Shift from a Zero-COVID strategy to a New-normal strategy for controlling SARS-COV-2 infections in Vietnam.

The aim of this study is to analyse the changing patterns in the transmission of COVID-19 in relation to changes in Vietnamese governmental policies, based on epidemiological data and policy actions in a large Vietnamese province, Bac Ninh, in 2021. Data on confirmed cases from January to December 2021 were collected, together with policy documents. There were three distinct periods of the COVID-19 pandemic in Bac Ninh province during 2021. During the first period, referred to as the 'Zero-COVID' period (01/04-07/04/2021), there was a low population vaccination rate, with less than 25% of the population receiving its first vaccine dose. Measures implemented during this period focused on domestic movement restrictions, mask mandates, and screening efforts to control the spread of the virus. The subsequent period, referred to as the 'Transition' period (07/05-10/22/2021), witnessed a significant increase in population vaccination coverage, with 80% of the population receiving their first vaccine dose. During this period, several days passed without any reported COVID-19 cases in the community. The local government implemented measures to manage domestic actions and reduce the time spent in quarantine, and encouraged home quarantining for the close contacts of cases with COVID-19. Finally, the 'New-normal' stage (10/23-12/31/2021), during which the population vaccination coverage with a second vaccine dose increased to 70%, and most of the mandates for the prevention and control of COVID-19 were reduced. In conclusion, this study highlights the importance of governmental policies in managing and controlling the transmission of COVID-19 and provides insights for developing realistic and context-specific strategies in similar settings.

Allogeneic Adipose-Derived Mesenchymal Stem Cell Transplantation Enhances the Expression of Angiogenic Factors in a Mouse Acute Hindlimb Ischemic Model.

Cell migration and molecular mechanisms during healing of damaged vascular or muscle tissues are emerging fields of interest worldwide. The study herein focuses on evaluating the role of allogenic adipose-derived mesenchymal stem cells (ADMSCs) in restoring damaged tissues. Using a hindlimb ischemic mouse model, ADMSC-mediated induction of cell migration and gene expression related to myocyte regeneration and angiogenesis were evaluated. ADMSCs were labeled with GFP (ADMSC-GFP). The proximal end of the femoral blood vessel of mice (over 6 months of age) are ligated at two positions then cut between the two ties. Hindlimb ischemic mice were randomly divided into two groups: Group I (n = 30) which was injected with PBS (100 µL) and Group II (n = 30) which was transplanted with ADMSC-GFP (106 cells/100 µL PBS) at the rectus femoris muscle. The migration of ADMSC-GFP in hindlimb was analyzed by UV-Vis system. The expression of genes related to angiogenesis and muscle tissue repair was quantified by real-time RT-PCR. The results showed that ADMSCs existed in the grafted hindlimb for 7 days. Grafted cells migrated to other damaged areas such as thigh and heel. In both groups the ischemic hindlimb showed an increased expression of several angiogenic genes, including Flt-1, Flk-1, and Ang-2. In particular, the expression of Ang-2 and myogenic-related gene MyoD was significantly increased in the ADMSC-treated group compared to the PBS-treated (control) group; the expression increased at day 28 compared to day 3. The other factors, such as VE-Cadherin, HGF, CD31, Myf5, and TGF-ß, were also more highly expressed in the ADMSC-treated group than in the control group. Thus, grafted ADMSCs were able to migrate to other areas in the injured hindlimb, persist for approximately 7 days, and have a significantly positive impact on stimulating expression of myogenic- and angiogenesis-related genes.

Safety, immunogenicity and efficacy of the self-amplifying mRNA ARCT-154 COVID-19 vaccine: pooled phase 1, 2, 3a and 3b randomized, controlled trials.

Combination of waning immunity and lower effectiveness against new SARS-CoV-2 variants of approved COVID-19 vaccines necessitates new vaccines. We evaluated two doses, 28 days apart, of ARCT-154, a self-amplifying mRNA COVID-19 vaccine, compared with saline placebo in an integrated phase 1/2/3a/3b controlled, observer-blind trial in Vietnamese adults (ClinicalTrial.gov identifier: NCT05012943). Primary safety and reactogenicity outcomes were unsolicited adverse events (AE) 28 days after each dose, solicited local and systemic AE 7 days after each dose, and serious AEs throughout the study. Primary immunogenicity outcome was the immune response as neutralizing antibodies 28 days after the second dose. Efficacy against COVID-19 was assessed as primary and secondary outcomes in phase 3b. ARCT-154 was well tolerated with generally mild-moderate transient AEs. Four weeks after the second dose 94.1% (95% CI: 92.1-95.8) of vaccinees seroconverted for neutralizing antibodies, with a geometric mean-fold rise from baseline of 14.5 (95% CI: 13.6-15.5). Of 640 cases of confirmed COVID-19 eligible for efficacy analysis most were due to the Delta (B.1.617.2) variant. Efficacy of ARCT-154 was 56.6% (95% CI: 48.7- 63.3) against any COVID-19, and 95.3% (80.5-98.9) against severe COVID-19. ARCT-154 vaccination is well tolerated, immunogenic and efficacious, particularly against severe COVID-19 disease.

Infection with high-risk HPV types among female sex workers in northern Vietnam.

Vaccines against two high-risk human papillomavirus (HPV) types, HPV-16, and HPV-18, are in use currently, with high efficacy for preventing infections with these HPV types and consequent cervical cancers. However, circulating HPV types can vary with geography and ethnicity. The aim of this study was to investigate the prevalence of HPV types and the association between HPV types and abnormal cervical cytology among female sex workers in Northern Vietnam. Cervical swabs and plasma samples were collected from 281 female sex workers at two health centers in Hanoi and Hai Phong in 2009. The HPV L1 gene was amplified by PCR using original and modified GP5(+)/6(+) primers. Amplified PCR products were genotyped by the microarray system GeneSquare (KURABO) and/or clonal sequencing. Of the 281 women, 139 (49.5%) were positive for HPV DNA. Among the HPV-positive samples, 339 strains and 29 different types were identified. Multiple-type and high risk-type HPV infections were found in 85 (61.2%) and 124 (89.2%) women, respectively. The most common genotype was HPV-52, followed by HPV-16, HPV-18, and HPV-58. Abnormal cervical cytology was detected in 3.2% (9/281) of the women, and all of these samples were positive for HPV-DNA. Age ≤25 years and infection with human immunodeficiency virus were associated positively with HPV infection among the women while ever smoking was associated negatively. These results show that HPV-52 is most prevalent among female sex workers in Northern Vietnam, most of whom had normal cervical cytology. This information may be important for designing vaccination strategies in Vietnam.

E6 and E7 variants of human papillomavirus-16 and -52 in Japan, the Philippines, and Vietnam.

Human papillomavirus (HPV) has several intragenotypic variants with different geographical and ethnic distributions. This study aimed to elucidate the distribution patterns of E6 and E7 (E6/E7) intragenotypic variants of HPV type 16 (HPV-16), which is most common worldwide, and HPV-52, which is common in Asian countries such as Japan, the Philippines, and Vietnam. In previous studies, genomic DNA samples extracted from cervical swabs were collected from female sex workers in these three countries and found to be positive for HPV-16 or HPV-52. Samples were amplified further for their E6/E7 genes using type-specific primers and analyzed genetically. Seventy-nine HPV-16 E6/E7 genes were analyzed successfully and grouped into three lineages: European (Prototype), European (Asian), and African-2. The prevalences of HPV-16 European (Prototype)/European (Asian) lineages were 19.4%/80.6% (n = 31) in Japan, 75.0%/20.8% (n = 24) in the Philippines, and 0%/95.8% (n = 24) in Vietnam. The 109 HPV-52 E6/E7 genes analyzed successfully were grouped into four lineages, A-D; the prevalences of lineages A/B/C/D were, respectively, 5.1%/92.3%/0%/2.6% in Japan (n = 39), 34.4%/62.5%/0%/3.1% in the Philippines (n = 32), and 15.8%/73.7%/7.9%/2.6% in Vietnam (n = 38). The distribution patterns of HPV-16 and HPV-52 lineages in these countries differed significantly (P < 0.000001 and P = 0.0048, respectively). There was no significant relationship between abnormal cervical cytology and either HPV-16 E6/E7 lineages or specific amino acid mutations, such as E6 D25E, E6 L83V, and E7 N29S. Analysis of HPV-16 and HPV-52 E6/E7 genes can be a useful molecular-epidemiological tool to distinguish geographical diffusion routes of these HPV types in Asia.

Exon deletion patterns of the dystrophin gene in 82 Vietnamese Duchenne/Becker muscular dystrophy patients.

Duchenne and Becker muscular dystrophies (DMD/BMD) are the most common inherited muscle diseases caused by mutations in the dystrophin gene. The reading frame rule explains the genotype-phenotype relationship in DMD/BMD. In Vietnam, extensive mutation analysis has never been conducted in DMD/BMD. Here, 152 Vietnamese muscular dystrophy patients were examined for dystrophin exon deletion by amplifying 19 deletion-prone exons and deletion ends were confirmed by dystrophin cDNA analysis if necessary. The result was that 82 (54%) patients were found to have exon deletions, thus confirming exact deletion ends. A further result was that 37 patterns of deletion were classified. Deletions of exons 45-50 and 49-52 were the most common patterns identified, numbering six cases each (7.3%). The reading frame rule explained the genotype-phenotype relationship, but not five (6.1%) DMD cases. Each of five patients had deletions of exons 11-27 in common. The applicability of the therapy producing semifunctional in frame mRNA in DMD by inducing skipping of a single exon was examined. Induction of exon 51 skipping was ranked at top priority, since 16 (27%) patients were predicted to have semifunctional mRNA skipping. Exons 45 and 53 were the next ranked, with 12 (20%) and 11 (18%) patients, respectively. The largest deletion database of the dystrophin gene, established in Vietnamese DMD/BMD patients, disclosed a strong indication for exon-skipping therapy.

Multidimensional Machine Learning for Assessing Parameters Associated With COVID-19 in Vietnam: Validation Study.

BACKGROUND: Machine learning (ML) is a type of artificial intelligence strategy. Its algorithms are used on big data sets to see patterns, learn from their results, and perform tasks autonomously without being instructed on how to address problems. New diseases like COVID-19 provide important data for ML. Therefore, all relevant parameters should be explicitly quantified and modeled. OBJECTIVE: The purpose of this study was to determine (1) the overall preclinical characteristics, (2) the cumulative cutoff values and risk ratios (RRs), and (3) the factors associated with COVID-19 severity in unidimensional and multidimensional analyses involving 2173 SARS-CoV-2 patients. METHODS: The study population consisted of 2173 patients (1587 mild status [mild group] and asymptomatic patients, 377 moderate status patients [moderate group], and 209 severe status patients [severe group]). The status of the patients was recorded from September 2021 to March 2022. Two correlation tests, relative risk, and RR were used to eliminate unbalanced parameters and select the most remarkable parameters. The independent methods of hierarchical cluster analysis and k-means were used to classify parameters according to their r values. Finally, network analysis provided a 3-dimensional view of the results. RESULTS: COVID-19 severity was significantly correlated with age (mild-moderate group: RR 4.19, 95% CI 3.58-4.95; P<.001), scoring index of chest x-ray (mild-moderate group: RR 3.29, 95% CI 2.76-3.92; P<.001; moderate-severe group: RR 3.03, 95% CI 2.4023-3.8314; P<.001), percentage of neutrophils (mild-moderate group: RR 3.18, 95% CI 2.73-3.70; P<.001; moderate-severe group: RR 3.32, 95% CI 2.6480-4.1529; P<.001), quantity of neutrophils (moderate-severe group: RR 3.15, 95% CI 2.6153-3.8025; P<.001), albumin (moderate-severe group: RR 0.46, 95% CI 0.3650-0.5752; P<.001), C-reactive protein (mild-moderate group: RR 3.4, 95% CI 2.91-3.97; P<.001), and ratio of lymphocytes (moderate-severe group: RR 0.34, 95% CI 0.2743-0.4210; P<.001). Significant inversion of correlations among the severity groups is important. Alanine transaminase and leucocytes showed a significant negative correlation (r=-1; P<.001) in the mild group and a significant positive correlation in the moderate group (r=1; P<.001). Transferrin and anion Cl showed a significant positive correlation (r=1; P<.001) in the mild group and a significant negative correlation in the moderate group (r=-0.59; P<.001). The clustering and network analysis showed that in the mild-moderate group, the closest neighbors of COVID-19 severity were ferritin and age. C-reactive protein, scoring index of chest x-ray, albumin, and lactate dehydrogenase were the next closest neighbors of these 3 factors. In the moderate-severe group, the closest neighbors of COVID-19 severity were ferritin, fibrinogen, albumin, quantity of lymphocytes, scoring index of chest x-ray, white blood cell count, lactate dehydrogenase, and quantity of neutrophils. CONCLUSIONS: This multidimensional study in Vietnam showed possible correlations between several elements and COVID-19 severity to provide clinical reference markers for surveillance and diagnostic management.

A case of response to combination treatment with autologous immunotherapy and bevacizumab in advanced non-small cell lung cancer.

Natural killer (NK) cells have developed as a potent tool in cancer immunotherapy. Especially, patients who have failed in the first-line or maintenance treatment received a good response with immunotherapy in association with other approaches. We report the case of a 61-year-old male patient with programmed cell death ligand - 1(PD-L1) expression in advanced non-small cell lung cancer (NSCLC) (stage IV). Even though the patient was treated with standard therapy using keytruda, he still appeared with new lesions. Therefore, the patient was treated in combination with autologous NK cells therapy, gemcitabine, bevacizumab. NK cells were expanded from peripheral blood mononuclear cells (PBMCs) of the patient, and after that, they were transferred back to the patient. After 6 infusions of autologous NK cells in combination with gemcitabine, bevacizumab, the patient decreased significantly the size of primary, metastatic lesions and had a marked improvement in the quality of life. Besides, during combination therapy, no side effects have been reported and there was no toxicity observed in the hematopoietic system, liver as well as kidneys. Our case suggests that this treatment regimen is a potential treatment approach for advanced NSCLC with PD-L1 expression.

A novel stop codon mutation in exon 5 (c.639G>A) of the cadherin-1 gene in a Vietnamese man with hereditary diffuse gastric cancer: a case report.

BACKGROUND: Germline pathogenic variants in the cadherin-1 (CDH1) gene cause a predisposition to hereditary diffuse gastric cancer (HDGC). We report an HDGC case in Vietnam and identify a novel mutation in the CDH1 gene. CASE PRESENTATION: A 28-year-old Vietnamese man was diagnosed with HDGC and a novel mutation at c.639G>A. All exons of CDH1 were sequenced in his pedigree, which revealed the c.639G>A mutation in the proband, his father, and uncle. The patient refused treatment and died 4 months after diagnosis. Endoscopic surveillance of the father and the uncle showed structural abnormalities in the father. CONCLUSION: In cases of HDGC, identification of the CDH1 gene mutation is very important for better counseling and more effective strategies to prevent the development of diseases, such as prophylactic gastrectomy for family members with genetic mutations.

Genetic analysis of 55 northern Vietnamese patients with Wilson disease: seven novel mutations in ATP7B.

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. The gene responsible for WD was discovered in 1993 and is located on chromosome 13 at 13q14.3. It encodes a copper-specific transporting P-type ATPase. Early diagnosis can improve treatment outcome and decrease the rate of disability or even mortality.We used Sanger sequencing to identify mutation hot spots in 55 northern Vietnamese with a clinical diagnosis of WD. Mutations were screened and detected by direct DNA sequencing. A total of 26 different ATP7B gene mutations were identified, including seven novel mutations (five nonsense and two missense mutations). The most frequent mutations were p.Ser105Ter (24.55%), p.Arg778Leu (5.45%) and p.Thr850Ile (4.55%). Mutation detection rate in exon 2 was 34.55% and ranked first, followed by exon 8 with 16.36%, and exon 18 with 10.91% each, thus, exons 2, 8 and 18 are the mutation hot spots for northern VietnameseWD patients. These findings were different from previous studies in Asia. Our research established a suitable strategy for ATP7B gene testing in northern Vietnamese WD patients.

Validation of ambiguous MLPA results by targeted next-generation sequencing discloses a nonsense mutation in the DMD gene.

BACKGROUND: Duchenne muscular dystrophy (DMD) is the most common inherited muscular disease and caused by mutations in the DMD gene on the X-chromosome. Multiplex ligation-dependent probe amplification (MLPA) is recognized as a convenient and reliable technique to detect exon deletion/duplication mutations in the DMD gene. Here, we applied targeted semi-conductor next-generation sequencing to clarify the cause of ambiguous MLPA results. METHODS: Targeted semi-conductor next-generation sequencing was carried out using the Inherited Disease Panel (IDP) on the Ion Torrent Personal Genome Machine (PGM). RESULTS: MLPA analysis disclosed unclassifiable relative peak ratio of exon 18 in a DMD boy. His female cousin was indicated to have exon 18 deletion in one allele. To validate these incompatible results, targeted next-generation sequencing was conducted. A nucleotide change, C.2227 C>T creating a premature stop codon, was in exon 18. Concomitantly, both C and T nucleotides were identified in his cousin's genome. Ambiguous values of the relative peak ratio in MLPA were considered due to the one nucleotide mismatch between the genomic sequence and the probe used in MLPA. CONCLUSION: Analysis using IDP on PGM disclosed a nonsense mutation in the DMD gene as a cause of ambiguous results of MLPA.

Rapid method for targeted prenatal diagnosis of Duchenne muscular dystrophy in Vietnam.

OBJECTIVE: Since there is no effective curative treatment for Duchenne muscular dystrophy (DMD), prevention mostly depends on genetic counseling and prenatal diagnosis. About two-thirds of the affected patients have large deletions or duplications, which can be detected by multiplex ligation-dependent amplification (MLPA). The remaining cases include small mutations, which cannot be easily identified by routine techniques. In such cases, linkage analysis may be a useful tool for prenatal diagnosis. Here we compared results obtained from linkage using short tandem repeats (STRs) with those by MLPA and sequencing analysis. MATERIALS AND METHODS: Eight Vietnamese pregnant women at risk of having a baby with DMD and requesting prenatal diagnosis were recruited in this study. MLPA and direct sequencing were applied to screen large rearrangements and point mutations in the dystrophin gene in the DMD probands and the fetal samples. STR linkage was also performed to analyze fetal mutation status. RESULTS: By MLPA and sequencing analysis, five DMD patients showed deletions of the dystrophin gene, and no deletions of exons were detected in seven amniotic fluid cell samples; one patient harbored the out-of-frame small deletion of exon 43, which was also found in the fetal sample of this family. STR analysis revealed the transmission of a mutant allele inside each family. CONCLUSION: Our results suggest that the combination of STR and MLPA could be a rapid, reliable, and affordable detection protocol for determination of the carrier's status and prenatal diagnosis of DMD in a developing country such as Vietnam.

AID mutant analyses indicate requirement for class-switch-specific cofactors.

Activation-induced cytidine deaminase (AID) is the essential and sole B cell-specific factor required for class-switch recombination (CSR) and somatic hypermutation (SHM). However, it is not known how AID differentially regulates these two independent events. Involvement of several cofactors interacting with AID has been indicated by scattered distribution of loss-of-function point mutations and evolutionary conservation of the entire 198-amino-acid protein. Here, we report that human AID mutant proteins with insertions, replacements or truncations in the C-terminal region retained strong SHM activity but almost completely lost CSR activity. These results indicate that AID requires interaction with a cofactor(s) specific to CSR.