Before blaming SARS-CoV-2 for intra-cerebral aneurysm formation and rupture, alternative mechanisms need to be ruled out.

Letter to the Editor

We eagerly read the article by Sato et al. about an 58 years-old female with severe COVID-19 requiring mechanical ventilation from day 10 after onset of the infection, who experienced subarachnoid bleeding (SAB) 21 days after onset of COVID-19 after an episode of arterial hypertension [1]. Computed tomography angiography (CTA) of the intracerebral arteries revealed an aneurysm of the right vertebral artery (VA) distal to the posterior inferior cerebellar artery (PICA) [1]. The patient profited significantly from ventricular drainage and endovascular coiling of the aneurysm and reached a modified Rankin scale score of 2 at the four months follow-up [1]. The study is appealing but raises concerns which require discussion.

We disagree with the notion that SARS-CoV-2 was causative for the aneurysm [1]. There is no proof that the aneurysm developed during the infection with SARS-CoV-2 [1]. It cannot be ruled out that the aneurysm was already present before the index patient developed COVID-19. A strong argument against SARS-CoV-2 as the cause of aneurysm formation is that there are no indications that the overall prevalence of cerebral aneurysms has increased since onset of the pandemic.

The hypothesis that obstruction of the vasa vasorum due to the hyperinflammatory state resulted in weakness of the vessel wall and consecutive aneurysm formation [1], remains unproven. Because the patient did not carry any risk factors for atherosclerosis [1], the second hypothesis of aneurysm formation due to SARS-CoV-2 that rupture of an atherosclerotic plaque could have led to intramural hematoma and consecutive aneurysm formation is not applicable to the index patient. There is also no evidence that the third hypothesis – local inflammation of the arterial wall (arteritis) due to systemic inflammation – is relevant, as CTA was not indicative for cerebral vasculitis [1]. Development of arteritis solely at a single location is rather unlikely.

Several essential information about the index patients were not provided [1]. Missing is the family history [1]. Because cerebral aneurysms can be hereditary [2], it is crucial that readers are informed if any of the first degree relatives had a history of SAB or a known cerebral aneurysm. Did any of the first-degree relatives undergo CTA?

Missing is the discussion about the sudden rise in arterial blood pressure 17 days after onset of COVID-19 [1]. We should be told if the sudden increase in arterial blood pressure was the cause of the aneurysm rupture or the reaction to the SAB. According to the case description it is conceivable that SAB occurred already on the 16th day post onset of the infection and became clinically apparent not earlier than after extubation. We should be told at which time exhumation had been carried out.

Missing is the medication the patient was regularly taking at home to assess if the previous medication may have contributed to arterial hypertension. Missing is also the entire medication the patients received for COVID-19 in a addition to midazolam, fentanyl, rocuronium, favipiravir, remdesivir, apixaban, toxilizumab, dexamethasone, , propofol, and, nicardipine [1].

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 for having caused intracerebral aneurysm formation, all differential causes need to be thoroughly ruled out.

Funding sources: no funding was received