Aneurysmal Subarachnoid Haemorrhage After COVID-19 Infection

Background SARS-CoV-2 virus infection leads to a severe and dysbalanced inammatory response with hypercytokinemia and immunodepression. Systemic inammation due to viral infections can potentially cause vascular damage including disruption of blood-brain barrier (BBB) and alterations in coagulation system that may also lead to cardiovascular and neurovascular events. Here, we report the rst case of COVID-19 infection leading to aneurysmal subarachnoid haemorrhage (aSAH).


Introduction
The number of SARS-CoV-2 virus infected patients is increasing dramatically and have now reached over two million con rmed infected individuals with over 200,000 deaths worldwide. World health organisation has now declared the COVID-19 disease as a pandemic. The disease started in December 2019 in Wuhan, China and spread rapidly in January 2020 to Japan and over February/March 2020 in Europe. From mid of March 2020, COVID-19 spread briskly to North America and North America now shows the fastest growing number of newly diagnosed COVID-19 patients. Intensive epidemiological and biological research led to identi cation of novel corona virus 2019 (COVID-19) that can infect both animals and human (1,2). COVID-19 infection is respiratory in nature and can range from common cold with mild symptoms to severe acute respiratory syndrome (SARS) with respiratory failure (3)(4)(5). COVID-19 infection typically presents with fever, fatigue, dry cough and shortness of breath (2,4,5) but can also involve other organs and systems including cardiovascular system and gastrointestinal tract (6). Involvement of other organs especially the cardiovascular system has been shown to pose signi cant additional mortality in COVID-19 infected patients (7). Involvement of central nervous system during COVID-19 infection is not well known. Recently, a case of encephalopathy in a COVID-19 positive patient was reported showing the possible accessibility of the virus to the brain and involvement of central nervous system (8). Until date there is no report showing an aneurysmal subarachnoid haemorrhage secondary to COVID-19 infection.

Case Description
A 61-year-old woman presented with dyspnea, cough and fever.,She was over weight with Body massindex of 34 and history of hypertension. No history of subarachnoid hemorrhage in the family. She was admitted in ICU due to low oxygen saturation (89%). A chest CT showed typical picture of COVID-19 pneumonia. Oropharyngeal swab with a PCR-based testing was COVID-19 positive. She was prescribed with favipiravir and hydroxychloroquine in addtion to oxygen support. On second day she experienced sudden headache and loss of conciousness. A computer tomography (CT) with CT-angiography revealed subarachnoid haemorrhage in basal cisterns from a ruptured anterior communicating artery aneurysm.

Treatment and outcome
The aneurysm was clipped microsurgically through a standard pterional approach. . All precautions including FFP-3 mask, glasses for eye protection and double gloves were used to protect surgical staff. The patient was admitted again to intensive care unit for further intensive medical treatment. Postoperative the patient showed slight motor dysphasia. No other neurological de cits.

Discussion
With increasing number of COVID-19 patients worldwide, multiple reports have shown that COVID-19 infection apart from lungs can also involve other organs including the brain (6)(7)(8). We present the rst case of COVID19 infection that led to aneurysmal subarachnoid haemorrhage from a ruptured anterior communicating artery aneurysm. Microsurgical clipping was performed (due to lacking endovascular facility) to exclude bleeding aneurysm from the circulation and pneumonia was treated with favipiravir and hydroxychloroquine in addtion to oxygen support in intensive medical ward. Post COVID-19 aneurysmal subarachnoid haemorrhage might be due to severe cough leading to increased pressure on aneurysm wall or due to secondary systemic in ammation with free radical load due to virus infection that may weaken the aneurysm wall. There are however, multiple mechanisms, how an intracranial aneurysm can possibly lead to vascular wall instability due to systemic in ammation during viral infection. Viral infections including COVID-19 are known to induce cytokine storm (hypercytokinemia) leading to elevated systemic in ammation (9)(10)(11). Systemic in ammation is known to cause vascular injury including breakdown of collagen and permeability of blood-brain barrier (12,13). In uenza A virus infection for example disturbs BBB through involvement of systemic elevated MMP-9 (12) that breaks collagen present in the basal membrane of every arterial wall and a high collagen turnover in the systemic circulation is a sign of instability of existing intracranial aneurysm (14) in patients with unruptured intracranial aneurysms. Moreover, COVID-19 infection has been reported to increase systemic in ammation through dysbalance of T helper cells with exaggerated Th1 response (15). Similar kind of alterations in T helper cells populations have been found in patients with intracranial aneurysms (16).
Moreover, a disturbed balance of macrophages and other in ammatory markers has been found in the wall of ruptured intracranial aneurysms (17,18) showing that in ammation is an important component of instable aneurysms. In our patient, we found elevated systemic leukoctyes as a sign of systemic in ammation that is probably due to both infection and SAH. We however could not analyse subpopulations of different leukocytes in systemic circulation that might be altered. Another possibility could be a direct invasion of virus in the brain as previously reported (8). An aneurysm wall biopsy and COVID-19 PCR can exactly show the direct effect of virus on the aneurysm wall. For the general practice the neurosurgeons should work closely with other disciplines to rapidly diagnose and treat such patients.
Taken together, aneurysm instability partially due to systemic in ammation after virus infection might be one possible reason leading to SAH. This is however a single case report with post COVID-19 subarachnoid hemorrhage. Therefore, further epidemiological/clinical studies are needed to con rm the relationship and animal experiments in controlled conditions are required to nd out exact mechanism. The patient has consented to the submission of the case report Availability of Data and Materials: Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

Competing Interests
The authors declare that they have no competing interests.

Funding
We acknowledge the funding support from EANS to SM Author's contribution SM wrote manuscript SN collected patient data MA and AG treated the patients and reviewed manuscript DH reviewed the manuscript critically.