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Background and Purpose: Patients with the Coronavirus Disease of 2019 are at increased risk for thrombotic events and mortality. Various anticoagulation regimens are now being considered for these patients. Anticoagulation is known to increase the risk for adverse bleeding events, of which intracranial hemorrhage (ICH) is one of the most feared. We present a retrospective study of 33 patients positive for COVID-19 with neuroimaging-documented ICH and examine anticoagulation use in this population. Methods: Patients over the age of 18 with confirmed COVID-19 and radiographic evidence of ICH were included in this study. Evidence of hemorrhage was confirmed and categorized by a fellowship trained neuroradiologist. Electronic health records were analyzed for patient information including demographic data, medical history, hospital course, laboratory values, and medications. Results: We identified 33 COVID-19 positive patients with ICH, mean age 61.6 years (range 37À83 years), 21.2% of whom were female. Parenchymal hemorrhages with mass effect and herniation occurred in 5 (15.2%) patients, with a 100% mortality rate. Of the remaining 28 patients with ICH, 7 (25%) had punctate hemorrhages, 17 (60.7%) had small-moderate size hemorrhages, and 4 (14.3%) had a large single site of hemorrhage without evidence of herniation. Almost all patients received either therapeutic dose anticoagulation (in 22 [66.7%] patients) or prophylactic dose (in 3 [9.1] patients) prior to ICH discovery. Conclusions: Anticoagulation therapy may be considered in patients with COVID-19 though the risk of ICH should be taken into account when developing a treatment regimen.

Summary Brain swelling is the major predictor of mortality in pediatric cerebral malaria (CM). However, the mechanisms leading to swelling remain poorly defined. Here, we combined neuroimaging, parasite transcript profiling, and laboratory blood profiles to develop machine learning models of malarial retinopathy and brain swelling. We found that parasite var transcripts encoding endothelial protein C receptor (EPCR) binding domains, in combination with high parasite biomass and low platelet levels, are strong indicators of CM cases with malarial retinopathy. Swelling cases presented low platelet levels and increased transcript abundance of parasite PfEMP1 DC8 and group A EPCR-binding domains. Remarkably, the dominant transcript in 50% of swelling cases encoded PfEMP1 group A CIDRα1.7 domains. Furthermore, a recombinant CIDRα1.7 domain from a pediatric CM brain autopsy inhibited the barrier protective properties of EPCR in human brain endothelial cells in vitro. Together, these findings suggest a detrimental role for EPCR-binding CIDRα1 domains in brain swelling.

Phytoestrogens and PCBs are environmental exposures that may delay breast development, especially in conjunction with BMI, which governs the endogenous hormonal milieu. Further research to confirm these findings may improve our understanding of the role of early life development in breast cancer risk and other chronic diseases related to obesity.

Cerebral malaria (CM) is a major contributor to malaria deaths, but its pathophysiology is not well understood. While sequestration of parasitized erythrocytes is thought to be critical, the roles of inflammation and coagulation are controversial. In a large series of Malawian children hospitalized with CM, HIV coinfection was more prevalent than in pediatric population estimates (15% versus 2%, P < 0.0001, chi-square test), with higher mortality than that seen in HIV-uninfected children (23% versus 17%, P = 0.0178, chi-square test). HIV-infected (HIV+) children with autopsy-confirmed CM were older than HIV-uninfected children (median age, 99 months versus 32 months, P = 0.0007, Mann-Whitney U test) and appeared to lack severe immunosuppression. Because HIV infection is associated with dysregulated inflammation and platelet activation, we performed immunohistochemistry analysis for monocytes, platelets, and neutrophils in brain tissue from HIV+ and HIV-uninfected children with fatal CM. Children with autopsy-confirmed CM had significantly (>9 times) more accumulations of intravascular monocytes and platelets, but not neutrophils, than did children with nonmalarial causes of coma. The monocyte and platelet accumulations were significantly (>2-fold) greater in HIV+ children than in HIV-uninfected children with autopsy-confirmed CM. Our findings indicate that HIV is a risk factor for CM and for death from CM, independent of traditional measures of HIV disease severity. Brain histopathology supports the hypotheses that inflammation and coagulation contribute to the pathogenesis of pediatric CM and that immune dysregulation in HIV+ children exacerbates the pathological features associated with CM.Importance  There are nearly 1 million malaria deaths yearly, primarily in sub-Saharan African children. Cerebral malaria (CM), marked by coma and sequestered malaria parasites in brain blood vessels, causes half of these deaths, although the mechanisms causing coma and death are uncertain. Sub-Saharan Africa has a high HIV prevalence, with 3 million HIV-infected (HIV+) children, but the effects of HIV on CM pathogenesis and mortality are unknown. In a study of pediatric CM in Malawi, HIV prevalence was high and CM-attributed mortality was higher in HIV+ than in HIV-uninfected children. Brain pathology in children with fatal CM was notable not only for sequestered malaria parasites but also for intravascular accumulations of monocytes and platelets that were more severe in HIV+ children. Our findings raise the possibility that HIV+ children at risk for malaria may benefit from targeted malaria prophylaxis and that adjunctive treatments targeting inflammation and/or coagulation may improve CM outcomes.

Background Evidence suggests that individuals with history of substance use disorder (SUD) are at increased risk of COVID-19, but little is known about relationships between SUDs, overdose and COVID-19 severity and mortality. This study investigated risks of severe COVID-19 among patients with SUDs. Methods We conducted a retrospective review of data from a hospital system in New York City. Patient records from 1 January to 26 October 2020 were included. We assessed positive COVID-19 tests, hospitalizations, intensive care unit (ICU) admissions and death. Descriptive statistics and bivariable analyses compared the prevalence of COVID-19 by baseline characteristics. Logistic regression estimated unadjusted and sex-, age-, race- and comorbidity-adjusted odds ratios (AORs) for associations between SUD history, overdose history and outcomes. Results Of patients tested for COVID-19 ( n = 188 653), 2.7% ( n = 5107) had any history of SUD. Associations with hospitalization [AORs (95% confidence interval)] ranged from 1.78 (0.85–3.74) for cocaine use disorder (COUD) to 6.68 (4.33–10.33) for alcohol use disorder. Associations with ICU admission ranged from 0.57 (0.17–1.93) for COUD to 5.00 (3.02–8.30) for overdose. Associations with death ranged from 0.64 (0.14–2.84) for COUD to 3.03 (1.70–5.43) for overdose. Discussion Patients with histories of SUD and drug overdose may be at elevated risk of adverse COVID-19 outcomes.

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BLI is a noninvasive technique that is useful for screening potential drugs and candidate vaccines with which to combat malaria. The prospect of cross-stage protective immunity increases the number of avenues to be explored in the development of an effective vaccine against malaria.