世界病毒学杂志(英文版)最新文献

Sickle cell disease (SCD) is a genetic disorder that predisposes affected individuals to a range of complications, including an increased susceptibility to viral infections. These infections present significant clinical challenges due to the underlying immunocompromised state in SCD patients. This review examines the interaction between viral infections and SCD, highlighting the vulnerabilities and the impact of these infections on morbidity and mortality in this population. Advances in antiviral therapies have significantly improved outcomes, yet managing viral infections in SCD patients requires special consideration due to drug-to-drug interactions, altered pharmacokinetics, and the potential exacerbation of SCD-related complications. Additionally, vaccination strategies against viral infections and the emerging role of prophylactic antiviral treatments are discussed as critical components of infection prevention. By focusing on both established and novel antiviral treatments, this article aims to provide a comprehensive overview of the challenges and opportunities in managing viral infections in patients with SCD.

Background: In the initial stages of the coronavirus disease 2019 (COVID-19) pandemic, healthcare workers (HCWs) who were immunologically naive to COVID-19, were exposed to a highly transmissible virus.

Aim: To compare infection risk among HCWs in high-risk (HR) and low-risk (LR) areas.

Methods: Data on reverse transcriptase-polymerase chain reaction confirmed clinical infection and samples for nucleocapsid, and spike protein antibodies were collected at five time-points (T1 to T5) from HCWs in the emergency department and intensive care unit (HR group) and pre-clinical and para-clinical areas (LR). For the sero-study, only participants who provided at least one baseline sample and one during the second wave (T4 or T5) were analysed. Since Covishield^TM elicits only spike protein antibodies, subclinical infection was diagnosed if asymptomatic unvaccinated and Covishield^TM vaccinated individuals tested positive for nucleocapsid antibody.

Results: Overall, by T5, clinical infection rate was similar in the HR (120/366, 32.8%) and LR (22/82, 26.8%) groups (P = 0.17). However, before vaccination (T3), more HCWs in the HR group developed COVID-19 infection (21.9% vs 8.8%, P = 0.046). In the sero-study group, clinical infection occurred in 31.5% (45/143) and 23.7% (14/59) in the HR and LR groups respectively (P = 0.23). Spike antibody was detected in 140/143 (97.9%) and 56/59 (94.9%) and nucleocapsid antibody was positive in 95/143 (66.4%) and 35/59 (59.3%) in the HR and LR groups respectively (P = 0.34). Subclinical infection rate (HR 34.9%, LR 35.6%, P = 0.37) and hospitalization rate were similar. There was no mortality.

Conclusion: Before vaccination, HCWs in HR areas had a higher risk of infection. Seroprevalence studies suggest that sub-clinical infection was not uncommon.

Rhabdomyolysis (RM) is characterized by disrupting muscle cells and releasing intracellular components into circulation. Some symptoms associated with RM include muscle weakness, discolored urine, and myalgia. RM can be caused by coronavirus disease 2019 (COVID-19) causing exaggerated immune response leading to muscle damage. Acute kidney injury (AKI), when presented with RM, leads to increased mortality. Examining RM-related AKI and its comparison to other AKI types in COVID-19 patients could improve the management of viral infections developing RM and AKI. RM potentially complicated COVID-19 infection course and is a major etiology of AKI. RM-related AKI had higher severity and mortality than other AKI types, with increased hypercoagulopathy and inflammatory markers. Findings also express procalcitonin use in follow-ups with severe COVID-19 patients. Study limitations include small sample size, absence of kidney biopsies, and focus on the first wave of the pandemic, which should be addressed in future research to generate accurate and relevant findings.

Background: The emergence of the Omicron variant (B.1.1.529) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) raised global concerns with its highly transmissible nature.

Aim: To investigate the genomic, clinical, and demographic characteristics of Omicron infections within the early outbreak cluster in western part of Sri Lanka.

Methods: We analyzed sequence data from January 2022 to April 2022 to understand variant dynamics, clinical presentation, and demographic associations.

Results: Whole-genome sequencing of 85 nasopharyngeal and throat swab samples collected in western part of Sri Lanka between January and April 2022 identified 70 (82.34%) of it as Omicron variants. BA.2 was the most prevalent sub-lineage (57%), followed by BA.1.1 (14.20%) and majority of them were from > 12 years old individuals. Phylogenetic analysis revealed clustering into four distinct clades (21I, 21K, 21L, and 21M), suggesting potential differences in transmission chains or evolutionary pressures.

Conclusion: This study found BA.2 to be the predominant Omicron sub-lineage in the western part of Sri Lanka during the first quarter of 2022, aligning with global trends. Phylogenetic analysis revealed diverse introductions and local transmission. Continued genomic surveillance and robust public health measures remain crucial for managing the evolving SARS-CoV-2 landscape.

Background: The upsurge of antibiotic resistance is a significant challenge to public health, and the dry pipeline of new antibiotics has prompted the discovery of alternative treatment approaches. Enterococcus faecalis (E. faecalis) isolates are often multidrug-resistant, posing challenges to antibiotic therapy. Bacteriophage therapy is being explored as an alternative method to treat the growing population of antibiotic-resistant infections. Nevertheless, many inherent limitations of phages diminish their therapeutic utility, notably the restricted host range and quick development of mutants. The specific types and quantities of bacteriophages and antibiotics may be crucial in generating the optimal phage-antibiotic synergy.

Aim: To optimize the doses, order, and timing to optimize the synergy of phages and vancomycin on different bacteria states.

Methods: A volume of 180 μL of E. faecalis bacteria in the logarithmic growth phase, with a concentration of approximately 1 × 10⁸ colony forming units (CFUs)/mL, was introduced onto a microtitre plate. Subsequently, 20 μL of phage suspension (1 × 10⁶ PFUs/mL), vancomycin (16 µg/mL), or a combination of both was introduced into the designated wells in the specified sequence and incubated at 37 °C for 48 hours. The number of live bacteria was counted at different time points using standardized CFU counting protocols.

Results: The biofilm model demonstrated that combining phages with vancomycin can eradicate the biofilm. Sequential therapy, involving phage application 8 hours before the antibiotic at a concentration of 10⁸ PFUs/mL, proved the most efficient in eliminating the biofilms and killing the planktonic form of E. faecalis.

Conclusion: The combination of phage ɸEFP01 at a higher concentration with a subinhibitory concentration of vancomycin yields a synergistic antibacterial outcome on E. faecalis strain resistant to vancomycin.

Chronic hepatitis delta virus (HDV) represents a rare but important co-infection in approximately 5% of patients with chronic hepatitis B virus (HBV) infection, and is associated with significant morbidity and mortality due to an increased risk for liver cirrhosis, liver failure, and hepatocellular carcinoma relative to HBV monoinfected individuals. The current treatment of chronic HDV infection includes the off-label use of pegylated interferon (IFN), which is limited by poor safety, tolerability, and efficacy. Guidelines of the major international liver organizations such as the American Association for the Study of Liver Diseases, European Association for the Study of the Liver, and Asian Pacific Association for the Study of the Liver provide recommendations for contemporary diagnosis and management of chronic HDV infection, including the incorporation of bulevirtide, a newly licensed antiviral agent in Europe. Significant unmet medical needs remain in the treatment of HDV, and recent advances in drug development offer hope for meaningful advances in drug therapy which may improve virologic response rates and clinical outcomes. This review summarizes trial design and available efficacy data from key phase 2 and 3 trials for investigational therapies including entry inhibitors (bulevirtide), prenylation inhibitors (lonafarnib), novel IFNs (peginterferon lambda), RNA interference molecules (JNJ-3989, elebsiran), monoclonal antibodies (tobevibart), and nucleic acid polymers (REP2139), and addresses future directions in HDV pharmacotherapy.

Background: Hepatitis C virus (HCV) infection process of progression encompasses multiple stages, commencing with inflammation and culminating in hepatocellular cancer. Numerous invasive and non-invasive procedures exist for diagnosing chronic HCV infection. Though beneficial, invasive procedures can cause morbidity and inadequate representation of the overall degree of fibrosis. Due to these reasons, non-invasive liver fibrosis biomarkers are becoming more prevalent to diagnose and track liver fibrosis without a liver biopsy. These biomarkers can detect liver fibrosis early, improving treatment and preventing cirrhosis and liver failure. Micro ribonucleic acid (MiRNA) dysregulation causes and worsens several diseases including liver disease. MiRNAs can facilitate the diagnosis of liver fibrosis and serve as a predictive tool to enhance patient care by minimizing invasive procedures and enabling more efficient and prompt therapy.

Aim: To investigate the diagnostic effectiveness of several miRNAs (miRNA-122, miRNA-21, miRNA-199a, miRNA-155) in assessing the liver fibrosis severity in untreated HCV patients from the Indian Punjab population. We seek to identify the intricate diagnostic relationship of miRNAs with the extent of fibrosis among individuals with HCV.

Methods: We considered 100 persons determined as HCV infected by a quantitative Real-Time Polymerase Chain Reaction examination. We employed statistical as well as probabilistic tools to ascertain the diagnostic validity of miRNAs for determining the liver fibrosis stages. We employed Bayesian Networks, to introduce a unique diagnostic paradigm for miRNAs that can be adopted as benchmark to evaluate the liver fibrosis severity in HCV cases.

Results: We found that miRNAs (miR-122, miR-155 and miR-21) showed significant upregulation when compared with control and according to severity of fibrosis (P ≤ 0.05). The area under the curve for miR-122, miR-155, miR-21 and miR-199a in HCV group in relation to Liver Stiffness Measurement was calculated as 0.889, 0.933, 0.912 and 0.035 respectively. MiR-199a was downregulated according to degree of fibrosis.

Conclusion: Depending on the diagnostic accuracy, we have concluded that miR-122, miR-155 and miR-21 are reliable markers to detect fibrosis in Hepatitis C patients.

Background: To prevent mother to child transmission (MTCT) of human immunodeficiency virus (HIV), sustained maternal viral load suppression (VLS) and early HIV testing among HIV exposed infants (HEI) is critical.

Aim: To investigate maternal viral load results and infant HIV testing uptake at 6-weeks, and 9-months and 18-months in Rwanda.

Methods: Between 2015 and 2022, VLS (< 200 copies/mL) was measured among pregnant women living with HIV (WLHIV) from 38-healthcare facilities. Viral loads (VL) were measured at 6-months, 12-months and 24-months, respectively. For maternal VL, the unit of analysis was visit-pair, and the pairs were created to define those with VL < 200 copies/mL at two consecutive visits as having sustained VLS, persistent viremia (VL ≥ 200 copies/mL at two consecutive visits), viral rebound (VL < 200 copies/mL at prior visit only) and newly suppressed (VL < 200 copies/mL at subsequent visit only). HEI were considered to have persistent HIV testing if they had all three HIV tests. Poisson regression models with generalized estimating equations were used to estimate the adjusted incidence rate ratio (aIRR) and 95%CI for factors associated with sustained VLS and persistent HIV testing.

Results: A total of 1145 mother-infant pairs were analyzed. Infant HIV testing uptake at 6- weeks, 9-months and 18-months was 1145 (100.0%), 1089 (95.1%), 1006 (87.9%) respectively. Nine hundred ninety-nine HEI (87.3%) tested for HIV persistently. At 18-months, the incidence of HIV among HEI was 8 (0.7%). Of 1145 mothers, 1076 (94.0%) had ≥ 2 VL results making a total of 2010 visit-pairs (142-single; 934-double visit-pairs). The incidence rate of sustained VLS, persistent viremia, viral rebound and new suppression were 91.0%, 1.3%, 3.6% and 4.0% respectively. Maternal disclosure of HIV status (aIRR = 1.08, 95%CI: 1.02-1.14) was associated with increased likelihood of sustained VLS. Having peer support (aIRR = 1.05 95%CI: 1.01-1.10) was associated with persistent HIV testing among HEI.

Conclusion: Sustained VLS is high among pregnant WLHIV in Rwanda. The low incidence of HIV among HEI may be attributed to high VLS levels. Targeted interventions, including enhanced HIV disclosure and peer support, are crucial for improving sustained VLS and increasing infant HIV testing uptake to reduce MTCT.

Background: The evolutionary mutational changes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) since its emergence in Chhattisgarh, India in 2020 have warranted the need for the characterization of every lineage/sublineage that has evolved until February 2024.

Aim: To unravel the evolutionary pathway of SARS-CoV-2 in Chhattisgarh from 2020 to February 2024.

Methods: A total of 635 coronavirus disease 2019 cases obtained between 2020 and February 2024 were investigated by whole genome sequencing.

Results: Whole genome sequencing analysis identified the evolution of SARS-CoV-2 into seventeen lineages from 2020 to 2024. SARS-CoV-2 initially emerged in Chhattisgarh in its Alpha (B.1.1.7) variant in 2020. Thereafter, it continuously underwent periodical mutational changes in the spike gene to further differentiate into various lineages/sublineages, viz., Kappa, Delta, BA.1, and BA.2 in 2021; the Omicron lineage (BA.5, BA.2.12.1, BA.2.75, BQ.1, and XBB) in 2022; the new Omicron lineage (XBB.1.5, XBB.1.16, XBB.1.9.1, and XBB.2.3) in 2023; and finally to JN.1 in January and February 2024. The predominant lineages over these 4 years were BA.1.1.7 (Alpha) in 2020, B.1.617.2 (Delta) in the period between 2021 and mid-2022, B.1.1.529 (Omicron) in late 2022 to 2023, and Omicron-JN.1 in early 2024. The presently circulating JN.1 lineage was observed harboring exclusive predominant mutations of E4554K, A570V, P621A, and P1143 L with 99% prevalence.

Conclusion: SARS-CoV-2 from 2020 to 2024 has evolved into 17 lineages/sublineages in Chhattisgarh. The presently circulating JN.1 harbored 40 mutations, especially E554K, A570V, P621S, and P1143 L, capacitating the virus with features of host cell entry, stability, replication, rapid transmissibility, and crucial immune evasion. Therefore, earlier immunity from either vaccination or prior infection may not protect against the current lineage and increases the possibility of future outbreaks. Thus, the periodical genomic surveillance of SARS-CoV-2 is essential for the genomic blueprint of the circulating virus, which may help in updating the vaccine strain and various basic research for developing appropriate therapeutics and diagnostics.