Journal of Clinical Virology最新文献

Background

SARS-CoV-2 variants of concern (VOC) may result in breakthrough infections (BTIs) in vaccinated individuals. The aim of this study was to investigate the effects of full primary (two-dose) COVID-19 vaccination with wild-type-based SARS-CoV-2 vaccines on symptoms and immunogenicity of SARS-CoV-2 VOC BTIs.

Methods

In a longitudinal multicenter controlled cohort study in Bavaria, Germany, COVID-19 vaccinated and unvaccinated non-hospitalized individuals were prospectively enrolled within 14 days of a PCR-confirmed SARS-CoV-2 infection. Individuals were visited weekly up to 4 times, performing a structured record of medical data and viral load assessment. SARS-CoV-2-specific antibody response was characterized by anti-spike-(S)- and anti-nucleocapsid-(N)-antibody concentrations, anti-S-IgG avidity and neutralization capacity.

Results

A total of 300 individuals (212 BTIs, 88 non-BTIs) were included with VOC Alpha or Delta SARS-CoV-2 infections. Full primary COVID-19 vaccination provided a significant effectiveness against five symptoms (relative risk reduction): fever (33 %), cough (21 %), dysgeusia (22 %), dizziness (52 %) and nausea/vomiting (48 %). Full primary vaccinated individuals showed significantly higher 50 % inhibitory concentration (IC₅₀) values against the infecting VOC compared to unvaccinated individuals at week 1 (269 vs. 56, respectively), and weeks 5–7 (1,917 vs. 932, respectively) with significantly higher relative anti-S-IgG avidity (78% vs. 27 % at week 4, respectively).

Conclusions

Full primary COVID-19 vaccination reduced symptom frequencies in non-hospitalized individuals with BTIs and elicited a more rapid and longer lasting neutralization capacity against the infecting VOC compared to unvaccinated individuals. These results support the recommendation to offer at least full primary vaccination to all adults to reduce disease severity caused by immune escape-variants.

Simultaneously characterising the genomic information of coronaviruses and the underlying nasal microbiome from a single clinical sample would help characterise infection and disease. Metatranscriptomic approaches can be used to sequence SARS-CoV-2 (and other coronaviruses) and identify mRNAs associated with active transcription in the nasal microbiome. However, given the large sequence background, unenriched metatranscriptomic approaches often do not sequence SARS-CoV-2 to sufficient read and coverage depth to obtain a consensus genome, especially with moderate and low viral loads from clinical samples. In this study, various enrichment methods were assessed to detect SARS-CoV-2, identify lineages and define the nasal microbiome. The methods were underpinned by Oxford Nanopore long-read sequencing and variations of sequence independent single primer amplification (SISPA). The utility of the method(s) was also validated on samples from patients infected seasonal coronaviruses. The feasibility of profiling the nasal microbiome using these enrichment methods was explored. The findings shed light on the performance of different enrichment strategies and their applicability in characterising the composition of the nasal microbiome.

Background

HTLV-1 infection is a neglected disease. Over 10 million people are infected worldwide, with hot spots of high endemicity across all continents. Roughly 5% of HTLV-1 carriers develop HTLV-1-associated myelopathy (HAM), a progressive subacute neurological disabling disease.

Methods

We report the main features of patients diagnosed with HAM up to date in Spain, a non-endemic country with a relatively high migrant flow from Latin America and Equatorial Africa, where HTLV-1 is endemic.

Results

A total of 451 cases of HTLV-1 had been recorded in Spain until the end of year 2022. HAM had been diagnosed in 58 (12.9%). The current incidence is of 2–3 new cases per year. Women represent 76%. Mean age at diagnosis is 49 years-old. Nearly 60% are Latin Americans. Although sexual transmission is the most likely route of HTLV-1 acquisition, up to 6 individuals had been infected following solid organ transplantation. Rapid onset myelopathy developed in all but one of these transplant recipients from three HTLV-1-positive donors. HTLV-1 subtype 1a transcontinental was the only variant recognized in HAM patients. HTLV-1 proviral load was significantly greater in HAM patients than in asymptomatic HTLV-1 carriers (677 vs 104 HTLV-1 DNA copies/10⁴ PBMC; p = 0.012). Symptom relief medications and physiotherapy have been the only treatment providing some benefit to HAM patients. Neither significant clinical nor virological efficacy was noticed using antiretrovirals in at least 9 HAM patients. Two thirds of HAM patients ended up in a wheelchair and with urinary/fecal sphincter incontinence.

Conclusion

HAM is the most frequent clinical manifestation of HTLV-1 infection in Spain, a non-endemic country. Middle aged women migrants from Latin America are the most frequently affected. Two thirds end up in a wheelchair despite using antiretroviral therapy.

Introduction

Public health measures aimed at controlling transmission of SARS-CoV-2, otherwise known as “lockdown” measures, had profound effects on circulation of non-SARS viruses, many of which decreased to very low levels. The interrupted transmission of these viruses may have lasting effects. Some of the influenza clades seem to have disappeared during this period, a phenomenon which is described as a “funnel effect”. It is currently unknown if the lockdown measures had any effect on the diversity of circulating viruses, other than influenza. Enteroviruses are especially interesting in this context, as the clinical presentation of an infection with a particular enterovirus-type may be clade-dependent.

Methods and materials

Enteroviruses were detected in clinical materials using a 5’UTR-based detection PCR, and partial VP-1 sequences were obtained, using methods described before. All samples with EV detections from a large part of the Netherlands were included in the study. The samples originated from general practitioners, general hospitals, university hospitals and public health offices.

Results

Five EV-genotypes circulated in significant numbers before and after the lockdown, EV-D68, E-11, CV-A6, CV-B5 and CV-A2. All five genotypes showed decreased genetic diversity after the lockdown, and four indicate a significant number of sequences clustering together with a very high sequence homology. Moreover, children with E-11 and CV-B5 detections were significantly older after the lockdown than before.

Conclusions

The reduced enterovirus transmission in the Netherlands during the pandemic, seems to have led to a decrease in genetic diversity in the five most commonly detected enterovirus serotypes

Background

Enterovirus-D68 (EV-D68) has appeared biennially in the United States following the 2014 outbreak. It has gained epidemiologic and clinical relevance and was identified as an important pathogen associated with severe respiratory and central nervous system diseases. We aim to describe the clinical and molecular characteristics of the post-pandemic 2022 Enterovirus-D68 outbreak in children evaluated in a tertiary pediatric hospital in Columbus, Ohio.

Methods

EV-D68 RT-PCR was performed on nasopharyngeal specimens collected during Jun—Nov 2022 from children (<18 years), identified by 1) physician-order or 2) random selection of 10–15 specimens weekly that were Rhinovirus/Enterovirus-positive by physician-ordered respiratory virus panel. Patients who tested positive for EV-D68 were identified and clinical data and outcomes were analyzed. Partial viral VP1 region was sequenced and characterized.

Results

Forty-four children positive for EV-D68 were identified, among which 88.6 % of patients presented with respiratory symptoms and 61.4 % required PICU admission. Two patients presented with AFM that was attributed to EV-D68. EV-D68 sequences from 2022 clustered within the B3 subclade.

Conclusions

A significant proportion of children identified with EV-D68 during the 2022 outbreak had respiratory compromise requiring PICU admission. As the virus continues evolving, it is important to monitor the activity of EV-D68, characterizing these strains clinically and genetically, which will help to understand the viral pathogenicity and virulence.

Background

The adverse impact of Zika (ZIKV), dengue (DENV), and chikungunya (CHIKV) virus infection in pregnancy has been recognized in Latin America and Asia but is not well studied in Africa. Although originally discovered in sub-Saharan Africa the non-specific clinical presentation of arbovirus infection may have hampered our detection of adverse clinical outcomes and outbreak.

Objective

This prospective study of arbovirus infection in pregnant women in north-central Nigeria sought to characterize the prevalence of acute arbovirus infection and determine the impact on pregnancy and infant outcomes.

Methods

In Nigeria, we screened 1006 pregnant women for ZIKV, DENV and CHIKV IgM/IgG by rapid test (2019–2022). Women with acute infection were recruited for prospective study and infants were examined for any abnormalities from delivery through six months. A subset of rapid test-reactive samples were confirmed using virus-specific ELISAs and neutralization assays.

Results

The prevalence of acute infection (IgM+) was 3.8 %, 9.9 % and 11.8 % for ZIKV, DENV and CHIKV, respectively; co-infections represented 24.5 % of all infections. The prevalence in asymptomatic women was twice the level of symptomatic infection. We found a significant association between acute maternal ZIKV/DENV/CHIKV infection and any gross abnormal birth outcome (p = 0.014).

Conclusions

Over three rainy seasons, regular acute infection with ZIKV, DENV, and CHIKV was observed with significantly higher rates in pregnant women without symptoms. The potential association arbovirus infection with abnormal birth outcome warrants further prospective study to ascertain the clinical significance of these endemic arboviruses in Africa.

Background

The National Health Service (NHS) in England commissioned opt-out testing in London Emergency Departments (ED) in April 2022 to allow early identification and management of hepatitis B (HBV) and hepatitis C virus (HCV) infection in patients unaware of their infection status.

Methods

All adults over the age of 16 undergoing blood tests in the ED at the Royal Free Hospital were tested for HBV surface antigen and anti-HCV IgG unless they opted out. Data was collected between the 12th of April and 22nd of August 2022.

Outcome

Of 11,215 patients tested for HCV, 164 patients were found to be anti-HCV IgG positive, giving a seroprevalence rate of 1.46 %. 52 of the anti-HCV IgG positive patients did not have any previous HCV serology result. 23 of the anti-HCV IgG positive patients were also HCV RNA positive giving an RNA seroprevalence of 0.21 %, and 17 of those were new diagnoses of HCV viraemia. For HBV testing, 82 (0.73 %) out of 11,192 patients tested were found to be HBsAg positive, including one patient who presented acutely with a positive HBV core IgM. 39 of the HBsAg positive patients were previously unknown to us; of these, 9 had an HBV viral load of more than 2000 IU/mL, including 3 patients with positive HBV e antigen and one patient with hepatitis D virus co-infection.

Conclusion

Opt-out screening of HBV and HCV in ED is effective at identifying patients with previously undiagnosed viral hepatitis infection and providing an opportunity to engage them in specialist care.

Introduction

CMV serology screening in the first trimester pregnancy is based on IgG and IgM testing followed by IgG avidity in cases with positive IgM. However, the sensitivity of this strategy to diagnose maternal primary infection has been questioned. The objective of the study was to compare this strategy 1 with a strategy 2 consisting of running avidity test on all samples with positive IgG (ignoring IgM results) using fully automated current generation CMV IgG, IgM and IgG avidity assays.

Population and methods

1516 consecutive pregnant women between 12 and 14 weeks were screened in one maternity. Strategy 1 was done prospectively with LIAISON® CMV IgG II and LIAISON® CMV IgM II, followed by LIAISON® CMV IgG Avidity II and VIDAS® CMV IgG avidity II testing in cases with positive or equivocal IgM. Strategy 2 was done retrospectively on the same population and consisted of running avidity with the LIAISON® CMV IgG Avidity II in all samples with positive IgG.

Results

The sensitivity to diagnose a confirmed or a possible maternal primary infection in the first trimester was 91.6 % and 83 % for strategy 1 and 2 respectively (p > 0.99). Strategy 1 missed one possible primary infection and strategy 2 missed 2 confirmed primary infection. Inconclusive results happened in 0 and 0.7 % of samples with strategy 1 and 2 respectively.

Conclusion

This study suggests that strategy 1 has better sensitivity and practicability than strategy 2. However, to achieve a good performance with strategy 1, using highly sensitive IgM assay is mandatory.

Molecular point-of-care (POC) tests offer high sensitivity, rapid turnaround times, relative ease of use, and the convenience of laboratory-grade testing in the absence of formal laboratory spaces and equipment, making them appealing options for infectious disease diagnosis in resource-limited settings. In this review, we discuss the role and potential of molecular POC tests in resource-limited settings and their associated logistical challenges. We discuss U.S. Food and Drug Administration approval, Clinical Laboratory Improvement Amendments complexity levels, and the REASSURED criteria as a starting point for assessing options currently available inside and outside of the United States. We then present POC tests currently in research and development phases that have potential for commercialization and implementation in limited-resource settings. Finally, we review published studies that have assessed the clinical impact of molecular POC testing in limited- and moderate-resource settings.

Diagnosis of gastrointestinal infections has been revolutionized by the development of in vitro diagnostic (IVD) multiplex molecular panels for the detection of viral nucleic acids. In addition to a high degree of accuracy, these panels are commercially available and relatively simple to perform in the clinical laboratory. However, use of these panels must be carefully considered owing to the laboratory costs of the test, limited reimbursement, and potential for overuse. In this review from the Pan American Society for Clinical Virology, we focus on the viral components of GI multiplex panels (GIPs), presenting a brief overview of pathogens included on most panels and a discussion of advantages and challenges of the inclusion of viral targets on GIPs that should be considered before implementation in the clinical laboratory.