Symptoms that predict positive COVID-19 testing and hospitalization: an analysis of 9,000 patients (preprint)

PurposeTo develop a reliable tool that predicts which patients are most likely to be COVID-19 positive and which ones have an increased risk of hospitalization. MethodsFrom February 2020 to April 2021, trained nurses recorded age, gender, and symptoms in an outpatient COVID-19 testing center. All positive patients were followed up by phone for 14 days or until symptom-free. We calculated the symptoms odds ratio for positive results and hospitalization and proposed a "random forest" machine-learning model to predict positive testing. ResultsA total of 8,998 patients over 16 years old underwent COVID-19 RT-PCR, with 1,914 (21.3%) positives. Fifty patients needed hospitalization (2.6% of positives), and three died (0.15%). Most common symptoms were: cough, headache, sore throat, coryza, fever, myalgia (57%, 51%, 44%, 36%, 35%, 27%, respectively). Cough, fever, and myalgia predicted positive COVID-19 test, while others behaved as protective factors. The best predictors of positivity were fever plus anosmia/ageusia (OR=6.31), and cough plus anosmia/ageusia (OR=5.82), both p<0.0001. Our random forest model had an ROC-AUC of 0.72 (specificity=0.70, sensitivity=0.61, PPV=0.38, NPV=0.86). Having steady fever during the first days of infection and persistent dyspnea increased the risk of hospitalization (OR=6.66, p<0.0001 and OR=3.13, p=0.003, respectively), while anosmia-ageusia (OR=0.36, p=0.009) and coryza (OR=0.31, p=0.014) were protective. ConclusionPresent study and algorithm may help identify patients at higher risk of having SARS-COV-2 (online calculator http://wdchealth.covid-map.com/shiny/calculator/), and also disease severity and hospitalization based on symptoms presence, pattern, and duration, which can help physicians and health care providers.

Time-analysis of COVID-19 dispersion among health care workers and the general population (preprint)

IntroductionHeath care workers with direct (HCW-D) or indirect (HCW-A) patient contact represent 4.2% to 17.8% of COVID-19 cases. We evaluate the temporal COVID-19 infection behavior among HCW-D, HCW-A, and non-HCW. MethodsFrom February 2020 to April 2021, trained nurses recorded age, gender, occupation, and symptoms in a COVID-19 testing outpatient health center. We allocated data into weekly time fractals and calculated the proportion of COVID-19 positive among HCW vs. non-HCW and incorporated an ARFIMA model (traditionally used in weather forecast) to predict future cases of COVID-19. ResultsAmong 8,998 COVID-19 RT-PCR tests, 3,462 (42%) patients were HCW-D, and 933 (11%) were HCW-A. Overall, 1,914 (21.3%) returned positive, representing 27%, 25% and 19% of HCW-D, HCW-A and non-HCW, respectively. HCW-D or HCW-A were significantly more likely to test positive for COVID-19 than non-HCW (OR=1.5, p<0.0001). The percentage of positive to negative test results remained steady over time. In the positive cases, the percentage of HCW to non-HCW declined significantly over time (Mann-Kendal trend test: tau=-0.58, p<0.0001). Our ARFIMA model showed a long-memory infection pattern in the occurrence of new COVID-19 cases lasting for months. Average error was 1.9 cases per week comparing predicted to actual values three months later (May-July 2021). ConclusionHCW have a sustained 50% higher risk of COVID-19 positivity in the pandemic. Time-series analysis showed a long-memory infection pattern with virus spread mainly among HCWs before the general population. The tool http://wdchealth.covid-map.com/shiny/covid-map/ will be updated according to population previous infection and vaccination impact.

Differentially expressed circulating microRNAs in Brazilian patients with COVID-19: a preliminary study on potential biomarkers for diagnosis and severity (preprint)

Background: Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is known that host microRNAs (miRNAs) can be modulated to favor viral infection or to protect the host. Objective: The aim of this study was to identify differentially expressed circulating miRNAs in Brazilian patients with COVID-19 as potential biomarkers for diagnosis and severity. Methods: miRNAs were extracted from the blood plasma of eight patients with COVID-19 (four patients with mild/moderate COVID-19 and four patients with severe/critical COVID-19) and four healthy controls. The patients and controls were matched for sex and age. miRNA expression levels were detected using high-throughput sequencing. Differential miRNA expression and enrichment analyses were further evaluated. Results: A total of 18 human miRNAs were differentially expressed between patients with COVID-19 (n = 8) and controls (n = 4), with 13 significantly upregulated and five significantly downregulated miRNAs. miR-4433b-5p, miR-6780b-3p, miR-6883-3p, miR-320b, miR-7111-3p, miR-4755-3p, miR-320c, and miR-6511a-3p were the most important miRNAs found significantly involved in the PI3K/AKT, Wnt/β-catenin, and STAT3 signaling pathways, which have a crucial role in viral infections. Moreover, 42 miRNAs were differentially expressed between severe/critical patients with COVID-19 (n = 4) and mild/moderate patients with COVID-19 (n = 4). miR-451a, miR-101-3p, miR-185-5p, miR-30d-5p, miR-25-3p, miR-342-3p, miR-30e-5p, miR-150-5p, miR-15b-5p, and miR-29c-3p were the most important miRNAs found to be significantly involved in the Wnt/β-catenin, NF-κβ, and STAT3 signaling pathways, which play crucial roles in immune response and inflammation. Conclusions: Differentially expressed miRNAs found in this study may be used as potential biomarkers for the diagnosis and severity of COVID-19. Larger studies are needed to validate these miRNAs as biomarkers of COVID-19. 

Skin imprints to provide noninvasive metabolic profiling of COVID-19 patients (preprint)

As the current COVID-19 pandemic progresses, more symptoms and signals related to how the disease manifests in the human body arise in the literature. Skin lesions and coagulopathies may be confounding factors on routine care and patient management. We analyzed the metabolic and lipidic profile of the skin from COVID-19 patients using imprints in silica plates as a non-invasive alternative, in order to better understand the biochemical disturbances caused by SARS-CoV-2 in the skin. One hundred and one patients (64 COVID-19 positive patients and 37 control patients) were enrolled in the study from April 2020 to June 2020 during the first wave of COVID-19 in Sao Paulo, Brazil. Fourteen biomarkers were identified related to COVID-19 infection (7 increased and 7 decreased in COVID-19 patients). Remarkably, oleamide has shown promising performance, providing 79.0% of sensitivity on a receiver operating characteristic curve model. Species related to coagulation and immune system maintenance such as phosphatidylserines were decreased in COVID-19 patients; on the other hand, cytokine storm and immunomodulation may be affected by molecules increased in the COVID-19 group, particularly primary fatty acid amides and N-acylethanolamines, which are part of the endocannabinoid system. Our results show that skin imprints may be a useful, noninvasive strategy for COVID-19 screening, by electing a pool of biomarkers with diagnostic potential.

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.