Critical illness-associated cerebral microbleeds for patients with severe COVID-19: etiologic hypotheses

Abstract

Background and purpose During the COVID-19 outbreak, the presence of extensive white matter microhemorrhages was detected by brain MRIs. The goal of this study was to investigate the origin of this atypical hemorrhagic complication. Methods Between March 17 and May 18, 2020, 80 patients with severe COVID-19 infections were admitted for acute respiratory distress syndrome to intensive care units at the University Hospitals of Strasbourg for whom a brain MRI for neurologic manifestations was performed. 19 patients (24%) with diffuse microhemorrhages were compared to 18 control patients with COVID-19 and normal brain MRI. Results The first hypothesis was hypoxemia. The latter seemed very likely since respiratory failure was longer and more pronounced in patients with microhemorrhages (prolonged endotracheal intubation (p = 0.0002), higher FiO 2 (p = 0.03), increased use of extracorporeal membrane oxygenation (p = 0.04)). A relevant hypothesis, the role of microangiopathy, was also considered, since patients with microhemorrhages presented a higher increase of the D-Dimers (p = 0.01) and a tendency to more frequent thrombotic events (p = 0.12). Another hypothesis tested was the role of kidney failure, which was more severe in the group with diffuse microhemorrhages (higher creatinine level [median of 293 µmol/L versus 112 µmol/L, p = 0.04] and more dialysis were introduced in this group during ICU stay [12 versus 5 patients, p = 0.04]). Conclusions Blood-brain barrier dysfunction secondary to hypoxemia and high concentration of uremic toxins seems to be the main mechanism leading to critical illness-associated cerebral microbleeds, and this complication remains to be frequently described in severe COVID-19 patients.

Neurologic Injury in Patients With COVID-19 Who Receive VV-ECMO Therapy: A Cohort Study

“… 4 Lersy et al found that CMBs in COVID-19 patients were significantly associated with high D-dimer levels. 15 These findings are consistent with our study, showing significantly higher D-dimer levels and SOFA scores in patients with neurological events vs. those without ( Table 3 ).…”

Cerebrovascular Complications and Vessel Wall Imaging in COVID-19 Encephalopathy—A Pilot Study

“…The pattern of the microbleeds distribution is unspecific in patients with COVID-19 encephalopathy and does not follow those reported in patients with amyloid angiopathy [19], in patients with hypertension [20] or in patients with critical illnesses [21]. Hypoxemia and high concentration of uremic toxins leading to BBB dysfunction in patients with COVID-19 have been suggested as the main mechanism leading to cerebral microbleeds in COVID-19 and may explain this atypical pattern of distribution and this increased prevalence of microbleeds [22].…”

Intracranial microhemorrhages in the setting of COVID-19: what we know so far

“…26 To address this, Lersy et al compared the clinical characteristics of patients with COVID-19 that had either (a) a normal brain MRI or (b) extensive white matter microhemorrhages. 27 The authors found that the patients with intracranial microhemorrhages were intubated for a longer period of time on average (24 days compared to 8 days, respectively; P¼0.0002), required higher levels of fractional inspired oxygen (FiO 2 ) (100% vs. 75%, respectively; P ¼ 0.03), and were more likely to be on ECMO (five patients versus no patients, respectively; P¼0.04). These findings would seem to indicate that at least some of the observed abnormalities are related to microhemorrhages of critical illness, rather than necessarily being specific to COVID-19.…”