We eagerly read the article by Valdes et al. [1] about the cognitive deficits among 215 patients 6 months after a SARS-CoV-2 infection requiring hospitalisation as assessed by the tMoCA test via telephone [1]. It was found that fewer years of education, black race and unemployment with baseline disability were associated with abnormal t-MoCA scores 6 months post-hospitalization for COVID-19 [1]. The study is appealing but raises concerns which require discussion. 

Cognitive dysfunction as a feature of post-COVID syndrome at 6 months after the infection will not only depend on the demographics and social determinants of health (SDOH) but also on the type and degree of CNS involvement (neuro-COVID) and the drugs given during or after the acute infection. Thus, cognitive dysfunction cannot be reliably assessed without knowing type and degree of neuro-COVID as assessed by clinical, blood chemical, cerebral imaging and Cerebro-Spinal Fluid (CSF) investigations. Type and extension of structural lesions on cerebral imaging need to be included in the evaluation as most of the cerebral manifestations of neuro-COVID go along with cognitive dysfunction [2]. Accordingly neuro-COVID manifestations such as ischemic stroke, cerebral bleeding, Acute Hemorrhaghic, Necrotising Encephalitis (AHNE), multifocal Posterior Reversible Encephalopathy Syndrome (PRES), Acute, Disseminated Encephalomyelitis (ADEM), Venous Sinus Thrombosis (VST), Reversible, Cerebral Vasoconstriction Syndrome (RCVS), meningitis, encephalitis, neuromyelitis optica, cerebral vasculitis and cerebral hypoxia need to be appropriately excluded by cerebral imaging as a possible cause of cognitive impairment following a SARS-CoV-2 infection.

Missing in the study is the status of SARS-CoV-2 vaccinations. Since SARS-CoV-2 vaccinations are potentially neurotoxic [3] and can be complicated by a myriad of CNS complications, it is crucial to include the vaccination status of each included patient in the evaluation. The most common neurological complications of SARS-CoV-2 vacciantions affecting the CNS include headache, VST, immune encephalitis, multiple sclerosis, neuromyelitis  optica,  stroke,  cerebral  bleeding  and ADEM [3]. 

To reliably asses the influence of SARS-CoV-2 infections on cognitive functions it would be appropriate to investigate COVID-19 patients already during the infection and several times after the acute stage of the infec6tion. Exploration of a COVID-19 patient only once will miss the dynamics and fluctuations of cognitive impairment and thus the influence of co-factors.

Another limitation of the study is that it was carried out by telephone interviews. Disadvantages of telephone interviews are that the identity of the patient remains unconfirmed, that no clinical neurologic exam can or on-site psychiatric exploration can be carried out and that the responsiveness to questions and tasks of a psychological tests will differ between an anonymous remote setting compared with face-to-face interactions.

A further limitation is that the current medication was not included in the assessment of cognitive dysfunction. From several drugs it is known that they can significantly influence cognitive functions (e.g., benzodiazepines, neuroleptics, serotonin-reuptake inhibitors).

Overall, the study has limitations which challenge the results and their interpretation. These limitations should be addressed to strengthen the conclusions. Causality of cognitive dysfunction following a SARS-CoV-2 infection is more widespread than anticipated.