Systems-level immunomonitoring from acute to recovery phase of severe COVID-19

The immune response to SARS-CoV2 is under intense investigation, but not fully understood att this moment. Severe disease is characterized by vigorous inflammatory responses in the lung, often with a sudden onset after 5-7 days of stable disease. Efforts to modulate this hyperinflammation and the associated acute respiratory distress syndrome, rely on the unraveling of the immune cell interactions and cytokines that drive such responses. Systems-level analyses are required to simultaneously capture all immune cell populations and the many protein mediators by which cells communicate. Since every patient analyzed will be captured at different stages of his or her infection, longitudinal monitoring of the immune response is critical. Here we report on a systems-level blood immunomonitoring study of 39 adult patients, hospitalized with severe COVID-19 and followed with up to 14 blood samples from acute to recovery phases of the disease. We describe an IFN{gamma} - Eosinophil axis activated prior to lung hyperinflammation and changes in cell-cell coregulation during different stages of the disease. We also map an immune trajectory during recovery that is shared among patients with severe COVID-19. HIGHLIGHTSSystems-level immunomonitoring from acute to recovery in severe COVID-19 An IFN{gamma} - Eosinophil axis involved in lung hyperinflammation Cell-cell coregulation differ during four disease stages Basophils and hyperinflammation modulate humoral responses A shared trajectory of immunological recovery in severe COVID-19

The Prevalence of Myopia and Factors Associated with It Among Secondary School Children in Rural Vietnam.

PURPOSE: To assess the prevalence of myopia and associated factors among secondary school children in a rural area of Vietnam. METHODS: A school-based cross-sectional study of children in grades six to nine was conducted in four secondary schools in Hoang Mai town, Nghe An Province, Vietnam, during December 2018 and January 2019. The status of myopia was defined as a spherical equivalent objective refractive error of -0.50 D or worse in either eye. A case-control study was conducted to explore factors associated with myopia, where children with myopia were considered to be cases, and children without myopia were considered to be controls. Factors associated with myopia were analyzed using univariate and multivariate logistic regression. RESULTS: The prevalence of myopia among secondary school children was 14.2% (95% CI: 12.7-15.7%) and tended to increase with grade, from 10.5% in grade six to 17.7% in grade nine. Myopia prevalence in girls was significantly higher than in boys. Factors associated with myopia were a mother with a college/university education (OR = 2.5, 95% CI = 1.2-5.3), parents who wore spectacles (OR = 2.0, 95% CI = 1.1-3.8), distance from near work (OR = 5.2, 95% CI = 3.5-7.9), and taking breaks after 30 minutes of continued reading (OR = 1.6, 95% CI = 1.1-2.5). However, there were inverse associations with myopia for children belonging to the wealthiest households (OR = 0.2, 95% CI = 0.1-0.5) and time spent performing outdoor activities (OR = 0.6, 95% CI = 0.4-0.9). CONCLUSION: Our study showed that the prevalence of myopia is considerable among secondary children in rural areas of Vietnam. The prevalence of myopia tended to increase among children in higher grade levels. Thus, appropriate interventions should be developed and conducted to deal with the issue of school-age myopia.

Epidemiology of Enterobacter cloacae strains producing a carbapenemase or metallo-beta-lactamase in Vietnamese clinical settings in 2014-2017.

Introduction. Little is known about the epidemiology of Enterobacter cloacae strains producing a carbapenemase or metallo-beta-lactamase in Vietnamese hospitals.Aim. This study analysed E. cloacae strains resistant to imipenem or meropenem that had been isolated from patients admitted to one of the largest hospitals in Vietnam in 2014-2017.Methodology. Eighteen Vietnamese (VN) strains were subjected to whole-genome sequencing and their sequences compared with those of 17 E. cloacae strains carrying a carbapenemase or metallo-beta-lactamase in the database (db strains).Results. Although the distribution of virulence factors did not differ significantly between VN and db strains, all 18 VN isolates harboured blaNDM-1, phylogenetic analysis revealed a high clonality of the VN strains. Bayesian phylogenetic analysis suggested that the VN strains speciated relatively recently.Conclusions. Several prevalent clones of carbapenem-resistant E. cloacae have circulated within Vietnamese hospitals. Adequate measures are needed to prevent their further spread.

Tuberculosis-induced acute respiratory distress syndrome treated with veno-venous extracorporeal membrane oxygenation.

Tuberculosis (TB) is a rare but known cause of acute respiratory distress syndrome (ARDS) with a high mortality. Veno-venous extracorporeal membrane oxygenation (VV-ECMO) may be an alternative option for treating TB-induced ARDS. However, the literature on TB-induced ARDS treated with VV-ECMO is limited and the most of them were prolonged therapy. We report on a-48-year-old man with TB-induced ARDS who was successfully treated by short-term use of VV-ECMO (5 days). He was developed symptoms and hospitalized with severe dyspnea in a local hospital for 3 days before admission to our hospital. At the time when he was transferred to our hospital, his chest computed tomography showed bilateral, diffuse and consolidative shadows all over the lungs, the ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) was 50 mmHg, and respiratory system compliance was 12.5 mL/cmH2O. Two days after admission, Mycobacterium tuberculosis was detected by a sputum smear examination and he was diagnosed with TB-induced ARDS. VV-ECMO support was then initiated with administration of anti-TB drugs and systemic corticosteroid treatment. On the 4thday of ECMO support, his PaO2/FiO2 increased to 400 mmHg and lung compliance increased to 45 mL/cmH2O. He was weaned from ECMO on the 5th day of ECMO support and was extubated at the 8th day. He was discharged from hospital on the 47th hospitalized day and continued anti-TB medication at home. VV-ECMO is effective for TB-induced ARDS even in short-term administration if progression of ARDS is rapid.

Antimicrobial susceptibility of Burkholderia pseudomallei isolates in Northern Vietnam.

OBJECTIVES: The antimicrobial susceptibility pattern of clinical Burkholderia pseudomallei (B. pseudomallei) in Vietnam has not been reported since the first publication in 2008. The present study aimed to determine the antimicrobial susceptibility pattern of B. pseudomallei isolated in a tertiary referral centre in Hanoi from January 2012 to December 2017. METHODS: A total of 312 B. pseudomallei isolates obtained from melioidosis patients admitted to a 2000-bed general hospital were analysed by the Etest method. Interpretation of the susceptibility testing results were reported using Clinical and Laboratory Standards Institute guidelines. RESULTS: All isolates were susceptible to ceftazidime, imipenem and amoxicillin-clavulanate (100%) with MIC90s relatively low (2µg/mL). Two isolates had intermediate resistance to doxycycline (0.6%) and 34 isolates were resistant to trimethoprim/sulfamethoxazole (10.9%). CONCLUSION: The results of this study suggest that currently recommended antibiotics for melioidosis treatment can be empirically used, but continuously monitoring antimicrobial susceptibility should be a concern.

Assessment of Bacteremia in a Large Tertiary Care Hospital in Northern Vietnam: a Single-Center Retrospective Surveillance Study.

The clinical analysis of cases of bacteremia is valuable. However, limited data on bacteremia are available in Vietnam. We conducted a single-center retrospective surveillance study at the Bach Mai Hospital, Hanoi, Vietnam between 2009 and 2012. In total, 45,366 blood cultures were analyzed. The number of blood cultures per 1,000 patient-days was 9.59 sets. The percentage of solitary blood culture sets was 49.6%, and the rate of positive blood cultures was 13.9%. The major pathogens isolated in adults were coagulase-negative Staphylococcus species (16.7%), followed by Escherichia coli (6.8%), Streptococcus spp. excluding Streptococcus pneumoniae (3.8%), and Staphylococcus aureus (5.2%). Other major pathogens identified were Klebsiella spp. (4.2%) and Acinetobacter spp. (2.2%). The number of blood cultures per 1,000 patient-days was lower and the percentage of solitary blood culture sets higher than that of a Japanese study (9.6 vs. 25.2 and 49.6% vs. 32.8%, respectively). The distribution of microorganisms was unique in terms of the relative predominance of cases of Acinetobacter bacteremia. The percentage of cases of healthcare-associated bacteremia may be relatively high.

Emergence of colistin-resistant Escherichia coli clinical isolates harboring mcr-1 in Vietnam.

The mcr-1 was first detected on a plasmid in colistin-resistant Escherichia coli from livestock and patients in China. We described here the emergence of colistin-resistant E. coli clinical isolates harboring mcr-1 on the chromosomes in Vietnam. To our knowledge, this is the first report of hospital-acquired E. coli isolates harboring mcr-1 in a medical setting in Vietnam.

Multidrug-Resistant Sequence Type 235 Pseudomonas aeruginosa Clinical Isolates Producing IMP-26 with Increased Carbapenem-Hydrolyzing Activities in Vietnam.

Forty clinical isolates of multidrug-resistant Pseudomonas aeruginosa were obtained in a medical setting in Hanoi, Vietnam. Whole genomes of all 40 isolates were sequenced by MiSeq (Illumina), and phylogenic trees were constructed from the single nucleotide polymorphism concatemers. Of these 40 isolates, 24 (60.0%) harbored metallo-ß-lactamase-encoding genes, including blaIMP-15, blaIMP-26, blaIMP-51, and/or blaNDM-1 Of these 24 isolates, 12 harbored blaIMP-26 and belonged to sequence type 235 (ST235). Escherichia coli expressing blaIMP-26 was significantly more resistant to doripenem and meropenem than E. coli expressing blaIMP-1 and blaIMP-15 IMP-26 showed higher catalytic activity against doripenem and meropenem than IMP-1 and against all carbapenems tested, including doripenem, imipenem, meropenem, and panipenem, than did IMP-15. These data suggest that clinical isolates of multidrug-resistant ST235 P. aeruginosa producing IMP-26 with increased carbapenem-hydrolyzing activities are spreading in medical settings in Vietnam.

Nutritional status and feeding practices in gastrointestinal surgery patients at Bach Mai Hospital, Hanoi, Vietnam.

BACKGROUND AND OBJECTIVES: The nutritional status and hospital feeding practices of surgical patients in Vietnam are not well documented. Based on a cross-sectional study at Bach Mai Hospital (BMH), the prevalence of malnutrition was found to be 33% in the surgical ward using a body mass index (BMI<18.5 kg/m(2). We conducted an observational study over a three month period to evaluate the feeding practices in the gastrointestinal (GI) surgery ward at Bach Mai Hospital (BMH) in Hanoi, Vietnam. METHODS AND STUDY DESIGN: Investigators from the U.S. and the Vietnamese National Institute of Nutrition (NIN) enrolled 72 subjects admitted for elective GI surgery in an observational study at BMH. Baseline anthropometrics and changes over time, body mass index (BMI), Subjective Global Assessment (SGA) and daily kcal and protein intake from oral diet, tube feeding, and parenteral nutrition (PN) from admission until discharge were documented. RESULTS: A total of 50% of subjects scored a B or C on the SGA; 48% of subjects had a BMI<18.5, while mean mid upper arm circumference was in the lownormal range (24±4 cm). Nearly all patients (98%) were given PN postoperatively, with oral feeding starting on an average of postoperative day 4. Only one patient was tube fed. Mean daily total calorie intake was 15 kcal/kg/day and protein intake was 0.61 g/kg/day during hospitalization. Micronutrient supplementation was minimal in subjects receiving PN. CONCLUSIONS: Hospital malnutrition in surgical patients in Vietnam is a significant problem, peri-operative feeding appears suboptimal and use of early postoperative PN was routine.

IMP-51, a novel IMP-type metallo-ß-lactamase with increased doripenem- and meropenem-hydrolyzing activities, in a carbapenem-resistant Pseudomonas aeruginosa clinical isolate.

A meropenem-resistant Pseudomonas aeruginosa isolate was obtained from a patient in a medical setting in Hanoi, Vietnam. The isolate was found to have a novel IMP-type metallo-ß-lactamase, IMP-51, which differed from IMP-7 by an amino acid substitution (Ser262Gly). Escherichia coli expressing blaIMP-51 showed greater resistance to cefoxitin, meropenem, and moxalactam than E. coli expressing blaIMP-7. The amino acid residue at position 262 was located near the active site, proximal to the H263 Zn(II) ligand.

Evaluation of the Etest method for detecting colistin susceptibility of multidrug-resistant Gram-negative isolates in Vietnam.

The minimum inhibitory concentrations (MICs) of colistin for 241 multidrug-resistant (MDR) Gram-negative pathogens were determined by the Etest and by the broth microdilution method (BMD). The two methods showed essential agreements of 76% (77/102) for Acinetobacter baumannii, 90% (36/40) for Pseudomonas aeruginosa and 84% (83/99) for Enterobacteriaceae isolates, with categorical agreements of 100%, 98%, and 100%, respectively. Of the 241 isolates, none showed a very major error and one (0.4%) showed a major error. MICs ranged from 0.125 to 0.5 µg/ml for all A. baumannii and most Enterobacteriaceae isolates, and from 1 to 2 µg/ml for most P. aeruginosa isolates. Of the 40 P. aeruginosa isolates, 27 (68%) showed higher colistin MICs by the Etest than by the BMD. In contrast, 77% (78/102) of the A. baumannii and 57% (56/99) of the Enterobacteriaceae isolates showed lower colistin MICs by the Etest than by the BMD. The Etest is a reliable and easy-to-use method to measure colistin MICs of MDR Gram-negative pathogens in clinical laboratories and can be used following validation by microdilution methods.

Prevalence of malnutrition in patients admitted to a major urban tertiary care hospital in Hanoi, Vietnam.

OBJECTIVES: To determine the prevalence of malnutrition using anthropometric measures among hospitalized pediatric and adult patients admitted at Bach Mai Hospital, Hanoi, Vietnam. METHODS: A one-day cross-sectional survey was used in selected wards (Pediatrics, Surgery, Intensive Care Unit, Renal Diseases, Gastroenterology Diseases, Respiratory Diseases, and Endocrinology). Unavailable patients and those discharged within 24 hours were excluded. Anthropometric data included body weight, height (or length), and mid-upper arm circumference. The type, severity, and prevalence rate of malnutrition were defined based on World Health Organization (WHO) criteria. RESULTS: The sample was hospitalized children and adults: 108 and 571 were children aged 6 months to 18.9 years old and adult patients, respectively. The overall rate of pediatric wasting (weight-for-height ≤ -2 SD or BMI ≤ -2 SD, kg/m²) was 19.0% (n= 19/100) and that of stunting (height-for-age ≤ -2 SD) was 13.9% (n=14/101). Using either the mid-upper arm circumference <11.5 cm or the weight-for-height and weight-for-length ≤ -3 SD, the rate of severe wasting among children aged 6-59 months old was 7.0% (n=3/43). None of the children were obese based on weight-for-length, weight-for-height, or BMI. In adults, the prevalence of under-nutrition (BMI<18.5 kg/m²) was 33.3% (n=141/423) while that of obesity (BMI ≥ 30 kg/m²) was 0.9% (n=4/423). Adults admitted to the Respiratory Diseases ward had the highest prevalence of under-nutrition, 40.9% (n=38/93). CONCLUSIONS: The prevalence of malnutrition was high in this cohort of hospitalized patients, particularly in adults, but comparable to other published reports. Obesity was nearly nonexistent in both children and adults.

Emergence of 16S rRNA methylase-producing Acinetobacter baumannii and Pseudomonas aeruginosa isolates in hospitals in Vietnam.

BACKGROUND: 16S rRNA methylase-producing Gram-negative bacteria are highly resistant to all clinically important aminoglycosides. We analyzed clinical strains of 16S rRNA methylase-producing Acinetobactor baumannii and Pseudomonas aeruginosa obtained from clinical isolates in medical settings in Vietnam. METHODS: From 2008 to 2011, 101 clinical strains of A. baumannii and 15 of P. aeruginosa were isolated from patients in intensive care units (ICUs) in two medical settings in Vietnam. Antimicrobial susceptibilities were determined using the microdilution method and epidemiological analysis was performed by pulsed-field gel electrophoresis and MLST. Genes encoding the 16S rRNA methylases, OXAs and CTX-Ms were analyzed by PCR and sequence analysis. RESULTS: 16S rRNA methylase-producing Gram-negative pathogens were detected in two hospitals in Vietnam. Of the 101 clinical isolates of A. baumannii and the 15 of P. aeruginosa isolated from two ICUs in these hospitals, 72 (71.3%) were highly resistant to amikacin, arbekacin and gentamicin, with MICs greater than 1,024 mg/L. The 16S rRNA methylases ArmA and RmtB were produced by 61 and 9 isolates of A. baumannii, respectively, and RmtB was produced by 2 isolates of P. aeruginosa. Moreover, 52 of the A. baumannii isolates producing 16S rRNA methylases harbored both blaOXA-23-like and blaOXA-51-like genes. Most A. baumannii isolates producing 16S rRNA methylase obtained in hospital A in Hanoi were ST91 and ST231, whereas most from hospital B in Ho Chi Minh City were ST136, ST195, and ST254. CONCLUSIONS: Gram-negative bacteria producing the 16S rRNA methylases ArmA and RmtB are emerging in medical settings in Vietnam. A. baumannii isolates in northern and southern regions of Vietnam may be of different lineages.