Severe Infections In Patients Research Articles

Automatic Detection of Severely and Mildly Infected COVID-19 Patients with Supervised Machine Learning Models

ObjectivesWhen the prognosis of COVID-19 disease can be detected early, the intense-pressure and loss of workforce in health-services can be partially reduced. The primary-purpose of this article is to determine the feature-dataset consisting of the routine-blood-values (RBV) and demographic-data that affect the prognosis of COVID-19. Second, by applying the feature-dataset to the supervised machine-learning (ML) models, it is to identify severely and mildly infected COVID-19 patients at the time of admission. Material and methodsThe sample of this study consists of severely (n = 192) and mildly (n = 4010) infected-patients hospitalized with the diagnosis of COVID-19 between March-September, 2021. The RBV-data measured at the time of admission and age-gender characteristics of these patients were analyzed retrospectively. For the selection of the features, the minimum-redundancy-maximum-relevance (MRMR) method, principal-components-analysis and forward-multiple-logistics-regression analyzes were used. The features set were statistically compared between mild and severe infected-patients. Then, the performances of various supervised-ML-models were compared in identifying severely and mildly infected-patients using the feature set. ResultsIn this study, 28 RBV-parameters and age-variable were found as the feature-dataset. The effect of features on the prognosis of the disease has been clinically proven. The ML-models with the highest overall-accuracy in identifying patient-groups were found respectively, as follows: local-weighted-learning (LWL)-97.86%, K-star (K*)-96.31%, Naive-Bayes (NB)-95.36% and k-nearest-neighbor (KNN)-94.05%. Also, the most successful models with the highest area-under-the-receiver-operating-characteristic-curve (AUC) values in identifying patient groups were found respectively, as follows: LWL-0.95%, K*-0.91%, NB-0.85% and KNN-0.75%. ConclusionThe findings in this article have significant a motivation for the healthcare professionals to detect at admission severely and mildly infected COVID-19 patients.

Super Dominant Pathobiontic Bacteria in the Nasopharyngeal Microbiota Cause Secondary Bacterial Infection in COVID-19 Patients.

ABSTRACTCoronavirus disease 2019 (COVID-19) is a respiratory infectious disease responsible for many infections worldwide. Differences in respiratory microbiota may correlate with disease severity. Samples were collected from 20 severe and 51 mild COVID-19 patients. High-throughput sequencing of the 16S rRNA gene was used to analyze the bacterial community composition of the upper and lower respiratory tracts. The indices of diversity were analyzed. When one genus accounted for >50% of reads from a sample, it was defined as a super dominant pathobiontic bacterial genus (SDPG). In the upper respiratory tract, uniformity indices were significantly higher in the mild group than in the severe group (P < 0.001). In the lower respiratory tract, uniformity indices, richness indices, and the abundance-based coverage estimator were significantly higher in the mild group than in the severe group (P < 0.001). In patients with severe COVID-19, SDPGs were detected in 40.7% of upper and 63.2% of lower respiratory tract samples. In patients with mild COVID-19, only 10.8% of upper and 8.5% of lower respiratory tract samples yielded SDPGs. SDPGs were present in both upper and lower tracts in seven patients (35.0%), among which six (30.0%) patients possessed the same SDPG in the upper and lower tracts. However, no patients with mild infections had an SDPG in both tracts. Staphylococcus, Corynebacterium, and Acinetobacter were the main SDPGs. The number of SDPGs identified differed significantly between patients with mild and severe COVID-19 (P < 0.001). SDPGs in nasopharyngeal microbiota cause secondary bacterial infection in COVID-19 patients and aggravate pneumonia.IMPORTANCE The nasopharyngeal microbiota is composed of a variety of not only the true commensal bacterial species but also the two-face pathobionts, which are one a harmless commensal bacterial species and the other a highly invasive and deadly pathogen. In a previous study, we found that the diversity of nasopharyngeal microbiota was lost in severe influenza patients. We named the genus that accounted for over 50% of microbiota abundance as super dominant pathobiontic genus, which could invade to cause severe pneumonia, leading to high fatality. Similar phenomena were found here for SARS-CoV-2 infection. The diversity of nasopharyngeal microbiota was lost in severe COVID-19 infection patients. SDPGs in nasopharyngeal microbiota were frequently detected in severe COVID-19 patients. Therefore, the SDPGs in nasopharynx microbiota might invade into low respiratory and be responsible for secondary bacterial pneumonia in patients with SARS-CoV-2 infection.

Comorbidities and laboratory parameters associated with SARS-CoV-2 infection severity in patients from the southeast of Mexico: a cross-sectional study.

Background. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic. Among the risk factors associated with the severity of this disease is the presence of several metabolic disorders. For this reason, the aim of this research was to identify the comorbidities and laboratory parameters among COVID-19 patients admitted to the intensive care unit (ICU), comparing the patients who required invasive mechanical ventilation (IMV) with those who did not require IMV, in order to determine the clinical characteristics associated with the COVID-19 severity. Methods. We carried out a cross-sectional study among 152 patients who were admitted to the ICU from April 1 st to July 31 st, 2021, in whom the comorbidities and laboratory parameters associated with the SARS-CoV-2 infection severity were identified. The data of these patients was grouped into two main groups: "patients who required IMV" and "patients who did not require IMV". The nonparametric Mann-Whitney U test for continuous data and the χ2 test for categorical data were used to compare the variables between both groups. Results. Of the 152 COVID-19 patients who were admitted to the ICU, 66 required IMV and 86 did not require IMV. Regarding the comorbidities found in these patients, a higher prevalence of type 2 diabetes mellitus (T2DM), hypertension and obesity was observed among patients who required IMV vs. those who did not require IMV ( p<0.05). Concerning laboratory parameters, only glucose, Interleukin 6 (IL-6), lactate dehydrogenase (LDH) and C-reactive protein (CRP) were significantly higher among patients who required IMV than in those who did not require IMV ( p<0.05). Conclusion. This study performed in a Mexican population indicates that comorbidities such as: T2DM, hypertension and obesity, as well as elevated levels of glucose, IL-6, LDH and CRP are associated with the COVID-19 severity.

Ceftazidime-Avibactam for the Treatment of Carbapenem-Resistant Klebsiella pneumoniae Infections in Patients With Liver Cirrhosis

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections in patients with cirrhosis represent a significant therapeutic challengeas they are associated with poor outcomes due to high rates of treatment failure, and frequently induce liver decompensation. To evaluate treatment failure and in-hospital mortality in two cohorts of patients with cirrhosis and with CRKP infectionstreated with antibiotic regimens including or excluding Ceftazidime-avibactam. Data from hospitalized patients with liver cirrhosis and CRKP infections were extracted and retrospectively analyzed. During the study period, 39 cirrhotic patients with confirmed invasive CRKP infections were enrolled. Overall, the median age was 60 years with a median MELD score of 16 points. Urinary tract infections were diagnosed in 46%, followed by pneumonia in 23%, and primary bacteremia in 18% of patients. Treatment failure was reported in 10 patients (26%), while in-hospital mortality in 15 patients (38%). A monotherapy was used in 8 patients (20.5%), while a combination therapy was required in 31 patients (79.5%). Ceftazidime-avibactam therapy was associated with lower rates of treatment failure (7% vs. 38%, P= 0.032) independent of severity of liver disease (Child Class) and mono or combination antibiotic therapy. Acute kidney injury, hepatorenal syndrome, and acute-on-chronic liver failure were the consequences more frequently observed in patients with treatment failure. In-hospital mortality was associated with treatment failure, and Ceftazidime-avibactam therapy improved in-hospital survival (log rank test: P= 0.035) adjusted for Child class and mono or combination therapy. Treatment including ceftazidime-avibactam was associated with a lower rate of treatment failure in cirrhotic patients with CRKP infections. Considering the favorable efficacy and outcomes of ceftazidime-avibactam, this drug should be considered for the treatment of these severe infections in patients with liver cirrhosis, though further investigation is required.

Extensive Study on Hematological, Immunological, Inflammatory Markers, and Biochemical Profile to Identify the Risk Factors in COVID-19 Patients.

Background Tissue damage caused by COVID-19 could be detected by several clinical indicators including hematological, immunological, biochemical, and inflammatory markers. This study was to detect these clinical parameters to reveal the correlation between the factors and their roles in the development of COVID-19, to explore the hazard factors in severe cases. Materials and Methods A total of 200 participants of both sexes were included in the study, with an age range of (25–72) years, categorized into three main groups: 50 healthy individuals, 62 mild infected patients, and 88 severe infected patients with pneumonia. Different hematological and clinical parameters were included in the analysis (Basrah city, Iraq). Serum levels of interleukin-6 (IL-6), ferritin, and high-sensitivity C-reactive protein (hs-CRP) were assessed for all participants using an enzyme-linked immunosorbent assay (ELISA). The liver, renal, and cardiac functions were assessed by clinical chemistry testing. Results COVID-19 patients had leukocytosis, with an increased number of neutrophils and a decreased lymphocyte count, according to our findings. In regard to inflammatory parameters, both ESR and hs-CRP showed significant differences between the two groups, whereas IL-6 was significantly higher in the total severe group compared to the other two groups. Biochemical results revealed that each lactate dehydrogenase (LDH), ferritin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) had significant changes in the total severe group. Among pneumonic with an O2 requirement and pneumonic without an O2 requirement, there were significant differences in immunological and inflammatory markers (p > 0.05). The neutrophils-lymphocytes ratio (NLR) was highly elevated in severe who required O2. Moreover, IL-6, lymphocytes, and neutrophils were possible risk factors for COVID-19 infection, with the strongest influence of IL-6 with a high odds ratio (OR: 24.138, 95% CI: 8.437–30.65, p < 0.01). Furthermore, there were significant correlations among the indicators. Conclusion Each of IL-6, lymphocytes, and neutrophils might represent major factors in the severity of COVID-19 and IL-6 plays the main role in inducing the inflammatory and pathophysiology process that is known as the cytokine storm.

Bacterial DNA load in Staphylococcus aureus bacteremia is significantly higher in intravascular infections.

ObjectivesDetermination of pathogen-specific bacterial DNA load (BDL) in blood has been shown to be directly correlated with severity of infection in patients with bacteremia. In the diagnostic work-up of patients with Staphylococcus aureus bacteremia (SAB), determination of the primary focus is imperative, because of implications for treatment duration, and ultimately prognosis. Here we investigate whether measurement of BDL in patients with SAB can distinguish between intravascular and extravascular foci of infection.MethodsIn a consecutive cohort of 43 patients with positive blood cultures with Staphylococcus aureus, we performed a quantitative PCR on whole blood to detect the bacterial DNA load. Infections were classified into 3 categories: i) soft tissue infections and phlebitis, ii) deep-seated infections and iii) endocarditis and other intravascular infections. Bacterial DNA loads and inflammatory parameters in the three categories were analyzed and compared.ResultsMedian BDL in patients with endocarditis and other intravascular infections was 1015 cfu/ml, significantly higher than BDL in the other two categories (28 and 31 cfu/ml respectively). In contrast, CRP and leukocytes were not significantly different between the three patient categories. BDL could be detected in all patients with intravascular causes and levels were generally 10–30 times higher than in the other infection categories. Median BDL in non-survivors was 85 cfu/ml, which was higher than in survivors with a median BDL of 29 cfu/ml, although not significant.ConclusionsIn Staphylococcus aureus bacteremia pathogen-specific BDL is distinctly higher in patients with intravascular infections compared to extravascular origins. As measurement of BDL by PCR can easily be implemented in routine diagnostics, it can improve the diagnostic work-up of SAB by rapidly identifying the subset of patients who need higher dosages of antibiotics and additional measures to improve outcome.

Identification of Key Factors for Anoxic Survival of B. cenocepacia H111.

Burkholderia cenocepacia is an opportunistic pathogen that can lead to severe infections in patients suffering from cystic fibrosis (CF) and chronic granulomatous disease. Being an obligate aerobe, B. cenocepacia is unable to grow in the absence of oxygen. In this study, we show that the CF isolate B. cenocepacia H111 can survive in the absence of oxygen. Using a transposon sequencing (Tn-seq) approach, we identified 71 fitness determinants involved in anoxic survival, including a Crp-Fnr family transcriptional regulatory gene (anr2), genes coding for the sensor kinase RoxS and its response regulator RoxR, the sigma factor for flagella biosynthesis (FliA) and subunits of a cytochrome bd oxidase (CydA, CydB and the potentially novel subunit CydP). Individual knockouts of these fitness determinants significantly reduced anoxic survival, and inactivation of both anr copies is shown to be lethal under anoxic conditions. We also show that the two-component system RoxS/RoxR and FliA are important for virulence and swarming/swimming, respectively.

Comorbidities and laboratory parameters associated with SARS-CoV-2 infection severity in patients from the southeast of Mexico: a cross-sectional study

Background . Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic. Among the risk factors associated with the severity of this disease is the presence of several metabolic disorders. For this reason, the aim of this research was to identify the comorbidities and laboratory parameters among COVID-19 patients admitted to the intensive care unit (ICU), comparing the patients who required invasive mechanical ventilation (IMV) with those who did not require IMV, in order to determine the clinical characteristics associated with the COVID-19 severity. Methods. We carried out a cross-sectional study among 152 patients who were admitted to the ICU from April 1 st to July 31 st, 2021, in whom the comorbidities and laboratory parameters associated with the SARS-CoV-2 infection severity were identified. The data of these patients was grouped into two main groups: “patients who required IMV” and “patients who did not require IMV”. The nonparametric Mann–Whitney U test for continuous data and the χ 2 test for categorical data were used to compare the variables between both groups. Results. Of the 152 COVID-19 patients who were admitted to the ICU, 66 required IMV and 86 did not require IMV. Regarding the comorbidities found in these patients, a higher prevalence of type 2 diabetes mellitus (T2DM), hypertension and obesity was observed among patients who required IMV vs. those who did not require IMV ( p<0.05). Concerning laboratory parameters, only glucose, Interleukin 6 (IL-6), lactate dehydrogenase (LDH) and C-reactive protein (CRP) were significantly higher among patients who required IMV than in those who did not require IMV ( p<0.05). Conclusion. This study performed in a Mexican population indicates that comorbidities such as: T2DM, hypertension and obesity, as well as elevated levels of glucose, IL-6, LDH and CRP are associated with the COVID-19 severity.

A simple score to predict early severe infections in patients with newly diagnosed multiple myeloma

Infections remain a common complication in patients with multiple myeloma (MM) and are associated with morbidity and mortality. A risk score to predict the probability of early severe infection could help to identify the patients that would benefit from preventive measures. We undertook a post hoc analysis of infections in four clinical trials from the Spanish Myeloma Group, involving a total of 1347 patients (847 transplant candidates). Regarding the GEM2010 > 65 trial, antibiotic prophylaxis was mandatory, so we excluded it from the final analysis. The incidence of severe infection episodes within the first 6 months was 13.8%, and majority of the patients experiencing the first episode before 4 months (11.1%). 1.2% of patients died because of infections within the first 6 months (1% before 4 months). Variables associated with increased risk of severe infection in the first 4 months included serum albumin ≤30 g/L, ECOG > 1, male sex, and non-IgA type MM. A simple risk score with these variables facilitated the identification of three risk groups with different probabilities of severe infection within the first 4 months: low-risk (score 0–2) 8.2%; intermediate-risk (score 3) 19.2%; and high-risk (score 4) 28.3%. Patients with intermediate/high risk could be candidates for prophylactic antibiotic therapies.

POS-127 Association between body mass index and severe infection in older adults with microscopic polyangiitis

Although previous studies have evaluated risk factors for the incidence of severe infection in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), the relationship between body mass index (BMI) and severe infection in AAV has not been elucidated. We hypothesized that older adults with AAV and a low BMI would be at a higher risk of infection. We therefore investigated the association between underweight status at AAV diagnosis and subsequent occurrence of severe infection in older adults with AAV.

POS-929 FOUR CASES OF SEVERE INFECTIONS AFTER RECENT COVID19

Some presentations of SARS cov-2 infections are characterized by inflammatory cytokine storms causing much more morbidity and mortality than direct viral toxicity. This state of hyper-inflammation can occur even after the acute episode of viraemia and can lead to severe infections. This study aims to describe the particularities of certain severe infections in patients with history of recent COVID 19.

Comorbidities and laboratory parameters associated with SARS-CoV-2 infection severity in patients from the southeast of Mexico: a cross-sectional study

Background . Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic. Among the risk factors associated with the severity of this disease is the presence of several metabolic disorders. For this reason, the aim of this research was to identify the comorbidities and laboratory parameters among COVID-19 patients admitted to the intensive care unit (ICU), comparing the patients who required invasive mechanical ventilation (IMV) with those who did not require IMV, in order to determine the clinical characteristics associated with the COVID-19 severity. Methods. We carried out a cross-sectional study among 152 patients who were admitted to the ICU from April 1 st to July 31 st, 2021, in whom the comorbidities and laboratory parameters associated with the SARS-CoV-2 infection severity were identified. The data of these patients was grouped into two main groups: "patients who required IMV" and "patients who did not require IMV". The nonparametric Mann-Whitney U test for continuous data and the χ 2 test for categorical data were used to compare the variables between both groups. Results. Of the 152 COVID-19 patients who were admitted to the ICU, 66 required IMV and 86 did not require IMV. Regarding the comorbidities found in these patients, a higher prevalence of type 2 diabetes mellitus (T2DM), hypertension and obesity was observed among patients who required IMV vs. those who did not require IMV ( p<0.05). Concerning laboratory parameters, only glucose, Interleukin 6 (IL-6), lactate dehydrogenase (LDH) and C-reactive protein (CRP) were significantly higher among patients who required IMV than in those who did not require IMV ( p<0.05). Conclusion. This study performed in a Mexican population indicates that comorbidities such as: T2DM, hypertension and obesity, as well as elevated levels of glucose, IL-6, LDH and CRP are associated with the COVID-19 severity.

Causes of severe infections in patients with systemic sclerosis and associated factors.

Systemic sclerosis (SSc) is a chronic systemic disease characterized by vascular damage, autoimmunity, and fibrosis in the skin and internal organs. In this study, we tried to determine the causes of severe infection in patients with SSc and to reveal the factors associated with severe infection. We retrospectively examined 214 SSc patients between January 2010 and August 2020. Forty-seven patients with at least one severe infection and 167 patients without severe infection were compared. A total of 76 episodes of severe infections were detected in 47 (22%) patients. Common infections included pneumonia, infected digital ulcer, urinary tract infections, and osteomyelitis. Female patients had a higher frequency in the group without severe infection (91.6% vs. 80.9%, p = 0.035). Patients with severe infections had a higher frequency of digital ulcers (p < 0.001), cardiac (p = 0.002), and GIS involvement (p < 0.001). In multivariable analysis, digital ulcer presence (OR: 2.849 [1.356-5.898] (p = 0.006) and cardiac involvement (OR: 2.801 [1.248-6.285]) were associated with severe infection. Of the patients with severe infections, 34% had recurrent severe infections. There was no difference in demographic and clinical characteristics between patients with recurrent and nonrecurrent severe infections. The presence of digital ulcer and cardiac involvement seem to be associated with a severe infection in patients with systemic sclerosis. In patients with cardiac involvement and digital ulcers, more careful attention may be required for the development of severe infections.

Comparison of hematological parameters in mild and severe COVID-19 infected patients: A retrospective observational study

Introduction and Aim: With the coronavirus disease 2019 (COVID-19) pandemic raging on, there is a need to identify clinical and laboratory predictors which predict progression towards severe and fatal forms of this illness. Our study aims to evaluate the ability of hematologic and biochemical biomarkers to discriminate between patients with and without severe or fatal forms of COVID-19. Materials and Methods: A retrospective study was conducted on 200 Covid positive patients;100 with mild disease and 100 with severe disease. Medical records were reviewed to collect demographic data and results of the following blood investigations were noted at admission: Hb, Platelet count, Total and Differential leukocyte count, CRP, AST, ALT, LDH, Ferritin and D-Dimer. Comparative analysis was performed between the 2 groups. Results: A significant difference in the basophil count (mean 2.35 and 5.92) among those with mild and severe disease respectively was noted as also with the eosinophil count (mean 6.88 and 1.79). The levels of CRP were higher in those with severe disease as compared to the mild disease group (mean 276.29 and 65.23). Ferritin levels were markedly increased severe disease patients (mean 1275.66 and 533.94). D-dimer was markedly increased in COVID-19 patients with severe disease (mean 3813.91 ng/ml) compared to those with mild disease group (mean 521.78 ng/ml). Conclusion: Hematological and biochemical markers positively correlate to the severity of covid infection, thus highlighting their role in the early diagnosis of the disease and can act as independent markers in predicting severity and prognosis of disease.

Multiplex proteomics as risk predictor of infection in patients treated with hemodialysis-A prospective multicenter study.

Severe infection is a major problem in hemodialysis patients. Multiplex proteomics might reveal novel insights into disease mechanisms increasing the risk of infection and might also be used as a risk prediction tool. The aims of this study were (1) to evaluate associations between 92 proteins assessed by a proximity extension assay and the development of severe infection in patients on hemodialysis and (2) to develop a risk prediction model for severe infection using prespecified clinical variables and proteomics. Prospective, observational multicenter cohort study with 5-year follow-up. Patients receiving in-center hemodialysis in five facilities in Denmark were included. The primary composite endpoint was death caused by infection, bacteremia, and infections requiring hospitalization of at least 2 days or prolonging a hospital stay. Of 331 patients included 210 patients reached the primary endpoint during follow-up. In adjusted Cox regression analyses, 14 plasma proteins were associated with severe infection. Correcting for multiple testing revealed only cathepsin-L1 and interleukin-6 significantly associated with the primary outcome. Cathepsin-L1-hazard ratio: 1.64 (95% confidence interval [CI] 1.24-2.17) and interleukin-6-hazard ratio: 1.16 (95% CI 1.05-1.29). Apparent C-statistics of the risk prediction model using clinical variables was 0.605, addition of cathepsin-L1 and interleukin-6 to the model improved discrimination slightly: C=0.625. Proteomic profiling identified cathepsin-L1 and interleukin-6 as markers for infectious risk in hemodialysis patients. Further studies are needed to replicate the results and to examine possible causality. The developed risk prediction models need considerable improvement before implementation in clinical practice is meaningful.

The role of coinfection with influenza viruses in the pathogenesis of severe infection in patients with COVID-19

BACKGROUND: Despite the continuing global spread of the coronavirus infection COVID-19 caused by the SARS-CoV-2 coronavirus, the mechanisms of the pathogenesis of severe infections remain poorly understood. The role of comorbidity with other seasonal viral infections, including influenza, in the pathogenesis of the severe course of COVID-19 remains unclear.&#x0D; MATERIALS AND METHODS: The present study used sera left over from ongoing laboratory studies of patients with varying degrees of severity of COVID-19. The study was approved by the Local Ethics Committee of the Federal State Budgetary Scientific Institution IEM (protocol 3/20 from 06/05/2020). We studied 28 paired samples obtained upon admission of patients to the hospital and after 57 days of hospital stay. Paired sera of patients with COVID-19 were tested for antibodies to influenza A and B viruses. The presence of IgG antibodies specific to the SARS-CoV-2 spike (S) protein was studied using an enzyme-linked immunosorbent assay (ELISA). The serum concentration of C-reactive protein and the neutrophil-lymphocyte ratio on the day of hospitalization were also assessed.&#x0D; RESULTS: At least a 4-fold increase in serum IgG antibodies to SARS-CoV-2 S protein was found both in patients with PCR-confirmed SARS-CoV-2 infection and without PCR confirmation. It was shown that out of 18 patients with moderate and severe forms of COVID-19 infection, six of them showed at least a 4-fold increase in antibodies to influenza A/H1N1, in one to influenza A/H3N2 and in two cases to the influenza B. Laboratory data in these two groups were characterized by significant increases in serum C-reactive protein and neutrophil-lymphocyte ratio concentrations compared with the moderate COVID-19 group.&#x0D; CONCLUSIONS: Serological diagnostics can additionally detect cases of coronavirus infection when the virus was not detected by PCR. In moderate and severe cases of COVID-19, coinfections with influenza A and B viruses have been identified. The results obtained confirm the need for anti-influenza immunization during the SARS-CoV-2 pandemic. Influenza virus screening can significantly improve patient management because recommended antiviral drugs (neuraminidase inhibitors) are available.

673. Unbiased Microbial Cell-free DNA Next-Generation Sequencing Resolves HHV6 Variant Specificity and Demonstrates a Predominance of HHV6B over HHV6A in Real-World Clinical Experience

Abstract Background Human herpesvirus 6 (HHV6) has been classified in two distinct variants, HHV6A and HHV6B. Although distinct epidemiology, disease association, biological and immunological properties, their genomes are 90% homologous. Less is known about HHV6A which is typically asymptomatic but can cause severe infection in patients with neurological disorders or HIV. HHV6B infection occurs during childhood, but can reactivate after solid organ and stem cell transplantation. Antibody assays may indicate previous, recent or current infection. Quantitative PCR cannot differentiate active from latent infections and some available qualitative PCR assays are unable to differentiate the two variants. A single open-ended test through plasma-based microbial cell-free DNA (mcfDNA) metagenomic next-generation sequencing (NGS) may overcome these limitations. Methods Karius TestTM (KT) developed and validated in Karius’s CLIA certified/CAP accredited lab, detects mcfDNA from plasma. mcfDNA is extracted, NGS performed, human sequences removed and remaining sequences aligned to a curated pathogen database of &amp;gt; 1500 organisms. Organisms present above a statistical threshold are reported and quantified. For &amp;gt; 85% of tests the time to result reporting is the next day from sample receipt. KT results were reviewed from November-2018 to May-2021 for detections of HHV6A and HHV6B. The comparative incidence of HHV6A and HHVB detections, their age distributions and their quantitative viral concentration in molecules/µL (MPM) were assessed. Results KT detected 322 cases of HHV6; 10% (n=32) were HHV6A and 90% (n=290) HHV6B (Table 1). HHV6B had a higher relative abundance in children (with a distribution into adolescence) compared to adults (Figure 1). The average HHV6A MPM was 860 (range 27 - 10,472); the average HHV6B MPM was 3,361 (range 21 - 131,518). Table 1. Summary of HHV-6 Detections Figure 1. Distribution of HHV6A and HHV6B by Age Group Conclusion The distribution of the HHV6 variants detected through KT shows an overwhelming 9:1 predominance of HHV6B to HHV6A. The application of mcfDNA metagenomic sequencing for open-ended detection, variant determination and quantification of HHV6 provides more specific resolution than serological and PCR methods. KT may lend important insights into the association of specific HHV6 variants with clinical syndromes affecting vulnerable populations. Disclosures Jose Alexander, MD, D(ABMM), FCCM, CIC, SM, MB(ASCP), BCMAS, Karius (Employee) Sivan Bercovici, PhD, Karius (Employee) Nicholas R. Degner, MD, MPH, MS, Karius Inc. (Employee, Shareholder) Ricardo Castillo-Galvan, MD MPH, Karius Inc. (Consultant) Aparna Arun, MD, Karius (Employee) Ann Macintyre, DO, Karius, Inc. (Employee) Bradley Perkins, MD, Karius, Inc. (Employee) Asim A. Ahmed, MD, Karius, Inc. (Employee) Matthew Smollin, PharmD, Karius, Inc. (Employee)

Utilization and Outcomes of Acute Revascularization Treatments in Ischemic Stroke Patients with SARS-CoV-2 Infection

ObjectivesAcute ischemic stroke patients with severe acute respiratory syndrome coronavirus maybe candidates for acute revascularization treatments (intravenous thrombolysis and/or mechanical thrombectomy). Materials and MethodsWe analyzed the data from 62 healthcare facilities to determine the odds of receiving acute revascularization treatments in severe acute respiratory syndrome coronavirus infected patients and determined the odds of composite of death and non-routine discharge with severe acute respiratory syndrome coronavirus infected and non-infected patients undergoing acute revascularization treatments after adjusting for potential confounders. ResultsAcute ischemic stroke patients with severe acute respiratory syndrome coronavirus infection were significantly less likely to receive acute revascularization treatments (odds ratio 0.6, 95% confidence interval 0.5–0.8, p = 0.0001). Among ischemic stroke patients who received acute revascularization treatments, severe acute respiratory syndrome coronavirus infection was associated with increased odds of death or non-routine discharge (odds ratio 3.0, 95% confidence interval 1.8–5.1). The higher odds death or non-routine discharge (odds ratio 2.1, 95% confidence interval 1.9–2.3) with severe acute respiratory syndrome coronavirus infection were observed in all ischemic stroke patients without any modifying effect of acute revascularization treatments (interaction term for death (p = 0.9) or death or non-routine discharge (p = 0.2). ConclusionsPatients with acute ischemic stroke with severe acute respiratory syndrome coronavirus infection were significantly less likely to receive acute revascularization treatments. Severe acute respiratory syndrome coronavirus infection was associated with a significantly higher rate of death or non-routine discharge among acute ischemic stroke patients receiving revascularization treatments.

Assessment of the Feasibility of Using Noninvasive Wearable Biometric Monitoring Sensors to Detect Influenza and the Common Cold Before Symptom Onset

Currently, there are no presymptomatic screening methods to identify individuals infected with a respiratory virus to prevent disease spread and to predict their trajectory for resource allocation. To evaluate the feasibility of using noninvasive, wrist-worn wearable biometric monitoring sensors to detect presymptomatic viral infection after exposure and predict infection severity in patients exposed to H1N1 influenza or human rhinovirus. The cohort H1N1 viral challenge study was conducted during 2018; data were collected from September 11, 2017, to May 4, 2018. The cohort rhinovirus challenge study was conducted during 2015; data were collected from September 14 to 21, 2015. A total of 39 adult participants were recruited for the H1N1 challenge study, and 24 adult participants were recruited for the rhinovirus challenge study. Exclusion criteria for both challenges included chronic respiratory illness and high levels of serum antibodies. Participants in the H1N1 challenge study were isolated in a clinic for a minimum of 8 days after inoculation. The rhinovirus challenge took place on a college campus, and participants were not isolated. Participants in the H1N1 challenge study were inoculated via intranasal drops of diluted influenza A/California/03/09 (H1N1) virus with a mean count of 106 using the median tissue culture infectious dose (TCID50) assay. Participants in the rhinovirus challenge study were inoculated via intranasal drops of diluted human rhinovirus strain type 16 with a count of 100 using the TCID50 assay. The primary outcome measures included cross-validated performance metrics of random forest models to screen for presymptomatic infection and predict infection severity, including accuracy, precision, sensitivity, specificity, F1 score, and area under the receiver operating characteristic curve (AUC). A total of 31 participants with H1N1 (24 men [77.4%]; mean [SD] age, 34.7 [12.3] years) and 18 participants with rhinovirus (11 men [61.1%]; mean [SD] age, 21.7 [3.1] years) were included in the analysis after data preprocessing. Separate H1N1 and rhinovirus detection models, using only data on wearble devices as input, were able to distinguish between infection and noninfection with accuracies of up to 92% for H1N1 (90% precision, 90% sensitivity, 93% specificity, and 90% F1 score, 0.85 [95% CI, 0.70-1.00] AUC) and 88% for rhinovirus (100% precision, 78% sensitivity, 100% specificity, 88% F1 score, and 0.96 [95% CI, 0.85-1.00] AUC). The infection severity prediction model was able to distinguish between mild and moderate infection 24 hours prior to symptom onset with an accuracy of 90% for H1N1 (88% precision, 88% sensitivity, 92% specificity, 88% F1 score, and 0.88 [95% CI, 0.72-1.00] AUC) and 89% for rhinovirus (100% precision, 75% sensitivity, 100% specificity, 86% F1 score, and 0.95 [95% CI, 0.79-1.00] AUC). This cohort study suggests that the use of a noninvasive, wrist-worn wearable device to predict an individual's response to viral exposure prior to symptoms is feasible. Harnessing this technology would support early interventions to limit presymptomatic spread of viral respiratory infections, which is timely in the era of COVID-19.

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Neutropenia is defined as a reduction in the absolute neutrophil count (ANC) below 1,500 cells/mcl in the blood. Neutropenia is a common laboratory finding in children. It is important to distinguish transient and benign causes from severe congenital neutropenia. Neutropenia can be classified in asymptomatic (mild), moderate, and severe form, the susceptibility to infection depending on ANC. Neutropenia can be either acquired or congenital. Infection, drugs, and immune disorders are the most common acquired causes while congenital causes are rare and confined mostly to infants and children. Transient neutropenia often accompanies viral infections in children, manifested in the period of acute viremia. Young children are characterized by autoimmune neutropenia (AIN), which has a benign course and a favorable prognosis. Autoimmune neutropenia is characterized by a decrease in the number of neutrophils as a result of the destruction of neutrophils in the peripheral blood by antineutrophil antibodies. The duration of AIN is usually 3–5 years. This is a self-limiting disease that in most cases does not require treatment. Despite the benign course, serious infectious complications can occur. Treatment of myeloid growth factors should be started after a previous bone marrow aspiration biopsy in children with severe infections or requiring surgical intervention. High doses of intravenous immunoglobulin and corticosteroids may be effective in treating AIN in patients with life-threating infections. The danger to the patient depends on the etiology, ANC and bone marrow status. The risk of infections is significantly increased in patients with ACN less than 500 cells/μ1. The most common loci of infections include the oral mucosa, skin, perirectal area, perineum. Oral ulcers and gingivitis are characteristic signs of clinically significant neutropenia, requiring the exclusion of its congenital causes. Severe infections in patients with neutropenia are caused by pyogenic or intestinal bacteria and Candida species. It is important to distinguish between transient or benign causes and severe congenital neutropenia or neutropenia associated with serious haematological or systemic disease. Clarification of the cause of neutropenia is important for determining management and prognosis. No conflict of interest was declared by the author. Key words: neutropenia, children, immunodeficiency, autoimmune neutropenia.