Disease trajectories in hospitalized COVID-19 patients are predicted by clinical and peripheral blood signatures representing distinct lung pathologies. (preprint)

Linking clinical biomarkers and lung pathology still is necessary to understand COVID-19 pathogenesis and the basis of progression to lethal outcomes. Resolving these knowledge gaps enables optimal treatment approaches of severe COVID-19. We present an integrated analysis of longitudinal clinical parameters, blood biomarkers and lung pathology in COVID-19 patients from the Brazilian Amazon. We identified core signatures differentiating severe recovered patients and fatal cases with distinct disease trajectories. Progression to early death was characterized by rapid and intense endothelial and myeloid activation, presence of thrombi, mostly driven by SARS-CoV-2 + macrophages. Progression to late death was associated with systemic cytotoxicity, interferon and Th17 signatures and fibrosis, apoptosis, and abundant SARS-CoV-2 + epithelial cells in the lung. Progression to recovery was associated with pro-lymphogenic and Th2-mediated responses. Integration of antemortem clinical and blood biomarkers with post-mortem lung-specific signatures defined predictors of disease progression, identifying potential targets for more precise and effective treatments.

Assessing glucose-6-phosphate dehydrogenase (G6PD) during COVID-19 requires caution: evidence on the impact of the infection upon enzyme activity (preprint)

Glucose-6 phosphate dehydrogenase deficiency (G6PDd) was suggested as a risk factor of severity in patients with COVID-19. In this article, we assessed the influence of G6PDd on the infection, severity, and clinical progression of patients with COVID-19. This prospective cohort study included adult participants ([≥]18 years old) who had clinical and/or radiological COVID-19 findings or positive RT-PCR results. Epidemiological and clinical data were extracted from electronic medical records. G6PD activity was measured in SD Biosensor STANDARD G6PD(R) equipment at admission and one year after discharge. Samples were genotyped for the three most common single nucleotide polymorphisms (SNPs) for G6PDd in the Brazilian Amazon s1050828, rs1050829 and rs5030868, corresponding to G6PD African A-(G202A, A376G), G6PD African A+(A376G) and G6PD Mediterranean(C563T), respectively. Seven hundred fifty-three patients were included, of which 123 (16.3%) were G6PDd. The G6PDd group had a higher mean hemoglobin, and lower values of C-reactive protein and leukocytes at admission. There was no association between G6PDd and COVID-19 severity, considering that the frequency of G6PDd who needed to be hospitalized (1.9%) or demanding invasive mechanical ventilation (16.0%) or died (21.1%) was lower than G6PD normal patients. Only 29 out of 116 (25%) participants carried the African genotype. Out of 30 participants tested as G6PDd during disease, only 11 (36.7%) results agreed one year after discharge. In conclusion, caution must be taken when G6PDd screening in patients with acute COVID-19.

Covid-19 automated diagnosis and risk assessment through Metabolomics and Machine-Learning (preprint)

COVID-19 is still placing a heavy health and financial burden worldwide. Impairments in patient screening and risk management play a fundamental role on how governments and authorities are directing resources, planning reopening, as well as sanitary countermeasures, especially in regions where poverty is a major component in the equation. An efficient diagnostic method must be highly accurate, while having a cost-effective profile. We combined a machine learning-based algorithm with instrumental analysis using mass spectrometry to create an expeditious platform that discriminate COVID-19 in plasma samples within minutes, while also providing tools for risk assessment, to assist healthcare professionals in patient management and decision-making. A cross-sectional study with 728 patients (369 confirmed COVID-19 and 359 controls) was enrolled from three Brazilian epicentres (Sao Paulo capital, Sao Paulo countryside and Manaus) in the months of April, May, June and July 2020. We were able to elect and identify 21 molecules that are related to the diseases pathophysiology and 26 features to patients health-related outcomes. With specificity >97% and sensitivity >83% from blinded data, this screening approach is understood as a tool with great potential for real-world application.