Dear Editor:

We read with interest the article by Yazar et al. about two patients, a 15-year-old female (patient-1) and a 12-year-old female (patient-2) with subdural empyema being attributed to infection with SARS-CoV-2 [1]. In both patients, the SARS-CoV-2 infection remained asymptomatic [1]. Both patients benefited from antibiotics and resection of the empyema and made an incomplete recovery until the last follow-up, 10 days after surgery (patient-1) and 1 week after surgery (patient-2) [1]. Patient-2 additionally required steroids for cerebral edema and anti-seizure drugs for seizures [1]. Cultures from the empyema grew Streptococcus constellatus in both patients [1]. The study is appealing but raises concerns that warrant further discussion.

We disagree with the notion that SARS-CoV-2 was responsible for subdural empyema [1]. No convincing arguments were provided that unequivocally prove that the virus was truly responsible for the empyema. Arguments against a causal relation are that the SARS-CoV-2 infection obviously remained asymptomatic and that subdural empyema has been only rarely reported in association with a SARS-CoV-2 infection [2]. It is quite conceivable that the positive PCR test for SARS-CoV-2 is a random finding and has nothing to do with the subdural empyema.

A limitation of the study is that both patients did not undergo cerebrospinal fluid (CSF) examinations [1]. Because subdural empyema can be a complication of meningitis, it is crucial that meningitis is ruled out by CSF examinations. Because the study claims that SARS-CoV-2 was the cause of subdural empyema [1], it is also required that the CSF is investigated for the presence or absence of the SARS-CoV-2 virus by RT-PCR. A further limitation of the study is that neither blood cultures for bacteria or fungi nor virus panels were carried out to assess if the patients had a bacterial or fungal infection or a viral infection other than SARS-CoV-2. Because blood tests were indicative of sepsis (elevated procalcitonin), it is necessary to confirm or rule out the presence of Streptococcus constellatus in the blood or other compartments. Furthermore, subdural empyema can be due to hematogenic spread from a focus outside the brain or the meninges [3], why it is necessary to rule out any infectious focus outside the central nervous system.

Another limitation is that the vaccination status of both patients was not reported [1]. Patient-1 was admitted in September 2021 and patient-2 in October 2021, which means at a time when SARS-CoV-2 vaccinations were already available.

A further limitation of the study is that sinusitis has not been ruled out as a cause of subdural empyema [1]. Sinusitis is a common cause of subdural empyema in children and adults [4]. There is also no mention of either patient had otitis media prior to the detection of the subdural empyema. Also, otitis media is a common cause of subdural empyema [5].

Because venous thrombosis has been suspected to play a pathophysiological role in the development of subdural empyema, it is crucial that venous sinus thrombosis (VST) be ruled out by magnetic resonance venography (MRV). There is also a need to rule out tuberculosis.

Overall, the study carries obvious limitations that require re-evaluation and discussion. Clarifying these weaknesses would strengthen the conclusions and could make the study even more interesting. Before attributing subdural empyema to infection with SARS-CoV-2, differential causes, particularly sinusitis, otitis, meningitis, mastoiditis, previous head surgery, and previous traumatic brain injury, must be thoroughly ruled out.