Introduction/Background: The COVID-19 pandemic has resulted in a large number of deaths and has caused a significant increase in population morbidity. This viral infection has been associated with different neurological symptoms and complications that do not have a clear pathophysiological mechanism and exact implications for these patients. Case Presentation: A 40-year-old man with COVID-19 and co-infection with Klebsiella pneumoniae KPC presented extensive pulmonary involvement and required comprehensive management in the intensive care unit (ICU). During his hospitalization, he developed neurological symptoms with evidence of involvement of the corpus callosum, which was attributed to the cytotoxic lesion of the corpus callosum (CLOCC). After several months of interdisciplinary management in the ICU, there was a progressive improvement in his general condition, with discharge from the hospital without significant sequelae, with follow-up images showing complete involvement of the corpus callosum due to what was considered an atypical cytotoxic lesion of the corpus callosum. Conclusion: Imaging features of CLOCCs are known to be temporary, but in the setting of COVID-19, it has not yet been determined if this is true and further studies are needed. Nonetheless, the one-year follow-up of our patient makes us believe that this atypical involvement of the corpus callosum described in severe SARS-CoV-2 infections is not transitory, even if there are no neurologic sequelae.

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