Targeted metabolomics identifies high performing diagnostic and prognostic biomarkers for COVID-19.

Research exploring the development and outcome of COVID-19 infections has led to the need to find better diagnostic and prognostic biomarkers. This cross-sectional study used targeted metabolomics to identify potential COVID-19 biomarkers that predicted the course of the illness by assessing 110 endogenous plasma metabolites from individuals admitted to a local hospital for diagnosis/treatment. Patients were classified into four groups (≈ 40 each) according to standard polymerase chain reaction (PCR) COVID-19 testing and disease course: PCR-/controls (i.e., non-COVID controls), PCR+/not-hospitalized, PCR+/hospitalized, and PCR+/intubated. Blood samples were collected within 2 days of admission/PCR testing. Metabolite concentration data, demographic data and clinical data were used to propose biomarkers and develop optimal regression models for the diagnosis and prognosis of COVID-19. The area under the receiver operating characteristic curve (AUC; 95% CI) was used to assess each models' predictive value. A panel that included the kynurenine: tryptophan ratio, lysoPC a C26:0, and pyruvic acid discriminated non-COVID controls from PCR+/not-hospitalized (AUC = 0.947; 95% CI 0.931-0.962). A second panel consisting of C10:2, butyric acid, and pyruvic acid distinguished PCR+/not-hospitalized from PCR+/hospitalized and PCR+/intubated (AUC = 0.975; 95% CI 0.968-0.983). Only lysoPC a C28:0 differentiated PCR+/hospitalized from PCR+/intubated patients (AUC = 0.770; 95% CI 0.736-0.803). If additional studies with targeted metabolomics confirm the diagnostic value of these plasma biomarkers, such panels could eventually be of clinical use in medical practice.

López-Hernández Y ，Monárrez-Espino J ，Oostdam AH ，Delgado JEC ，Zhang L ，Zheng J ，Valdez JJO ，Mandal R ，González FLO ，Moreno JCB ，Trejo-Medinilla FM ，López JA ，Moreno JAE ，Wishart DS ... -  《Scientific Reports》

Immunometabolic signatures predict risk of progression to sepsis in COVID-19.

Herrera-Van Oostdam AS ，Castañeda-Delgado JE ，Oropeza-Valdez JJ ，Borrego JC ，Monárrez-Espino J ，Zheng J ，Mandal R ，Zhang L ，Soto-Guzmán E ，Fernández-Ruiz JC ，Ochoa-González F ，Trejo Medinilla FM ，López JA ，Wishart DS ，Enciso-Moreno JA ，López-Hernández Y ... -  《PLoS One》

Evaluation of simple and cost-effective immuno- haematological markers to predict outcome in hospitalized severe COVID-19 patients, with a focus on diabetes mellitus - A retrospective study in Andhra Pradesh, India.

COVID-19 pandemic has strained the health infrastructure globally, providing an opportunity to identify cost-effective biomarkers. We aimed to identify simple hematological prognostic markers in hospitalized severe COVID-19 patients with and without diabetes. Retrospective study of RT-PCR confirmed hospitalized severe COVID-19 patients (total: n = 154 patients, including diabetic subset n = 57) were analyzed. Clinically applicable cut-offs were derived using receiver operating characteristic (ROC) curve analysis for total leucocyte count (TLC), absolute neutrophil count (ANC), neutrophil lymphocyte ratio (NLR), and derived neutrophil lymphocyte ratio (dNLR) in order to prognosticate the outcome. Among 154 severe COVID-19 patients, significant association with mortality was seen with respect to TLC(p < 0.001), ANC (p < 0.001), NLR(p < 0.001) and dNLR(p < 0.001). In the total cohort, applicable cut-offs based on ROC curve in predicting outcome were, for TLC 8950 cells/mm3 (area under curve (AUC)-0.764, odds ratio (OR)-7.53), ANC 7679 cells/mm3 (AUC-0.789, OR-8.14), NLR 5.13 (AUC-0.741, OR-4.77), dNLR 3.44 (AUC -0.741, OR-4.43) respectively.In diabetic subset, the cut-offs for TLC was 8950 cells/mm3 (AUC -0.762, OR-14.9), ANC 6510 cells/mm3 (AUC -0.773, OR-16.8), NLR 5.13(AUC -0.678, OR-6) and dNLR 3.25(AUC -0.685, OR-4.7) respectively. In severe COVID-19 patients irrespective of diabetes, a simple, applicable total leucocyte count cut-off, 8950 cells/mm3 , together with easily derived cut-offs for ANC, NLR, dNLR may serve as cost-effective prognosticators of clinical outcome. A normal TLC may be misleading in the intensive care and the above applicable cut-off for TLC serves as an early warning tool for high-risk identification and better in-hospital management. Even with similar or lower cut-offs, diabetics had a higher mortality.

Ramesh J ，Reddy SLS ，Rajesh M ，Varghese J ... -  《-》

Routine laboratory testing to determine if a patient has COVID-19.

Specific diagnostic tests to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and resulting COVID-19 disease are not always available and take time to obtain results. Routine laboratory markers such as white blood cell count, measures of anticoagulation, C-reactive protein (CRP) and procalcitonin, are used to assess the clinical status of a patient. These laboratory tests may be useful for the triage of people with potential COVID-19 to prioritize them for different levels of treatment, especially in situations where time and resources are limited. To assess the diagnostic accuracy of routine laboratory testing as a triage test to determine if a person has COVID-19. On 4 May 2020 we undertook electronic searches in the Cochrane COVID-19 Study Register and the COVID-19 Living Evidence Database from the University of Bern, which is updated daily with published articles from PubMed and Embase and with preprints from medRxiv and bioRxiv. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions. We included both case-control designs and consecutive series of patients that assessed the diagnostic accuracy of routine laboratory testing as a triage test to determine if a person has COVID-19. The reference standard could be reverse transcriptase polymerase chain reaction (RT-PCR) alone; RT-PCR plus clinical expertise or and imaging; repeated RT-PCR several days apart or from different samples; WHO and other case definitions; and any other reference standard used by the study authors. Two review authors independently extracted data from each included study. They also assessed the methodological quality of the studies, using QUADAS-2. We used the 'NLMIXED' procedure in SAS 9.4 for the hierarchical summary receiver operating characteristic (HSROC) meta-analyses of tests for which we included four or more studies. To facilitate interpretation of results, for each meta-analysis we estimated summary sensitivity at the points on the SROC curve that corresponded to the median and interquartile range boundaries of specificities in the included studies. We included 21 studies in this review, including 14,126 COVID-19 patients and 56,585 non-COVID-19 patients in total. Studies evaluated a total of 67 different laboratory tests. Although we were interested in the diagnotic accuracy of routine tests for COVID-19, the included studies used detection of SARS-CoV-2 infection through RT-PCR as reference standard. There was considerable heterogeneity between tests, threshold values and the settings in which they were applied. For some tests a positive result was defined as a decrease compared to normal vaues, for other tests a positive result was defined as an increase, and for some tests both increase and decrease may have indicated test positivity. None of the studies had either low risk of bias on all domains or low concerns for applicability for all domains. Only three of the tests evaluated had a summary sensitivity and specificity over 50%. These were: increase in interleukin-6, increase in C-reactive protein and lymphocyte count decrease. Blood count Eleven studies evaluated a decrease in white blood cell count, with a median specificity of 93% and a summary sensitivity of 25% (95% CI 8.0% to 27%; very low-certainty evidence). The 15 studies that evaluated an increase in white blood cell count had a lower median specificity and a lower corresponding sensitivity. Four studies evaluated a decrease in neutrophil count. Their median specificity was 93%, corresponding to a summary sensitivity of 10% (95% CI 1.0% to 56%; low-certainty evidence). The 11 studies that evaluated an increase in neutrophil count had a lower median specificity and a lower corresponding sensitivity. The summary sensitivity of an increase in neutrophil percentage (4 studies) was 59% (95% CI 1.0% to 100%) at median specificity (38%; very low-certainty evidence). The summary sensitivity of an increase in monocyte count (4 studies) was 13% (95% CI 6.0% to 26%) at median specificity (73%; very low-certainty evidence). The summary sensitivity of a decrease in lymphocyte count (13 studies) was 64% (95% CI 28% to 89%) at median specificity (53%; low-certainty evidence). Four studies that evaluated a decrease in lymphocyte percentage showed a lower median specificity and lower corresponding sensitivity. The summary sensitivity of a decrease in platelets (4 studies) was 19% (95% CI 10% to 32%) at median specificity (88%; low-certainty evidence). Liver function tests The summary sensitivity of an increase in alanine aminotransferase (9 studies) was 12% (95% CI 3% to 34%) at median specificity (92%; low-certainty evidence). The summary sensitivity of an increase in aspartate aminotransferase (7 studies) was 29% (95% CI 17% to 45%) at median specificity (81%) (low-certainty evidence). The summary sensitivity of a decrease in albumin (4 studies) was 21% (95% CI 3% to 67%) at median specificity (66%; low-certainty evidence). The summary sensitivity of an increase in total bilirubin (4 studies) was 12% (95% CI 3.0% to 34%) at median specificity (92%; very low-certainty evidence). Markers of inflammation The summary sensitivity of an increase in CRP (14 studies) was 66% (95% CI 55% to 75%) at median specificity (44%; very low-certainty evidence). The summary sensitivity of an increase in procalcitonin (6 studies) was 3% (95% CI 1% to 19%) at median specificity (86%; very low-certainty evidence). The summary sensitivity of an increase in IL-6 (four studies) was 73% (95% CI 36% to 93%) at median specificity (58%) (very low-certainty evidence). Other biomarkers The summary sensitivity of an increase in creatine kinase (5 studies) was 11% (95% CI 6% to 19%) at median specificity (94%) (low-certainty evidence). The summary sensitivity of an increase in serum creatinine (four studies) was 7% (95% CI 1% to 37%) at median specificity (91%; low-certainty evidence). The summary sensitivity of an increase in lactate dehydrogenase (4 studies) was 25% (95% CI 15% to 38%) at median specificity (72%; very low-certainty evidence). Although these tests give an indication about the general health status of patients and some tests may be specific indicators for inflammatory processes, none of the tests we investigated are useful for accurately ruling in or ruling out COVID-19 on their own. Studies were done in specific hospitalized populations, and future studies should consider non-hospital settings to evaluate how these tests would perform in people with milder symptoms.

Stegeman I ，Ochodo EA ，Guleid F ，Holtman GA ，Yang B ，Davenport C ，Deeks JJ ，Dinnes J ，Dittrich S ，Emperador D ，Hooft L ，Spijker R ，Takwoingi Y ，Van den Bruel A ，Wang J ，Langendam M ，Verbakel JY ，Leeflang MM ，Cochrane COVID-19 Diagnostic Test Accuracy Group ... -  《-》

Untargeted metabolomics of COVID-19 patient serum reveals potential prognostic markers of both severity and outcome.

Roberts I ，Wright Muelas M ，Taylor JM ，Davison AS ，Xu Y ，Grixti JM ，Gotts N ，Sorokin A ，Goodacre R ，Kell DB ... -  《-》