Mathematical modelling of SARS-CoV-2 variant outbreaks reveals their probability of extinction

When a virus spreads, it may mutate into, e.g., vaccine resistant or fast spreading lineages, as was the case for the Danish Cluster-5 mink variant (belonging to the B.1.1.298 lineage), the British B.1.1.7 lineage, and the South African B.1.351 lineage of the SARS-CoV-2 virus. A way to handle such spreads is through a containment strategy, where the population in the affected area is isolated until the spread has been stopped. Under such circumstances, it is important to monitor whether the mutated virus is extinct via massive testing for the virus sub-type. If successful, the strategy will lead to lower and lower numbers of the sub-type, and it will eventually die out. An important question is, for how long time one should wait to be sure the sub-type is extinct? We use a hidden Markov model for infection spread and an approximation of a two stage sampling scheme to infer the probability of extinction. The potential of the method is illustrated via a simulation study. Finally, the model is used to assess the Danish containment strategy when SARS-CoV-2 spread from mink to man during the summer of 2020, including the Cluster-5 sub-type. In order to avoid further spread and mink being a large animal virus reservoir, this situation led to the isolation of seven municipalities in the Northern part of the country, the culling of the entire Danish 17 million large mink population, and a bill to interim ban Danish mink production until the end of 2021

A clinical proteomics study of exhaled breath condensate and biomarkers for pulmonary embolism

Pulmonary Embolism (PE) can be a diagnostic challenge. Current diagnostic markers for PE are unspecific and new diagnostic tools are needed. The air we exhale is a possible new source for biomarkers which can be tapped into by analysing the exhaled breath condensate (EBC). We analysed the EBC from patients with PE and controls to investigate if the EBC is a useful source for new diagnostic biomarkers of PE. We collected and analysed EBC samples from patients with suspected PE and controls matched on age and sex. Patients in whom PE was ruled out after diagnostic work-up were included in the control group to increase the sensitivity and generalizability of the identified markers. EBC samples were collected using an RTube™. The protein composition of the EBCs were analysed using data dependent label-free quantitative nano liquid chromatography-tandem mass spectrometry. EBC samples from 28 patients with confirmed PE, and 49 controls were analysed. A total of 928 EBC proteins were identified in the 77 EBC samples. As expected, a low protein concentration was determined which resulted in many proteins with unmeasurable levels in several samples. The levels of HSPA5, PEBP1 and SFTPA2 were higher and levels of POF1B, EPPK1, PSMA4, ALDOA, and CFL1 were lower in PE compared with controls. In conclusion, the human EBC contained a variety of endogenous proteins and may be a source for new diagnostic markers of PE and other diseases. The project is registered at ClinicalTrials.gov (Identifier NCT04010760).</p

The mutational profile of immune surveillance genes in diagnostic and refractory/relapsed DLBCLs

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoid neoplasm among adults,and approximately 30–40% of patients will experience relapse while 5–10% will suffer from primary refractory disease caused by different mechanisms, including treatment-induced resistance. For refractory and relapsed DLBCL (rrDLBCL) patients, early detection and understanding of the mechanisms controlling treatment resistance are of great importance to guide therapy decisions. Here, we have focused on genetic variations in immune surveillance genes in diagnostic DLBCL (dDLBCL) and rrDLBCL patients to elaborate on the suitability of new promising immunotherapies. METHODS: Biopsies from 30 dDLBCL patients who did not progress or relapse during follow up and 17 rrDLBCL patients with refractory disease or who relapsed during follow up were analyzed by whole-exome sequencing, including matched individual germline samples to include only somatic genetic variants in downstream analysis of a curated list of 58 genes involved in major immune surveillance pathways. RESULTS: More than 70% of both dDLBCLs and rrDLBCLs harbored alterations in immune surveillance genes, but rrDLBCL tumor samples have a lower number of genes affected compared to dDLBCL tumor samples. Increased gene mutation frequencies in rrDLBCLs were observed in more than half of the affected immune surveillance genes than dDLBCLs. CONCLUSION: Genetic variants in the antigen-presenting genes affect a higher number of rrDLBCL patients supporting an important role for these genes in tumor progression and development of refractory disease and relapse. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08556-3