European Journal of Clinical Microbiology & Infectious Diseases

Zhang, Pingping; Gao, Qi; Wang, Tang; Ke, Yuehua; Mo, Fei; Jia, Ruizhong; Liu, Wanbing; Liu, Lei; Zheng, Shangen; Liu, Yuzhen; Li, Luping; Wang, Yao; Xu, Lei; Hao, Kun; Min, Wei; Liu, Xiaoli; Yang, Ruifu; Li, Shiyue; Lin, Changqing; Zhao, Yong

doi: 10.1007/s10096-020-04102-4pmid: 33184753

Serological test is a valuable diagnostic tool for coronavirus disease 2019 (COVID-19). However, considerable improvements to these tests are needed, especially in the detection sensitivity. In this study, six recombinant nucleocapsid and spike proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were prepared and evaluated, including three prokaryotic expression nucleocapsid proteins (rN, rN1, rN2) and three eukaryotic expression spike proteins (rS1, rS-RBD, rS-RBD-mFc). The recombinant proteins with the highest ELISA titers (rS1 and rS-RBD-mFc) were selected to develop a double-antigen sandwich colloidal gold immunochromatography assay (GICA) to detect total antibodies against SARS-CoV-2. The clinical evaluation results showed that the sensitivity and specificity of GICA were 92.09% (419/455) and 99.44% (706/710), respectively. Moreover, a significant number (65.63%, 21/32) of COVID-19 patients with undetectable viral RNA were correctly diagnosed by the GICA method. In conclusion, the eukaryotic expression spike proteins (rS1 and rS-RBD-mFc) are more suitable than the prokaryotic expression nucleocapsid proteins for serological diagnosis of SARS-CoV-2. The proposed GICA for detection of total antibodies could be a powerful complement to the current RNA tests for COVID-19.

You, Enqing; Wang, Ling; Zhang, Lei; Wu, Jinju; Zhao, Kefu; Huang, Fen

doi: 10.1007/s10096-020-04098-xpmid: 33188497

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by the SFTS virus (SFTSV) of family Phenuiviridae. Since the virus was first identified in 2009, it has been rapidly spread in many Asian countries including Myanmar, Korea, Japan, and central China. In this study, we investigated the epidemiological characteristics of SFTS patients in Hefei from 2011 to 2018. In addition, we conducted a serological survey of SFTSV-specific antibody among healthy residents of five counties. We performed a retrospective observational study of SFTS cases reported to Hefei Center for Disease Control and Prevention (CDC) during Jan 2011 to Dec 2018. Almost every patient completed a structure questionnaire including clinical examination, course of disease, and history of epidemiology. A total of 754 serum specimens were collected and tested for IgG antibody with double-antigen sandwich ELISA method. Of 257 cases reported during that period, 33 died, with a case fatality rate of 13.0%. We found no significant difference between 30 non-survivors and 198 survivors except for age. The overall rate of seropositivity for SFTSV antibodies among healthy residents were 20.16%. We demonstrated that living in hilly areas, direct contact with domestic livestock and knowledge of tick-borne disease were significantly associated with positive serology result. SFTSV infection was prevalent among farming-related populations. Our study identified a relatively high seroprevalence of SFTSV-specific antibody in healthy residents, which provided the basis for asymptomatic SFTSV infections. More attention should be given to susceptible population and prevent SFTSV outbreak in high-endemic areas.

Ogura, Sho; Kimura, Muneyoshi; Takagi, Shinsuke; Mitsuki, Takashi; Yuasa, Mitsuhiro; Kageyama, Kosei; Kaji, Daisuke; Nishida, Aya; Taya, Yuki; Ishiwata, Kazuya; Yamamoto, Hisashi; Asano-Mori, Yuki; Yamamoto, Go; Uchida, Naoyuki; Wake, Atsushi;

Wu, Yuhong; Yan, Li; Wang, Huaquan; Liu, Hong; Xing, Limin; Fu, Rong; Shao, Zonghong

doi: 10.1007/s10096-020-04054-9pmid: 33219473

The aim of this study is to compare the curative effect of empirical with diagnostic-driven (pre-emptive) therapy of voriconazole in severe aplastic anaemia patients (SAAs) with invasive fungal disease (IFD) after intensive immunosuppressive therapy (IST). Patients undergoing voriconazole antifungal therapy were randomized to empirical therapy group and diagnostic-driven therapy group. Empirical therapy group accounted for 48.5% of all cases, and diagnostic-driven therapy group accounted for 51.5%. The morbidity of IFD (probable and proven cases) was slightly increased in diagnostic-driven therapy group compared with empirical therapy group (P > 0.05). The total effective rate was 62.1%. The effective rate in empirical therapy group was 78.1%, which was significantly increased compared with diagnostic-driven therapy group (47.1%) (P < 0.05). This value was especially significant in possible IFD cases (P < 0.05). The efficacy of possible IFD cases in empirical therapy group was the best (84%) followed by the probable and proven cases in empirical therapy group (57.1%). In diagnostic-driven therapy group, the efficacy of possible IFD cases was 50%, and the efficacy of probable and proven cases was only 37.5%. The difference was statistically significant (P < 0.05). Absolute neutrophil count (ANC) is the key anti-infection factor. The efficacy of patients whose ANC ˂ 0.1 × 109/L was 39.28%, which was significantly reduced compared with that of patients whose ANC ≥ 0.1 × 109/L (78.95%) (P < 0.05). This finding was especially obvious in diagnostic-driven therapy group. As empirical therapy is superior to diagnostic-driven therapy, we recommend that empirical therapy should be started for high-risk patients, and efforts should be made to definitively diagnose the disease.

Gutiérrez-Cobos, Ainhoa; Gómez de Frutos, Sara; Domingo García, Diego; Navarro Lara, Eva; Yarci Carrión, Ayla; Fontán García-Rodrigo, Leticia; Fraile Torres, Arturo Manuel; Cardeñoso Domingo, Laura

doi: 10.1007/s10096-020-04092-3pmid:

Sacristan, María Simón; Collazos-Blanco, Ana; Cintas, Maria Isabel Zamora; García, Alicia Serrano; de Villavicencio, Carmen Ybarra; Maestre, María Mateo

doi: 10.1007/s10096-020-04091-4pmid: 33236270

Coronavirus disease-19 (COVID19), the novel respiratory illness caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), is associated with severe morbidity and mortality. The aim of our study was to compare different immunoassays. We evaluated three immunochromatographic test (The StrongStep®SARS-CoV-2 IgG/IgM kit, AllTest COV-19 IgG/IgM kit, and Wondfo® SARS-CoV-2 Antibody) and two chemiluminescence immunoassays (CMIA) (Covid-19 VIRCLIA® IgM+IgA/IgG monotest and the Abbott SARS-CoV-2 IgG assay) in COVID-19 patients. The assays were performed using serum samples of three group patients, i.e., healthy controls, patients with SARS-CoV-2 PCR positive, and patients with SARS-CoV-2 PCR negative clinically diagnosed of COVID-19 infection. The detection percentages of IgG with the StrongStep® SARS-CoV-2 IgG/IgM kit and AllTest COV-19 IgG/IgM kit were similar in both groups (83.3% and 80.6%, respectively in group 2, p = 0.766) and (42.9% and 50.0%, respectively in group 3, p = 0.706). There were some differences on IgM detection between StrongStep® SARS-CoV-2 IgG/IgM kit and AllTest COV-19 IgG/IgM kit (11.1% and 30.6%, respectively in group 2, p = 0.042 and 0.0% and 28.6%, respectively in group 3, p = 0.031). The positive rate of IgG in group 2 is higher compared to group 3 with the two immunoassays tested. We observe the same positive rates of IgG with the two CMIA. Our study shows excellent performance of CMIA compared to immunochromatographic test and confirms its potential use in the diagnosis of the new SARS-CoV-2.

Zheng, Hong; Zhong, Fangming; Yu, Guocan; Shen, Yanqin

doi: 10.1007/s10096-020-04113-1pmid: 33242168

To compare the diagnostic efficacy of CapitalBio Mycobacterium real-time polymerase chain reaction (RT-PCR) detection test and the first-generation Xpert MTB/RIF in smear-negative pulmonary tuberculosis (PTB). In this retrospective study of smear-negative PTB, we reviewed patient medical records to determine the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of Xpert MTB/RIF, CapitalBio Mycobacterium detection test, and the parallel test (positive result for either of the Xpert MTB/RIF and CapitalBio Mycobacterium detection tests) to evaluate their diagnostic accuracy against a composite reference standard. In total, 1553 patients were evaluated. The sensitivity, specificity, PPV, NPV, and AUC of Xpert MTB/RIF, CapitalBio Mycobacterium detection test, and the parallel test were 57.1%, 92.9%, 81.1%, 95.9%, and 0.75; 53.4%, 97.7%, 98.6%, 41.5%, and 0.76; and 66.2%, 90.8%, 95.5%, 47.7%, and 0.79, respectively. For the bronchoalveolar lavage fluid (BALF) specimens, these values for Xpert MTB/RIF, CapitalBio Mycobacterium detection test, and the parallel test were 68.8%, 97.7%, 99.2%, 43.9%, and 0.83; 61.7%, 97.7%, 99.1%, 38.9%, and 0.80; and 77.0%, 95.5%, 98.6%, 50.9%, and 0.86, respectively. CapitalBio Mycobacterium detection test had moderate accuracy for smear-negative PTB, similar to Xpert MTB/RIF. The parallel test improved the sensitivity. BALF significantly improved the sensitivity and diagnostic accuracy of the test. The maximum diagnostic accuracy for smear-negative PTB was obtained with the parallel test and BALF specimens. BALF was the most effective specimen for diagnosing smear-negative PTB.

Berneking, Laura; Both, Anna; Berinson, Benjamin; Hoffmann, Armin; Lütgehetmann, Marc; Aepfelbacher, Martin; Rohde, Holger

doi: 10.1007/s10096-020-04094-1pmid: 33245470

Increasing worldwide, prevalence of carbapenem-resistant gram-negative bacteria demands urgent a need for rapid detection and accurate identification of carbapenemases. The BD Phoenix CPO detect (PCD) assay possesses an in-built capacity for parallel susceptibility testing and detection of carbapenemases. Here, the ability of the assay to detect and classify carbapenemase production was tested in a collection of carbapenem-resistant Enterobacterales and non-fermentative gram-negative rods. The ability of the PCD assay to detect and classify carbapenemases was investigated in a collection of 194 clinical, carbapenem-resistant isolates (Enterobacterales [n = 65]; non-fermentative gram-negative rods [n = 129]). AST results were compared to MICS determined by gradient diffusion to determine accuracy of the PCD assay. The accuracy of the PCD assay to detect carbapenemases was compared to the results of molecular isolate characterization using a LDT multiplex carbapenemase PCR assay. All 194 isolates classified as carbapenem-resistant by reference susceptibility testing were also classified correctly as CRO by the PCD assay. Performance analysis of the PCD assay to detect carbapenemase production revealed an overall sensitivity of 98.29% and specificity of 17.95% for the detection of carbapenemase production. For the classification of carbapenemases classes A, B, and D, the PCD correctly classified 79.17% Enterobacterales and 67.16% non-fermentative gram-negative rods. The PCD assay is a reliable tool for the detection of carbapenem resistance and allows for parallel analysis of carbapenemase production. However, while sensitivity is high, low specificity in carbapenemase detection and erroneous classification demands mandatory confirmation by alternative methods, especially in non-fermentative gram-negative bacteria.

D’Onofrio, Valentino; Van Steenkiste, Eveline; Meersman, Agnes; Waumans, Luc; Cartuyvels, Reinoud; Van Halem, Karlijn; Messiaen, Peter; Gyssens, Inge C.

doi: 10.1007/s10096-020-04109-xpmid: 33274416

There is a need for a quick assessment of severely ill patients presenting to the hospital. The objectives of this study were to identify clinical, laboratory and imaging parameters that could differentiate between influenza and COVID-19 and to assess the frequency and impact of early bacterial co-infection. A prospective observational cohort study was performed between February 2019 and April 2020. A retrospective cohort was studied early in the COVID-19 pandemic. Patients suspected of sepsis with PCR-confirmed influenza or SARS-CoV-2 were included. A multivariable logistic regression model was built to differentiate COVID-19 from influenza. In total, 103 patients tested positive for influenza and 110 patients for SARS-CoV-2, respectively. Hypertension (OR 6.550), both unilateral (OR 4.764) and bilateral (OR 7.916), chest X-ray abnormalities, lower temperature (OR 0.535), lower absolute leukocyte count (OR 0.857), lower AST levels (OR 0.946), higher LDH (OR 1.008), higher ALT (OR 1.044) and higher ferritin (OR 1.001) were predictive of COVID-19. Early bacterial co-infection was more frequent in patients with influenza (10.7% vs. 2.7%). Empiric antibiotic usage was high (76.7% vs. 84.5%). Several factors determined at presentation to the hospital can differentiate between influenza and COVID-19. In the future, this could help in triage, diagnosis and early management. Clinicaltrial.gov Identifier: NCT03841162

Baron, Sophie Alexandra; Pascale, Léa-Marie; Million, Matthieu; Briantais, Antoine; Durand, Jean-Marc; Hadjadj, Linda; Rolain, Jean-Marc

doi: 10.1007/s10096-020-04080-7pmid: 33184752

We described three clinical cases of pyogenic liver abscess caused by hypervirulent Klebsiella pneumoniae (hvKp) successfully treated by prolonged antibiotherapy, in which one case was complicated by endophthalmitis. Whole genome sequencing helped to confirm the diagnosis of these hvKp strains, which belong to clonal complexes CC86 and CC23 and carried hvKp-associated genes (magA and/or rmpA). This syndrome is increasingly reported in France and Europe and raises questions about the source of infection.