Markers of blood-brain barrier disruption increase early and persistently in COVID-19 patients with neurological manifestations

BackgroundCoronavirus disease 2019 (COVID-19) leads to peripheral and central disorders, frequently with neurological implications. Blood-brain barrier disruption (BBBd) has been hypothesized as a mechanisms in the acute phase. We tested whether markers of BBBd, brain injury and inflammation could help identify a blood signature for disease severity and neurological complications. MethodsBiomarkers of BBBd (MMP-9, GFAP), neuronal damage (NFL) and inflammation (PPIA, IL-10, TNF) were measured by SIMOA, AlphaLISA and ELISA, in two COVID-19 patient cohorts with high disease severity (ICU Covid; n=79) and neurological complications (NeuroCovid; n=78), and in two control groups with no COVID-19 history: healthy subjects (n=20) and patients with amyotrophic lateral sclerosis (ALS; n=51). ResultsBiomarkers of BBBd and neuronal damage were high in COVID-19 patients, with levels similar to or higher than in ALS. NeuroCovid patients had lower levels of PPIA but higher levels of MMP-9 than ICU Covid patients. There was evidence of different temporal dynamics in ICU Covid compared to NeuroCovid patients with PPIA and IL-10 levels highest in ICU Covid patients in the acute phase. In contrast, MMP-9 was higher in the acute phase in NeuroCovid patients, with severity-dependency in the long term. We also found clear severity-dependency of NFL and GFAP. ConclusionsThe overall picture points to an increased risk of neurological complications in patients with high levels of biomarkers of BBBd. Our observations may provide hints for therapeutic approaches mitigating BBBd to reduce the neurological damage in the acute phase and potential dysfunction in the long term.

Glycosylated Hemoglobin in Subjects Affected by Iron-Deficiency Anemia

Previous studies have suggested that iron-deficiency anemia affects glycosylated hemoglobin (HbA1c) measurements, but the results were contradictory. We conducted a retrospective case-control study to determine the effects of iron deficiency on HbA1c levels. Starting with the large computerized database of the Italian Hospital of Desio, including data from 2000 to 2016, all non-pregnant individuals older than 12 years of age with at least one measurement of HbA1c, cell blood count, ferritin, and fasting blood glucose on the same date of blood collection were enrolled. A total of 2,831 patients met the study criteria. Eighty-six individuals were diagnosed with iron-deficiency anemia, while 2,745 had a normal iron state. The adjusted means of HbA1c were significantly higher in anemic subjects (5.59% [37.37 mmol/mol]), than those measured in individuals without anemia (5.34% [34.81 mmol/mol]) (P<0.0001). These results suggest that clinicians should be cautious about diagnosing prediabetes and diabetes in individuals with anemia.

No Effect of Serotoninergic Gene Variants on Response to Interpersonal Counseling and Antidepressants in Major Depression

OBJECTIVE: Gene variants within the serotonin pathway have been associated with major depressive disorder (MDD) treatment outcomes, however a possible different modulation on pharmacological or psychological treatments has never been investigated. METHODS: One hundred sixty MDD patients were partially randomized to either inter-personal counseling (IPC) or antidepressants. The primary outcome was remission at week 8. Five serotonergic polymorphisms were investigated (COMT rs4680, HTR1A rs6295, HTR2A rs2224721, HTR2A rs7997012 and SLC6A4 rs421417). RESULTS: IPC (n=43) and antidepressant (n=117) treated patients did not show any difference in remission rates at week 8 (corrected for baseline severity, age and center). None of the studied gene variants impacted on response and remission rates at week 8 neither in the IPC nor in the antidepressant group. An analysis of the whole sample showed a trend of association between rs7997012 AA genotype and a better treatment outcome. CONCLUSION: Our study confirms that IPC is an effective psychological intervention comparable to antidepressants in mild-moderate MDD. Polymorphisms related to the serotonin system did not exert a major effect on clinical outcomes in none of the treatment groups.