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An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

Abstract Background Multiple studies have provided evidence of suboptimal or poor immune responses to SARS-CoV-2 vaccines in recipients of hematopoietic stem cell transplantation (HSCT) and chimeric antigen receptor-T (CAR-T) cell therapy compared to healthy individuals. Given the dynamic nature of SARS-CoV2, characterized by the emergence of many viral variations throughout the general population, there is ongoing discussion regarding the optimal quantity and frequency of additional doses required to sustain protection against SARS-CoV2 especially in this susceptible population. This systematic review and meta-analysis investigated the immune responses of HSCT and CAR-T cell therapy recipients to additional doses of the SARS-CoV-2 vaccines. Methods Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the study involved a comprehensive search across PubMed, Scopus, Web of Science Core Collection, Embase, and Cochrane Biorxiv and medRxiv, focusing on the serological responses to the third and fourth vaccine doses in HSCT and CAR-T cell patients. Results This study included 32 papers, with 31 qualifying for the meta-analysis. Results showed that after the third dose, the seroconversion rate in HSCT and CAR-T cell therapy recipients who didn’t respond to the second dose was 46.10 and 17.26%, respectively. Following the fourth dose, HSCT patients had a seroconversion rate of 27.23%. Moreover, post-third-dose seropositivity rates were 87.14% for HSCT and 32.96% for CAR-T cell therapy recipients. Additionally, the seropositive response to the fourth dose in the HSCT group was 90.04%. Conclusion While a significant portion of HSCT recipients developed antibodies after additional vaccinations, only a minority of CAR-T cell therapy patients showed a similar response. This suggests that alternative vaccination strategies are needed to protect these vulnerable groups effectively. Moreover, few studies have reported cellular responses to additional SARS-CoV-2 vaccinations in these patients. Further studies evaluating cellular responses are required to determine a more precise assessment of immunogenicity strength against SARS-CoV-2 after additional doses.

Abstract Background Rift Valley fever (RVF) is a zoonotic viral disease of increasing intensity among humans in Africa and the Arabian Peninsula. In Uganda, cases reported prior to 2016 were mild or not fully documented. We report in this paper on the severe morbidity and hospital-based mortality of human cases in Uganda. Methods Between November 2017 and March 2020 human cases reported to the Uganda Virus Research Institute (UVRI) were confirmed by polymerase chain reaction (PCR). Ethical and regulatory approvals were obtained to enrol survivors into a one-year follow-up study. Data were collected on socio-demographics, medical history, laboratory tests, potential risk factors, and analysed using Stata software. Results Overall, 40 cases were confirmed with acute RVF during this period. Cases were not geographically clustered and nearly all were male (39/40; 98%), median age 32 (range 11–63). The median definitive diagnosis time was 7 days and a delay of three days between presumptive and definitive diagnosis. Most patients (31/40; 78%) presented with fever and bleeding at case detection. Twenty-eight (70%) cases were hospitalised, out of whom 18 (64%) died. Mortality was highest among admissions in regional referral (11/16; 69%) and district (4/5; 80%) hospitals, hospitalized patients with bleeding at case detection (17/27; 63%), and patients older than 44 years (9/9; 100%). Survivors mostly manifested a mild gastro-intestinal syndrome with nausea (83%), anorexia (75%), vomiting (75%), abdominal pain (50%), and diarrhoea (42%), and prolonged symptoms of severe disease including jaundice (67%), visual difficulties (67%), epistaxis (50%), haemoptysis (42%), and dysentery (25%). Symptom duration varied between two to 120 days. Conclusion RVF is associated with high hospital-based mortality, severe and prolonged morbidity among humans that present to the health care system and are confirmed by PCR. One-health composite interventions should be developed to improve environmental and livestock surveillance, prevent infections, promptly detect outbreaks, and improve patient outcomes.

Newborn piglets' health is seriously threatened by the porcine epidemic diarrhea virus (PEDV), which also has a significant effect on the pig industry. The gut microbiota produces butyrate, an abundant metabolite that modulates intestinal function through many methods to improve immunological and intestinal barrier function. The objective of this investigation was to ascertain how elevated butyrate concentrations impacted the host transcriptional profile of PEDV CV777 strain infection. Our findings showed that higher concentrations of butyrate have a stronger inhibitory effect on PEDV CV777 strain infection. According to RNA-seq data, higher concentrations of butyrate induced more significant transcriptional changes in IPEC-J2 cells, and signaling pathways such as PI3K-AKT may play a role in the inhibition of PEDV CV777 strain by high concentrations of butyrate. Ultimately, we offer a theoretical and experimental framework for future research and development of novel approaches to harness butyrate's antiviral infection properties. [ABSTRACT FROM AUTHOR]

Background: Rabies is a fatal zoonotic disease whose pathogenesis has not been fully elucidated, and vaccination is the only effective method for protecting against rabies virus infection. Most inactivated vaccines are produced using Vero cells, which are African green monkey kidney cells, to achieve large-scale production. However, there is a potential carcinogenic risk due to nonhuman DNA contamination. Thus, replacing Vero cells with human diploid cells may be a safer strategy. In this study, we developed a novel 2BS cell-adapted rabies virus strain and analysed its sequence, virulence and immunogenicity to determine its application potential as a human diploid cell inactivated vaccine. Methods and results: The 2BS cell-adapted rabies virus strain 2aG4-B40 was established by passage for 40 generations and selection of plaques in 2BS cells. RNA sequence analysis revealed that mutations in 2BS cell-adapted strains were not located at key sites that regulate the production of neutralizing antibodies or virulence in the aG strain (GQ412744.1). The gradual increase in virulence (remaining above 7.0 logLD50/ml from the 40th to 55th generation) and antigen further indicated that these mutations may increase the affinity of the adapted strains for human diploid cells. Identification tests revealed that the 2BS cell-adapted virus strain was neutralized by anti-rabies serum, with a neutralization index of 19,952. PrEP and PEP vaccination and the NIH test further indicated that the vaccine prepared with the 2aG4-B40 strain had high neutralizing antibody levels (2.24 to 46.67 IU/ml), immunogenicity (protection index 270) and potency (average 11.6 IU/ml). Conclusions: In this study, a 2BS cell-adapted strain of the 2aG4 rabies virus was obtained by passage for 40 generations. The results of sequencing analysis and titre determination of the adapted strain showed that the mutations in the adaptive process are not located at key sequence regions of the virus, and these mutations may enhance the affinity of the adapted strain for human diploid cells. Moreover, vaccines made from the adapted strain 2aG4-B40 had high potency and immunogenicity and could be an ideal candidate rabies virus strain for inactivated vaccine preparation. [ABSTRACT FROM AUTHOR]

Background: Canine enteric coronavirus (CECoV) is a prevalent infectious disease among dogs worldwide, yet its epidemiology in mainland China remains poorly understood. This systematic review and meta-analysis aimed to assess the prevalence of CECoV in mainland China and identify factors influencing its prevalence. Methods: A comprehensive literature search was conducted across multiple databases for studies regarding CECoV epidemiology of China. PubMed, CNKI, Wanfang, and CQVIP were searched to obtain the studies. Eligible studies were selected based on predefined criteria, and data were extracted and synthesized. The quality the studies was assessed using the JBI assessment tool. Heterogeneity was checked using I2 test statistics followed by subgroup and sensitivity analysis. Subgroup analyses were performed to explore variations in CECoV prevalence by factors such as year, region, season, health status, social housing type, gender, age, and breed. Publication bias was assessed using a funnel plot and eggers test that was followed by trim and fill analysis. Results: A total of 27 studies involving 21,034 samples were included in the meta-analysis. The overall pooled prevalence of CECoV in mainland China was estimated to be 0.30 (95% CI 0.24–0.37), indicating persistent circulation of the virus. Subgroup analyses revealed higher prevalence rates in younger dogs, multi-dog households, apparently healthy dogs, and certain regions such as southwest China. Seasonal variations were observed, with lower prevalence rates in summer. However, no significant differences in prevalence were found by gender. Conclusions: This study provides valuable insights into the epidemiology of CECoV in mainland China, highlighting the persistent circulation of the virus and identifying factors associated with higher prevalence rates. Continuous monitoring and surveillance efforts, along with research into accurate detection methods and preventive measures, are essential for the effective control of CECoV and mitigation of its potential impact on animal and human health. [ABSTRACT FROM AUTHOR]

Wild waterfowl serve as a reservoir of some astroviruses. Fecal samples from wild waterfowl collected at Hong Kong's Marshes were tested using pan-astrovirus reverse transcription-PCR. Positive samples underwent subsequent host identification using DNA barcoding. Based on deduced partial sequences, noteworthy samples from three astrovirus groups (mammalian, avian and unclassified astroviruses) were further analyzed by next-generation sequencing. One sample of Avastrovirus 4 clade, MP22-196, had a nearly complete genome identified. The results of ORF2 phylogenetic analysis and genetic distance analysis indicate that Avastrovirus 4 is classified as a distinct subclade within Avastrovirus. MP22-196 has typical astrovirus genome characteristics. The unique characteristics and potential differences of this genome, compared to other avian astrovirus sequences, involve the identification of a modified sgRNA sequence situated near the ORF2 start codon, which precedes the ORF1b stop codon. Additionally, the 3' UTR of MP22-196 is shorter than other avian astroviruses. This study expands our understanding of the Avastrovirus 4 clade. [ABSTRACT FROM AUTHOR]

Background: High-risk human papillomavirus (HR-HPV) infection is an important factor for the development of cervical cancer. HPV18 is the second most common HR-HPV after HPV16. Methods: In this study, MEGA11 software was used to analyze the variation and phylogenetic tree of HPV18 E6-E7 and L1 genes. The selective pressure to E6, E7 and L1 genes was estimated using pamlX. In addition, the B cell epitopes of L1 amino acid sequences and T cell epitopes of E6-E7 amino acid sequences in HPV18 were predicted by ABCpred server and IEDB website, respectively. Results: A total of 9 single nucleotide variants were found in E6-E7 sequences, of which 2 were nonsynonymous variants and 7 were synonymous variants. Twenty single nucleotide variants were identified in L1 sequence, including 11 nonsynonymous variants and 9 synonymous variants. Phylogenetic analysis showed that E6-E7 and L1 sequences were all distributed in A lineage. In HPV18 E6, E7 and L1 sequences, no positively selected site was found. The nonconservative substitution R545C in L1 affected hypothetical B cell epitope. Two nonconservative substitutions, S82A in E6, and R53Q in E7, impacted multiple hypothetical T cell epitopes. Conclusion: The sequence variation data of HPV18 may lay a foundation for the virus diagnosis, further study of cervical cancer and vaccine design in central China. [ABSTRACT FROM AUTHOR]

Porcine reproductive and respiratory syndrome (PRRS) is endemic worldwide, seriously affecting the development of the pig industry, but vaccines have limited protective effects against PRRSV transmission. The aim of this study was to identify potential anti-PRRSV drugs. We examined the cytotoxicity of seven compounds formulated based on the mass ratio of glycyrrhizic acid to matrine and calculated their inhibition rates against PRRSV in vitro. The results showed that the seven compounds all had direct killing and therapeutic effects on PRRSV, and the compounds inhibited PRRSV replication in a time- and dose-dependent manner. The compound with the strongest anti-PRRSV effect was selected for subsequent in vivo experiments. Pigs were divided into a control group and a medication group for the in vivo evaluation. The results showed that pigs treated with the 4:1 compound had 100% morbidity after PRRSV challenge, and the mortality rate reached 75% on the 8th day of the virus challenge. These results suggest that this compound has no practical anti-PRRSV effect in vivo and can actually accelerate the death of infected pigs. Next, we further analyzed the pigs that exhibited semiprotective effects following vaccination with the compound to determine whether the compound can synergize with the vaccine in vivo. The results indicated that pigs treated with the compound had higher mortality rates and more severe clinical reactions after PRRSV infection (p < 0.05). The levels of proinflammatory cytokines (IL-6, IL-8, IL-1β, IFN-γ, and TNF-α) were significantly greater in the compound-treated pigs than in the positive control-treated pigs (p < 0.05), and there was no synergistic enhancement with the live attenuated PRRSV vaccine (p < 0.05). The compound enhanced the inflammatory response, prompted the body to produce excessive levels of inflammatory cytokines and caused body damage, preventing a therapeutic effect. In conclusion, the present study revealed that the in vitro effectiveness of these agents does not indicate that they are effective in vivo or useful for developing anti-PRRSV drugs. Our findings also showed that, to identify effective anti-PRRSV drugs, comprehensive drug screening is needed, for compounds with solid anti-inflammatory effects both in vitro and in vivo. Our study may aid in the development of new anti-PRRSV drugs. [ABSTRACT FROM AUTHOR]

Background: HIV-1 produces Tat, a crucial protein for transcription, viral replication, and CNS neurotoxicity. Tat interacts with TAR, enhancing HIV reverse transcription. Subtype C Tat variants (C31S, R57S, Q63E) are associated with reduced transactivation and neurovirulence compared to subtype B. However, their precise impact on Tat-TAR binding is unclear. This study investigates how these substitutions affect Tat-TAR interaction. Methods: We utilized molecular modelling techniques, including MODELLER, to produce precise three-dimensional structures of HIV-1 Tat protein variants. We utilized Tat subtype B as the reference or wild type, and generated Tat variants to mirror those amino acid variants found in Tat subtype C. Subtype C-specific amino acid substitutions were selected based on their role in the neuropathogenesis of HIV-1. Subsequently, we conducted molecular docking of each Tat protein variant to TAR using HDOCK, followed by molecular dynamic simulations. Results: Molecular docking results indicated that Tat subtype B (TatWt) showed the highest affinity for the TAR element (-262.07), followed by TatC31S (-261.61), TatQ63E (-256.43), TatC31S/R57S/Q63E (-238.92), and TatR57S (-222.24). However, binding free energy analysis showed higher affinities for single variants TatQ63E (-349.2 ± 10.4 kcal/mol) and TatR57S (-290.0 ± 9.6 kcal/mol) compared to TatWt (-247.9 ± 27.7 kcal/mol), while TatC31S and TatC31S/R57SQ/63E showed lower values. Interactions over the protein trajectory were also higher for TatQ63E and TatR57S compared to TatWt, TatC31S, and TatC31S/R57SQ/63E, suggesting that modifying amino acids within the Arginine/Glutamine-rich region notably affects TAR interaction. Single amino acid mutations TatR57S and TatQ63E had a significant impact, while TatC31S had minimal effect. Introducing single amino acid variants from TatWt to a more representative Tat subtype C (TatC31S/R57SQ/63E) resulted in lower predicted binding affinity, consistent with previous findings. Conclusions: These identified amino acid positions likely contribute significantly to Tat-TAR interaction and the differential pathogenesis and neuropathogenesis observed between subtype B and subtype C. Additional experimental investigations should prioritize exploring the influence of these amino acid signatures on TAR binding to gain a comprehensive understanding of their impact on viral transactivation, potentially identifying them as therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: The persistent infection of high-risk Human papillomavirus(HPV) is considered the main cause of cervical intraepithelial neoplasia and cervical cancer. But various cervical lesions caused by HPV infection can be properly prevented by timely vaccination. However, the distribution of HPV genotypes varies geographically. Methods: Retrospective analysis of high-risk HPV prevalence of 16,150 women from 2020 to 2022 in xianning of China. HPV genotyping was performed using a PCR-RDB Kit that can detect 18 high-risk HPV genotypes recommended by China's National Medical Products Administration. The prevalence of 18 high-risk HPV genotypes and their relationship with cervical lesions as well as vaccine efficacy were analyzed. Results: A total of 2431 women were confirmed to have different types of high-risk HPV infections. The overall positive rate reached 15.05%(2431/16,150). The most prevalent high-risk HPV genotypes were HPV52, 16, 58, 53, and 51. The prevalence of high-risk HPV reached peak at age ≤ 20(20.95%) and age ≥ 61(20.56%). The most prevalent high-risk HPV genotypes were HPV16, 58, 18, 33 and 52 in cervical cancer cases, HPV16, 52, 58, 33 and 18 in CIN2/3 cases, and HPV52, 58, 16, 53 and 18 in CIN1 cases, respectively. Conclusion: HPV16, 58 and 18 are the most dangerous and carcinogenic genotypes in xianning, China. Conducting epidemiological investigations on high-risk HPV has significant clinical value in guiding HPV vaccination work. [ABSTRACT FROM AUTHOR]

Background: Long coronavirus disease (COVID) after COVID-19 infection is continuously threatening the health of people all over the world. Early prediction of the risk of Long COVID in hospitalized patients will help clinical management of COVID-19, but there is still no reliable and effective prediction model. Methods: A total of 1905 hospitalized patients with COVID-19 infection were included in this study, and their Long COVID status was followed up 4–8 weeks after discharge. Univariable and multivariable logistic regression analysis were used to determine the risk factors for Long COVID. Patients were randomly divided into a training cohort (70%) and a validation cohort (30%), and factors for constructing the model were screened using Lasso regression in the training cohort. Visualize the Long COVID risk prediction model using nomogram. Evaluate the performance of the model in the training and validation cohort using the area under the curve (AUC), calibration curve, and decision curve analysis (DCA). Results: A total of 657 patients (34.5%) reported that they had symptoms of long COVID. The most common symptoms were fatigue or muscle weakness (16.8%), followed by sleep difficulties (11.1%) and cough (9.5%). The risk prediction nomogram of age, diabetes, chronic kidney disease, vaccination status, procalcitonin, leukocytes, lymphocytes, interleukin-6 and D-dimer were included for early identification of high-risk patients with Long COVID. AUCs of the model in the training cohort and validation cohort are 0.762 and 0.713, respectively, demonstrating relatively high discrimination of the model. The calibration curve further substantiated the proximity of the nomogram's predicted outcomes to the ideal curve, the consistency between the predicted outcomes and the actual outcomes, and the potential benefits for all patients as indicated by DCA. This observation was further validated in the validation cohort. Conclusions: We established a nomogram model to predict the long COVID risk of hospitalized patients with COVID-19, and proved its relatively good predictive performance. This model is helpful for the clinical management of long COVID. [ABSTRACT FROM AUTHOR]

Background: The Porcine Epidemic Diarrhea Virus (PEDV) has caused significant economic losses in the global swine industry. As a potential drug for treating diarrhea, the antiviral properties of attapulgite deserve further study. Methods: In this study, various methods such as RT-qPCR, Western blot, viral titer assay, Cytopathic Effect, immunofluorescence analysis and transmission electron microscopy were used to detect the antiviral activity of attapulgite and to assess its inhibitory effect on PEDV. Results: When exposed to the same amount of virus, there was a significant decrease in the expression of the S protein, resulting in a viral titer reduction from 10-5.613 TCID50/mL to 10-2.90 TCID50/mL, which represents a decrease of approximately 102.6 folds. Results of cytopathic effect and indirect immunofluorescence also indicate a notable decrease in viral infectivity after attapulgite treatment. Additionally, it was observed that modified materials after acidification had weaker antiviral efficacy compared to powdered samples that underwent ultrasonic disintegration, which showed the strongest antiviral effects. Conclusion: As a result, Attapulgite powders can trap and adsorb viruses to inhibit PEDV in vitro, leading to loss of viral infectivity. This study provides new materials for the development of novel disinfectants and antiviral additives. [ABSTRACT FROM AUTHOR]

Background: During the pandemic, whole genome sequencing was critical to characterize SARS-CoV-2 for surveillance, clinical and therapeutical purposes. However, low viral loads in specimens often led to suboptimal sequencing, making lineage assignment and phylogenetic analysis difficult. We propose an alternative approach to sequencing these specimens that involves sequencing in triplicate and concatenation of the reads obtained using bioinformatics. This proposal is based on the hypothesis that the uncovered regions in each replicate differ and that concatenation would compensate for these gaps and recover a larger percentage of the sequenced genome. Results: Whole genome sequencing was performed in triplicate on 30 samples with Ct > 32 and the benefit of replicate read concatenation was assessed. After concatenation: i) 28% of samples reached the standard quality coverage threshold (> 90% genome covered > 30x); ii) 39% of samples did not reach the coverage quality thresholds but coverage improved by more than 40%; and iii) SARS-CoV-2 lineage assignment was possible in 68.7% of samples where it had been impaired. Conclusions: Concatenation of reads from replicate sequencing reactions provides a simple way to access hidden information in the large proportion of SARS-CoV-2-positive specimens eliminated from analysis in standard sequencing schemes. This approach will enhance our potential to rule out involvement in outbreaks, to characterize reinfections and to identify lineages of concern for surveillance or therapeutical purposes. [ABSTRACT FROM AUTHOR]

Objective: Cystic echinococcosis (CE) represents a profoundly perilous zoonotic disease. The advent of viral macrogenomics has facilitated the exploration of hitherto uncharted viral territories. In the scope of this investigation, our objective is to scrutinize disparities in the intestinal microbiotic ecosystems of canines dwelling in elevated terrains and those afflicted by Echinococcus infection, employing the tool of viral macrogenomics. Methods: In this study, we collected a comprehensive total of 1,970 fecal samples from plateau dogs infected with Echinococcus, as well as healthy control plateau dogs from the Yushu and Guoluo regions in the highland terrain of China. These samples were subjected to viral macrogenomic analysis to investigate the viral community inhabiting the canine gastrointestinal tract. Results: Our meticulous analysis led to the identification of 136 viral genomic sequences, encompassing eight distinct viral families. Conclusion: The outcomes of this study hold the potential to enhance our comprehension of the intricate interplay between hosts, parasites, and viral communities within the highland canine gut ecosystem. Through the examination of phage presence, it may aid in early detection or assessment of infection severity, providing valuable insights into Echinococcus infection and offering prospects for potential treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease. SFTS virus (SFTSV) is transmitted by tick bites and contact with the blood or body fluids of SFTS patients. Animal-to-human transmission of SFTS has been reported in Japan, but not in China. In this study, the possible transmission route of two patients who fed and cared for farm-raised fur animals in a mink farm was explored. Method: An epidemiological investigation and a genetic analysis of patients, animals and working environment were carried out. Results: It was found that two patients had not been bitten by ticks and had no contact with patients infected with SFTS virus, but both of them had skinned the dying animals. 54.55% (12/22) of the farm workers were positive for SFTS virus antibody. By analyzing the large, medium and small segments sequences, the viral sequences from the two patients, animals and environments showed 99.9% homology. Conclusion: It is suspected that the two patients may be directly infected by farm-raised animals, and that the virus may have been transmitted by aerosols when skinning dying animals. Transmission by direct blood contacts or animal bites cannot be ignored. [ABSTRACT FROM AUTHOR]

In 2018, SGS Belgium NV developed RSV-NICA (Respiratory Syncytial Virus-Nasobronchial Infective Challenge Agent), an RSV type A challenge agent for use in RSV Controlled Human Infection Model (CHIM) studies. It is widely recognized that the stability of RSV can be influenced by a variety of environmental parameters, such as temperature and pH. Consequently, our objective was to evaluate the stability of the viral titer of RSV-NICA following five years of controlled storage and to determine the uniformity of the viral titers across different vials of a GMP-qualified batch of RSV-NICA. In addition, we examined the capacity of RSV-NICA to infect human primary airway epithelial cells (MucilAir™), the principal target cells of RSV, and evaluated the influence of single and recurrent freeze–thaw cycles on the infectious viral titer of the challenge agent. The aliquoted RSV-NICA virus stock was subjected to standard virological and molecular methods to gather data on the titer and consistency of the viral titer contained within 24 representative vials of the stock. Our findings illustrate that over a span of five years of cryo-storage, the infectious viral titer in 75% of the tested vials exhibited a comparable average infectious viral titer (4.75 ± 0.06 vs 4.99 ± 0.11; p-value = 0.14). A considerable reduction down to an undetectable level of infectious virus was observed in the remaining vials. RSV-NICA demonstrated its capacity to effectively infect differentiated human airway epithelial cells, with active virus replication detected in these cells through increasing RSV genome copy number over time. Virus tropism for ciliated cells was suggested by the inhibition of cilia beating coupled with an increase in viral RNA titers. No discernable impact on membrane barrier function of the epithelial lung tissues nor cytotoxicity was detected. Pooling of vials with infectious titers > 4.0 log10 TCID50/ml and freeze-thawing of these combined vials showed no deterioration of the infectious titer. Furthermore, pooling and re-aliquoting of vials spanning the entire range of viral titers (including vials with undetectable infectious virus) along with subjecting the vials to three repeated freeze–thaw cycles did not result in a decrease of the infectious titers in the tested vials. Taken together, our findings indicate that long-term cryo-storage of vials containing RSV-NICA challenge agent may influence the infectious viral titer of the virus, leading to a decrease in the homogeneity of this titer throughout the challenge stock. However, our study also demonstrates that when heterogeneity of the infectious titer of an RSV stock is observed, rounds of pooling, re-aliquoting and subsequent re-titration serve as an effective method not only to restore the homogeneity of the infectious titer of an RSV-A stock, but also to optimize patient-safety, scientific and operational aspects of viral inoculation of study participants during at least the period of one RSV CHIM trial. RSV-NICA is a stable, suitable CHIM challenge agent that can be utilized in efficacy trials for RSV vaccines and antiviral entities. [ABSTRACT FROM AUTHOR]

Background: The immature and suppressed immune response makes transplanted children a special susceptible group to Parvovirus B19 (PVB19). However, the clinical features of transplanted children with PVB19 infection haven't been comprehensively described. Methods: We searched the medical records of all the transplant recipients who attended the Children's Hospital of Fudan University from 1 Oct 2020 to 31 May 2023, and reviewed the medical literature for PVB19 infection cases among transplanted children. Results: A total of 10 cases of PVB19 infection were identified in 201 transplanted children at our hospital, and the medical records of each of these cases were shown. Also, we retrieved 40 cases of PVB19 infection among transplanted children from the literature, thus summarizing a total of 50 unique cases of PVB19 infection. The median time to the first positive PVB19 DNA detection was 14 weeks post-transplantation. PVB19 IgM and IgG were detected in merely 26% and 24% of the children, respectively. The incidence of graft loss/dysfunction was as high as 36%. Hematopoietic stem cell transplant (HSCT) recipients showed higher PVB19 load, lower HGB level, greater platelet damage, lower PVB19 IgM/IgG positive rates, and more graft dysfunction than solid-organ transplant (SOT) recipients, indicating a more incompetent immune system. Conclusions: Compared with the published data of transplanted adults, transplanted children displayed distinct clinical features upon PVB19 infection, including lower PVB19 IgM/IgG positive rates, more graft dysfunction, and broader damage on hematopoietic cell lines, which was even more prominent in HSCT recipients, thus should be of greater concern. [ABSTRACT FROM AUTHOR]