Vaccines against SARS-CoV-2 are safe to administer in patients with antibodies to pegaspargase.

OBJECTIVE: Allergic reactions to pegaspargase during ALL therapy are typically due to antibodies against polyethylene glycol (PEG), which is also used as a stabilizing agent in mRNA-based SARS-CoV-2 vaccines. To evaluate the safety of these vaccines in patients with anti-pegaspargase antibodies. METHODS: We retrospectively reviewed the records of patients treated for ALL who had received SARS-CoV-2 vaccinations. All patients had antibodies against pegaspargase assayed during ALL therapy prospectively and in response to clinical allergies. Symptoms of intolerance to vaccination were gathered retrospectively from chart abstraction. RESULTS: SARS-CoV-2 vaccination was well tolerated in all 78 patients with prior exposure to pegaspargase as part of their leukemia therapy. No reactions were observed in the 54 patients without a history of anti-pegaspargase antibodies or in 19 patients with antibodies who received mRNA vaccination. 1 patient who received the polysorbate containing Janssen vaccine experienced mild symptoms after vaccination not meeting the criteria of clinical allergy which spontaneously resolved within 25 minutes. CONCLUSION: SARS-CoV-2 vaccination is safe in this population.

Individual-specific functional epigenomics reveals genetic determinants of adverse metabolic effects of glucocorticoids.

Glucocorticoids (GCs) are widely used as anti-inflammatory drugs, but their long-term use has severe metabolic side effects. Here, by treating multiple individual adipose stem cell-derived adipocytes and induced pluripotent stem cell-derived hepatocytes with the potent GC dexamethasone (Dex), we uncovered cell-type-specific and individual-specific GC-dependent transcriptomes and glucocorticoid receptor (GR) cistromes. Individual-specific GR binding could be traced to single-nucleotide polymorphisms (SNPs) that altered the binding motifs of GR or its cooperating factors. We also discovered another set of genetic variants that modulated Dex response through affecting chromatin accessibility or chromatin architecture. Several SNPs that altered Dex-regulated GR binding and gene expression controlled Dex-driven metabolic perturbations. Remarkably, these genetic variations were highly associated with increases in serum glucose, lipids, and body mass in subjects on GC therapy. Knowledge of the genetic variants that predispose individuals to metabolic side effects allows for a precision medicine approach to the use of clinically relevant GCs.