Cerebral Microvascular Injury in Severe COVID-19

Structured AbstractO_ST_ABSImportanceC_ST_ABSCerebral microvascular lesions are common in patients with severe COVID-19. Radiologic-pathologic correlation in one case suggests a combination of microvascular hemorrhagic and ischemic lesions that may reflect an underlying hypoxic mechanism of injury, which requires validation in larger studies. ObjectiveTo determine the incidence, distribution, and clinical and histopathologic correlates of microvascular lesions in patients with severe COVID-19. DesignObservational, retrospective cohort study: March to May 2020. SettingSingle academic medical center. ParticipantsConsecutive patients (n=16) admitted to the intensive care unit with severe COVID-19, undergoing brain MRI for evaluation of coma or focal neurologic deficits. ExposuresNot applicable. Main Outcome and MeasuresHypointense microvascular lesions identified by a prototype ultrafast high-resolution susceptibility-weighted imaging (SWI) MRI sequence, counted by two neuroradiologists and categorized by neuroanatomic location. Clinical and laboratory data (most recent measurements before brain MRI). Brain autopsy and cerebrospinal fluid PCR for SARS-CoV-2 in one patient who died from severe COVID-19. ResultsEleven of 16 patients (69%) had punctate and linear SWI lesions in the subcortical and deep white matter, and eight patients (50%) had >10 SWI lesions. In 4/16 patients (25%), lesions involved the corpus callosum. Brain autopsy in one patient revealed that SWI lesions corresponded to widespread microvascular injury, characterized by perivascular and parenchymal petechial hemorrhages and microscopic ischemic lesions. Conclusions and RelevanceSWI lesions are common in patients with neurological manifestations of severe COVID-19 (coma and focal neurologic deficits). The distribution of lesions is similar to that seen in patients with hypoxic respiratory failure, sepsis, and disseminated intravascular coagulation. Collectively, these radiologic and histopathologic findings suggest that patients with severe COVID-19 are at risk for multifocal microvascular hemorrhagic and ischemic lesions in the subcortical and deep white matter. Key Points SectionO_ST_ABSQuestionC_ST_ABSWhat is the prevalence and pathophysiology of cerebral microvascular injury in patients with severe COVID-19? FindingsIn this retrospective cohort study of 16 patients undergoing MRI for neurologic complications of severe COVID-19, microvascular lesions were observed in 11 patients and showed an anatomic distribution similar to that seen in patients with hypoxic respiratory failure and sepsis. In one patient who died, brain autopsy revealed widespread microvascular injury, including perivascular microhemorrhages and microscopic ischemic lesions. MeaningMicrovascular injury is common in patients with severe COVID-19. Radiologic-pathologic correlation, though limited to a single case, provides insights into possible mechanisms of injury.

COVID-19 Outpatient Screening: a Prediction Score for Adverse Events

BackgroundWe sought to develop an automatable score to predict hospitalization, critical illness, or death in patients at risk for COVID-19 presenting for urgent care during the Massachusetts outbreak. MethodsSingle-center study of adult outpatients seen in respiratory illness clinics (RICs) or the emergency department (ED), including development (n = 9381, March 7-May 2) and prospective (n = 2205, May 3-14) cohorts. Data was queried from Partners Enterprise Data Warehouse. Outcomes were hospitalization, critical illness or death within 7 days. We developed the COVID-19 Acuity Score (CoVA) using automatically extracted data from the electronic medical record and learning-to-rank ordinal logistic regression modeling. Calibration was assessed using predicted-to-observed ratio (E/O). Discrimination was assessed by C-statistics (AUC). ResultsIn the development cohort, 27.3%, 7.2%, and 1.1% of patients experienced hospitalization, critical illness, or death, respectively; and in the prospective cohort, 26.1%, 6.3%, and 0.5%. CoVA showed excellent performance in the development cohort (concurrent validation) for hospitalization (E/O: 1.00, AUC: 0.80); for critical illness (E/O: 1.00, AUC: 0.82); and for death (E/O: 1.00, AUC: 0.87). Performance in the prospective cohort (prospective validation) was similar for hospitalization (E/O: 1.01, AUC: 0.76); for critical illness (E/O 1.03, AUC: 0.79); and for death (E/O: 1.63, AUC=0.93). Among 30 predictors, the top five were age, diastolic blood pressure, blood oxygen saturation, COVID-19 testing status, and respiratory rate. ConclusionsCoVA is a prospectively validated automatable score to assessing risk for adverse outcomes related to COVID-19 infection in the outpatient setting.

Development of a Triplet-Triplet Absorption Ruler: DNA- and Chromatin-Mediated Drug Molecule Release from a Nanosurface.

Triplet-triplet (T-T) absorption spectroscopy has been used successfully as a molecular ruler to understand the actual release process of sanguinarine as a drug molecule from a gold nanoparticle surface in the presence of cell components, that is, DNA and chromatin. The obtained results have been verified by fluorescence and surface-enhanced Raman spectroscopy (SERS), and a plausible explanation has been put forward to describe the underestimation and overestimation of the percentage (%) of the release of drug molecules measured by fluorescence- and SERS-based techniques, respectively, over the highlighted T-T absorption spectroscopy. Because of the intrinsic nature of absorption, the reported T-T absorption spectroscopic assay overpowers fluorescence- and SERS-based assays, which are limited by the long-range interaction and nonlinear dependence of the concentration of analytes, respectively.