Genetic features of SARS-CoV-2 Alpha, Delta, and Omicron variants and their association with the clinical severity of COVID-19 in Vietnam.

Objectives: We investigated the genetic variations in the Alpha, Delta, and Omicron variants of SARS-CoV-2 and their association with clinical status and treatment outcomes in patients with COVID-19. Methods: MiSeq was used to sequence the Alpha, Delta, and Omicron genomes, and MEGA 6.6 was used to define the nucleotide variations. We determined the association between clinical severity and treatment outcomes for the SARS-CoV-2 variants. Results: The BA.1.1 and BA.2 lineages of the Omicron variant had 57-59 mutations, which is 2-2.7-fold higher than that of the B.1.1.7 (Alpha), B.1.617.2, and AY.57 (Delta) lineages. We found distinct mutations in SARS-CoV-2: five in Alpha (C26305T, G26558T, G7042T, C14120T, and C27509T); seven in Delta (C26408T, C1403T, C5184T, C9891T, T11418C, C11514T, and C22227T); and three in Omicron (C26408T, C8991T, and C25810T). Patients with the Delta variant had a severe rate of 23.8%, a critical rate of 53.7%, and a mortality rate of 38.9%, which were significantly higher than those with the Omicron and Alpha variants. Conclusions: The Alpha, Delta, and Omicron variants in this study had genetic diversity and differed from the strains reported in other countries, with the Delta variant producing significantly more clinical severity and mortality than the Alpha and Omicron variants.

Characteristics of Cervical Cancer Caused by the Human Papillomavirus 18 and Its Genetic Variations in Vietnamese Women.

BACKGROUND: The involvement of HPV18 in cervical cancer pathogenesis, as well as its high oncogenic potential and influence on the variation of cervical cancer distribution in different geographical regions, makes assessing the characteristics of cervical cancer and its variants the basis for considering potential carcinogenic HPV18 sequence variations and vaccine strategies. METHODS: A prospective study was conducted at Vietnam Central Obstetrics Hospital from January 1, 2019 to December 31, 2020. HPV18 infection was confirmed in cervical cancer patients using molecular diagnostics. Nucleotide sequences of the HPV18 E6, E7, and L1 genes were used to analyze genetic variations. The demographic, clinical, and laboratory data of the patients were collected and statistically analyzed. RESULTS: Among 48 patients with HPV18-infected cervical cancer, 79.2% were between the ages of 35-54; while only 20.8% were < 35 and > 54 years old. 100% of patients have been pregnant at some point in their lives, with ≥3 pregnancies accounting for 83.3%. Patients with cervical cancer caused by HPV18 infection were predominantly in stages 0 and I, with no patients in stages II, III, or IV. A single HPV18 infection generates much more cervical cancer cases than multiple HPV18 infections. Symptoms such as lower abdomen pain, unusual anginal discharge, and vaginal bleeding were observed in both stages 0 and I; however, vaginal bleeding after sex was only detected in women with stage I cervical cancer. Cervicitis, cervical ectropion, and ulcers are reported in cervical status stages 0 and I; however, warts and ulcers were only present in stage I. Magnetic resonance imaging produces far superior outcomes than ultrasound. All cytology and pathology tests confirmed L/HSIL, SCC, AC, and CIS. On the other hand, a single HPV18 infection was associated with a significantly higher risk of L/HSIL, SCC, AC, and CIS than multiple HPV18 infections. Nulceotide sequences of the E6, E7, and L1 genes revealed 20 mutations, including three (E6), five (E7), and twelve (L1) mutations. High-frequency mutations (95.8%-100% of HPV18 samples had mutations) occur at the following positions: C287G - P61P (E6 gene), G5503A - R25Q, C5701G - P91R, C6460G - P344R, C6625G - P399R, and C6842G - P471R (L1 gene). A phylogenetic tree based on the E6/E7/L1 gene sequence revealed that 100% belonged to A lineage, with 97.9% belonging AA (Asian Amerindian - A1) and 2.1% belonging to the E (European - A5). CONCLUSION: Patients with a single HPV18 infection have a higher risk of cervical cancer than those infected with HPV18 and other high-risk strains simultaneously. HPV18 single-infection, on the other hand, had considerably higher incidences of L/HSIL, SCC, AC, and CIS than HPV18 co-infection. The HPV18 strain that was found in Vietnam belonged to lineage A (A1 and A5), which contains several oncogene mutations.

COVID-19 patients hospitalized after the fourth wave of the pandemic period in Vietnam: Clinical, laboratory, therapeutic features, and clinical outcomes.

BACKGROUND/PURPOSE: Despite having relatively high COVID-19 vaccine coverage in Vietnam, a fraction of COVID-19 patients required hospitalization due to severe symptoms. The purpose of this study was to describe the clinical, laboratory, complications, and treatment of COVID-19 patients hospitalized during the pandemic's fourth wave. METHODS: Genome sequencing was performed on COVID-19 patients. Data on clinical characteristics, treatment, complications, and outcomes were consistently collected. RESULTS: The clinical classifications were mild (37.43%), moderate (24.2%), and severe (38.37%). Patients with co-morbidities, high fever >39 °C, hypertension, tachycardia, tachypnea, and SpO2<90%, had a 1.2-4 folds higher of severe progression than those with mild/moderate. Serious consequences were much more common in the severe patients than in the mild/moderate. The respiratory system of severe patients was generally documented as fine, coarse crackles, and CT scanner shown ground glass, consolidation, and opacity, with Delta variant accounting for 92.6%. Complications were common in the severe patients, including bacteria pneumonia (36.42%), ARDS (61.11%), blood clotting disorder (7.14%), infection (46.92%), and acute kidney injury (12.35%). Antiviral, antifungal, corticosteroid, anticoagulant, and ECMO regimens were utilized. Patients died mostly as a result of co-morbidities, low SpO2, lung injury, and complications such as bacterial + fungal pneumonia (83.9%), ARDS (83.9%), bacteremia (56.5%), injury acute renal failure (27.4%), and coagulopathy (12.9%). CONCLUSION: Severe and critical COVID-19 patients frequently have several comorbidities, multiple lung lesions along with a variety of clinical signs. Despite receiving antivirals, antibiotics, corticosteroids, anticoagulants, and even ECMO therapy, the patient encountered multiple complications, with a fatality rate of up to 38.27%.

Spatiotemporal Evolution of SARS-CoV-2 Alpha and Delta Variants during Large Nationwide Outbreak of COVID-19, Vietnam, 2021.

We analyzed 1,303 SARS-CoV-2 whole-genome sequences from Vietnam, and found the Alpha and Delta variants were responsible for a large nationwide outbreak of COVID-19 in 2021. The Delta variant was confined to the AY.57 lineage and caused >1.7 million infections and >32,000 deaths. Viral transmission was strongly affected by nonpharmaceutical interventions.

The prevalence of SARS-CoV-2 antibodies in quarantine workers and high-risk communities in Vietnam.

Objective: The aim of this study was to determine the seroprevalence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) antibodies in high-risk communities and quarantine workers in Vietnam. Methods: The prevalence of SARS-CoV-2 antibodies was measured in household contacts, close contacts, community members, and migrant workers from two sub-communes in which COVID-19 outbreaks occurred in early 2021: Bac Ma 1 and Tien. The prevalence of SARS-CoV-2 antibodies was also evaluated among quarantine workers at two facilities responsible for quarantining of contacts of COVID-19 cases. Results: Among 2069 participants from the two sub-communes, six individuals (0.3%) had detectable SARS-CoV-2 antibodies despite no history of COVID-19. This included one Vietnamese migrant worker, two community members, two household contacts, and one close contact of known COVID-19 cases. Among 50 workers at two COVID-19 quarantine facilities, including 15 health care workers (HCWs), one of the HCWs tested positive for SARS-CoV-2 antibodies (1/50, 2.0%) despite no known disease. Conclusion: The prevalence of SARS-CoV-2 antibodies was low in Vietnamese 'hotspots', suggesting limited community transmission.

Strongyloidiasis in northern Vietnam: epidemiology, clinical characteristics and molecular diagnosis of the causal agent.

BACKGROUND: Strongyloidiasis is a health problem in Vietnam, but appropriate information is still limited. The aim of this study was to determine the prevalence, geographical distribution, epidemiological aspects, symptoms and other health indicators of Strongyloides stercoralis infections in patients from 27 provinces of northern Vietnam attending the Hanoi Medical University Hospital during 2016 and 2017. METHODS: Blood samples of 2000 patients were analyzed for S. stercoralis infection with an IgG ELISA test. Seroprevalence was analyzed by gender, age group, locality of origin (rural or urban areas) and symptoms. Stools from the seropositive patients were examined for the detection of worms which were subsequently used for species identification by morphology and rDNA ITS1 sequencing. RESULTS: A seroprevalence of 20% was detected, showing an increasing prevalence from young to older age groups but without significant gender difference. Seroprevalence was higher in rural areas than in urban areas, both in general and individually in all provinces without exception, and lower in the mountainous areas than in the large valley lowlands. The follow-up of the 400 patients showed eosinophilia in 100% of cases, diarrhoea in 64.5%, digestion difficulties in 58.0%, stomachache in 45.5%, stomach and duodenal ulcers in 44.5%, itching in 28.0% and fever in 9.5%. The prevalence of symptoms and signs were also higher in older age groups than in younger age groups. Worms were detected in stools of 10.5% of the patients. Sequencing of a 501-bp nuclear ribosomal DNA ITS1 fragment allowed for the verification of infection by Strongyloides stercoralis. CONCLUSIONS: To our knowledge, this study is the largest survey of human strongyloidiasis in Vietnam so far and the first molecular identification of this nematode species in this country. Long-term chronicity may probably be usual in infected subjects, mainly in the older age groups.

Genetic characterization of Enterovirus 71 strains circulating in Vietnam in 2012.

BACKGROUND: Enterovirus 71 subgenogroup C4 caused the largest outbreak of Hand, Foot and Mouth Disease (HFMD) in Vietnam during 2011-2012, resulting in over 200,000 hospitalisations and 207 fatalities. METHODS: A total of 1917 samples with adequate volume for RT-PCR analysis were collected from patients hospitalised with HFMD throughout Vietnam and 637 were positive for EV71. VP1 gene (n=87) and complete genome (n=9) sequencing was performed. Maximum-likelihood phylogenetic analysis was performed to characterise the B5, C4 and C5 strains detected. RESULTS: Sequence analyses revealed that the dominant subgenogroup associated with the 2012 outbreak was C4, with B5 and C5 strains representing a small proportion of these cases. CONCLUSIONS: Numerous countries in the region including Malaysia, Taiwan and China have a large influence on strain diversity in Vietnam and understanding the transmission of EV71 throughout Southeast Asia is vital to inform preventative public health measures and vaccine development efforts.

Proteome profiling of heat, oxidative, and salt stress responses in Thermococcus kodakarensis KOD1.

The thermophilic species, Thermococcus kodakarensis KOD1, a model microorganism for studying hyperthermophiles, has adapted to optimal growth under conditions of high temperature and salinity. However, the environmental conditions for the strain are not always stable, and this strain might face different stresses. In the present study, we compared the proteome response of T. kodakarensis to heat, oxidative, and salt stresses using two-dimensional electrophoresis, and protein spots were identified through MALDI-TOF/MS. Fifty-nine, forty-two, and twenty-nine spots were induced under heat, oxidative, and salt stresses, respectively. Among the up-regulated proteins, four proteins (a hypothetical protein, pyridoxal biosynthesis lyase, peroxiredoxin, and protein disulphide oxidoreductase) were associated with all three stresses. Gene ontology analysis showed that these proteins were primarily involved metabolic and cellular processes. The KEGG pathway analysis suggested that the main metabolic pathways involving these enzymes were related to carbohydrate metabolism, secondary metabolite synthesis, and amino acid biosynthesis. These data might enhance our understanding of the functions and molecular mechanisms of thermophilic Archaea for survival and adaptation in extreme environments.

Structural and functional characterization of osmotically inducible protein C (OsmC) from Thermococcus kodakaraensis KOD1.

Osmotically inducible protein C (OsmC) is involved in the cellular defense mechanism against oxidative stress caused by exposure to hyperoxides or elevated osmolarity. OsmC was identified by two-dimensional electrophoresis (2DE) analysis as a protein that is overexpressed in response to osmotic stress, but not under heat and oxidative stress. Here, an OsmC gene from T. kodakaraensis KOD1 was cloned and expressed in Escherichia coli. TkOsmC showed a homotetrameric structure based on gel filtration and electron microscopic analyses. TkOsmC has a significant peroxidase activity toward both organic and inorganic peroxides in high, but not in low temperature.

Oligomeric structure of the ATP-dependent protease La (Lon) of Escherichia coli.

Lon, also known as protease La, belongs to a class of ATP-dependent serine protease. It plays an essential role in degradation of abnormal proteins and of certain short-lived regulatory proteins, and is thought to possess a Ser-Lys catalytic dyad. To examine the structural organization of Lon, we performed an electron microscope analysis. The averaged images of Lon with end-on orientation revealed a six-membered, ring-shaped structure with a central cavity. The side-on view showed a two-layered structure with an equal distribution of mass across the equatorial plane of the complex. Since a Lon subunit possesses two large regions containing nucleotide binding and proteolytic domains, each layer of the Lon hexamer appears to consist of the side projections of one of the major domains arranged in a ring. Lon showed a strong tendency to form hexamers in the presence of Mg(2+), but dissociated into monomers and/or dimers in its absence. Moreover, Mg(2+)-dependent hexamer formation was independent of ATP. These results indicate that Lon has a hexameric ring-shaped structure with a central cavity, and that the establishment of this configuration requires Mg(2+), but not ATP.