scholarly journals Clinical characterization and Genomic analysis of COVID-19 breakthrough infections during second wave in different states of India

2021 ◽  
Author(s):  
Nivedita Gupta ◽  
Harmanmeet Kaur ◽  
Pragya Yadav ◽  
Labanya Mukhopadhyay ◽  
Rima R Sahay ◽  
...  
Keyword(s):  
Hospital Admission ◽  
Clinical Data ◽  
Throat Swab ◽  
Genomic Analysis ◽  
Clinical Samples ◽  
Post Vaccination ◽  
Genome Coverage ◽  
Nasal Swabs ◽  
Second Wave ◽  
Lineage Iv

During March to June 2021 India has experienced a deadly second wave of COVID19 with an increased number of post vaccination breakthrough infections reported across the country. To understand the possible reason of these breakthroughs we collected 677 clinical samples (throat swab/ nasal swabs) of individuals who had received two doses (n=592) and one dose (n=85) of vaccines (Covishield and Covaxin,) and tested positive for COVID19, from 17 states/Union Territories of country. These cases were telephonically interviewed and clinical data was analyzed. A total of 511 SARS-CoV-2 genomes were recovered with genome coverage of higher than 98% from both the cases. Analysis of both the cases determined that 86.69% (n=443) of them belonged to the Delta variant along with Alpha, Kappa, Delta AY.1 and Delta AY.2. The Delta variant clustered into 4 distinct sub-lineages. Sub-lineage I had mutations: ORF1ab, A1306S, P2046L, P2287S, V2930L, T3255I, T3446A, G5063S, P5401L, A6319V and N G215C; Sub lineage II : ORF1ab P309, A3209V, V3718A, G5063S, P5401L and ORF7a L116F; Sub lineage III : ORF1ab A3209V, V3718A, T3750I, G5063S, P5401L and Spike A222V; Sub-lineage IV ORF1ab P309L, D2980N, F3138S and spike K77T. This study indicated that majority of the clinical cases in the breakthrough were infected with the Delta variant and only 9.8% cases required hospitalization while fatality was observed in only 0.4% cases. This clearly suggests that the vaccination does provide reduction in hospital admission and mortality.

scholarly journals Clinical Characterization and Genomic Analysis of Samples from COVID-19 Breakthrough Infections during the Second Wave among the Various States of India

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1782
Author(s):  
Nivedita Gupta ◽  
Harmanmeet Kaur ◽  
Pragya Dhruv Yadav ◽  
Labanya Mukhopadhyay ◽  
Rima R. Sahay ◽  
...  
Keyword(s):  
Hospital Admission ◽  
Clinical Data ◽  
Throat Swab ◽  
Genomic Analysis ◽  
Clinical Samples ◽  
Post Vaccination ◽  
Genome Coverage ◽  
Nasal Swabs ◽  
Second Wave ◽  
Lineage Iv

From March to June 2021, India experienced a deadly second wave of COVID-19, with an increased number of post-vaccination breakthrough infections reported across the country. To understand the possible reason for these breakthroughs, we collected 677 clinical samples (throat swab/nasal swabs) of individuals from 17 states/Union Territories of the country who had received two doses (n = 592) and one dose (n = 85) of vaccines and tested positive for COVID-19. These cases were telephonically interviewed and clinical data were analyzed. A total of 511 SARS-CoV-2 genomes were recovered with genome coverage of higher than 98% from both groups. Analysis of both groups determined that 86.69% (n = 443) of them belonged to the Delta variant, along with Alpha, Kappa, Delta AY.1, and Delta AY.2. The Delta variant clustered into four distinct sub-lineages. Sub-lineage I had mutations in ORF1ab A1306S, P2046L, P2287S, V2930L, T3255I, T3446A, G5063S, P5401L, and A6319V, and in N G215C; Sub-lineage II had mutations in ORF1ab P309L, A3209V, V3718A, G5063S, P5401L, and ORF7a L116F; Sub-lineage III had mutations in ORF1ab A3209V, V3718A, T3750I, G5063S, and P5401L and in spike A222V; Sub-lineage IV had mutations in ORF1ab P309L, D2980N, and F3138S and spike K77T. This study indicates that majority of the breakthrough COVID-19 clinical cases were infected with the Delta variant, and only 9.8% cases required hospitalization, while fatality was observed in only 0.4% cases. This clearly suggests that the vaccination does provide reduction in hospital admission and mortality.

scholarly journals Abnormal upregulation of cardiovascular disease biomarker PLA2G7 induced by proinflammatory macrophages in COVID-19 patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yang Li ◽  
Yongzhong Jiang ◽  
Yi Zhang ◽  
Naizhe Li ◽  
Qiangling Yin ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Normal Limit ◽  
Genomic Analysis ◽  
High Rate ◽  
Hub Gene ◽  
Viral Loads ◽  
Protein Levels ◽  
Nasal Swabs ◽  
Positive Rate ◽  
Validation Stage

AbstractHigh rate of cardiovascular disease (CVD) has been reported among patients with coronavirus disease 2019 (COVID-19). Importantly, CVD, as one of the comorbidities, could also increase the risks of the severity of COVID-19. Here we identified phospholipase A2 group VII (PLA2G7), a well-studied CVD biomarker, as a hub gene in COVID-19 though an integrated hypothesis-free genomic analysis on nasal swabs (n = 486) from patients with COVID-19. PLA2G7 was further found to be predominantly expressed by proinflammatory macrophages in lungs emerging with progression of COVID-19. In the validation stage, RNA level of PLA2G7 was identified in nasal swabs from both COVID-19 and pneumonia patients, other than health individuals. The positive rate of PLA2G7 were correlated with not only viral loads but also severity of pneumonia in non-COVID-19 patients. Serum protein levels of PLA2G7 were found to be elevated and beyond the normal limit in COVID-19 patients, especially among those re-positive patients. We identified and validated PLA2G7, a biomarker for CVD, was abnormally enhanced in COVID-19 at both nucleotide and protein aspects. These findings provided indications into the prevalence of cardiovascular involvements seen in patients with COVID-19. PLA2G7 could be a potential prognostic and therapeutic target in COVID-19.

scholarly journals Assessment of Viral Targeted Sequence Capture Using Nanopore Sequencing Directly from Clinical Samples

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1358
Author(s):  
Leonard Schuele ◽  
Hayley Cassidy ◽  
Erley Lizarazo ◽  
Katrin Strutzberg-Minder ◽  
Sabine Schuetze ◽  
...  
Keyword(s):  
Influenza A ◽  
Simultaneous Detection ◽  
Clinical Samples ◽  
Metagenomic Sequencing ◽  
Genome Coverage ◽  
Sequence Capture ◽  
Shotgun Metagenomic Sequencing ◽  
Oxford Nanopore ◽  
The One ◽  
Targeted Sequence Capture

Shotgun metagenomic sequencing (SMg) enables the simultaneous detection and characterization of viruses in human, animal and environmental samples. However, lack of sensitivity still poses a challenge and may lead to poor detection and data acquisition for detailed analysis. To improve sensitivity, we assessed a broad scope targeted sequence capture (TSC) panel (ViroCap) in both human and animal samples. Moreover, we adjusted TSC for the Oxford Nanopore MinION and compared the performance to an SMg approach. TSC on the Illumina NextSeq served as the gold standard. Overall, TSC increased the viral read count significantly in challenging human samples, with the highest genome coverage achieved using the TSC on the MinION. TSC also improved the genome coverage and sequencing depth in clinically relevant viruses in the animal samples, such as influenza A virus. However, SMg was shown to be adequate for characterizing a highly diverse animal virome. TSC on the MinION was comparable to the NextSeq and can provide a valuable alternative, offering longer reads, portability and lower initial cost. Developing new viral enrichment approaches to detect and characterize significant human and animal viruses is essential for the One Health Initiative.

Large-Scale Analysis of Genetic and Clinical Patient Data

2018 ◽  
Vol 1 (1) ◽  
pp. 263-274 ◽  
Author(s):  
Marylyn D. Ritchie
Keyword(s):  
Clinical Data ◽  
Large Scale ◽  
Data Science ◽  
Genomic Analysis ◽  
Genomic Data ◽  
Data Sets ◽  
Biomedical Data ◽  
Data Types ◽  
Phenotypic Data ◽  
Clinical Patient

Biomedical data science has experienced an explosion of new data over the past decade. Abundant genetic and genomic data are increasingly available in large, diverse data sets due to the maturation of modern molecular technologies. Along with these molecular data, dense, rich phenotypic data are also available on comprehensive clinical data sets from health care provider organizations, clinical trials, population health registries, and epidemiologic studies. The methods and approaches for interrogating these large genetic/genomic and clinical data sets continue to evolve rapidly, as our understanding of the questions and challenges continue to emerge. In this review, the state-of-the-art methodologies for genetic/genomic analysis along with complex phenomics will be discussed. This field is changing and adapting to the novel data types made available, as well as technological advances in computation and machine learning. Thus, I will also discuss the future challenges in this exciting and innovative space. The promises of precision medicine rely heavily on the ability to marry complex genetic/genomic data with clinical phenotypes in meaningful ways.

scholarly journals Shedding and transmission of a live attenuated influenza A virus vaccine in pre-weaned pigs under field conditions

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246690
Author(s):  
Gustavo Lopez Moreno ◽  
Jayaveeramuthu Nirmala ◽  
Christa Goodell ◽  
Marie Culhane ◽  
Montserrat Torremorell
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Rt Pcr ◽  
Pcr Assay ◽  
Post Vaccination ◽  
Nasal Swabs ◽  
Common Strategy ◽  
Low Levels ◽  
Live Attenuated Influenza Virus ◽  
Pig Health

Influenza A virus (IAV) is one of the most important respiratory viruses affecting pig health and vaccination is the most common strategy to control influenza infections. In this field study we assessed the onset and duration of shedding of a live attenuated influenza virus (LAIV) vaccine, its ability to transmit to non-vaccinated pigs and whether the LAIV could be aerosolized and detected in the environment. Thirty-three litters (n = 33) of a farm using the LAIV vaccine were selected for the study, a subset of them (n = 12) were left unvaccinated and a subset of piglets (n = 3) in vaccinated litters were also left unvaccinated to serve as sentinels. Selected piglets from the litters were sampled multiple days post vaccination (DPV) by collecting nasal swabs and blood, and were tested using a LAIV vaccine specific RT-PCR assay and hemagglutination inhibition assay against the LAIV strains respectively. Environmental specimens consisting of air and surface wipes were also collected. One hundred percent (21/21) of the vaccinated litters tested LAIV positive 1 DPV and until 6 DPV. In contrast, only five (5/33) of the thirty-three non-vaccinated pigs tested positive during the course of the study. Viable LAIV was confirmed in vaccinated pigs by cell culture and whole genome sequencing. In addition, low levels of LAIV RNA (RT-PCR Ct values ranging between 33 and 38) were detected in all air specimens collected on the day of vaccination and until 6 DPV (3/10). Pigs had maternally derived antibodies reactive against the LAIV strains which may have influenced the degree of shedding observed. Under the conditions of this study, shedding of the LAIV from vaccinated pigs was limited in time, resulted in minimal transmission to non-vaccinated pigs and was detected in low levels in aerosols collected in the vaccinated rooms likely influenced by the presence of maternally derived antibodies against the LAIV strains.

scholarly journals Post-vaccination COVID-19: A case-control study and genomic analysis of 119 breakthrough infections in partially vaccinated individuals

2021 ◽  
Author(s):  
Ioannis Baltas ◽  
Florencia A T Boshier ◽  
Charlotte A Williams ◽  
Nadua Bayzid ◽  
Marius Cotic ◽  
...  
Keyword(s):  
Length Of Stay ◽  
Hospital Admissions ◽  
Genomic Analysis ◽  
Hospital Length ◽  
Hospital Length Of Stay ◽  
Escape Mutation ◽  
Number Needed To Treat ◽  
Sequencing Analysis ◽  
Full Genome Sequencing ◽  
Post Vaccination

Abstract Background Post-vaccination infections challenge the control of the COVID-19 pandemic. Methods We matched 119 cases of post-vaccination SARS-CoV-2 infection with BNT162b2 mRNA, or ChAdOx1 nCOV-19, to 476 unvaccinated patients with COVID-19 (Sept 2020-March 2021), according to age and sex. Differences in 60-day all-cause mortality, hospital admission, and hospital length of stay were evaluated. Phylogenetic, single nucleotide polymorphism (SNP) and minority variant allele (MVA) full genome sequencing analysis was performed. Results 116/119 cases developed COVID-19 post first vaccination dose (median 14 days, IQR 9 – 24 days). Overall, 13/119 (10∙9%) cases and 158/476 (33∙2%) controls died (p<0.001), corresponding to 4∙5 number needed to treat (NNT). Multivariably, vaccination was associated with 69∙3% (95%CI 45∙8 – 82∙6) relative risk (RR) reduction in mortality. Similar results were seen in subgroup analysis for patients with infection onset ≥14 days after first vaccination (RR reduction 65∙1%, 95%CI 27∙2 – 83∙2, NNT 4∙5), and across vaccine subgroups (BNT162b2: RR reduction 66%, 95%CI 34∙9 – 82∙2, NNT 4∙7, ChAdOx1: RR reduction 78∙4%, 95%CI 30∙4 – 93∙3, NNT 4∙1). Hospital admissions (OR 0∙80, 95%CI 0∙51 – 1∙28), and length of stay (-1∙89 days, 95%CI -4∙57 – 0∙78) were lower for cases, while Ct values were higher (30∙8 versus 28∙8, p = 0.053). B.1.1.7 was the predominant lineage in cases (100/108, 92.6%) and controls (341/446, 76.5%). Genomic analysis identified one post-vaccination case harboring the E484K vaccine escape mutation (B.1.525 lineage). Conclusions Previous vaccination reduces mortality when B.1.1.7 is the predominant lineage. No significant lineage-specific genomic changes during phylogenetic, SNP and MVA analysis were detected.

scholarly journals Nasal Carriage and Methicillin Resistance of Staphylococcus Aureus Among Schoolchildren in Sana’a City, Yemen

2020 ◽  
Author(s):  
Arwa Mohammed Othman ◽  
Belques Sharaf Al-Huraibi ◽  
Rowa Mohammed Assayaghi ◽  
Huda Zaid Al-Shami
Keyword(s):  
Staphylococcus Aureus ◽  
Hospital Admission ◽  
Methicillin Resistance ◽  
Positive Culture ◽  
Nasal Carriage ◽  
Cross Sectional Study ◽  
High Morbidity ◽  
Carriage Rate ◽  
Cross Sectional ◽  
Nasal Swabs

Abstract Background: Staphylococcus aureus (S. aureus) is a frequent cause of serious health problems with high morbidity and mortality. The risk of S. aureus infections is increased with the emergence of methicillin-resistant S. aureus (MRSA). The aim of this study is to determine the nasal carriage rate of both S. aureus and MRSA among schoolchildren in Sana’a city.Methods: This is a cross-sectional study conducted from January 2018 to May 2020. Five hundred and eighty eight students were enrolled. Nasal swabs were collected from each student for culturing and methicillin susceptibility testing. Results: Out 588 nasal swab, 536 yielded bacterial growth. Students with positive culture were 271(51%) males and 265(49%) females. Their age ranged from 5 to 19 years old with mean age and standard deviation equaled to 13.3±3.5 years. S. aureus was isolated from 129 (24%) students whereas the overall prevalence of MRSA was 8(1.5%). S. aureus was significantly recovered from students at age group 10-14 years (χ2 = 7.02, p = 0.03), females than males (OR= 1.96, χ2 = 10.75, p = 0.001), and students who were admitted into hospitals (OR= 1.6, χ2 = 4.89, p = 0.03). Nevertheless, there were no significant differences between MRSA carriage and students’ age (χ2 = 2.3, p = 0.32), gender (OR= 1.02, χ2 = 0.001, p = 0.63), and hospital admission (OR= 1.4, χ2 = 0.25, p = 0.62). Conclusions: The prevalence of MRSA is low among schoolchildren in Sana’a city. Age, gender and previous hospital admission were statistically associated with nasal carriage of S. aureus but not MRSA nasal carriage.

scholarly journals Hybrid capture-based sequencing enables unbiased recovery of SAR-CoV-2 genomes from fecal samples and characterization of the dynamics of intra-host variants

2020 ◽  
Author(s):  
Yi Xu ◽  
Lu Kang ◽  
Zijie Shen ◽  
Xufang Li ◽  
Weili Wu ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Genomic Diversity ◽  
Clinical Samples ◽  
Frequency Change ◽  
Random Drift ◽  
Genome Coverage ◽  
Fecal Samples ◽  
Hybrid Capture ◽  
Capture Method ◽  
Frequency Changes

AbstractBackgroundIn response to the current COVID-19 pandemic, it is crucial to understand the origin, transmission, and evolution of SARS-CoV-2, which relies on close surveillance of genomic diversity in clinical samples. Although the mutation at the population level had been extensively investigated, how the mutations evolve at the individual level is largely unknown, partly due to the difficulty of obtaining unbiased genome coverage of SARS-CoV-2 directly from clinical samples.MethodsEighteen time series fecal samples were collected from nine COVID-19 patients during the convalescent phase. The nucleic acids of SARS-CoV-2 were enriched by the hybrid capture method with different rounds of hybridization.ResultsBy examining the sequencing depth, genome coverage, and allele frequency change, we demonstrated the impeccable performance of the hybrid capture method in samples with Ct value < 34, as well as significant improvement comparing to direct metatranscriptomic sequencing in samples with lower viral loads. We identified 229 intra-host variants at 182 sites in 18 fecal samples. Among them, nineteen variants presented frequency changes > 0.3 within 1-5 days, reflecting highly dynamic intra-host viral populations. Meanwhile, we also found that the same mutation showed different frequency changes in different individuals, indicating a strong random drift. Moreover, the evolving of the viral genome demonstrated that the virus was still viable in the gastrointestinal tract during the convalescent period.ConclusionsThe hybrid capture method enables reliable analyses of inter- and intra-host variants of SARS-CoV-2 genome, which changed dramatically in the gastrointestinal tract; its clinical relevance warrants further investigation.

scholarly journals Oxidative Stress Index Predicts the Severity of COVID-19

2020 ◽  
Vol 2 (4) ◽  
Author(s):  
Harold I. Zeliger ◽  
Harvey Kahaner
Keyword(s):  
Oxidative Stress ◽  
Hospital Admission ◽  
Clinical Data ◽  
Risk Score ◽  
Stress Index ◽  
Clinical Risk Score ◽  
Oxidative Stress Index ◽  
Clinical Risk

We have hypothesized that the Oxidative Stress Index (OSI) can be used to predict the severity of COVID-19. The recently published Clinical Risk Score Calculation (CRSC), based upon clinical data ascertained at the time of hospital admission for patients in 575 hospitals in China following the COVID-19 outbreak, confirms and validates our hypothesis.

scholarly journals Genomic investigation of clinically significant coagulase-negative staphylococci

2021 ◽  
Author(s):  
Kevin Cole ◽  
Bridget Atkins ◽  
Martin Llewelyn ◽  
John Paul
Keyword(s):  
High Resolution ◽  
Genomic Analysis ◽  
Staphylococcal Infection ◽  
Clinical Samples ◽  
Future Research ◽  
Emerging Pathogens ◽  
Coagulase Negative Staphylococci ◽  
Content Type ◽  
History Of ◽  
Clinically Significant

Introduction. Coagulase-negative staphylococci have been recognized both as emerging pathogens and contaminants of clinical samples. High-resolution genomic investigation may provide insights into their clinical significance. Aims. To review the literature regarding coagulase-negative staphylococcal infection and the utility of genomic methods to aid diagnosis and management, and to identify promising areas for future research. Methodology. We searched Google Scholar with the terms ( Staphylococcus ) AND (sequencing OR (infection)). We prioritized papers that addressed coagulase-negative staphylococci, genomic analysis, or infection. Results. A number of studies have investigated specimen-related, phenotypic and genetic factors associated with colonization, infection and virulence, but diagnosis remains problematic. Conclusion. Genomic investigation provides insights into the genetic diversity and natural history of colonization and infection. Such information allows the development of new methodologies to identify and compare relatedness and predict antimicrobial resistance. Future clinical studies that employ suitable sampling frames coupled with the application of high-resolution whole-genome sequencing may aid the development of more discriminatory diagnostic approaches to coagulase-staphylococcal infection.

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