Journal of Clinical Virology最新文献

Background

Before the advent of COVID-19 vaccines, hospitalizations due to SARS-CoV-2 infection during 2020 collapsed most medical centers worldwide. Disruptions in health care for clinical conditions other than COVID-19 were not uniform. Herein, we report the impact of COVID-19 on hospitalizations due to viral hepatitis in Spain.

Methods

Retrospective study of all hospitalizations in Spain during 10 months before (pre-pandemic period) and after (pandemic period) March 1st 2020. Admissions with a diagnosis of hepatitis B, C and/or delta were retrieved and compared using the Spanish National Registry of Hospital Discharges.

Results

Nationwide hospitalizations declined 14.6% during the pandemic period, from 3,144,164 to 2,684,845. This reduction was significantly more pronounced for admissions due to viral hepatitis (18.1% drop), falling from 46,521 to 38,115. During the pandemic period, patients admitted with viral hepatitis died significantly more frequently than during the pre-pandemic period (7.2% vs 6.1%; p < 0.001). Liver transplants significantly declined during the pandemic period. COVID-19 was diagnosed in 10.3% of patients hospitalized with viral hepatitis during the pandemic period. This subset of patients was older and died 2.4-fold more frequently than the rest, despite having advanced liver disease less frequently.

Conclusion

Hospitalizations due to viral hepatitis significantly declined in Spain during the COVID-19 pandemic. Patients admitted with viral hepatitis experienced a greater mortality during the pandemic period. Deaths were more pronounced when coinfected with SARS-CoV-2 despite having advanced liver disease less frequently.

Background

The challenges of rapid upscaling of testing capacity were a major lesson from the COVID-19 pandemic response. The need for process adjustments in high-throughput testing laboratories made sample pooling a challenging option to implement.

Objective

This study aimed to evaluate whether pooling samples at source (swab pooling) was as effective as qRT-PCR testing of individuals in identifying cases of SARS-CoV-2 in real-world community testing conditions using the same high-throughput pipeline.

Methods

Two cohorts of 10 (Pool10: 1,030 participants and 103 pools) and 6 (Pool6: 1,284 participants and 214 pools) samples per pool were tested for concordance, sensitivity, specificity, and Ct value differences with individual testing as reference.

Results

Swab pooling allowed unmodified application of an existing high-throughput SARS-Cov-2 testing pipeline with only marginal loss of accuracy. For Pool10, concordance was 98.1% (95% Confidence interval: 93.3–99.8%), sensitivity was 95.7% (85.5–99.5%), and specificity was 100.0% (93.6–100.0%). For Pool6, concordance was 97.2% (94.0–99.0%), sensitivity was 97.5% (93.7–99.3%), and specificity was 96.4% (87.7–99.6%). Differences of outcomes measure between pool size were not significant. Most positive individual samples, which were not detected in pools, had very low viral concentration. If only individual samples with a viral concentration > 400 copies/ml (i.e. Ct value < 30) were considered positive, the overall sensitivity of pooling increased to 99.5%.

Conclusion

The study demonstrated high sensitivity and specificity by swab pooling and the immediate capability of high-throughput laboratories to implement this method making it an option in planning of rapid upscaling of laboratory capacity for future pandemics.

Background

Although cervical screening using Human Papillomavirus (HPV) testing is globally recommended public health policy, there has been no international proficiency studies specifically targeting HPV testing for cervical screening.

Objective

To obtain the first global overview of the current proficiency of HPV testing services for cervical cancer screening.

Study design

A coded proficiency panel of 12 samples containing HPV types 16, 18, 31, 33, 45, 52, 58 or 35/39/51/56/59/68 in human DNA in varying amounts as well as control. Datasets detecting at least a) 10 International Units (IU) of HPV16 and 18, b) 1000 IU of HPV types 31, 33, 45, 52, 58 and c) having no false positives were considered proficient.

Results

In total, 84 laboratories worldwide submitted 158 datasets (some laboratories used >1 HPV testing platform). Of those, 122 (77%) were 100% proficient. Only 14/158 datasets (9%) contained false positive results. Comparison of results with assays approved by the Food and Drug Administration (FDA) suggest that future proficiency requirements should also accommodate assays detecting only 100 IU of HPV16/18. A pool of low oncogenicity HPV types that contributed very little to sensitivity, but adversely affected specificity, was detectable by most datasets.

Conclusion

Internationally recognized proficiency studies of HPV screening, traceable to international standards, provided an overview of current testing performance. There was a high level of proficiency in terms of sensitivity and few false positives, but specificity was not optimal and further research on optimal specificity of HPV screening tests may be warranted.

Even though Brazil is a country where the dengue virus (DENV) is endemic, until recently, Southern states did not have significant viral circulation, such as Rio Grande do Sul (RS), and some municipalities were even considered dengue-free. During 2022, these places have shown a sharp increase in the incidence of the disease, apparently following a worldwide growth pattern. Therefore, in this study, we monitor and characterize the genetic diversity of DENV circulating in southern Brazil through next-generation sequencing during an outbreak in 2022. We generated 70 DENV-1 genome sequences, all characterized as genotype V, divided into two clade clusters in the L1 lineage. Furthermore, unique mutations have been described in each clade of L1 lineage. Our results are essential in managing outbreaks since these data provide important information during the emergence of DENV circulation in RS. Since the south of Brazil has a lower viral circulation when compared to other Brazilian states, RS still lacks data that can help in understanding the transmission, dissemination, and evolution of the dengue virus. Hence, genomic surveillance efforts are essential to increase the accuracy of preventive actions and to control viral dissemination.

Background

Human T-cell leukemia virus type 1 (HTLV-1) is a blood-borne virus, and mandatory testing of donated blood for HTLV-1 antibodies has been adopted by Japanese Red Cross blood centers since 1986. A confirmatory line immunoassay was initiated in 2019 for individuals who were seroreactive in the screening test. This decreased the incidence of indeterminate individuals, however, donors with indeterminate results are not informed of their HTLV-1 seroreactivity and they can continue to donate blood.

Objectives

To clarify the characteristics of indeterminate line immunoassay results among Japanese blood donors.

Study design

Of 759,259 blood donors in the Kyushu district of Japan, an area endemic for HTLV-1, 101 cases were classified as indeterminate by line immunoassay testing. We examined these cases using alternative secondary antibodies, anti-human-Ig (IgG/IgM/IgA) and -IgM antibodies, to detect the early phase of HTLV infection.

Results

Using anti-human-Ig and -IgM antibodies, HTLV infection status was confirmed in 37 individuals (HTLV-1-positive, 2; HTLV-positive, 27; HTLV-negative, 8). Among the remaining 64 indeterminate individuals, we identified one HTLV-2-infected 18-year-old female. A previous blood donation from this individual showed a negative anti-HTLV screening test result (signal-to-cutoff ratio = 0.1). Therefore, this case was considered to be an HTLV-2 seroconversion case.

Conclusions

These results indicate that the procedure for diagnosing HTLV infection should be reconsidered and that an accurate detection system for the early phase of HTLV infection is urgently needed for public health in Japan. Moreover, the issue of HTLV-2 infection needs a higher profile in Japan.

Background

Rapid detection of SARS-CoV-2 is crucial for reduction of transmission and clinical decision-making. Several rapid (<30 min) molecular point-of-care (POC) tests based on nucleic acid amplification exist for diagnosis of SARS-CoV-2 & Influenza A/B infections.

Methods

This unblinded, pre-post study enrolled consecutive patients with symptoms/signs consistent with SARS-CoV-2 infection presenting to the University of California, Davis emergency department (ED). Outcomes following implementation of the cobas® SARS-CoV-2 & Influenza A/B test for use on the cobas Liat System (intervention: December 2020–May 2021) were compared with previous standard-of-care using centralized laboratory reverse transcriptase polymerase chain reaction (RT-PCR) methods (control: April 2020–October 2020).

Results

Electronic health records of 8879 symptomatic patient visits were analyzed, comprising 4339 and 4540 visits and 538 and 638 positive SARS-CoV-2 PCR test results in the control and intervention periods, respectively. Compared with the control period, turnaround time (TAT) was shorter in the intervention period (median 0.98 vs 12.30 h; p < 0.0001). ED length of stay (LOS) was generally longer in the intervention period compared with the control period, but for those SARS-CoV-2-negative who were admitted, ED LOS was shorter (median 12.53 vs 17.93 h; p < 0.0001). The rate of antibiotic prescribing was lower in the intervention than in the control period (42.86% vs 49.16%; p < 0.0001) and antiviral prescribing was higher (7.64% vs 5.49%; p < 0.0001).

Conclusion

This real-world study confirms faster TAT with a POC RT-PCR method in an emergency care setting and highlights the importance of rapid SARS-CoV-2 detection to aid patient management and inform treatment decisions.

Background

Tixagevimab-cilgavimab has been approved as primary pre-exposure prophylaxis in immunocompromised patients as support or replacement for vaccination, even though the Omicron variant of concern (VOC) was spreading at the time.

Objectives

The aim of our study was to evaluate the post-injection neutralising activity (NT₉₀-Abs titre) against the Omicron BA.5 variant in fully vaccinated immunocompromised patients.

Study design

NT₉₀-Abs titres against BA.5 and 20A.EU1 as well as anti-spike and anti-receptor-binding domain IgG were evaluated 0, 14, and 30 d after tixagevimab-cilgavimab administration. The primary end point was NT₉₀-Abs titres ≥ 80 against BA.5 in ≥ 25% of patients, and the secondary end point was NT₉₀-Abs titres ≥ 1280 against 20A.EU1 in >50% of patients on day 14.

Results

At baseline, 35.2%, 37.02%, and 32.5% of booster vaccinated patients exhibited undetectable levels of anti-S and anti-RBD IgG antibodies such as NT₉₀-Abs titres against A20.EU1. Moreover, 35 patients (61.5%) had undetectable NT₉₀-Abs titres against BA.5. On day 14, IgG anti-S and anti-RBD levels were 3880 BAU/mL and 776.6 AU/mL, respectively. Only 12.5% of patients met a NT₉₀-Abs titres ≥ 80 against BA.5, whereas the median NT₉₀-Abs titre against 20A.EU1 was 1280. NT₉₀-Abs titres against BA.5 were 64-fold lower than those against A20.EU1. Four patients (7.5%) had a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the 3 months after treatment, all with a time gap between the booster vaccination and injection.

Conclusions

To date, tixagevimab-cilgavimab cannot be considered a substitute for vaccination but may be a useful supporting therapy if the recommended dose for pre-exposure prophylaxis is doubled.

Background

Hepatitis E virus (HEV) is a leading cause of acute hepatitis and can cause chronic infections in immunocompromised patients. Although HEV infections can be treated with ribavirin, antiviral efficacy is hampered by resistance mutations, normally detected by virus sequencing.

Objectives

High-throughput sequencing (HTS) allows for cost-effective complete viral genome sequencing. This enables the discovery and delineation of new subtypes, and revised the recognition of quasispecies and putative resistance mutations. However, HTS is challenged by factors including low viral load, sample degradation, high host background, and high viral diversity.

Study design

We apply complete genome sequencing strategies for HEV, including a targeted enrichment approach. These approaches were used to investigate sequence diversity in HEV RNA-positive animal and human samples and intra-host diversity in a chronically infected patient.

Results

Here, we describe the identification of potential novel subtypes in a blood donation (genotype 3) and in an ancient livestock sample (genotype 7). In a chronically infected patient, we successfully investigated intra-host virus diversity, including the presence of ribavirin resistance mutations. Furthermore, we found convincing evidence for HEV compartmentalization, including the central nervous system, in this patient.

Conclusions

Targeted enrichment of viral sequences enables the generation of complete genome sequences from a variety of difficult sample materials. Moreover, it enables the generation of greater sequence coverage allowing more advanced analyses. This is key for a better understanding of virus diversity. Investigation of existing ribavirin resistance, in the context of minorities or compartmentalization, may be critical in treatment strategies of HEV patients.