Improving the accuracy of clinical interpretation of serological testing for the diagnosis of acute hepatitis a infection.

BACKGROUND: Hepatitis A (HA) remains a common infection globally that results in a self-limiting hepatitis with gastrointestinal and systemic symptoms. Direct detection of the virus in blood or stool is often not possible once symptomatic. Serological testing is frequently performed to investigate abnormal liver function tests - and interpretation of equivocal and low-level positive anti-hepatitis A virus (HAV) IgM is difficult even in the context of accurate epidemiological and clinical information. OBJECTIVES: The aim of this project was to characterise the association between low-level reactive anti-HAV IgM results and clinical disease. STUDY DESIGN: Anti-HAV serology results recorded over 22 months were analysed. Equivocal and positive Architect anti-HAV IgM results were matched with available clinical and demographical data to identify confirmed and probable cases of acute HAV infection. RESULTS: Reactive anti-HAV IgM results were recorded for 88/7661 (1.15%) samples. Using clinical and laboratory data, 35 patients were confirmed to have acute HAV infection. Acute HA was associated with a mean Architect anti-HAV IgM value of 9.4 (SD 6.8-12.0). Cases of HA had a mean peak ALT value of 1920 (SD 682-3158). All confirmed cases (35/35) of acute HAV were associated with at least one clinical indicator, with 28/31 cases (90%) having a documented jaundice. All 35 (100%) cases of acute HAV infection had anti-HAV IgM > 4.0. A diagnosis other than acute HA was identified in 7/11 (63.6%) of low-level reactive anti-HAV IgM results (clinical data unavailable for further 4/11, 36.3%). Where clinical information was available, acute HA was excluded in all 31 patients with equivocal or low-level reactive anti-HAV IgM results. CONCLUSIONS: The accuracy of reports sent out to the clinician showed room for improvement. An interpretive algorithm is proposed including a clinically significant cut-off value for anti-HAV IgM.

Bizarre Chorionic-type Trophoblast in Second-trimester and Third-trimester Placentas: Clinicopathologic Characterization of a Placental Pseudoneoplastic Lesion.

Bizarre (atypical/symplastic) cells have been described in various gynecologic normal tissues and benign neoplasms. This type of bizarre cytologic change is usually an incidental finding and is regarded as a benign process. We describe 17 cases of bizarre chorionic-type trophoblast in second-trimester and third-trimester placentas that created concern for an underlying/undersampled or incipient intraplacental trophoblastic neoplasm, predominantly found in intervillous trophoblastic islands (11/17), placental septae (6/17), chorionic plate (1/17), and/or the chorion layer of fetal membranes (2/17). The bizarre trophoblastic cells exhibited sheet-like or nested architecture, had a multifocal/patchy distribution, and/or were present as individual cells within hyaline stroma; they were characterized by large nuclei with smudgy chromatin and occasional intranuclear pseudoinclusions. The degree of atypia was classified as mild (0/17), moderate (3/17), or severe (14/17). Mitotic figures and necrosis were not identified. A dual immunohistochemical stain for trophoblast (hydroxyl-delta-5-steroid dehydrogenase) and a proliferation marker (Ki-67), performed in 15 cases, demonstrated 0% to very low proliferative activity within the bizarre trophoblast (0% to 2% [10/15], 3% to 8% [5/15]). Immunohistochemical stains for fumarate hydratase showed intact/retained expression in the bizarre cells in 7 of 7 cases. Clinical follow-up ranged from 1 to 45 months, and all patients were alive and well without subsequent evidence of a gestational trophoblastic or other neoplasms. We conclude that bizarre chorionic-type trophoblast in second-trimester or third-trimester placentas have the potential to mimic an intraplacental trophoblastic neoplasm but are likely a benign degenerative change. This study expands the spectrum of bizarre cells that occur in the gynecologic tract.

Evaluation of 2 commercial anti-SARS-CoV-2 antibody assays in an immunocompetent and immunocompromised inpatient population with COVID-19.

INTRODUCTION: During the COVID-19 pandemic, widespread introduction of SARS-CoV-2 antibody testing was introduced without a full understanding of the assays performance or the antibody kinetics following infection with SARS-CoV-2. METHODS: We performed an evaluation of 2 anti-SARS-CoV-2 antibody assays with a more detailed look into the effect of immune status on antibody sensitivity. RESULTS: Both assays demonstrated 100% specificity. The overall sensitivity of the Roche was 92.1% at ≥14 days and 94.8% at ≥21 days, and the overall sensitivity of the Abbott was 94.4% at ≥14 days and 98.2% at ≥21 days. 7/41 (17%) of patients included in this cohort were immunocompromised. Seroconversion was seen less commonly in the immunocompromised (4/7 [57.1%] seroconverted) and after excluding these patients 100% sensitivity was seen in both assays at ≥21 days. DISCUSSION: Performance of both assays in the immunocompetent appeared excellent after 21 days postsymptom onset. Both assays are highly specific.

Disparities of SARS-CoV-2 Nucleoprotein-Specific IgG in Healthcare Workers in East London, UK.

Introduction: SARS-CoV-2 antibody detection serves as an important diagnostic marker for past SARS-CoV-2 infection and is essential to determine the spread of COVID-19, monitor potential COVID-19 long-term effects, and to evaluate possible protection from reinfection. A study was conducted across three hospital sites in a large central London NHS Trust in the UK, to evaluate the prevalence and duration of SARS-CoV-2 IgG antibody positivity in healthcare workers. Methods: A matrix equivalence study consisting of 228 participants was undertaken to evaluate the Abbott Panbio™ COVID-19 IgG/IgM rapid test device. Subsequently, 2001 evaluable healthcare workers (HCW), representing a diverse population, were enrolled in a HCW study between June and August 2020. A plasma sample from each HCW was evaluated using the Abbott Panbio™ COVID-19 IgG/IgM rapid test device, with confirmation of IgG-positive results by the Abbott ArchitectTM SARS-CoV-2 IgG assay. 545 participants, of whom 399 were antibody positive at enrolment, were followed up at 3 months. Results: The Panbio™ COVID-19 IgG/IgM rapid test device demonstrated a high concordance with laboratory tests. SARS-CoV-2 antibodies were detected in 506 participants (25.3%) at enrolment, with a higher prevalence in COVID-19 frontline (28.3%) than non-frontline (19.9%) staff. At follow-up, 274/399 antibody positive participants (68.7%) retained antibodies; 4/146 participants negative at enrolment (2.7%) had seroconverted. Non-white ethnicity, older age, hypertension and COVID-19 symptoms were independent predictors of higher antibody levels (OR 1.881, 2.422-3.034, 2.128, and 1.869 respectively), based on Architect™ index quartiles; participants in the first three categories also showed a greater antibody persistence at 3 months. Conclusion: The SARS-CoV-2 anti-nucleocapsid IgG positivity rate among healthcare staff was high, declining by 31.3% during the 3-month follow-up interval. Interestingly, the IgG-positive participants with certain risk factors for severe COVID-19 illness (older age, Black or Asian Ethnicity hypertension) demonstrated greater persistence over time when compared to the IgG-positive participants without these risk factors.

Genomic diversity of SARS-CoV-2 during early introduction into the Baltimore-Washington metropolitan area.

The early COVID-19 pandemic was characterized by rapid global spread. In Maryland and Washington, DC, United States, more than 2500 cases were reported within 3 weeks of the first COVID-19 detection in March 2020. We aimed to use genomic sequencing to understand the initial spread of SARS-CoV-2 - the virus that causes COVID-19 - in the region. We analyzed 620 samples collected from the Johns Hopkins Health System during March 11-31, 2020, comprising 28.6% of the total cases in Maryland and Washington, DC. From these samples, we generated 114 complete viral genomes. Analysis of these genomes alongside a subsampling of over 1000 previously published sequences showed that the diversity in this region rivaled global SARS-CoV-2 genetic diversity at that time and that the sequences belong to all of the major globally circulating lineages, suggesting multiple introductions into the region. We also analyzed these regional SARS-CoV-2 genomes alongside detailed clinical metadata and found that clinically severe cases had viral genomes belonging to all major viral lineages. We conclude that efforts to control local spread of the virus were likely confounded by the number of introductions into the region early in the epidemic and the interconnectedness of the region as a whole.