Coronavirus disease 2019 and type 1 diabetes mellitus.

PURPOSE OF REVIEW: Type 2 diabetes (T2DM) is a major comorbidity of coronavirus disease 2019 (COVID-19) but less is known about COVID-19 and type 1 diabetes (T1DM). Thus, our goal was to review the literature on COVID and T1DM. RECENT FINDINGS: We identified 21 reports focusing on COVID-19 infections among patients with preexisting T1DM (n = 7), incident T1DM presentations during the COVID-19 quarantine (n = 6), and outpatient management of T1DM during the COVID-19 quarantine (n = 8). These studies showed that patients with preexisting T1DM and COVID-19 infection often present with hyperglycemia and/or diabetic ketoacidosis (DKA). Although the risk of in-hospital mortality may be increased, hospitalization rates among patients with T1DM mirror that of the general population. The numbers of patients presenting with incident T1DM during COVID-19 quarantine have remained stable, but cases with severe DKA may have increased. COVID-19 quarantine has also impacted outpatient T1DM management and studies examining changes in glycemic control have shown mixed results. SUMMARY: COVID-19 has important implications for patients with type 1 diabetes, but additional studies with larger numbers of patients and longer term follow-up are needed to confirm the early findings highlighted in this review.

Competence in Streptococcus pneumoniae is a response to an increasing mutational burden.

Competence for genetic transformation in Streptococcus pneumoniae has previously been described as a quorum-sensing trait regulated by a secreted peptide pheromone. Recently we demonstrated that competence is also activated by reduction in the accuracy of protein biosynthesis. We have now investigated whether errors upstream of translation in the form of random genomic mutations can provide a similar stimulus. Here we show that generation of a mutator phenotype in S. pneumoniae through deletions of mutX, hexA or hexB enhanced the expression of competence. Similarly, chemical mutagenesis with the nucleotide analog dPTP promoted development of competence. To investigate the relationship between mutational load and the activation of competence, replicate lineages of the mutX strain were serially passaged under conditions of relaxed selection allowing random accumulation of secondary mutations. Competence increased with propagation in these lineages but not in control lineages having wild-type mutX. Resequencing of these derived strains revealed between 1 and 9 single nucleotide polymorphisms (SNPs) per lineage, which were broadly distributed across the genome and did not involve known regulators of competence. Notably, the frequency of competence development among the sequenced strains correlated significantly with the number of nonsynonymous mutations that had been acquired. Together, these observations provide support for the hypothesis that competence in S. pneumoniae is regulated in response to the accumulated burden of coding mutations in the bacterial genome. In contrast to previously described DNA damage response systems that are activated by physical lesions in the chromosome, this pneumococcal pathway may represent a unique stress response system that monitors the coding integrity of the genome.