Project description:AimsEarly in the COVID-19 pandemic, evidence emerged suggesting that people with diabetic retinopathy (DR) or other microvascular diseases had greater risk of severe short-term outcomes. This study evaluated longer-term outcomes, providing more generalisable evidence.MethodsWe identified a cohort of UKBiobank participants with diabetes and retrieved their diagnostic codes for a variety of microvascular diseases, complications of diabetes and systemic comorbidities. We investigated relationships between diagnoses and the study outcome: admission to Critical Care or death from COVID-19, taking age, sex and diabetes duration into account. We tested relationships, adding baseline covariates and weighting diagnostic codes according to their recency prior to COVID-19 diagnosis.ResultsIn univariate analyses, DR (OR: 1·519, p = 0·016) and microvascular disease (OR: 2·001, p = 0·000) were associated with greater risk of the outcome. In multivariate analyses, as expected, respiratory disease was most strongly associated with the study outcome, microvascular disease second. Adjusting analyses by number of admissions (general health proxy) and weighted diagnostic coding (comorbidity severity at COVID-19 diagnosis indicator), did not improve predictive power of the model.ConclusionsThe presence of microvascular disease in routinely-collected healthcare data predicts risk of COVID-19 severe outcomes, independently of general health, in a cohort of people with diabetes.
Project description:Manuscript describes the daily dynamics of transcriptional responses in whole blood, from acute to convalescent phase, in severe and non-severe COVID-19 patients.
Project description:Several autopsy studies showed microthrombi in pulmonary circulation of severe COVID-19 patients. The major limitation of these investigations is that the autopsy provided static information. Some of these alterations could be secondary to the disseminated intravascular coagulation (DIC) observed as the final standard route to the multisystem organ failure exhibited in critically ill patients. We report preliminary results of an in vivo evaluation of sublingual microcirculation in thirteen patients with severe COVID-19 requiring mechanical ventilation. We observed multiple filling defects moving within the microvessels indicative of thrombi in most of the cases 11/13 (85%). This is the first imaging documentation of microvascular thrombosis in living severe COVID-19 patients since the beginning of the hospitalization. The clinical relevance of microvascular thrombosis in this disease requires further research.
Project description:Early in the COVID-19 pandemic, type 2 diabetes (T2D) was marked as a risk-factor for severe disease. Inflammation is central to the aetiology of both conditions where immune responses influence disease course. Identifying at-risk groups through immuno-inflammatory signatures can direct personalised care and help develop potential targets for precision therapy. This observational study characterised immunophenotypic variation associated with COVID-19 severity in T2D. Broad-spectrum immunophenotyping quantified 15 leukocyte populations in circulation from a cohort of 45 hospitalised COVID-19 patients with and without T2D. Lymphocytopenia, of CD8+ lymphocytes, was associated with severe COVID-19 and intensive care admission in non-diabetic and T2D patients. A morphological anomaly of increased monocyte size and monocytopenia of classical monocytes were specifically associated with severe COVID-19 in patients with T2D requiring intensive care. Over-expression of inflammatory markers reminiscent of the type-1 interferon pathway underlaid the immunophenotype associated with T2D. These changes may contribute to severity of COVID-19 in T2D. These findings show characteristics of severe COVID-19 in T2D as well as provide evidence that type-1 interferons may be actionable targets for future studies.
Project description:We evaluated the incidence, distribution, and histopathologic correlates of microvascular brain lesions in patients with severe COVID-19. Sixteen consecutive patients admitted to the intensive care unit with severe COVID-19 undergoing brain MRI for evaluation of coma or neurologic deficits were retrospectively identified. Eleven patients had punctate susceptibility-weighted imaging (SWI) lesions in the subcortical and deep white matter, eight patients had >10 SWI lesions, and four patients had lesions involving the corpus callosum. The distribution of SWI lesions was similar to that seen in patients with hypoxic respiratory failure, sepsis, and disseminated intravascular coagulation. Brain autopsy in one patient revealed that SWI lesions corresponded to widespread microvascular injury, characterized by perivascular and parenchymal petechial hemorrhages and microscopic ischemic lesions. Collectively, these radiologic and histopathologic findings add to growing evidence that patients with severe COVID-19 are at risk for multifocal microvascular hemorrhagic and ischemic lesions in the subcortical and deep white matter.
Project description:In order to identify differentially abundant proteins, human plasma samples from COVID-19 patients with either a mild or moderate (MM) or a critical or severe (CS) disease course from acute phase of infection were analyzed on antibody microarrays 998 different proteins by 1,425 antibodies.
Project description:In order to identify differentially abundant proteins, human plasma samples from COVID-19 patients with either a mild or moderate (MM) or a critical or severe (CS) disease course from the acute phases of infection were analyzed on antibody microarrays targeting 351 different proteins by 517 antibodies.
Project description:Analysis of COVID-19 hospitalized patients, with different kind of symptoms, by human rectal swabs collection and 16S sequencing approach.