Demographic, clinical, radiological and laboratory findings
| Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | |
| Demographic characteristics | ||||||
| Age, years | 64 | 53 | 85 | 61 | 83 | 73 |
| Sex | Male | Female | Male | Male | Male | Male |
| Medical history | Nil | Hypertension, diabetes, mitral valve replacement, atrial fibrillation, heart failure with a permanent pacemaker | Hypertension, hypercholesterolaemia, atrial fibrillation, ischaemic heart disease, prostate cancer (Gleason Score 4+5) | Hypertension, stroke, chronic leg ulcers | Hypertension, diabetes, ischaemic heart disease, smoking and alcohol consumption | Gastric carcinoma (resected), benign essential tremor |
| Symptoms at COVID-19 disease onset | Cough, shortness of breath, fever, myalgia, loss of appetite | Malaise, dry cough, shortness of breath, fever | Cough | Fever, cough, shortness of breath, tachypnoea | Fever, cough, shortness of breath, fatigue | Shortness of breath, tachypnoea |
| Initial treatment | Antibiotics, oxygen therapy | Supportive | Supportive | Antibiotics | Antibiotics, oxygen therapy | Antibiotics, oxygen therapy |
| Days from COVID-19 symptom onset to ischaemic stroke symptom onset | 15 | 24 | 10 | −2 (stroke preceded COVID-19 symptoms by 2 days) | 15 | 8 |
| Clinical symptoms of ischaemic stroke | Word-finding difficulties, bilateral incoordination, right homonymous hemianopia | Acute confusion, incoordination, reduced consciousness (GCS 13/15) | Dysarthria, right facial droop and right-sided weakness | Dysarthria, left facial droop and left-sided weakness | Dysarthria, left facial droop, left-sided weakness and left-sided sensory inattention | Aphasia, right facial droop and right-sided weakness |
| ICU admission and disease severity | ||||||
| Days from COVID-19 symptom onset to ICU admission | 14 | 25 | Did not go to ICU | Did not go to ICU | Did not go to ICU | Did not go to ICU |
| COVID-19 disease severity | Severe | Critical | Moderate to severe | Moderate | Severe | Severe |
| Laboratory findings on the day of first or only ischaemic stroke event | ||||||
| Haemoglobin (g/L) | 119↓ | 94↓ | 128↓ | 126↓ | 121↓ | 142 |
| White cell count (/mm3) | 6750 | 23 050↑ | 5080 | 8970 | 11 030↑ | 7300 |
| Differential count (/mm3) | ||||||
| Neutrophils | 5810 | 19 200↑ | 4440 | 6390 | 8330↑ | 5800 |
| Lymphocytes | 470↓ | 2070 | 402↓ | 1310 | 1630 | 890↓ |
| Monocytes | 370 | 1660↑ | 180↓ | 900 | 830 | 470 |
| Platelet count (/mm3) | 305 000 | 254 000 | 173 000 | 408 000↑ | 197 000 | 403 000↑ |
| Albumin (g/L) | 28↓ | 28↓ | 33↓ | 31↓ | 32↓ | 32↓ |
| Alanine aminotransferase (U/L) | 137 ↑ | 27 | 32 | 24 | 37 | 75 ↑ |
| Bilirubin (µmol/L) | 11 | 29↑ | 17 | 13 | 11 | 10 |
| Lactate dehydrogenase (U/L) | 654↑ | 664↑ | 461↑ | 444↑ | 353↑ | 439↑ |
| Creatinine (μmol/L) | 57 | 75 | 77 | 107 | 100 | 68 |
| EGFR (ml/min/1.73 m2) | >90 | 74 | 87 | 63 | 64 | >90 |
| High-sensitivity cardiac troponin I (pg/ml) | 9 | 42↑ | 32 ↑ | 30↑ | 66↑ | 8 |
| Prothrombin time (s) | 12.5↑ | 34.4↑ | 11.3 | 10.9 | 11.7 | 12.3↑ |
| International normalised ratio (INR) | 1.14 | 3.6↑* | 1.03 | 0.99 | 1.07 | 1.13 |
| Activated partial-thromboplastin time (APPT) (s) | 35 | 41↑ * | 33 | 24↓ | 30 | 32 |
| APPT ratio | 1.1 | 1.3↑ | 1 | 0.8 | 1.0 | 1 |
| Fibrinogen (g/L) | 9.5 ↑ | 7.03 | 5.3↑ | 4.63↑ | 4.96↑ | – |
| D-dimer (μg/L) | >80 000 ↑ | 7,750↑ | 16,100↑ | 27,190↑ | 19,450↑ | 1,080↑ |
| Serum ferritin (μg/L) | 4927 ↑ | 1,853↑ | 1,027↑ | 1,167↑ | 655↑ | |
| High-sensitivity C reactive protein (mg/L) | 305.4 ↑ | 150.1↑ | 161.2↑ | 12.8 | 27.7↑ | 179.9↑ |
| Antiphospholipid antibodies: Anticardiolipin (aCL) Anti-β2-glycoprotein-1 (aβ2GPI) | Medium titre IgM aCL IgG aCL negative Low titre IgG and IgM aβ2GP1 | IgG and IgM aCL and aβ2GP1 negative | IgG and IgM aCL and aβ2GP1 negative | IgG and IgM aCL and aβ2GP1 negative | IgG and IgM aCL and aβ2GP1 negative | IgG and IgM aCL and aβ2GP1 negative |
| Lupus anticoagulant | Positive | Positive | Negative | Positive | Positive | Positive |
| Imaging features | ||||||
| Brain (see online supplementary figure S1s and S2) | MRI including diffusion-weighted and susceptibility-weighted imaging showed acute left vertebral artery thrombus and acute left posterior-inferior cerebellar artery territory infarction with petechial haemorrhagic transformation. 7 days later, diffusion-weighted MRI showed bilateral acute posterior cerebral artery territory infarcts despite therapeutic anticoagulation | Non-contrast CT showed acute right parietal cortical and left cerebellar infarct with mass effect and hydrocephalus, despite therapeutic anticoagulation | Non-contrast CT showed hyperdensity consistent with thrombus in the left posterior cerebral artery and acute infarction in the left temporal stem and cerebral peduncle | Diffusion-weighted MRI showed acute infarction in the right corpus striatum suggesting transient occlusion of the M1 segment of the right middle cerebral artery; fluid attenuated inversion recovery MRI showed an established infarct in the same region with moderate background cerebral small vessel disease | CT and CT angiogram showed thrombotic occlusion of a proximal M2 branch of the right middle cerebral artery; a repeat CT at 24 hours showed a focus of parenchymal low density involving the right insular cortex in keeping with an evolving right middle cerebral artery territory infarct | Diffusion-weighted MRI showed acute infarction in the right thalamus, left pons, right occipital lobe and right cerebellar hemisphere. Time-of-flight images showed thrombotic material in the basilar artery and bilateral mild-to-moderate P2 segment stenosis |
| Chest | Chest X-ray: Bilateral pulmonary infiltrates CT pulmonary angiogram: Bilateral pulmonary embolism; semiocclusive right middle lobe segmental and right lower lobe subsegmental, non-occlusive lower lobe subsegmental embolus | CT chest: Bilateral ground-glass change and consolidation CT pulmonary angiogram: No large pulmonary embolus within the main or segmental pulmonary arteries | Chest X-ray: Bilateral peripheral airspace opacities throughout both lungs, worse on the right | CT chest: Bilateral patchy subpleural airspace opacification in both lungs CT pulmonary angiogram: Pulmonary embolus in the left upper lobe segmental artery | Chest X-ray: few ill-defined patchy airspace opacifications seen peripherally in both lung fields mid-zones and lower zones, mild amount right-sided pleural effusion. CT pulmonary angiogram: No large pulmonary embolus within the main or segmental pulmonary arteries | Chest X-ray: Bilateral predominantly peripheral airspace opacities, most confluent at the mid-zones and the lung bases CT pulmonary angiogram: No large pulmonary embolus within the main or segmental pulmonary arteries |
| Other vascular imaging | Lower limb Doppler ultrasound: occlusive DVT in the left posterior tibial vein and the left peroneal vein | |||||
*Patient taking warfarin.
DVT, Deep Vein Thrombosis ; EGFR, Estimated Glomerular Filtration Rate; GCS, Glasgow Coma Score ; ICU, intensive care unit.