In global term, as of November 30, 2020, over 30 million people has been infected by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and more than 10,000,000 of them died of acute organ failure. Our reviews have shown that coronavirus disease 2019 (COVID-19) patients with pneumonia and acute respiratory distress syndrome (ARDS) have life-threatening acute brain dysfunction (ABD), ranging from altered mental status/delirium to stupor/coma. Altered mental status/delirium was the most common manifestation of ABD caused by severe COVID-19. The prevalence of altered mental status and/or delirium was up to 66-79.5%, and prevalence of coma was 10%. The most common clinical type of COVID-19-associated ABD was COVID-19-associated acute stroke including ischemic and hemorrhagic stroke (n > 350 cases), followed by COVID-19-associated encephalopathy (n > 200 cases), and COVID-19-associated central nervous system (CNS) infection (n > 70 cases). According to the Sepsis-3 criteria, we confess that severe COVID-19-associated ABD with ARDS and altered mental status is related to sepsis. Moreover, we also review the diagnosis and treatment of COVID-19-associated ABD with sepsis. In view of the fact that COVID-19 is at the peak of epidemic worldwide, we hope that this review will provide evidence of COVID-19 sepsis threating to the brain dysunction. Thus, recognizing the COVID-19-associated ABD related to sepsis is very important for early empirical combination therapy to survive severe COVID-19.

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