COVID-19-related hyperglycemia is associated with infection of hepatocytes and stimulation of gluconeogenesis.

Occurrence of hyperglycemia upon infection is associated with worse clinical outcome in COVID-19 patients. However, it is still unknown whether SARS-CoV-2 directly triggers hyperglycemia. Herein, we interrogated whether and how SARS-CoV-2 causes hyperglycemia by infecting hepatocytes and increasing glucose production. We performed a retrospective cohort study including patients that were admitted at a hospital with suspicion of COVID-19. Clinical and laboratory data were collected from the chart records and daily blood glucose values were analyzed to test the hypothesis on whether COVID-19 was independently associated with hyperglycemia. Blood glucose was collected from a subgroup of nondiabetic patients to assess pancreatic hormones. Postmortem liver biopsies were collected to assess the presence of SARS-CoV-2 and its transporters in hepatocytes. In human hepatocytes, we studied the mechanistic bases of SARS-CoV-2 entrance and its gluconeogenic effect. SARS-CoV-2 infection was independently associated with hyperglycemia, regardless of diabetic history and beta cell function. We detected replicating viruses in human hepatocytes from postmortem liver biopsies and in primary hepatocytes. We found that SARS-CoV-2 variants infected human hepatocytes in vitro with different susceptibility. SARS-CoV-2 infection in hepatocytes yields the release of new infectious viral particles, though not causing cell damage. We showed that infected hepatocytes increase glucose production and this is associated with induction of PEPCK activity. Furthermore, our results demonstrate that SARS-CoV-2 entry in hepatocytes occurs partially through ACE2- and GRP78-dependent mechanisms. SARS-CoV-2 infects and replicates in hepatocytes and exerts a PEPCK-dependent gluconeogenic effect in these cells that potentially is a key cause of hyperglycemia in infected patients.

Evaluation of Patients with Parkinson's Disease in Intensive Care Units: A Cohort Study.

BACKGROUND: Parkinson's disease affects approximately 1% of the worldwide population older than 60 years. This number is estimated to double by 2030, increasing the global burden of the disease. Patients with Parkinson's disease are hospitalized 1.5 times more frequently and for longer periods than those without the disease, increasing health-related costs. OBJECTIVE: To compare the characteristics and outcome of patients with and without Parkinson's disease admitted to intensive care units (ICUs). METHODS: Historical cohort study of ICU admissions in a Brazilian city over 18 years. All patients with Parkinson's disease identified were matched for age, sex, year, and place of hospitalization with patients without the disease randomly selected from the same database. RESULTS: The study included 231 patients with Parkinson's disease (PD group) and 462 controls without the disease (NPD group). Compared with patients in the NPD group, those in the PD group were more frequently admitted with lower level of consciousness and increased APACHE II severity score but required less frequently vasoactive drugs. In total, 42.4% of the patients in the PD group were admitted to the ICUs due to sepsis or trauma. Although these patients had longer hospital stay, the mortality rates were comparable between groups. Parkinson's disease was not associated with mortality, even when controlled for associated factors of disease severity. CONCLUSION: Although patients with Parkinson's disease were admitted with higher severity scores and remained in the ICU for a longer time, their mortality rate was not higher than that in patients without the disease.