SARS-CoV-2 anti-nucleocapsid assay performance in healthcare workers at baseline and 6 months.

INTRODUCTION: Serological SARS-CoV-2 assays have an important role in guiding the pandemic response. This research aimed to compare the performance of 2 antinucleocapsid assays. METHODS: Serum from 49 HCWs was analysed at baseline and 6 months using the Abbott diagnostics SARS-CoV-2 IgG assay and the Roche Diagnostics Elecsys Anti-SARS-CoV-2 total antibody assay. RESULTS: At baseline, 14/49 participants (29%) demonstrated antibody reactivity using the Abbott assay. At 6 months, 4/14 participants (29%) continued to demonstrate reactivity. A total of 14/49 (29%) participants had detectable antibodies at baseline using the Roche assay. In total, 13/14 (93%) of participants demonstrated antibody reactivity at 6 months. The Abbott assay showed a statistically significant difference in the signal-to-threshold values of baseline reactive samples when repeated at 6 months (p = 0.001). This was not seen with the Roche assay (p = 0.51). CONCLUSION: In this small study, the Roche Diagnostics Elecsys Anti-SARS-CoV-2 total antibody assay appears superior in performance to the Abbott diagnostics SARS-CoV-2 IgG assay in accurately detecting participants with a history of confirmed COVID-19 disease at 6 months follow-up. This finding should be born in mind in the planning of future seroprevalence studies, especially when considering the use of anti-nucleocapsid assays.

SARS-CoV-2 Antibody Testing in Health Care Workers: A Comparison of the Clinical Performance of Three Commercially Available Antibody Assays.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies are an excellent indicator of past COVID-19 infection. As the COVID-19 pandemic progresses, retained sensitivity over time is an important quality in an antibody assay that is to be used for the purpose of population seroprevalence studies. We compared 5,788 health care worker (HCW) serum samples by using two serological assays (Abbott SARS-CoV-2 anti-nucleocapsid immunoglobulin G (IgG) and Roche anti-SARS-CoV-2 anti-nucleocapsid total antibody) and a subset of samples (all Abbott assay positive or grayzone, n = 485) on Wantai SARS-CoV-2 anti-spike antibody enzyme-linked immunosorbent assay (ELISA). For 367 samples from HCW with a previous PCR-confirmed SARS-CoV-2 infection, we correlated the timing of infection with assay results. Overall, seroprevalence was 4.2% on Abbott and 9.5% on Roche. Of those with previously confirmed infection, 41% (150/367) and 95% (348/367) tested positive on Abbott and Roche, respectively. At 21 weeks (150 days) after confirmed infection, positivity on Abbott started to decline. Roche positivity was retained for the entire study period (33 weeks). Factors associated (P ≤ 0.050) with Abbott seronegativity in those with previous PCR-confirmed infection included sex (odds ratio [OR], 0.30 male ; 95% confidence interval [CI], 0.15 to 0.60), symptom severity (OR 0.19 severe symptoms; 95% CI, 0.05 to 0.61), ethnicity (OR, 0.28 Asian ethnicity; 95% CI, 0.12 to 0.60), and time since PCR diagnosis (OR, 2.06 for infection 6 months previously; 95% CI, 1.01 to 4.30). Wantai detected all previously confirmed infections. In our population, Roche detected antibodies up to at least 7 months after natural infection with SARS-CoV-2. This finding indicates that the Roche total antibody assay is better suited than Abbott IgG assay to population-based studies. Wantai demonstrated high sensitivity, but sample selection was biased. The relationship between serological response and functional immunity to SARS-CoV-2 infection needs to be delineated. IMPORTANCE As the COVID-19 pandemic progresses, retained sensitivity over time is an important quality in an antibody assay that is to be used for the purpose of population seroprevalence studies. There is a relative paucity of published literature in this field to help guide public health specialists when planning seroprevalence studies. In this study, we compared results of 5,788 health care worker blood samples tested by using two assays (Roche and Elecsys, anti-nucleocapsid antibody) and by testing a subset on a third assay (Wantai enzyme-linked immunosorbent assay [ELISA] anti-spike antibody). We found significant differences in the performance of these assays, especially with distance in time from PCR-confirmed COVID-19 infection, and we feel these results may significantly impact the choice of assay for others conducting similar studies.

Interaction of bacteria and stem cells in health and disease.

Adult stem and progenitor cells possess unique qualities of proliferative capacity and phenotypic plasticity making their potential interactions with pathogenic and commensal bacteria a significant factor in health and disease. This interaction may result in the hindrance of regenerative capacity and degenerative disease. In other contexts, bacterial-stem cell cross-talk plays an important role in regulating stem cell renewal and maintaining homeostasis. Some stems cells are involved in combating infections and modulating immune responses. The results of these interactions contribute significantly to the outcome of infectious disease. The unique characteristics of stem and progenitor cells also make them attractive targets for bacterial pathogenicity strategies. Several bacterial species have been shown to utilize stem cells as cellular niches or as a means to manipulate host-pathogen interactions. In some cases, bacteria can reprogram end-differentiated tissue cells towards stem-like cells, taking advantage of their unique properties for dissemination and persistence. The ability of bacteria to interfere in stem cell regulatory pathways can also contribute to hyperplastic growth and the development of cancer. In this review, we present current knowledge on the diverse interactions between bacteria and stem cells highlighting the consequences for health and disease.

Prevalence of multidrug-resistant organisms in refugee patients, medical tourists and domestic patients admitted to a German university hospital.

BACKGROUND: Patients with contact to healthcare-system in high-prevalence countries (HPC) and refugee patients in hospital settings (REF) have previously been identified to be at risk of carrying multidrug-resistant organisms (MDRO). Comparative studies addressing the epidemiology of MDRO in patients transferred from hospitals abroad (ABROAD) and REF are lacking but are necessary to introduce refined infection control measures. METHODS: From December 2015 to June 2016, 117 REF, 84 ABROAD and 495 patients admitted to intensive care unit, with no refugee history or pre-treatment abroad (ICU), at University Hospital Frankfurt, Germany (UHF) were screened for MDRO on day of admittance. Data within these groups were compared and set in an epidemiological context. RESULTS: 52.1% (95% confidence interval = 42.7-61.5) of REF and 41.6% (31.0-52.9) of ABROAD, were positive for at least one MDRGN, respectively. In contrast, 7.9% (5.6-10.6) of ICU were positive for MDRGN. Thereof, 0.9% (0.0-4.7) of REF, 15.5% (8.5-25.0) of ABROAD and 0% (0.0-0.7) of ICU were positive for at least one MDRGN with carbapenem resistance (CR). In total, 19 MDRGN with CR were detected in ABROAD, with the most frequent species with CR being A. baumannii with 42.1% (20.3-66.5). Regarding MRSA, 10.3% (5.4-17.2) of REF, 5.9% (1.9-13.3) of ABROAD and a significantly lower proportion 1.4% (0.6-2.9) of ICU, respectively, were tested positive. CONCLUSIONS: Both REF and ABROAD pose a relevant hospital hygiene risk. High prevalence of MDRGN with CR in ABROAD was observed. Concise screening and infection control guidelines are needed in patient cohorts with increased risk for MDRO carriage.

Bartonella spp. - a chance to establish One Health concepts in veterinary and human medicine.

Infectious diseases remain a remarkable health threat for humans and animals. In the past, the epidemiology, etiology and pathology of infectious agents affecting humans and animals have mostly been investigated in separate studies. However, it is evident, that combined approaches are needed to understand geographical distribution, transmission and infection biology of "zoonotic agents". The genus Bartonella represents a congenial example of the synergistic benefits that can arise from such combined approaches: Bartonella spp. infect a broad variety of animals, are linked with a constantly increasing number of human diseases and are transmitted via arthropod vectors. As a result, the genus Bartonella is predestined to play a pivotal role in establishing a One Health concept combining veterinary and human medicine.

Multidrug-resistant organisms detected in refugee patients admitted to a University Hospital, Germany June‒December 2015.

Multidrug-resistant Gram-negative bacteria (MDR GNB) were found to colonise 60.8% (95% confidence interval: 52.3-68.9) of 143 refugee patients mainly from Syria (47), Afghanistan (29), and Somalia (14) admitted to the University Hospital Frankfurt, Germany, between June and December 2015. This percentage exceeds the prevalence of MDR GNB in resident patients four-fold. Healthcare personnel should be aware of this and the need to implement or adapt adequate infection control measures.

Reprogramming of myeloid angiogenic cells by Bartonella henselae leads to microenvironmental regulation of pathological angiogenesis.

The contribution of myeloid cells to tumour microenvironments is a decisive factor in cancer progression. Tumour-associated macrophages (TAMs) mediate tumour invasion and angiogenesis through matrix remodelling, immune modulation and release of pro-angiogenic cytokines. Nothing is known about how pathogenic bacteria affect myeloid cells in these processes. Here we show that Bartonella henselae, a bacterial pathogen causing vasculoproliferative diseases (bacillary angiomatosis), reprogrammes human myeloid angiogenic cells (MACs), a pro-angiogenic subset of circulating progenitor cells, towards a TAM-like phenotype with increased pro-angiogenic capacity. B. henselae infection resulted in inhibition of cell death, activation of angiogenic cellular programmes and induction of M2 macrophage polarization. MACs infected with B. henselae incorporated into endothelial sprouts and increased angiogenic growth. Infected MACs developed a vascular mimicry phenotype in vitro, and expression of B. henselae adhesin A was essential in inducing these angiogenic effects. Secretome analysis revealed that increased pro-angiogenic activities were associated with the creation of a tumour-like microenvironment dominated by angiogenic inflammatory cytokines and matrix remodelling compounds. Our results demonstrate that manipulation of myeloid cells by pathogenic bacteria can contribute to microenvironmental regulation of pathological tissue growth and suggest parallels underlying both bacterial infections and cancer.

Adhesins of Bartonella spp.

Adhesion to host cells represents the first step in the infection process and one of the decisive features in the pathogenicity of Bartonella spp. B. henselae and B. quintana are considered to be the most important human pathogenic species, responsible for cat scratch disease, bacillary angiomatosis, trench fever and other diseases. The ability to cause vasculoproliferative disorders and intraerythrocytic bacteraemia are unique features of the genus Bartonella. Consequently, the interaction with endothelial cells and erythrocytes is a focus in Bartonella research. The genus harbours a variety of trimeric autotransporter adhesins (TAAs) such as the Bartonella adhesin A (BadA) of B. henselae and the variably expressed outer-membrane proteins (Vomps) of B. quintana, which display remarkable variations in length and modular construction. These adhesins mediate many of the biologically-important properties of Bartonella spp. such as adherence to endothelial cells and extracellular matrix proteins and induction of angiogenic gene programming. There is also significant evidence that the laterally acquired Trw-conjugation systems of Bartonella spp. mediate host-specific adherence to erythrocytes. Other potential adhesins are the filamentous haemagglutinins and several outer membrane proteins. The exact molecular functions of these adhesins and their interplay with other pathogenicity factors (e.g., the VirB/D4 type 4 secretion system) need to be analysed in detail to understand how these pathogens adapt to their mammalian hosts.

Bartonella spp.: throwing light on uncommon human infections.

After 2 decades of Bartonella research, knowledge on transmission and pathology of these bacteria is still limited. Bartonella spp. have emerged to be important pathogens in human and veterinary medicine. For humans, B. henselae is considered to represent the most relevant zoonotic Bartonella species and is responsible for cat scratch disease, bacillary angiomatosis, and other disorders. Over the years, many Bartonella species have been isolated from humans, cats, dogs, and other mammals, and infections range from an asymptomatic state (e.g., animal-specific species) to even life-threatening diseases (e.g., Oroya fever). It is obvious that the analysis of pathogenicity mechanisms underlying Bartonella infections is needed to increase our understanding of how these pathogens adapt to their mammalian hosts resulting in acute or chronic diseases.