Exercise intolerance is a major manifestation of post-acute sequelae of severe acute respiratory syndrome coronavirus infection (PASC, or “long-COVID”). Exercise intolerance in PASC is associated with higher arterial blood lactate accumulation and lower fatty acid oxidation rates during graded exercise tests to volitional exertion, suggesting altered metabolism and mitochondrial dysfunction. It remains unclear whether the profound disturbances in metabolism that have been identified in plasma from patients suffering from acute coronavirus disease 2019 (COVID-19) are also present in PASC. To bridge this gap, individuals with a history of previous acute COVID-19 infection that did not require hospitalization were enrolled at National Jewish Health (Denver, CO, USA) and were grouped into those that developed PASC (n = 29) and those that fully recovered (n = 16). Plasma samples from the two groups were analyzed via mass spectrometry-based untargeted metabolomics and compared against plasma metabolic profiles of healthy control individuals (n = 30). Observational demographic and clinical data were retrospectively abstracted from the medical record. Compared to plasma of healthy controls or individuals who recovered from COVID-19, PASC plasma exhibited significantly higher free- and carnitine-conjugated mono-, poly-, and highly unsaturated fatty acids, accompanied by markedly lower levels of mono-, di- and tricarboxylates (pyruvate, lactate, citrate, succinate, and malate), polyamines (spermine) and taurine. Plasma from individuals who fully recovered from COVID-19 exhibited an intermediary metabolic phenotype, with milder disturbances in fatty acid metabolism and higher levels of spermine and taurine. Of note, depletion of tryptophan—a hallmark of disease severity in COVID-19—is not normalized in PASC patients, despite normalization of kynurenine levels—a tryptophan metabolite that predicts mortality in hospitalized COVID-19 patients. In conclusion, PASC plasma metabolites are indicative of altered fatty acid metabolism and dysfunctional mitochondria-dependent lipid catabolism. These metabolic profiles obtained at rest are consistent with previously reported mitochondrial dysfunction during exercise, and may pave the way for therapeutic intervention focused on restoring mitochondrial fat-burning capacity.

Objectives: To determine the risk and risk factors for mental illness among colorectal cancer (CRC) survivors across short-and long-term follow-up periods.Methods: We used the Utah Cancer Registry to identify CRC survivors diagnosed between 1997 and 2013. Mental health diagnoses were available in electronic medical records and statewide facilities data that were linked by the Utah Population Database. CRC survivors were matched to individuals from a general population cohort. The risk of developing a mental illness was compared between cohorts. The association between mental illness and mortality was also analyzed.Results: 8,961 CRC survivors and 35,897 individuals in a general population cohort were identified. CRC survivors were at increased risk for any mental health diagnosis at 0-2 years (HR

Background: Eczema herpeticum (EH) is a rare complication of atopic dermatitis (AD) caused by disseminated herpes simplex virus (HSV) infection. The role of rare and/or deleterious genetic variants in disease etiology is largely unknown. This study aimed to identify genes that harbor damaging genetic variants associated with HSV infection in AD with a history of recurrent eczema herpeticum (ADEH+). Methods: Whole genome sequencing (WGS) was performed on 49 recurrent ADEH+ (≥3 EH episodes), 491 AD without a history of eczema herpeticum (ADEH−) and 237 non-atopic control (NA) subjects. Variants were annotated, and a gene-based | 2511 BIN et al. | INTRODUC TI ONAtopic dermatitis (AD) is the most common inflammatory skin disease. 1-6 A subset of AD patients have disseminated herpes simplex virus (HSV) infections, a rare complication known as eczema herpeticum (ADEH+). 7 HSV-1 and HSV-2 are common human pathogens that are often present in latency in human sensory neurons and autonomous ganglions, typically causing mild and self-restricted infections. 8 In ADEH+patients, however, HSV-1 infections lead to 1U19AI117673-01 and 1UM1AI151958; National Center for Advancing Translational Sciences, Grant/Award Number: UL1 TR000154; National Center for Research Resources, Grant/Award Number: UL1 RR025780approach (SKAT-O) was used to identify genes harboring damaging genetic variants associated with ADEH+. Genes identified through WGS were studied for effects on HSV responses and keratinocyte differentiation.

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