Search

Short Summary Severe acute respiratory syndrome coronavirus 2 infection from the Omicron variant in children/adolescents is less severe than infection from the Delta variant. Those 6 to Background There are limited data assessing coronavirus 2019 (COVID-19) disease severity in children/adolescents infected with the Omicron variant. Methods We identified children and adolescents Results Among 1735 cases with Delta variant infection between 1 June and 6 November 2021, and 32 635 cases with Omicron variant infection between 1 January and 15 January 2022, who did not have prior infection and were not vaccinated, we identified 985 propensity score–matched pairs. Among those who were Delta infected, 84.2% had mild, 15.7% had moderate, and 0.1% had severe/critical disease. Among those who were Omicron infected, 97.8% had mild, 2.2% had moderate, and none had severe/critical disease (P Conclusions Omicron variant infection in children/adolescents is associated with less severe disease than Delta variant infection as measured by hospitalization rates and need for ICU care or mechanical ventilation. Those 6 to

Human respiratory syncytial virus (RSV) is a leading ubiquitous respiratory pathogen in newborn infants, young children, and the elderly, with no vaccine available to date. The viral fusion glycoprotein (RSV F) plays an essential role in the infection process, and it is a primary target of neutralizing antibodies, making it an attractive site for vaccine development. With this in view, there is a persistent need to identify selective antiviral drugs against RSV, targeting the major antigenic sites on the F protein. We aimed to conduct a robust in silico high-throughput drug screening of one million compounds to explore potential inhibitors that bind the major antigenic site Ø and site II on RSV F protein, which are the main target of neutralizing antibodies (NAb). We utilized the three-dimensional crystallographic structure of both antigenic site Ø on pre-F and antigenic II on post-F to screen for potential anti-RSV inhibitors. A library of one million small compounds was docked to explore lead binders in the major antigenic sites by using virtual lab bench CLC Drug Discovery. We also performed Quantitative Structure-Activity and Relationship (QSAR) for the lead best binders known for their antiviral activity. Among one million tested ligands, seven ligands (PubChem ID: 3714418, 24787350, 49828911, 24802036, 79824892, 49726463, and 3139884) were identified as the best binders to neutralizing epitopes site Ø and four ligands (PubChem ID: 865999, 17505357, 24802036, and 24285058) to neutralizing epitopes site II, respectively. These binders exhibited significant interactions with neutralizing epitopes on RSV F, with an average of six H bonds, docking energy of − 15.43 Kcal·mol−1, and minimum interaction energy of − 7.45 Kcal·mol−1. Using in silico virtual screening, we identified potential RSV inhibitors that bind two major antigenic sites on the RSV F protein. Using structure-based design and combination-based drug therapy, identified molecules could be modified to generate the next generation anti-RSV drugs.Other Information Published in: Emergent Materials License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1007/s42247-021-00213-6

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection currently remains one of the biggest global challenges that can lead to acute respiratory distress syndrome (CARDS) in severe cases. In line with this, prior pulmonary tuberculosis (TB) is a risk factor for long-term respiratory impairment. Post-TB lung dysfunction often goes unrecognized, despite its relatively high prevalence and its association with reduced quality of life. In this study, we used a metabolomics analysis to identify potential biomarkers that aid in the prognosis of COVID-19 morbidity and mortality in post-TB infected patients. This analysis involved blood samples from 155 SARS-CoV-2 infected adults, of which 23 had a previous diagnosis of TB (post-TB), while 132 did not have a prior or current TB infection. Our analysis indicated that the vast majority (~92%) of post-TB individuals showed severe SARS-CoV-2 infection, required intensive oxygen support with a significantly high mortality rate (52.2%). Amongst individuals with severe COVID-19 symptoms, we report a significant decline in the levels of amino acids, notably the branched chains amino acids (BCAAs), more so in the post-TB cohort (FDR

Cross-reactivity between different human coronaviruses (HCoVs) might contribute to COVID-19 outcomes. Here, we aimed to predict conserved peptides among different HCoVs that could elicit cross-reacting B cell and T cell responses. Three hundred fifty-one full-genome sequences of HCoVs, including SARS-CoV-2 (51), SARS-CoV-1 (50), MERS-CoV (50), and common cold species OC43 (50), NL63 (50), 229E (50), and HKU1 (50) were downloaded aligned using Geneious Prime 20.20. Identification of epitopes in the conserved regions of HCoVs was carried out using the Immune Epitope Database (IEDB) to predict B- and T-cell epitopes. Further, we identified sequences that bind multiple common MHC and modeled the three-dimensional structures of the protein regions. The search yielded 73 linear and 35 discontinuous epitopes. A total of 16 B-cell and 19 T-cell epitopes were predicted through a comprehensive bioinformatic screening of conserved regions derived from HCoVs. The 16 potentially cross-reactive B-cell epitopes included 12 human proteins and four viral proteins among the linear epitopes. Likewise, we identified 19 potentially cross-reactive T-cell epitopes covering viral proteins. Interestingly, two conserved regions: LSFVSLAICFVIEQF (NSP2) and VVHSVNSLVSSMEVQSL (spike), contained several matches that were described epitopes for SARS-CoV. Most of the predicted B cells were buried within the SARS-CoV-2 protein regions’ functional domains, whereas T-cell stretched close to the functional domains. Additionally, most SARS-CoV-2 predicted peptides (80%) bound to different HLA types associated with autoimmune diseases. We identified a set of potential B cell and T cell epitopes derived from the HCoVs that could contribute to different diseases manifestation, including autoimmune disorders. Supplementary Information The online version contains supplementary material available at 10.1007/s00251-021-01250-5.

Several studies have reported serological cross-reactivity of the immune responses between SARS-CoV-2 and DENV. Most of the available studies are based on the point of care (POC) rapid testing kits. However, some rapid test kits have low specificity and can generate false positives. Hence, we aimed to investigate the potential serological cross-reactivity between SARS-CoV-2 and DENV IgG antibodies using advanced assays including chemiluminescence immunoassay (CLIA) and ELISA test. A total of 90 DENV-IgG-ELISA positive and 90 negative pre-pandemic sera were tested for anti-SARS-CoV-2-IgG using the automated CL-900i CLIA assay. Furthermore, a total of 91 SARS-CoV-2-IgG-CLIA positive and 91 negative post-pandemic sera were tested for anti-DENV-IgG using the Novalisa ELISA assay. The DENV-IgG positive sera resulted in five positives and 85 negatives for SARS-CoV-2-IgG. Similarly, the DENV-IgG negative sera also resulted in five positives and 85 negatives for SARS-CoV-2-IgG. No statistically significant difference in specificity between the DENV-IgG positive and DENV-IgG negative sera was found (p-value=1.00). The SARS-CoV-2-IgG positive sera displayed 43 positives, 47 negatives, and one equivocal for DENV-IgG. Whereas the SARS-CoV-2-IgG negative sera resulted in 50 positives, 40 negatives, and one equivocal for DENV-IgG. No statistically significant difference in the proportion that is DENV-IgG positive between the SARS-CoV-2-IgG positive and SARS-CoV-2-IgG negative sera (p-value=0.58). In conclusion, there is a low risk of serological cross-reactivity between the DENV, and SARS-CoV-2 IgG antibodies when using advanced detection assays. . L.J.A. acknowledges the support of the Biomedical Research Program and the Biostatistics, Epidemiology, and Biomathematics Research Core, both at Weill Cornell Medicine-Qatar. This work was made possible by Grant Nos. RRC-2-032 and UREP19-013-3-001 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the authors. In addition, G.K.N. would also like to acknowledge funds from Qatar University’s internal Grant QUERG-CMED-2020-2.

Background Rotavirus (RV) is a leading cause of pediatric diarrhea and mortality worldwide. The virus causes acute gastroenteritis characterized by moderate to severe vomiting, diarrhea, dehydration, and fever. Microbial dysbiosis caused by RV infection may significantly influence disease prognosis and the development of other chronic diseases. The gut microbiome plays a vital role in enteric immune response for rotavirus vaccine (RVV) that requires further elucidations. The current study evaluates the gut microbiome of RV positive children and compares gastroenteritis manifestation in children admitted to the Pediatric Emergency Centre, Hamad Medical Cooperation, Doha, Qatar. Stool samples were collected from thirty-nine RV positive and eight healthy control children. 16S rRNA sequence was performed using the Illumina MiSeq platform. Results The data demonstrated a significant increase in microbiome diversity denoted by higher relative abundances of phylum Proteobacteria (p = 0.031), Fusobacteria (p = 0.044) and genus Streptococcus (p ≤ 0.001) in the infected group relative to the control. Similarly, district clustering pattern (PERMANOVA p = 0.01) and higher species richness (Shannon entropy p = 0.018) were observed in the children who received two RVV doses compared with the non-vaccinated or single-dose groups. These microbiome changes were represented by over-abundance of phylum Bacteroidetes (p = 0.003) and Verrucomicrobia (p ≤ 0.001), and lower expression of family Enterobacteriaceae in two RVV doses group. However, microbiome composition was not associated with diarrhea, vomiting, and other parameters of gastroenteritis. Conclusions The observations assert significant microbial signatures of RVV, which is dose-dependent, and suggest manipulating these microbes as a novel approach for improving RVV efficacy. Further studies are warranted to investigate the immune status of these patients and mechanistic investigation to enhance RVV seroconversion.Other Information Published in: Gut Pathogens License: http://creativecommons.org/licenses/by/4.0/See article on publisher's website: http://dx.doi.org/10.1186/s13099-021-00411-x

Background Influenza surveillance is necessary for detection of emerging variants of epidemiologic and clinical significance. This study describes the epidemiology of influenza types A and B, and molecular characteristics of surface glycoproteins (hemagglutinin [HA] and neuraminidase [NA]) of influenza A subtypes: pH1N1 and H3N2 circulated in Arabian Gulf, Levant and North Africa regions during 2009–2017. Methods Analysis of phylogenetics and evolution of HA and NA genes was done using full HA and NA sequences (n = 1229) downloaded from Influenza Research Database (IRD). Results In total, 130,354 influenza positive cases were reported to WHO during study period. Of these, 50.8% were pH1N1 positive, 15.9% were H3N2 positives and 17.2% were influenza B positive. With few exceptions, all three regions were showing the typical seasonal influenza peak similar to that reported in Northern hemisphere (December–March). However, influenza activity started earlier (October) in both Gulf and North Africa while commenced later during November in Levant countries. The molecular analysis of the HA genes (influenza A subtypes) revealed similar mutations to those reported worldwide. Generally, amino acid substitutions were most frequently found in head domain in H1N1 pandemic viruses, while localized mainly in the stem region in H3N2 viruses. Expectedly, seasons with high pH1N1 influenza activity was associated with a relatively higher number of substitutions in the head domain of the HA in pH1N1 subtype. Furthermore, nucleotide variations were lower at the antigenic sites of pH1N1 viruses compared to H3N2 viruses, which experienced higher variability at the antigenic sites, reflecting the increased immunological pressure because of longer circulation and continuous vaccine changes. Analysis of NA gene of pH1N1 viruses revealed sporadic detections of oseltamivir-resistance mutation, H275Y, in 4% of reported sequences, however, none of NAI resistance mutations were found in the NA of H3N2 viruses. Conclusions Molecular characterization of H1N1 and H3N2 viruses over 9 years revealed significant differences with regard to position and function of characterized substitutions. While pH1N1 virus substitutions were mainly found in HA head domain, H3N2 virus substitutions were mostly found in HA stem domain. Additionally, more fixed substitutions were encountered in H3N2 virus compared to larger number of non-fixed substitutions in pH1N1. Electronic supplementary material The online version of this article (10.1186/s12879-019-3930-6) contains supplementary material, which is available to authorized users.

Background There is an urgent need to elucidate the epidemiology of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and characterize its potential impact. Investing in characterising the SARS-CoV2 will help plan and improve the response to the pandemic. Furthermore, it will help identify the most efficient ways of managing the pandemic, avoiding public health policies and interventions that may be unduly restrictive of normal activity or unnecessarily costly. This paper describes the design and reports findings of a population based epidemiological study undertaken to characterise SARS-CoV2 in Qatar using limited resources in a timely manner. Methods Asymptomatic individuals ≥10 years registered with Qatar’s publicly funded primary health provider were eligible. A stratified random sampling technique was utilized to identify the study sample. Participants were invited to an appointment where they completed a questionnaire and provided samples for polymerase chain reaction and Immunoglobulin M and G immunoassay tests. Data collected were analyzed to calculate point and period prevalence by sociodemographic, lifestyle and clinical characteristics. Results Of 18,918 individuals invited for the study, 2084 participated (response rate 10.8%). The overall point prevalence and period prevalence were estimated to be 1.6% (95% CI 1.1–2.2) and 14.6% (95% CI 13.1–16.2) respectively. Period prevalence of SARS-CoV2 infection was not considerably different across age groups (9.7–19.8%). It was higher in males compared to females (16.2 and 12.7% respectively). A significant variation was observed by nationality (7.1 to 22.2%) and municipalities (6.9–35.3%). Conclusions The study provides an example of a methodologically robust approach that can be undertaken in a timely manner with limited resources. It reports much-needed epidemiological data about the spread of SARS-CoV2. Given the low prevalence rates, majority of the population in Qatar remains susceptible. Enhanced surveillance must continue to be in place, particularly due to the large number of asymptomatic cases observed. Robust contact tracing and social distancing measures are key to prevent future outbreaks.Other Information Published in: BMC Infectious Diseases License: https://creativecommons.org/licenses/by/4.0See article on publisher's website: http://dx.doi.org/10.1186/s12879-021-06251-z