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1.
Crit Care Med ; 49(10): 1664-1673, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1452743

ABSTRACT

OBJECTIVES: The rapid diagnosis of acute infections and sepsis remains a serious challenge. As a result of limitations in current diagnostics, guidelines recommend early antimicrobials for suspected sepsis patients to improve outcomes at a cost to antimicrobial stewardship. We aimed to develop and prospectively validate a new, 29-messenger RNA blood-based host-response classifier Inflammatix Bacterial Viral Non-Infected version 2 (IMX-BVN-2) to determine the likelihood of bacterial and viral infections. DESIGN: Prospective observational study. SETTING: Emergency Department, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Germany. PATIENTS: Three hundred twelve adult patients presenting to the emergency department with suspected acute infections or sepsis with at least one vital sign change. INTERVENTIONS: None (observational study only). MEASUREMENTS AND MAIN RESULTS: Gene expression levels from extracted whole blood RNA was quantified on a NanoString nCounter SPRINT (NanoString Technologies, Seattle, WA). Two predicted probability scores for the presence of bacterial and viral infection were calculated using the IMX-BVN-2 neural network classifier, which was trained on an independent development set. The IMX-BVN-2 bacterial score showed an area under the receiver operating curve for adjudicated bacterial versus ruled out bacterial infection of 0.90 (95% CI, 0.85-0.95) compared with 0.89 (95% CI, 0.84-0.94) for procalcitonin with procalcitonin being used in the adjudication. The IMX-BVN-2 viral score area under the receiver operating curve for adjudicated versus ruled out viral infection was 0.83 (95% CI, 0.77-0.89). CONCLUSIONS: IMX-BVN-2 demonstrated accuracy for detecting both viral infections and bacterial infections. This shows the potential of host-response tests as a novel and practical approach for determining the causes of infections, which could improve patient outcomes while upholding antimicrobial stewardship.


Subject(s)
Bacterial Infections/diagnosis , RNA, Messenger/analysis , Virus Diseases/diagnosis , Aged , Aged, 80 and over , Area Under Curve , Bacterial Infections/blood , Bacterial Infections/physiopathology , Berlin , Biomarkers/analysis , Biomarkers/blood , Emergency Service, Hospital/organization & administration , Emergency Service, Hospital/statistics & numerical data , Female , Humans , Male , Middle Aged , Prospective Studies , RNA, Messenger/blood , ROC Curve , Virus Diseases/blood , Virus Diseases/physiopathology
3.
Infection ; 49(4): 757-762, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1171404

ABSTRACT

Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Type I interferons are important in the defense of viral infections. Recently, neutralizing IgG auto-antibodies against type I interferons were found in patients with severe COVID-19 infection. Here, we analyzed expression of CD169/SIGLEC1, a well described downstream molecule in interferon signaling, and found increased monocytic CD169/SIGLEC1 expression levels in patients with mild, acute COVID-19, compared to patients with severe disease. We recommend further clinical studies to evaluate the value of CD169/SIGLEC1 expression in patients with COVID-19 with or without auto-antibodies against type I interferons.


Subject(s)
COVID-19/immunology , Monocytes/immunology , SARS-CoV-2/physiology , Sialic Acid Binding Ig-like Lectin 1/blood , Aged , Female , Hospitalization , Humans , Longitudinal Studies , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Sialic Acid Binding Ig-like Lectin 1/biosynthesis , Up-Regulation
4.
TH Open ; 5(1): e43-e55, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1075296

ABSTRACT

COVID-19 (coronavirus disease 2019) patients often show excessive activation of coagulation, associated with increased risk of thrombosis. However, the diagnostic value of coagulation at initial clinical evaluation is not clear. We present an in-depth analysis of coagulation in patients presenting to the emergency department (ED) with suspected COVID-19. N = 58 patients with clinically suspected COVID-19 in the ED were enrolled. N = 17 subsequently tested positive using SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) polymerase chain reaction (PCR) swabs, while in n = 41 COVID-19 was ruled-out. We analyzed both standard and extended coagulation parameters, including thromboplastin time (INR), activated partial thromboplastin time (aPTT), antithrombin, plasminogen, plasminogen activator inhibitor-1 (PAI-1), D-dimers, and fibrinogen at admission, as well as α2-antiplasmin, activated protein C -resistance, factor V, lupus anticoagulant, protein C, protein S, and von Willebrand diagnostics. These data, as well as mortality and further laboratory parameters, were compared across groups based on COVID-19 diagnosis and severity of disease. In patients with COVID-19, we detected frequent clotting abnormalities, including D-dimers. The comparison cohort in the ED, however, showed similarly altered coagulation. Furthermore, parameters previously shown to distinguish between severe and moderate COVID-19 courses, such as platelets, plasminogen, fibrinogen, aPTT, INR, and antithrombin, as well as multiple nonroutine coagulation analytes showed no significant differences between patients with and without COVID-19 when presenting to the ED. At admission to the ED the prevalence of coagulopathy in patients with COVID-19 is high, yet comparable to the non-COVID-19 cohort presenting with respiratory symptoms. Nevertheless, coagulopathy might worsen during disease progression with the need of subsequent risk stratification.

5.
Biomarkers ; 26(3): 213-220, 2021 May.
Article in English | MEDLINE | ID: covidwho-1030957

ABSTRACT

BACKGROUND: In the emergency department (ED) setting, rapid testing for SARS-CoV-2 is likely associated with advantages to patients and healthcare workers, for example, enabling early but rationale use of limited isolation resources. Most recently, several SARS-CoV-2 rapid point-of-care antigen tests (AGTEST) became available. There is a growing need for data regarding their clinical utility and performance in the diagnosis of SARS-CoV-2 infection in the real life setting EDs. METHODS: We implemented AGTEST (here: Roche/SD Biosensor) in all four adult and the one paediatric EDs at Charité - Universitätsmedizin Berlin in our diagnostic testing strategy. Test indication was limited to symptomatic suspected COVID-19 patients. Detailed written instructions on who to test were distributed and testing personnel were trained in proper specimen collection and handling. In each suspected COVID-19 patient, two sequential deep oro-nasopharyngeal swabs were obtained for viral tests. The first swab was collected for nucleic acid testing through SARS-CoV-2 real-time reverse transcriptase (rt)-PCR diagnostic panel (PCRTEST) in the central laboratory. The second swab was collected to perform the AGTEST. Analysis of routine data was prospectively planned and data were retrieved from the medical records after the inclusion period in the adult or paediatric ED. Diagnostic performance was calculated using the PCRTEST as reference standard. False negative and false positive AGTEST results were analysed individually and compared with viral concentrations derived from the calibrated PCRTEST. RESULTS: We included n = 483 patients including n = 202 from the paediatric ED. N = 10 patients had to be excluded due to missing data and finally n = 473 patients were analysed. In the adult cohort, the sensitivity of the AGTEST was 75.3 (95%CI: 65.8/83.4)% and the specificity was 100 (95%CI: 98.4/100)% with a SARS-CoV-2 prevalence of 32.8%; the positive predictive value was 100 (95%CI: 95.7/100)% and the negative predictive value 89.2 (95%CI: 84.5/93.9)%. In the paediatric cohort, the sensitivity was 72.0 (95%CI: 53.3/86.7)%, the specificity was 99.4 (95%CI:97.3/99.9)% with a prevalence of 12.4%; the positive predictive value was 94.7 (95%CI: 78.3/99.7)% and the negative predictive value was 96.2 (95%CI:92.7/98.3)%. Thus, n = 22 adult and n = 7 paediatric patients showed false negative AGTEST results and only one false positive AGTEST occurred, in the paediatric cohort. Calculated viral concentrations from the rt-PCR lay between 3.16 and 9.51 log10 RNA copies/mL buffer. All false negative patients in the adult ED cohort, who had confirmed symptom onset at least seven days earlier had less than 5 × 105 RNA copies/mL buffer. CONCLUSIONS: We conclude that the use of AGTEST among symptomatic patients in the emergency setting is useful for the early identification of COVID-19, but patients who test negative require confirmation by PCRTEST and must stay isolated until this result becomes available. Adult patients with a false negative AGTEST and symptom onset at least one week earlier have typically a low SARS-CoV-2 RNA concentration and are likely no longer infectious.


Subject(s)
Antigens, Viral/blood , COVID-19/diagnosis , Emergency Service, Hospital , Immunoassay/methods , SARS-CoV-2/immunology , COVID-19/virology , Humans , SARS-CoV-2/isolation & purification
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