Relative hypercoagulopathy of the SARS-CoV-2 Beta and Delta variants when compared to the less severe Omicron variants is related to TEG parameters, the extent of fibrin amyloid microclots, and the severity of clinical illness. (preprint)

Earlier variants of SARS-CoV-2 have been associated with plasma hypercoagulability (as judged by thromboelastography) and an extensive formation of fibrin amyloid microclots, which are considered to contribute to the pathology of the coronavirus 2019 disease (COVID-19). The newer Omicron variants appear to be far more transmissible, but less virulent, even when taking immunity acquired from previous infections or vaccination into account. We here show that while the clotting parameters associated with Omicron variants are significantly raised over those of healthy, matched controls, they are only raised to levels significantly lower than those seen with more severe variants such as Beta and Delta. We also observed that individuals infected with Omicron variants manifested less extensive microclot formation in platelet poor plasma compared to those harbouring the more virulent variants. The measurement of clotting effects between the different variants acts as a kind of ‘internal control’ that demonstrates the relationship between the extent of coagulopathies and the virulence of the variant of interest. This adds to the evidence that microclots play an important role in determining the severity of symptoms observed in COVID-19.

Lipidomic Signatures Align with Inflammatory Patterns and Outcomes in Critical Illness (preprint)

Alterations in lipid metabolism have the potential to be markers as well as drivers of the pathobiology of acute critical illness. Here, we took advantage of the temporal precision offered by trauma as a common cause of critical illness to identify the dynamic patterns in the circulating lipidome in critically ill humans. The major findings include an early loss of all classes of circulating lipids followed by a delayed and selective lipogenesis in patients destined to remain critically ill. Early in the clinical course, Fresh Frozen Plasma administration led to improved survival in association with preserved lipid levels that related to favorable changes in coagulation and inflammation biomarkers. Late over-representation of phosphatidylethanolamines with critical illness led to the validation of a Lipid Reprogramming Score that was prognostic not only in trauma but also severe COVID-19 patients. Our lipidomic findings provide a new paradigm for the lipid response underlying critical illness.

Development and validation of multivariable machine learning algorithms to predict risk of cancer in symptomatic patients referred urgently from primary care (preprint)

Background Urgent Suspected Cancer (Two Week Wait, 2WW) referrals have improved early cancer detection but are increasingly a major burden on NHS services. This has been exacerbated by the COVID-19 pandemic. Method We developed and validated tests to assess the risk of any cancer for 2WW patients. The tests use routine blood measurements (FBC, U&E, LFTs, tumour markers), combining them using machine learning and statistical modelling. Algorithms were developed and validated for nine 2WW pathways using retrospective data from 371,799 referrals to Leeds Teaching Hospitals Trust (development set 224,669 referrals, validation set 147,130 referrals). A minimum set of blood measurements were required for inclusion, and missing data were modelled internally by the algorithms. Results We present results for two clinical use-cases. In use-case 1, the algorithms identify 20% of patients who do not have cancer and may not need an urgent 2WW referral. In use-case 2, they identify 90% of cancer cases with a high probability of cancer that could be prioritised for review. Conclusions Combining a panel of widely available blood markers produces effective blood tests for cancer for NHS 2WW patients. The tests are affordable, can be deployed rapidly to any NHS pathology laboratory with no additional hardware requirements.

Accelerating COVID-19 Therapeutic Interventions and Vaccines 4 ACUTE