Towards risk stratification and prediction of disease severity and mortality in COVID-19: Next generation metabolomics for the measurement of host response to COVID-19 infection

This study investigated the association between COVID-19 infection and host metabolic signatures as prognostic markers for disease severity and mortality. We enrolled 82 patients with RT-PCR confirmed COVID-19 infection who were classified as mild, moderate, or severe/critical based upon their WHO clinical severity score and compared their results with 31 healthy volunteers. Data on demographics, comorbidities and clinical/laboratory characteristics were obtained from medical records. Peripheral blood samples were collected at the time of clinical evaluation or admission and tested by quantitative mass spectrometry to characterize metabolic profiles using selected metabolites. The findings in COVID-19 (+) patients reveal changes in the concentrations of glutamate, valeryl-carnitine, and the ratios of Kynurenine/Tryptophan (Kyn/Trp) to Citrulline/Ornithine (Cit/Orn). The observed changes may serve as predictors of disease severity with a (Kyn/Trp)/(Cit/Orn) Receiver Operator Curve (ROC) AUC = 0.95. Additional metabolite measures further characterized those likely to develop severe complications of their disease, suggesting that underlying immune signatures (Kyn/Trp), glutaminolysis (Glutamate), urea cycle abnormalities (Cit/Orn) and alterations in organic acid metabolism (C5) can be applied to identify individuals at the highest risk of morbidity and mortality from COVID-19 infection. We conclude that host metabolic factors, measured by plasma based biochemical signatures, could prove to be important determinants of Covid-19 severity with implications for prognosis, risk stratification and clinical management.

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Current Status of a Medical Information System

Methods of Information in Medicine ◽

10.1055/s-0038-1636005 ◽

1970 ◽

Vol 09 (03) ◽

pp. 149-160 ◽

Cited By ~ 1

Author(s):

E. Van Brunt ◽

L. S. Davis ◽

J. F. Terdiman ◽

S. Singer ◽

E. Besag ◽

...

Keyword(s):

Information System ◽

Medical Records ◽

Medical Information ◽

Clinical Laboratory ◽

Development Program ◽

Medical Data ◽

Direct Access ◽

Medical Information System ◽

Current Status ◽

Central System

A pilot medical information system is being implemented and currently is providing services for limited categories of patient data. In one year, physicians’ diagnoses for 500,000 office visits, 300,000 drug prescriptions for outpatients, one million clinical laboratory tests, and 60,000 multiphasic screening examinations are being stored in and retrieved from integrated, direct access, patient computer medical records.This medical information system is a part of a long-term research and development program. Its major objective is the development of a multifacility computer-based system which will support eventually the medical data requirements of a population of one million persons and one thousand physicians. The strategy employed provides for modular development. The central system, the computer-stored medical records which are therein maintained, and a satellite pilot medical data system in one medical facility are described.

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Disorders of Organic Acid Metabolism

Scandinavian Journal of Clinical and Laboratory Investigation ◽

10.3109/00365518809168515 ◽

1988 ◽

Vol 48 ◽

pp. 78-78

Author(s):

L. Dorland ◽

M. Duran ◽

J. B. C. de Klerk ◽

F. J. Van Sprang ◽

S. K. Wadman

Keyword(s):

Organic Acid ◽

Acid Metabolism ◽

Organic Acid Metabolism

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Viral Dynamics and Real-Time RT-PCR Ct Values Correlation with Disease Severity in COVID-19

Diagnostics ◽

10.3390/diagnostics11061091 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1091

Author(s):

Ali A. Rabaan ◽

Raghavendra Tirupathi ◽

Anupam A Sule ◽

Jehad Aldali ◽

Abbas Al Mutair ◽

...

Keyword(s):

Viral Load ◽

Real Time ◽

Disease Severity ◽

False Negative ◽

Influential Factors ◽

Confirmatory Test ◽

Acid Extraction ◽

Rt Pcr ◽

Viral Kinetics ◽

Ct Value

Real-time RT-PCR is considered the gold standard confirmatory test for coronavirus disease 2019 (COVID-19). However, many scientists disagree, and it is essential to understand that several factors and variables can cause a false-negative test. In this context, cycle threshold (Ct) values are being utilized to diagnose or predict SARS-CoV-2 infection. This practice has a significant clinical utility as Ct values can be correlated with the viral load. In addition, Ct values have a strong correlation with multiple haematological and biochemical markers. However, it is essential to consider that Ct values might be affected by pre-analytic, analytic, and post-analytical variables such as collection technique, specimen type, sampling time, viral kinetics, transport and storage conditions, nucleic acid extraction, viral RNA load, primer designing, real-time PCR efficiency, and Ct value determination method. Therefore, understanding the interpretation of Ct values and other influential factors could play a crucial role in interpreting viral load and disease severity. In several clinical studies consisting of small or large sample sizes, several discrepancies exist regarding a significant positive correlation between the Ct value and disease severity in COVID-19. In this context, a revised review of the literature has been conducted to fill the knowledge gaps regarding the correlations between Ct values and severity/fatality rates of patients with COVID-19. Various databases such as PubMed, Science Direct, Medline, Scopus, and Google Scholar were searched up to April 2021 by using keywords including “RT-PCR or viral load”, “SARS-CoV-2 and RT-PCR”, “Ct value and viral load”, “Ct value or COVID-19”. Research articles were extracted and selected independently by the authors and included in the present review based on their relevance to the study. The current narrative review explores the correlation of Ct values with mortality, disease progression, severity, and infectivity. We also discuss the factors that can affect these values, such as collection technique, type of swab, sampling method, etc.

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1410. Neonatal Herpes Simplex Virus (HSV) Infection: Is It the Only Pathogen?

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1592 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S712-S713

Author(s):

Alvaro Dendi ◽

Ingrith Viviana Hoyos Garcia ◽

Asuncion Mejias ◽

Cory T Hanlon ◽

Pablo J Sanchez

Keyword(s):

Medical Records ◽

Viral Infections ◽

Clinical Laboratory ◽

Central Nervous System Infection ◽

Panel Member ◽

Outcome Data ◽

Viridans Streptococci ◽

Review Panel ◽

Co Detection ◽

Neonatal Herpes Simplex

Abstract Background Neonatal HSV infection is associated with substantial morbidity and mortality. Therefore, prompt identification and treatment of infected neonates is paramount. At Nationwide Children’s Hospital (NCH), Columbus, OH all neonates admitted in the first 2 weeks (up to 2010) and 4 weeks (since 2010) of age are evaluated for HSV infection in addition to routine bacterial and other viral infections. The frequency of co-infection with HSV and other potential pathogens is not fully known. Methods Retrospective review of the medical records of infants admitted to NCH with a diagnosis of neonatal HSV infection from 2001 to 2019. Patients less than 6 weeks of age were identified by review of the NCH Virology and Molecular Laboratory results for all positive HSV PCRs obtained from any body site as well as by discharge ICD-9 and ICD-10 codes for HSV infection. Medical records were reviewed for demographic, clinical, laboratory, outcome data, and maternal history of genital HSV lesions at or before delivery. Occurrence of positive bacterial and/or viral co-detection were identified. The data were managed using REDCap electronic data capture tools hosted at NCH. Results There were 93 infants with neonatal HSV infection (mean age, 9.5 days [IQR, 7-15]; 42%, HSV1; 53%, HSV-2). 32 infants had central nervous system infection (CNS) while 31 had Skin-Eye-Mouth (SEM) infection and 30 had Disseminated Disease. Mortality was 15% (n=14). Only 3 mothers had active genital HSV lesions at delivery. Of the 93 infants, 5 (5%) had bacterial (n=2) or viral (n=3) co-infections. All of the infants only had mucosal sites positive for HSV 1 (n=4) or 2 (n=1). Of the 2 infants with bacterial infection, 1 had bacteremia due to viridans streptococci while the other one had necrotizing enterocolitis and a positive blood culture for Clostridium butyricum. The 3 infants with viral co-detection also were full term and all had positive enterovovirus PCR tests (1, blood, throat; 1, blood and ceerebrospinal fluid (CSF); 1, CSF) Conclusion 5% of infants with neonatal HSV infection had bacterial or enteroviral co-infection. These findings have important implications in the management of neonates evaluated for possible sepsis. Disclosures Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Advisor or Review Panel member)Roche (Advisor or Review Panel member)

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HPV Strain Predicts Severity of Juvenile-Onset Recurrent Respiratory Papillomatosis with Implications for Disease Screening

Cancers ◽

10.3390/cancers13112556 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2556

Author(s):

Mary C. Bedard ◽

Alessandro de Alarcon ◽

Yann-Fuu Kou ◽

David Lee ◽

Alexandra Sestito ◽

...

Keyword(s):

Gene Expression ◽

Disease Severity ◽

Disease Onset ◽

Tissue Bank ◽

Benign Neoplasm ◽

Recurrent Respiratory Papillomatosis ◽

Clinical Severity ◽

Viral Gene ◽

Juvenile Onset ◽

Severity Scores

Juvenile-onset recurrent respiratory papillomatosis (JoRRP) is the most common benign neoplasm of the larynx in children, presenting with significant variation in clinical course and potential for progression to malignancy. Since JoRRP is driven by human papillomavirus (HPV), we evaluated viral factors in a prospective cohort to identify predictive factors of disease severity. Twenty children with JoRRP undergoing routine debridement of papillomas were recruited and followed for ≥1 year. Demographical features, clinical severity scores, and surgeries over time were tabulated. Biopsies were used to establish a tissue bank and primary cell cultures for HPV6 vs. HPV11 genotyping and evaluation of viral gene expression. We found that patients with HPV11+ disease had an earlier age at disease onset, higher frequency of surgeries, increased number of lifetime surgeries, and were more likely to progress to malignancy. However, the amplitude of viral E6/E7 gene expression did not account for increased disease severity in HPV11+ patients. Determination of HPV strain is not routinely performed in the standard of care for JoRRP patients; we demonstrate the utility and feasibility of HPV genotyping using RNA-ISH for screening of HPV11+ disease as a biomarker for disease severity and progression in JoRRP patients.

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Current Perspectives on Neonatal Screening for Propionic Acidemia in Japan: An Unexpectedly High Incidence of Patients with Mild Disease Caused by a Common PCCB Variant

International Journal of Neonatal Screening ◽

10.3390/ijns7030035 ◽

2021 ◽

Vol 7 (3) ◽

pp. 35

Author(s):

Go Tajima ◽

Reiko Kagawa ◽

Fumiaki Sakura ◽

Akari Nakamura-Utsunomiya ◽

Keiichi Hara ◽

...

Keyword(s):

Neonatal Screening ◽

Acid Metabolism ◽

Neonatal Period ◽

Propionic Acidemia ◽

Cardiac Complications ◽

Mild Disease ◽

Follow Up Study ◽

Organic Acid Metabolism ◽

High Incidence

Propionic acidemia (PA) is a disorder of organic acid metabolism which typically presents with acute encephalopathy-like symptoms associated with metabolic acidosis and hyperammonemia during the neonatal period. The estimated incidence of symptomatic PA in Japan is 1/400,000. The introduction of neonatal screening using tandem mass spectrometry has revealed a far higher disease frequency of approximately 1/45,000 live births due to a prevalent variant of c.1304T>C (p.Y435C) in PCCB, which codes β-subunit of propionyl-CoA carboxylase. Our questionnaire-based follow-up study reveals that most of these patients remain asymptomatic. However, reports on symptomatic patients exhibiting cardiac complications such as cardiomyopathy and QT prolongation have been increasing. Moreover, there were even cases in which these cardiac complications were the only symptoms related to PA. A currently ongoing study is investigating the risk of cardiac complications in patients with neonatal screening-detected PA caused by this common variant.

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440. Clinical Characteristics of Early Noncritical Hospitalized Patients with Coronavirus Disease 2019 (COVID-19): A Single-Center Retrospective Study in New York City

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.633 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S287-S288

Author(s):

Michelle Lee ◽

Mona Fayad ◽

Tarub Mabud ◽

Paulino Tallon de Lara ◽

Adiac Espinosa Hernandez ◽

...

Keyword(s):

New York ◽

New York City ◽

York City ◽

Clinical Laboratory ◽

Clinical Symptoms ◽

New York State ◽

General Medicine ◽

Retrospective Chart Review ◽

Clinical Severity ◽

Study Cohort

Abstract Background COVID-19 first originated in Wuhan, China, in December 2019. As of April 9, 2020, New York State had become the single largest global epicenter of COVID-19. Methods This is a retrospective chart review of the first 33 patients with RT-PCR-confirmed COVID-19 admitted from the emergency department to a general medicine unit in a single academic hospital in New York City between March 11th to March 27th, 2020. Patient’s demographic, clinical, laboratory, radiographic investigations, treatments and clinical outcomes were retrospectively extracted from the electronic medical record and followed until April 10th, 2020. Patients were divided into severe and nonsevere sub-cohorts. Statistics were descriptive in nature. Results The study cohort (median age 68 yr, 67% male) presented with subjective fevers (82%), cough (88%), and dyspnea (76%). The median incubation period was 3 days. Most cases met SIRS criteria upon admission (76%). Patients had elevated inflammatory markers. Patients were treated with antimicrobials, corticosteroids, hydroxychloroquine, and varying levels of supplemental oxygen. Mortality was 15% and 18% of the cohort required intensive care services. Conclusion Patient age, presenting clinical symptoms, comorbidity profile, laboratory biomarkers, and radiographic features are consistent with findings published from China. Severe patients had peaks in inflammatory biomarkers later in the hospitalization, which may be useful to trend. Further studies are necessary to create guidelines to better risk-stratify COVID-19 patients based on clinical severity. Disclosures All Authors: No reported disclosures

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CHEST X RAY SCORE AND CLINICAL SEVERITY IN COVID-19 PATIENTS

10.36106/ijsr/2506669 ◽

2021 ◽

pp. 31-32

Author(s):

Sheeba Rana ◽

Vicky Bakshi ◽

Yavini Rawat ◽

Zaid Bin Afroz

Keyword(s):

Retrospective Study ◽

Medical Records ◽

Scoring Systems ◽

Clinical Severity ◽

X Rays ◽

Antigen Test ◽

X Ray ◽

Classi Cation ◽

Chest X Ray ◽

Male Subjects

INTRODUCTION: Various chest X-ray scoring systems have been discovered and are employed to correlate with clinical severity, outcome and progression of diseases. With, the coronavirus outbreak, few chest radiograph classication were formulated, like the BSTI classication and the Brixia chest X-ray score. Brixia CXR scoring is used for assessing the clinical severity and outcome of COVID-19. This study aims to compare the Brixia CXR score with clinical severity of COVID-19 patients. MATERIAL& METHODS:This was a retrospective study in which medical records of patients aged 18 years or above, who tested for RTPCR or st st Rapid Antigen Test (RAT) for COVID positive from 1 February 2021 to 31 July 2021 (6 months) were taken. These subjects were stratied into mild, moderate and severe patients according to the ICMR guidelines. Chest X Rays were obtained and lesions were classied according to Brixia scoring system. RESULTS: Out of these 375 patients, 123 (32.8%) were female and 252 (67.2%) were male subjects. The average brixia score was 11.12. Average Brixia CXR score for mild, moderate and severe diseased subjects were 5.23, 11.20, and 14.43 respectively. DISCUSSION:The extent of chest x-ray involvement is proportional to the clinical severity of the patient. Although, a perplexing nding was that the average Brixia score of the female subjects were slightly higher than their male counterparts in the same clinical groups. CONCLUSION: Brixia CXR score correlates well with the clinical severity of the COVID-19.

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