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Mohammad Rabiul Halim,1,&ast; Shuvajit Saha,2,&ast; Injamam Ull Haque,1 Sadia Jesmin,1 Rahatul Jannat Nishat,3 ASMD Ashraful Islam,2 Seema Roy,4 Miah Md Akiful Haque,5 Md Motiul Islam,1 Tarikul Hamid,1 Kazi Nuruddin Ahmed,1 Md Azharul Islam Talukder,1 Arif Ahmed,1 Emran Hasan,2 Nurjahan Ananna,1 Faroque Md Mohsin,6 Mohammad Delwer Hossain Hawlader7 1Department of Critical Care Medicine, Central Police Hospital, Dhaka, Bangladesh; 2Department of Maternal and Child Health, Projahnmo Research Foundation, Dhaka, Bangladesh; 3Department of Physiology, Sir Salimullah Medical College, Dhaka, Bangladesh; 4Department of Medicine, Popular Medical College, Dhaka, Bangladesh; 5Department of Epidemiology, Public Health Professional Development Initiative (PPDI), Dhaka, Bangladesh; 6Directorate General of Health Services (DGHS), Ministry of Health and Family Welfare, Dhaka, Bangladesh; 7Department of Public Health, North South University, Dhaka, Bangladesh&ast;These authors contributed equally to this workCorrespondence: Mohammad Delwer Hossain Hawlader Email mohammad.hawlader@northsouth.eduPurpose: The world is heavily suffering from the COVID-19 pandemic for more than a year, with over 191 million confirmed cases and more than 4.1 million deaths to date. Previous studies have explored several risk factors for coronavirus disease 2019 (COVID-19), but there is still a lack of association with ABO blood type. This study aimed to find out the relationship between the ABO blood group and COVID-19 outcomes in Bangladesh.Subjects and Methods: This retrospective cross-sectional study was conducted in the intensive care unit (ICU) of a tertiary-level COVID-dedicated hospital in Dhaka city, Bangladesh, between April 2020 and November 2020. Records from 771 critically ill patients were extracted who were confirmed for COVID-19 by reverse transcriptase-polymerase chain reaction (RT-PCR) assay, and blood grouping records were available in the health records.Results: The blood groups were 37.35%, 17.38%, 26.46%, and 18.81% for A, B, AB, and O type, respectively. Clinical symptoms were significantly more common in patients with blood type A (p < 0.05). Patients with blood type A had higher WBC counts and peak serum ferritin levels and both were statistically significant (p < 0.001). Patients with blood type A had a greater need for supplemental oxygen, and they were more likely to die in comparison to the patients with other blood types (p < 0.05). In multivariable analysis, our primary outcome death was significantly associated with blood type A (AOR: 3.49, 95% CI: 1.57– 7.73) while adjusting for age, male gender, and non-communicable diseases.Conclusion: Based on this study results, it can be concluded that the COVID-19 patients with blood type A have a higher chance of death and other complications. The authors recommend blood grouping before treating the COVID-19 patients, and healthcare workers should prioritize treating the patients based on that result.Keywords: COVID-19, ICU, ABO blood group, Bangladesh

HM Adnan Hameed, 1, 2,* Yaoju Tan, 3,* Md Mahmudul Islam, 1, 2 Zhili Lu, 1 Chiranjibi Chhotaray, 1, 2 Shuai Wang, 1, 2 Zhiyong Liu, 1 Cuiting Fang, 1, 2 Shouyong Tan, 3 Wing Wai Yew, 4 Nanshan Zhong, 5 Jianxiong Liu, 3 Tianyu Zhang 1, 2, 5 1State Key Laboratory of Respiratory Disease, Guangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Guangzhou, People’s Republic of China; 2University of Chinese Academy of Sciences (UCAS), Beijing, People’s Republic of China; 3State Key Laboratory of Respiratory Disease, Guangzhou Chest Hospital, Guangzhou, People’s Republic of China; 4Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 5National Clinical Research Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tianyu ZhangGuangzhou Institutes of Biomedicine and Health (GIBH), Chinese Academy of Sciences (CAS), Room A132, 190 Kaiyuan Ave, Science Park, Huangpu District, Guangzhou 510530, People’s Republic of ChinaTel +86-2032015270Email zhang_tianyu@gibh.ac.cnJianxiong LiuGuangzhou Chest Hospital, 62 Hengzhigang Road, Yuexiu District, Guangzhou 510095, People’s Republic of ChinaTel +86-2083595977Email ljxer64@qq.comObjective: Pyrazinamide (PZA) is a cornerstone of modern tuberculosis regimens. This study aimed to investigate the performance of genotypic testing of pncA+ upstream region, rpsA, panD, Rv2783c, and clpC1 genes to add insights for more accurate molecular diagnosis of PZA-resistant (R) Mycobacterium tuberculosis.Methods: Drug susceptibility testing, sequencing analysis of PZA-related genes including the entire operon of pncA (Rv2044c-pncA-Rv2042c) and PZase assay were performed for 448 M. tuberculosis clinical isolates.Results: Our data showed that among 448 M. tuberculosis clinical isolates, 113 were MDR, 195 pre-XDR and 70 XDR TB, while the remaining 70 strains had other combinations of drug-resistance. A total of 60.04% (269/448) M. tuberculosis clinical isolates were resistant to PZA, of which 78/113 were MDR, 119/195 pre-XDR and 29/70 XDR TB strains. PZAR isolates have predominance (83.3%) of Beijing genotype. Genotypic characterization of Rv2044c-pncA-Rv2042c revealed novel nonsynonymous mutations in Rv2044c with negative PZase activity which led to confer PZAR. Compared with phenotypic data, 84.38% (227/269) PZAR strains with mutations in pncA+ upstream region exhibited 83.64% sensitivity but the combined evaluation of the mutations in rpsA 2.60% (7/269), panD 1.48% (4/269), Rv2783c 1.11% (3/269) and Rv2044c 0.74% (2/269) increased the sensitivity to 89.59%. Fifty-seven novel mutations were identified in this study. Interestingly, a frameshift deletion (C− 114del) in upstream of pncAwt nullified the effect of A− 11G mutation and induced positive PZase activity, divergent from five PZase negative A− 11G PZAR mutants. Twenty-six PZAR strains having wild-type-sequenced genes with positive or negative PZase suggest the existence of unknown resistance mechanisms.Conclusion: Our study revealed that PZAR rate in MDR and pre-XDR TB was markedly higher in southern China. The concomitant evaluation of pncA+ UFR, rpsA, panD, Rv2783c, and Rv2044c provides more dependable genotypic results of PZA resistance. Fifty-seven novel mutations/indels in this study may play a vital role as diagnostic markers. The upstream region of pncA and PZase regulation are valuable to explore the unknown mechanism of PZA-resistance.Keywords: tuberculosis, pyrazinamidase, drug resistance, molecular diagnosis, novel mutations, frameshift deletion

Shakhinur Islam Mondal,1,6,* Sabiha Ferdous,1,* Nurnabi Azad Jewel,1 Arzuba Akter,2,6 Zabed Mahmud,1 Md Muzahidul Islam,1 Tanzila Afrin,3 Nurul Karim4,5 1Genetic Engineering and Biotechnology Department, Shahjalal University of Science and Technology, Sylhet, Bangladesh; 2Biochemistry and Molecular Biology Department, Shahjalal University of Science and Technology, Sylhet, Bangladesh; 3Department of Pharmacy, East West University, Aftabnagar, Bangladesh; 4Biochemistry and Molecular Biology Department, Jahangirnagar University, Savar, Bangladesh; 5Division of Parasitology, 6Division of Microbiology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan *These authors contributed equally to this work Abstract: Bacterial enteric infections resulting in diarrhea, dysentery, or enteric fever constitute a huge public health problem, with more than a billion episodes of disease annually in developing and developed countries. In this study, the deadly agent of hemorrhagic diarrhea and hemolytic uremic syndrome, Escherichia coli O157:H7 was investigated with extensive computational approaches aimed at identifying novel and broad-spectrum antibiotic targets. A systematic in silico workflow consisting of comparative genomics, metabolic pathways analysis, and additional drug prioritizing parameters was used to identify novel drug targets that were essential for the pathogen’s survival but absent in its human host. Comparative genomic analysis of Kyoto Encyclopedia of Genes and Genomes annotated metabolic pathways identified 350 putative target proteins in E. coli O157:H7 which showed no similarity to human proteins. Further bioinformatic approaches including prediction of subcellular localization, calculation of molecular weight, and web-based investigation of 3D structural characteristics greatly aided in filtering the potential drug targets from 350 to 120. Ultimately, 44 non-homologous essential proteins of E. coli O157:H7 were prioritized and proved to have the eligibility to become novel broad-spectrum antibiotic targets and DNA polymerase III alpha (dnaE) was the top-ranked among these targets. Moreover, druggability of each of the identified drug targets was evaluated by the DrugBank database. In addition, 3D structure of the dnaE was modeled and explored further for in silico docking with ligands having potential druggability. Finally, we confirmed that the compounds N-coeleneterazine and N-(1,4-dihydro-5H-tetrazol-5-ylidene)-9-oxo-9H-xanthene-2-sulfonamide were the most suitable ligands of dnaE and hence proposed as the potential inhibitors of this target protein. The results of this study could facilitate the discovery and release of new and effective drugs against E. coli O157:H7 and other deadly human bacterial pathogens. Keywords: E. coli O157:H7, KEGG metabolic pathways, novel and broad-spectrum antibiotic targets, DNA polymerase III alpha, homology modeling