Activation of the cGAS/STING Axis in Genome-Damaged Hematopoietic Cells Does Not Impact Blood Cell Formation or Leukemogenesis.

Genome damage is a main driver of malignant transformation, but it also induces aberrant inflammation via the cGAS/STING DNA-sensing pathway. Activation of cGAS/STING can trigger cell death and senescence, thereby potentially eliminating genome-damaged cells and preventing against malignant transformation. Here, we report that defective ribonucleotide excision repair (RER) in the hematopoietic system caused genome instability with concomitant activation of the cGAS/STING axis and compromised hematopoietic stem cell function, ultimately resulting in leukemogenesis. Additional inactivation of cGAS, STING, or type I IFN signaling, however, had no detectable effect on blood cell generation and leukemia development in RER-deficient hematopoietic cells. In wild-type mice, hematopoiesis under steady-state conditions and in response to genome damage was not affected by loss of cGAS. Together, these data challenge a role of the cGAS/STING pathway in protecting the hematopoietic system against DNA damage and leukemic transformation. SIGNIFICANCE: Loss of cGAS/STING signaling does not impact DNA damage-driven leukemogenesis or alter steady-state, perturbed or malignant hematopoiesis, indicating that the cGAS/STING axis is not a crucial antioncogenic mechanism in the hematopoietic system. See related commentary by Zierhut, p. 2807.

SARS-CoV-2 Seroprevalence in Preschool and School-Age Children­Population Screening Findings From January 2020 to June 2022

BACKGROUND: The SARS-CoV-2 pandemic is ongoing in Germany. Children and adolescents are increasingly being infected, and many cases presumably remain undetected and unreported. Sero-epidemiological studies can help estimate the true number of infections. METHODS: From January 2020 to June 2022, 59 786 persons aged 1-17 years were tested for SARS-CoV-2 antibodies as part of a screening program for presymptomatic type 1 diabetes in the German federal state of Bavaria (the Fr1da study). RESULTS: In June 2022, the seroprevalence in the overall population was 73.5%. The seroprevalence was significantly higher in school-age children (from 5 to 10 years of age) than in preschool children (ages 1-4): 84.4% vs. 66.6%, p <0.001. In contrast, in November 2021, before the appearance of the omicron variant, the overall seroprevalence was 14.7% (16.2% of school-age children, 13.0% of preschool children, p = 0.06). In the overall collective, seroprevalence increased fivefold from the fall of 2021 to June 2022 (by a factor of 5.2 in school-age children and 5.1 in preschool children). Similar seroprevalences, with smaller case numbers, were observed in June 2022 in the corresponding Fr1da studies in Saxony and Northern Germany: 87.8% and 76.7%, respectively. CONCLUSION: Monthly case counts reveal a substantial rise in SARS-CoV-2-infections among children and adolescents from late 2021 to mid-2022. The high percentage of preschool and school-age children who have been infected with SARS-CoV-2, in a population that has low vaccination coverage, should be taken into account in the development of health policies.