COVID-19 mortality attenuated during widespread Omicron transmission, Denmark, 2020 to 2022

BACKGROUND: It sparked considerable attention from international media when Denmark lifted restrictions against COVID-19 in February 2022 amidst widespread transmission of the new SARS-CoV-2 Omicron variant and a steep rise in reported COVID-19 mortality based on the 30-day COVID-19 death count. AIM: Our aim was to investigate how coincidental infections affected COVID-19 mortality estimates following the introduction of the Omicron variant in late 2021. METHODS: We compared the 30-day COVID-19 death count with the observed mortality using three alternative mortality estimation methods; (i) a mathematical model to correct the 30-day COVID-19 death count for coincidental deaths, (ii) the Causes of Death Registry (CDR) and (iii) all-cause excess mortality. RESULTS: There was a substantial peak in the 30-day COVID-19 death count following the emergence of the Omicron variant in late 2021. However, there was also a substantial change in the proportion of coincidental deaths, increasing from 10–20% to around 40% of the recorded COVID-19 deaths. The high number of 30-day COVID-19 deaths was not reflected in the number of COVID-19 deaths in the CDR and the all-cause excess mortality surveillance. CONCLUSION: Our analysis showed a distinct change in the mortality pattern following the introduction of Omicron in late 2021 with a markedly higher proportion of people estimated to have died with, rather than of, COVID-19 compared with mortality patterns observed earlier in the COVID-19 pandemic. Our findings highlight the importance of incorporating alternative mortality surveillance methods to more correctly estimate the burden of COVID-19 as the pandemic continues to evolve

Mathematical Modeling of MPNs Offers Understanding and Decision Support for Personalized Treatment

(1) Background: myeloproliferative neoplasms (MPNs) are slowly developing hematological cancers characterized by few driver mutations, with JAK2V617F being the most prevalent. (2) Methods: using mechanism-based mathematical modeling (MM) of hematopoietic stem cells, mutated hematopoietic stem cells, differentiated blood cells, and immune response along with longitudinal data from the randomized Danish DALIAH trial, we investigate the effect of the treatment of MPNs with interferon-α2 on disease progression. (3) Results: At the population level, the JAK2V617F allele burden is halved every 25 months. At the individual level, MM describes and predicts the JAK2V617F kinetics and leukocyte- and thrombocyte counts over time. The model estimates the patient-specific treatment duration, relapse time, and threshold dose for achieving a good response to treatment. (4) Conclusions: MM in concert with clinical data is an important supplement to understand and predict the disease progression and impact of interventions at the individual level