Attribute fatal, multiple cavitary lesions with air-fluid levels and hemorraghe to SARS-CoV-2 or ECMO only after ruling out differentials.

Letter to the Editor

We eagerly read the article by Osman et al. about a 53 years-old male with severe COVID-19 who required mechanical ventilation for acute respiratory distress syndrome (ARDS) and extra-corporal membrane oxygenation (ECMO) therapy for hypoxigenation. On the first day after transfer to a tertiary hospital, the patient developed dilated pupils and cerebral CT (CCT) showed multiple cavitary lesions with air-fluid levels, hemorrhagic transformations, and cerebral edema. Intracerebral bleedings (ICBs) and edema progressed over the following days. Despite additional treatment with tocilizumab, antivirals, antibiotics, and steroids the patient died on the 11th day on ECMO. The study is appealing but raises concerns which require discussion.

A shortcoming of the study is that no cerebral magnetic resonance imaging (MRI) had been performed. Because bleeding can occur in association with immune encephalitis, in association with acute, hemorrhagic leucoencephalopathy (AHLE), and in association with acute, hemorrhagic, necrotizing encephalitis (AHNE), it is crucial to perform MRI with contrast medium. Cerebral MRI could be also helpful to explain the cause of the multiple cavitary lesions with air-fluid levels and hemorrhagic transformation. Readers should know if air embolism and multiple abscesses were appropriately ruled out. Missing is also the computed tomography angiography (CTA) respectively magnetic resonance angiography (MRA) to rule out vasculitis, vascular malformations, and aneurysms.

A further shortcoming is that the patient had not undergone lumbar puncture and cerebrospinal fluid (CSF) investigations. Before attributing ICB to ECMO, it is crucial to thoroughly rule out all possible differential diagnoses. To rule out infectious encephalitis, meningitis, subarachnoid bleeding not visible on CCT, analysis of the CSF is mandatory. It is quite conceivable that the described cerebral lesions developed already before transfer to the tertiary unit but became symptomatic not earlier than after progression beyond a critical point.

ICB in COVID-19 patients can also result from dysfunctional thrombocytes. Dysfunctional thrombocytes can, for example, occur together with immune thrombocytopenia, which can be complicated by bleeding. To rule out dysfunctional thrombocytes, it is crucial that the index patient had undergone testing of thrombocyte function and determination of the d-dimer. Missing in this respect is the thrombocyte count. We should also know if the patient ever experienced thrombosis in any of the veins. Particularly, there is a need to rule out venous sinus thrombosis (VST). VST has been repeatedly reported as a complication of SARS-CoV-2 infections and is commonly complicated by ischemic stroke or bleeding..

A further limitation is that a PCR for SARS-CoV-2 was ordered but that the results of the examination were not provided. Therefore, COVID-19 has not been confirmed in the index patient.

Overall, the interesting study has several limitations which challenge the results and their interpretation. Clarifying these weaknesses would strengthen the conclusions and could improve the study. Before blaming SARS-CoV-2 and ECMO for ICB, a number of differential diagnoses have to be ruled out.

Ethics approval: was in accordance with ethical guidelines. The study was approved by the institutional review board.

Consent to participate: was obtained from the patient.

Consent for publication: was obtained from the patient.

Availability of data: all data are available from the corresponding author.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.