discolouration and gangrene to involve midfoot. (O) Coronal reformatted view of HRCT chest scan at 6 weeks of onset, showing significant resolution of the extensive ground glass opacification and consolidation, with some areas of hyperlucency; a diffuse background ‘haze’ persists. (P) Coronal reformatted view of HRCT chest scan at 6 months of onset, showing near normal lung with some areas of opacities, possibly representing fibrosis, in the left upper zone. (Q) Current status of foot, post amputation and with completely healed suture line.

Hospital stay and treatment

The patient was started on inj. dexamethasone 6 mg per day, inj. enoxaprin 60 mg two times per day, tab. azithromycin 500 mg per day, tab. paracetamol 500 mg four times per day, 2.5 mg salbutamol nebulisation four times per day, non-invasive ventilation and prone positioning for 18 hours a day. He was given inj. remdesivir 200 mg intravenous on day 1 followed by 100 mg intravenous daily for 4 days. His condition did not improve, although the fever subsided on the third day of admission. As his SpO₂ dropped to 60% intermittently, non-invasive ventilation was performed. Two doses of inj. tocilizumab and convalescent plasma transfusion were also given as per notified institutional guidelines.

On the 14th day of admission, he started complaining of burning sensation of right great toe, and a day later, discolouration of the toes of the right lower limb was noticed with slight oedema (figure 1C). A bedside colour Doppler examination showed no evidence of deep venous thrombosis and normal colour filling of femoral, popliteal and infrapopliteal arteries. The toe discolouration was thought of as ‘COVID-19 toes’ and was managed conservatively. However, on the 18th day of admission, pain and paraesthesia increased; hence, a CT angiography (CTA) was performed which showed complete occlusion of the posterior tibial artery (PTA) and the peroneal artery (PA) from origin and occlusion of the anterior tibial artery (ATA) from mid leg. The CTA was a dual phase study and the second phase also did not show any collateral or delayed opacification of the occluded arteries (figure 1D and E).

After interdepartmental discussion, endovascular therapy was offered and the patient consented, considering his poor clinical status which precluded long anaesthesia duration required for surgical revascularisation.

The endovascular treatment was done on a Philips Allura Clarity digital subtraction angiography (DSA) machine under local anaesthesia. Ten millilitres of 1% plain lidocaine was used first, and further 10 mL was given after 1.5 hours of the procedure. A long sheath was inserted into the right common femoral artery under ultrasound guidance and thrombectomy was done using Navien (Medtronic; Irvine, California, USA) 6Fr aspiration catheter (figure 1F–K). Multiple passes were made to recanalize the ATA and PTA. Most of the clots were fragmented and of dark colour with few hard, white coloured ‘rubbery’ plaques also noticed in the retrieved material (figure 1L). The distal segments of the arteries required angioplasty with 3.0 and 2.0 mm sized balloons (BD Ultraverse peripheral balloon, Abbott NC Trek coronary balloon). The PTA was recanalized in its entire length with the distalmost segment still having some clot remnants, and the ATA was recanalized until just above the ankle. The dorsalis pedis artery (DPA), plantar arch and digital arteries did not opacify well even though late and slow filling of the medial and lateral plantar arteries was visible. Angioplasty of the DPA and plantar arch was done with long 2.0 mm sized balloons but the vessels collapsed immediately after balloon removal. Then injection urokinase was infused in the terminal ATA, PTA, DPA, lateral plantar artery and the plantar arch using a Terumo Progreat 2.7F microcatheter. A total of 500 000 units of drug was given as 10 000 unit bolus over 10 min at each of these sites. However, persistent contrast filling of DPA and plantar arch could not be achieved. The digital arteries remained unopacified. The patient had immediate on-table relief of pain and paraesthesia. The long sheath was replaced with a short sheath, stitched in place, attached to a heparinised pressure flush line (2 units of heparin per millilitre of saline) and the patient was transferred to the dedicated COVID-19 intensive care unit for further management. The entire procedure lasted for approximately 3 hours.

Microscopy of the retrieved fragments showed fibrinous material, haemorrhage and mixed inflammatory cells along with focal fibrous tissue (figure 1M). Histopathological features were in favour of an organised thrombus.

Inj. enoxaprin 60 mg two times per day was continued and oral aspirin 325 mg daily, clopidogrel 150 mg daily and atorvastatin 40 mg daily were added to the treatment. A colour Doppler was done daily and showed normal values in the ATA and PTA with no flow in DPA and monophasic flow in metatarsal and digital arteries. From the third postoperative day, DPA and metatarsals also had biphasic flow.

Outcome and follow-up

Patient’s pain and paraesthesia improved; however, the discolouration progressively extended to involve the midfoot and forefoot (figure 1N). Medical management was continued, with progressive improvement in general health, and he was discharged on day 40 of admission with SpO₂ 94% on room air. A chest CT done at 6 weeks and later at 6 months showed significant improvement, and the patient was able to walk and perform all daily activities independently (figure 1O and P). A two-stage Lisfranc amputation of the right foot was done at 2 months to treat the gangrene of the foot.

He continues to improve and has normal daily activities as of now with healed and healthy flaps (figure 1Q).