Following SARS‐CoV‐2 infection, some patients develop lingering neurologic symptoms of post‐acute sequelae of COVID‐19 (PASC) that commonly include fatigue and “brain fog.” PASC symptoms are also linked with reduced growth hormone (GH) secretion, but GH treatment has not been tested to relieve symptoms. We enrolled 13 adults with neurologic PASC symptoms and peak stimulated GH secretion less than 10 ng/mL (glucagon stimulation) in a pilot study to receive 9 months of daily GH injections and an additional 3 months of off‐treatment assessment. We compared peak stimulated GH secretion at baseline and 12 months and assessed measures of cognition, metabolism, body composition, and physical performance over the first 6 months of treatment. Patient‐reported outcomes of fatigue, quality of life, sleep, and mood were recorded at baseline and compared with timepoints at 6, 9, and 12 months. GH treatment was associated with significantly improved scores for Brief Fatigue Inventory, Multidimensional Fatigue Symptom Inventory, Quality of Life Assessment of Growth Hormone Deficiency in Adults, Profile of Mood States, and Beck Depression Inventory‐II, with no significant change in Pittsburgh Sleep Quality Index. Six months of adjunct GH treatment was not associated with significant changes in cognition, body composition, resting energy expenditure, or physical performance. Peak stimulated GH secretion was not altered at 12 months following 9 months of GH treatment. GH treatment significantly improved neurologic symptoms in PASC patients but cognition, sleep, and physical performance were not significantly altered.

Many cancer patients undergoing treatment experience cancer-related fatigue (CRF). Inflammatory markers are correlated with CRF but are not routinely targeted for treatment. We previously demonstrated in an NIH-funded placebo-controlled, double-blind, randomized clinical trial (NCT00878995, closed to follow-up) that seven weekly injections of 100 mg adjunct testosterone preserved lean body mass in cancer patients undergoing standard-of-care treatment in a hospital setting. Because testosterone therapy can reduce circulating proinflammatory cytokines, we conducted an ancillary analysis to determine if this testosterone treatment reduced inflammatory burden and improved CRF symptoms and health-related quality of life. Randomization was computer-generated and managed by the pharmacy, which dispensed testosterone and placebo in opaque syringes to the administering study personnel. A total of 24 patients were randomized (14 placebo, 10 testosterone), and 21 were included in the primary analysis (11 placebo, 10 testosterone). Testosterone therapy did not ameliorate CRF symptoms (placebo to testosterone difference in predicted mean multidimensional fatigue symptom inventory scores: −5.6, 95% CI: −24.6 to 13.3), improve inflammatory markers, or preserve health-related quality of life and functional measures of performance in late-stage cancer patients.

Phosphodiesterase‐5 inhibitors have beneficial pleiotropic effects and hold promise as adjuvant treatments for cancer, dementia, and other disorders. Sixteen men and women aged 50–60 were administered daily sildenafil/tadalafil for 1 month. We characterized molecular signatures of sildenafil/tadalafil treatment via analyses and multi‐omics integration of the serum metabolome and skeletal muscle proteome and transcriptome. In serum, eicosanoids decreased and arginine biosynthesis pathway components increased following sildenafil/tadalafil. In skeletal muscle following sildenafil, blood vessel development and immune response genes increased, indicating augmented angiogenesis and possible inflammation at proximate biopsy sites. Proteins related to telomere maintenance and protein folding increased, suggesting reduced cellular senescence and cellular stress or functional adaptations. In skeletal muscle following tadalafil, there were no differentially expressed genes, and despite reduction of many proteins there were no enriched biological processes. Notably, sildenafil resulted in a more cohesive and substantial molecular signal in skeletal muscle. Multi‐omics integration for both treatments revealed significant coexpression patterns. Phosphodiesterase‐5 inhibitors showed systemic anti‐inflammatory effects, as indicated by reduced serum levels of pro‐inflammatory eicosanoids. However, this did not translate to immunohistochemical changes. Additional research is warranted to investigate PDE‐5 inhibitor effects on various tissues, which can inform prospective applications for drug repurposing.