ImportanceSARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals.ObjectiveTo develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections.Design, Setting, and ParticipantsProspective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling.ExposureSARS-CoV-2 infection.Main Outcomes and MeasuresPASC and 44 participant-reported symptoms (with severity thresholds).ResultsA total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months.Conclusions and RelevanceA definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.

Objective Ketogenic diets (KD) are low in carbohydrates and high in fat which force cells to rely more heavily upon mitochondrial oxidation of fatty acids for energy. Cancer cells, relative to normal cells, are believed to exist under a condition of chronic mitochondrial oxidative stress that is compensated for by increases in glucose metabolism to generate reducing equivalents. The current study tests the hypothesis that consuming a KD while receiving concurrent radiation and chemotherapy would be clinically tolerable in locally advanced non-small cell lung (NSCLC) and pancreatic cancer and could potentially exploit cancer cell oxidative metabolism to improve therapeutic outcomes. Methods Mice bearing MIA PaCa-2 pancreatic cancer xenografts were fed either a KD or standard rodent chow, treated with conventionally fractionated radiation (2 Gy / fx), and tumor growth rates were assessed daily. Tumors were assessed for immuno-reactive 4-hydroxy-2-nonenal-(4HNE) modified proteins as a marker of oxidative stress. Based on this and another previously published pre-clinical study, phase I clinical trials in locally advanced NSCLC and pancreatic cancer were initiated combining standard radiation and chemotherapy with a KD (lung 6 weeks duration; pancreas 5 weeks duration). Results Xenograft experiments demonstrated prolonged survival and increased 4HNE modified proteins in animals consuming a KD combined with radiation compared to radiation alone. In the phase I clinical trial, over a period of three years, seven NSCLC subjects enrolled in the study. Of these, four were unable to comply with the diet and withdrew, two completed the study, and one was withdrawn due to a dose limiting toxicity. Over the same time period, two pancreatic cancer patients enrolled in the trial. Of these, one completed the study and the other was withdrawn due to a dose limiting toxicity. Conclusion The pre-clinical experiments demonstrate that a KD increases radiation sensitivity in a pancreatic cancer xenograft model. However, subjects with locally advanced NSCLC and pancreatic cancer receiving concurrent radiation and chemotherapy had suboptimal oral KD compliance and hence poor tolerance.

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The active ingredient in sunless tanning products (STPs) is a simple sugar, dihydroxyacetone (DHA). Several studies have demonstrated that DHA is absorbed within the viable layers of skin and not fully contained within the stratum corneum. Additionally, spray tanning and other aerosolized application methods have increased the risk of internal exposure through mucous membranes and inhalation. Beyond its presence in STPs, DHA also occurs as an endogenous by-product of fructose metabolism, and an excess of DHA in cells can induce advanced glycation end (AGE) products and oxidative stress. Therefore, exogenous and endogenous exposures to DHA may be harmful to cells, and it has already been demonstrated that exogenous exposure to DHA is cytotoxic in immortalized keratinocytes. Still, little is known about the exogenous DHA exposure effects on other skin components. In this study, we explore the effects of exogenous DHA exposure in a human melanoma cell line, A375P. Melanoma cells were sensitive to DHA and displayed a transient burst of reactive oxygen species within an hour of exposure. Cell cycle arrest at G2/M was observed within 24 h of exposure, and apoptosis, monitored by the cleavage of PARP-1 and Caspase-3, was detected within 72 h of exposure to DHA. Together, these demonstrate that exogenous exposure to DHA has cytotoxic effects in our selected cell model and indicates the need to further investigate the exogenous exposure effects of DHA in other relevant exposure models.