iarjmcrIARJMCRIARJMCR2709-3220https://doi.org/10.47310/iarjmcr.2022.v03i01.011Response to Santos et al., “Risk factors for delirium among SARS-CoV-2 positive veterans”JosefFinstererWe eagerly read the article by Santos et al [1] about a retrospective study of the risk factors for delirium in a cohort of 162 American veterans hospitalised for a SARS-CoV-2 infection between March 1 2020 and April 20 2020 [1]. It was found that length of hospitalisation and newly diagnosed cardiac disease were the only factors increasing the odds for delirium in a logistic regression [1]. The study is appealing but raises concerns which require discussion.  The main limitation of the study is its retrospective design implicating that work up for delirium in each individual patient may have focused on different aspects and investigations with variable results but no results of a defined battery of prospective investigations. A further limitation is that results of cerebral imaging (cerebral computed tomography (CCT), cerebral magnetic resonance imaging (cMRI)), of electroencephalography (EEG) recordings, and cerebro-spinal fluid (CSF) investigation were not included in the study. Several manifestations of neuro-COVID may go along with delirium. These include autoimmune encephalitis, venous sinus thrombosis [2], meningitis [3], ischemic stroke [4], and intra-cerebral bleeding. In a retrospective study of 32 patients with SARS-CoV-2 associated meningitis/encephalitis, 19% of the patients manifested with delirium [3]. In a study of 1017 patients with COVID-19 pneumonia, 16% developed a delirium. Interestingly, 79% of these patients were under mechanical ventilation when delirium was diagnosed. Twenty-three percent of those with a delirium died. Against that, there was no association between respiratory failure and delirium in the index study [1].  Missing are data about how many of the included patients were alcoholics or drug-dependent and developed delirium in the context of a withdrawal syndrome. Missing is the information about the current medication the included patients were taking until admission. Several drugs, particularly benzodiazepines or antidepressants may be associated with delirium in case of immediate discontinuation. Missing is the information about the severity of COVID-19 infection in the 162 included patients [1]. Generally, there is an increased risk of developing delirium among COVID-19 patients requiring mechanical ventilation, patients requiring extra-corporal membrane oxygenation (ECMO), and patients with sepsis, immune thrombocytopenia, or hypercoagulability syndrome.  Missing is the information about the drugs the included patients newly received during hospitalisation. One of the drugs frequently applied for the treatment of COVID-19 is the interleukin (IL)-6 inhibitor tocilizumab. A 70yo male with COVID-pneumonia who was treated off-label with tocilizumab developed a prolonged delirium. Favipiravir has been reported to cause malignant neuroleptic syndrome in some COVID-19 patients which may be associated with delirium. Another drug frequently applied for the treatment of COVID-19 is chloroquine. In a retrospective evaluation of data from the FDA Adverse Event Reporting System (FAERS) database, 520 patients were identified who developed neuropsychiatric adverse events following the use of chloroquine. Using a multilevel model, exposure to chloroquine was associated with high reporting of delirium, amnesia, hallucinations, depression, and loss of consciousness.  Overall, the study has limitations which challenge the results and their interpretation. These limitations should be met to strengthen the conclusions. The number of risk factors for developing delirium during COVUD-19 is higher than presented.  DeclarationsThe authors declare no conflicts of interestNo funding was received Author contributionJF: design, literature search, discussion, first draft, critical commentsInformed consent: was obtainedThe study was approved by the institutional review board