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1.
J Evol Biol ; 34(6): 910-923, 2021 06.
Article in English | MEDLINE | ID: covidwho-2097796

ABSTRACT

Climate change is impacting locally adapted species such as the keystone tree species cork oak (Quercus suber L.). Quantifying the importance of environmental variables in explaining the species distribution can help build resilient populations in restoration projects and design forest management strategies. Using landscape genomics, we investigated the population structure and ecological adaptation of this tree species across the Mediterranean Basin. We applied genotyping by sequencing and derived 2,583 single nucleotide polymorphism markers genotyped from 81 individuals across 17 sites in the studied region. We implemented an approach based on the nearest neighbour haplotype 'coancestry' and uncovered a weak population structure along an east-west climatic gradient across the Mediterranean region. We identified genomic regions potentially involved in local adaptation and predicted differences in the genetic composition across the landscape under current and future climates. Variants associated with temperature and precipitation variables were detected, and we applied a nonlinear multivariate association method, gradient forest, to project these gene-environment relationships across space. The model allowed the identification of geographic areas within the western Mediterranean region most sensitive to climate change: south-western Iberia and northern Morocco. Our findings provide a preliminary assessment towards a potential management strategy for the conservation of cork oak in the Mediterranean Basin.


Subject(s)
Adaptation, Biological , Climate Change , Quercus , Ecosystem , Gene-Environment Interaction , Mediterranean Region , Models, Statistical , Polymorphism, Single Nucleotide
2.
OMICS ; 26(11): 594-607, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2097271

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, emanated from the Wuhan Province in China and rapidly spread across the globe causing extensive morbidity and mortality rate, and affecting the global economy and livelihoods. Contrary to early predictions of "body bags" across Africa, the African COVID-19 pandemic was marked by apparent low case numbers and an overall mortality rate when compared with the other geographical regions. Factors used to describe this unexpected pattern included a younger population, a swifter and more effective national health policy, limited testing capacities, and the possibility of inadequate reporting of the cases, among others. However, despite genomics contributing to interindividual variations in many diseases across the world, there are inadequate genomic and multiomics data on COVID-19 in Africa that prevent richer transdisciplinary discussions on the contribution of genomics to the spread of COVID-19 pandemic. To invite future debates on comparative studies of COVID-19 genomics and the pandemic spread around the world regions, this expert review evaluates the reported frequency distribution of genetic variants in candidate genes that are likely to affect COVID-19 infection dynamics/disease outcomes. We propose here that genomic variation should be considered among the many factors determining the COVID-19 infection and its outcomes in African populations and across the world.


Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , COVID-19/genetics , Pandemics/prevention & control , SARS-CoV-2/genetics , Health Policy , Genomics
3.
Appl Environ Microbiol ; : e0087422, 2022 Oct 26.
Article in English | MEDLINE | ID: covidwho-2088398

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/coronavirus disease 2019 (COVID-19) pandemic has highlighted an important role for efficient surveillance of microbial pathogens. High-throughput sequencing technologies provide valuable surveillance tools, offering opportunities to conduct high-resolution monitoring from diverse sample types, including from environmental sources. However, given their large size and potential to contain mixtures of lineages within samples, such genomic data sets can present challenges for analyzing the data and communicating results with diverse stakeholders. Here, we report MixviR, an R package for exploring, analyzing, and visualizing genomic data from potentially mixed samples of a target microbial group. MixviR characterizes variation at both the nucleotide and amino acid levels and offers the RShiny interactive dashboard for exploring data. We demonstrate MixviR's utility with validation studies using mixtures of known lineages from both SARS-CoV-2 and Mycobacterium tuberculosis and with a case study analyzing lineages of SARS-CoV-2 in wastewater samples over time at a sampling location in Ohio, USA. IMPORTANCE High-throughput sequencing technologies hold great potential for contributing to genomic-based surveillance of microbial diversity from environmental samples. However, the size of the data sets, along with the potential for environmental samples to contain multiple evolutionary lineages of interest, present challenges around analyzing and effectively communicating inferences from these data sets. The software described here provides a novel and valuable tool for exploring such data. Though originally designed and used for monitoring SARS-CoV-2 lineages in wastewater, it can also be applied to analyses of genomic diversity in other microbial groups.

4.
Infect Genet Evol ; 106: 105381, 2022 Oct 26.
Article in English | MEDLINE | ID: covidwho-2086565

ABSTRACT

Island communities are interesting study sites for microbial evolution during epidemics, as their insular nature reduces the complexity of the population's connectivity. This was particularly true on Reunion Island during the first half of 2021, when international travel was restricted in order to mitigate the risk for SARS-CoV-2 introductions. Concurrently, the SARS-CoV-2 Beta variant became dominant and started to circulate at high levels for several months before being completely replaced by the Delta variant as of October 2021. Here, we explore some of the particularities of SARS-CoV-2 genomic evolution within the insular context of Reunion Island. We show that island isolation allowed the amplification and expansion of unique genetic lineages that remained uncommon across the globe. Islands are therefore potential hotspots for the emergence of new genetic variants, meaning that they will play a key role in the continued evolution and propagation of COVID-19 as the pandemic persists.

5.
iScience ; 25(11): 105438, 2022 Nov 18.
Article in English | MEDLINE | ID: covidwho-2083129

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly evolving RNA virus that mutates within hosts and exists as viral quasispecies. Here, we evaluated the within-host diversity among vaccinated and unvaccinated individuals (n = 379) infected with different SARS-CoV-2 Variants of Concern. The majority of samples harbored less than 14 intra-host single-nucleotide variants (iSNVs). A deep analysis revealed a significantly higher intra-host diversity in Omicron samples than in other variants (p value < 0.05). Vaccination status and type had a limited impact on intra-host diversity except for Beta-B.1.315 and Delta-B.1.617.2 vaccinees, who exhibited higher diversity than unvaccinated individuals (p values: <0.0001 and <0.0021, respectively). Three immune-escape mutations were identified: S255F in Delta and R346K and T376A in Omicron-B.1.1.529. The latter 2 mutations were fixed in BA.1 and BA.2 genomes, respectively. Overall, the relatively higher intra-host diversity among vaccinated individuals and the detection of immune-escape mutations, despite being rare, suggest a potential vaccine-induced immune pressure in vaccinated individuals.

6.
iScience ; 25(11): 105412, 2022 Nov 18.
Article in English | MEDLINE | ID: covidwho-2083114

ABSTRACT

Live-attenuated vaccines are generally highly effective. Here, we aimed to develop one against SARS-CoV-2, based on the identification of three types of temperature-sensitive (TS) strains with mutations in nonstructural proteins (nsp), impaired proliferation at 37°C-39°C, and the capacity to induce protective immunity in Syrian hamsters. To develop a live-attenuated vaccine, we generated a virus that combined all these TS-associated mutations (rTS-all), which showed a robust TS phenotype in vitro and high attenuation in vivo. The vaccine induced an effective cross-reactive immune response and protected hamsters against homologous or heterologous viral challenges. Importantly, rTS-all rarely reverted to the wild-type phenotype. By combining these mutations with an Omicron spike protein to construct a recombinant virus, protection against the Omicron strain was obtained. We show that immediate and effective live-attenuated vaccine candidates against SARS-CoV-2 variants may be developed using rTS-all as a backbone to incorporate the spike protein of the variants.

7.
Cell Syst ; 13(10): 808-816.e5, 2022 Oct 19.
Article in English | MEDLINE | ID: covidwho-2075982

ABSTRACT

Human immunoglobulin heavy chain (IGH) locus on chromosome 14 includes more than 40 functional copies of the variable gene (IGHV), which are critical for the structure of antibodies that identify and neutralize pathogenic invaders as a part of the adaptive immune system. Because of its highly repetitive sequence composition, the IGH locus has been particularly difficult to assemble or genotype when using standard short-read sequencing technologies. Here, we introduce ImmunoTyper-SR, an algorithmic tool for the genotyping and CNV analysis of the germline IGHV genes on Illumina whole-genome sequencing (WGS) data using a combinatorial optimization formulation that resolves ambiguous read mappings. We have validated ImmunoTyper-SR on 12 individuals, whose IGHV allele composition had been independently validated, as well as concordance between WGS replicates from nine individuals. We then applied ImmunoTyper-SR on 585 COVID patients to investigate the associations between IGHV alleles and anti-type I IFN autoantibodies, which were previously associated with COVID-19 severity.


Subject(s)
COVID-19 , Immunoglobulin Variable Region , Humans , Immunoglobulin Variable Region/genetics , Genotype , COVID-19/genetics , High-Throughput Nucleotide Sequencing , Immunoglobulin Heavy Chains/genetics , Autoantibodies/genetics
8.
Microb Pathog ; 173(Pt A): 105828, 2022 Oct 13.
Article in English | MEDLINE | ID: covidwho-2069488

ABSTRACT

The ongoing global pandemic of novel coronavirus pneumonia (COVID-19) caused by the SARS-CoV-2 has a significant impact on global health and economy system. In this context, there have been some landmark advances in vaccine development. Over 100 new coronavirus vaccine candidates have been approved for clinical trials, with ten WHO-approved vaccines including four inactivated virus vaccines, two mRNA vaccines, three recombinant viral vectored vaccines and one protein subunit vaccine on the "Emergency Use Listing". Although the SARS-CoV-2 has an internal proofreading mechanism, there have been a number of mutations emerged in the pandemic affecting its transmissibility, pathogenicity and immunogenicity. Of these, mutations in the spike (S) protein and the resultant mutant variants have posed new challenges for vaccine development and application. In this review article, we present an overview of vaccine development, the prevalence of new coronavirus variants and their impact on protective efficacy of existing vaccines and possible immunization strategies coping with the viral mutation and diversity.

9.
Viruses ; 14(10)2022 09 27.
Article in English | MEDLINE | ID: covidwho-2066541

ABSTRACT

Despite unprecedented global sequencing and surveillance of SARS-CoV-2, timely identification of the emergence and spread of novel variants of concern (VoCs) remains a challenge. Several million raw genome sequencing runs are now publicly available. We sought to survey these datasets for intrahost variation to study emerging mutations of concern. We developed iSKIM ("intrahost SARS-CoV-2 k-mer identification method") to relatively quickly and efficiently screen the many SARS-CoV-2 datasets to identify intrahost mutations belonging to lineages of concern. Certain mutations surged in frequency as intrahost minor variants just prior to, or while lineages of concern arose. The Spike N501Y change common to several VoCs was found as a minor variant in 834 samples as early as October 2020. This coincides with the timing of the first detected samples with this mutation in the Alpha/B.1.1.7 and Beta/B.1.351 lineages. Using iSKIM, we also found that Spike L452R was detected as an intrahost minor variant as early as September 2020, prior to the observed rise of the Epsilon/B.1.429/B.1.427 lineages in late 2020. iSKIM rapidly screens for mutations of interest in raw data, prior to genome assembly, and can be used to detect increases in intrahost variants, potentially providing an early indication of novel variant spread.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/diagnosis , COVID-19/epidemiology , Mutation , Spike Glycoprotein, Coronavirus/genetics
10.
Front Microbiol ; 13: 922393, 2022.
Article in English | MEDLINE | ID: covidwho-2065588

ABSTRACT

Coronavirus disease 2019 (COVID-19) has been a pandemic disease reported in almost every country and causes life-threatening, severe respiratory symptoms. Recent studies showed that various environmental selection pressures challenge the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infectivity and, in response, the virus engenders new mutations, leading to the emergence of more virulent strains of WHO concern. Advance prediction of the forthcoming virulent SARS-CoV-2 strains in response to the principal environmental selection pressures like temperature and solar UV radiation is indispensable to overcome COVID-19. To discover the UV-solar radiation-driven genomic adaption of SARS-CoV-2, a curated dataset of 2,500 full-grade genomes from five different UVindex regions (25 countries) was subjected to in-depth downstream genome-wide analysis. The recurrent variants that best respond to UV-solar radiations were extracted and extensively annotated to determine their possible effects and impacts on gene functions. This study revealed 515 recurrent single nucleotide variants (rcntSNVs) as SARS-CoV-2 genomic responses to UV-solar radiation, of which 380 were found to be distinct. For all discovered rcntSNVs, 596 functional effects (rcntEffs) were detected, containing 290 missense, 194 synonymous, 81 regulatory, and 31 in the intergenic region. The highest counts of missense rcntSNVs in spike (27) and nucleocapsid (26) genes explain the SARS-CoV-2 genomic adjustment to escape immunity and prevent UV-induced DNA damage, respectively. Among all, the most commonly observed rcntEffs were four missenses (RdRp-Pro327Leu, N-Arg203Lys, N-Gly204Arg, and Spike-Asp614Gly) and one synonymous (ORF1ab-Phe924Phe) functional effects. The highest number of rcntSNVs found distinct and were uniquely attributed to the specific UVindex regions, proposing solar-UV radiation as one of the driving forces for SARS-CoV-2 differential genomic adaptation. The phylogenetic relationship indicated the high UVindex region populating SARS-CoV-2 as the recent progenitor of all included samples. Altogether, these results provide baseline genomic data that may need to be included for preparing UVindex region-specific future diagnostic and vaccine formulations.

11.
Nature ; 610(7931):237, 2022.
Article in English | PubMed | ID: covidwho-2062182
12.
Chest ; 162(4):A394, 2022.
Article in English | EMBASE | ID: covidwho-2060582

ABSTRACT

SESSION TITLE: Global Case Reports in Critical Care SESSION TYPE: Global Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Our world has been ravaged by SARS-COV2 over 2 years resulting in mortality in excess of six million lives. More insights have been known in lights of pathophysiology, natural history and modalities of therapy. Cytokine release syndrome, as one of the most dreadful consequences after acute COVID-19 infection, can lead to severe ARDS and deaths. Typically, CRS happens in the first 5-10 days after the initial date on infection. Multiple modes of treatments have been proposed and become standard of care for this life-threatening condition. CASE PRESENTATION: 86 -year-old female with CAD, HTN, SSS, dementia developed 3-day history of fever with dyspnea (SpO2 75% on ambient air). COVID vaccine history was AZ, AZ and Moderna 1 month ago. She was admitted to ICU and placed on oxygen high flow FiO2 50%. She was promptly started on IV Remdesivir, Dexamethasone and Tocilizumab. Then, SARS-COV2 Omicron strain had dominated Thailand reaching almost 99%. Thus, she was given IV Sotrovimab. She gradually improved and was able to wean off from oxygen high flow. As we anticipate transferring her out of ICU once the RT-PCR for COVID-19 reached the safety threshold, those subsequent PCR tests have been in the range of active replication of virus. On ICU day 24, her condition deteriorated with fever spike and more dyspnea needed the use of O2 NHF once again. Studies had revealed that more virus replication and cytokine storm had resumed as evidenced by rising CRP and IL-6 level. This moment, we suspected that she could have contracted a Delta strain. Therefore, we decided to give IV Casirivimab/Imdevimab along with Dexamethasone for this second CRS. NP swab had been sent to Thai genomics lab to identify the virus strain. This time, she gradually recovered over 7 days. Finally, the RT-PCR on day 31 had been in the safe zone and she was discharged home. Subsequent result from genomic study had confirmation of Omicron strain of the COVID-19. DISCUSSION: Typically, cytokine storm after COVID-19 pneumonia happens within 7-10 days after the onset of infection. Without appropriate treatments, this can result in severe pneumonia/ARDS and eventual death. To our knowledge, after the successful treatment of the first wave of CRS, the patient should either recover gradually or succumb to the severe systemic effects. This case has highlighted that there can be a second wave of cytokine storm especially if the virus continued to replicate even with appropriate therapies. Repeated dose of antiviral drugs and possible a different kind of monoclonal antibody might come into role and can potentially save life in this uncommon event. CONCLUSIONS: We report an interesting case of CRS resulting in severe ARDS with unusually prolonged active viral replication despite of treatments. More surprisingly, this patient also had developed a double resurgence of cytokine storm from this particularly sustained viral replication. Reference #1: 1. David C. Fajgenbaum, M.D., and Carl H. June, M.D. Cytokine Storm N Engl J Med 2020;383:2255-2273 DOI: 10.1056/NEJMra2026131 Reference #2: 2. Yujun Tang, Jiajia Liu, […], and Chengping Wen Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies Front Immunol 2020;11:1708 DISCLOSURES: No relevant relationships by Kasem Sirithanakul

13.
Curr Protoc ; 2(10): e534, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2059363

ABSTRACT

Genome sequencing holds the promise for great public health benefits. It is currently being used in the context of rare disease diagnosis and novel gene identification, but also has the potential to identify genetic disease risk factors in healthy individuals. Genome sequencing technologies are currently being used to identify genetic factors that may influence variability in symptom severity and immune response among patients infected by SARS-CoV-2. The GENCOV study aims to look at the relationship between genetic, serological, and biochemical factors and variability of SARS-CoV-2 symptom severity, and to evaluate the utility of returning genome screening results to study participants. Study participants select which results they wish to receive with a decision aid. Medically actionable information for diagnosis, disease risk estimation, disease prevention, and patient management are provided in a comprehensive genome report. Using a combination of bioinformatics software and custom tools, this article describes a pipeline for the analysis and reporting of genetic results to individuals with COVID-19, including HLA genotyping, large-scale continental ancestry estimation, and pharmacogenomic analysis to determine metabolizer status and drug response. In addition, this pipeline includes reporting of medically actionable conditions from comprehensive gene panels for Cardiology, Neurology, Metabolism, Hereditary Cancer, and Hereditary Kidney, and carrier screening for reproductive planning. Incorporated into the genome report are polygenic risk scores for six diseases-coronary artery disease; atrial fibrillation; type-2 diabetes; and breast, prostate, and colon cancer-as well as blood group genotyping analysis for ABO and Rh blood types and genotyping for other antigens of clinical relevance. The genome report summarizes the findings of these analyses in a way that extensively communicates clinically relevant results to patients and their physicians. © 2022 Wiley Periodicals LLC. Basic Protocol 1: HLA genotyping and disease association Basic Protocol 2: Large-scale continental ancestry estimation Basic Protocol 3: Dosage recommendations for pharmacogenomic gene variants associated with drug response Support Protocol: System setup.


Subject(s)
Blood Group Antigens , COVID-19 , COVID-19/genetics , Computational Biology/methods , Genomics , Humans , Male , SARS-CoV-2/genetics
14.
Environmental and Molecular Mutagenesis ; 63:7, 2022.
Article in English | EMBASE | ID: covidwho-2059392

ABSTRACT

The world population is getting older, but a great challenge is how to increase health span and not only lifespan. What is the role of genetics versus environment? Several recent breakthroughs such as the human genome project, the IPS stem-cells and the CRISPR technology for gene editing will allow a revolution in gene therapy, precision and regenerative medicine and xenotransplantation. Aiming to contribute to a healthier longevity, our group is developing several projects including the characterization of the genome of our elderly highly admixed population. We have performed whole genome sequencing of about 1500 healthy Brazilians older than 60, which represents the largest genome databank in Latin America. Our aims were a) to have a database from our population in order to improve the interpretation of pathogenicity of rare unknown variants in patients with undiagnosed genetic disorders and precision medicine b) identify “protective” variants underlying healthy longevity. We found 2 million genetic variants which were not present in the international databanks (Naslavsky et al., 2022). Since the advent of COVID-19 pandemic, we are investigating genetic variants in individuals, who were exposed to SARS-Cov-2 and remained asymptomatic. To address this question, we investigated discordant couples where one was infected and develop COVID-19 while the partner remained asymptomatic and serum negative. We collected samples from nonagenarians and centenarians who survived COVID-19 or remained asymptomatic. We will infect different IPS derived cell lines from “resistant” centenarians with SARS-Cov2 in an attempt to increase our understanding on “resistant genetic variants and mechanisms”.

15.
Investigative Ophthalmology and Visual Science ; 63(7):2345-A0014, 2022.
Article in English | EMBASE | ID: covidwho-2057902

ABSTRACT

Purpose : One major effect of the COVID-19 pandemic has been a delay in presentation and interruptions in delivery of care to patients with many different cancer types. The purpose of our study is to compare the clinical and genomic variables of uveal melanoma patients presenting before and after the start of the pandemic to assess the effect of the pandemic on a delay in care. Methods : This study is a retrospective chart review of uveal melanoma patients presenting during two time periods: May 2019 to February 2020 (Group 1: Before the COVID-19 pandemic declaration by the WHO in March 2020) and May 2020 to March 2021 (Group 2: After the start of the COVID-19 pandemic). Disease stages at presentation were analyzed by clinical and genomic variables including: thickness and largest base diameter of tumor, COMS size class, AJCC stage, GEP class, and Prame status. Results : A total of 80 patients with uveal melanoma were studied [Group 1: 40 (50%) and Group 2: 40 (50%);mean age: 62.5 years (range 25-84) and 64 years (range 30-91)]. There was no statistically significant difference between the tumor thickness, largest base dimension, and COMS size class between Group 1 (Pre-COVID) and Group 2 (During COVID). The majority of patients were found to be in AJCC class I/IIA in both groups [Group 1: 26 (65%) and Group 2: 27 (67.5%)] with no statistically significant difference in staging between the groups. Analyzed genomic data of GEP class and Prame expression also failed to show a difference between Group 1 and Group 2, with majority of patients found to be GEP Class IA [Group 1: 27 (69.2%) and Group 2: 25 (62.5%)] and Prame negative [Group 1: 28 (71.8%) and Group 2: 28 (70%)] for both groups. Conclusions : The study showed that the COVID-19 pandemic had no effect on the presentation of uveal melanoma patients at our center across various tumor characteristics that can be used as a surrogate marker for delayed presentation, including size, staging, and genomic data. A large-scale, long-term study is necessary to analyze the long-term consequences of the pandemic on uveal melanoma patients.

16.
22nd International Workshop on Algorithms in Bioinformatics, WABI 2022 ; 242, 2022.
Article in English | Scopus | ID: covidwho-2055786

ABSTRACT

We apply Invertible Bloom Lookup Tables (IBLTs) to the comparison of k-mer sets originated from large DNA sequence datasets. We show that for similar datasets, IBLTs provide a more space-efficient and, at the same time, more accurate method for estimating Jaccard similarity of underlying k-mer sets, compared to MinHash which is a go-to sketching technique for efficient pairwise similarity estimation. This is achieved by combining IBLTs with k-mer sampling based on syncmers, which constitute a context-independent alternative to minimizers and provide an unbiased estimator of Jaccard similarity. A key property of our method is that involved data structures require space proportional to the difference of k-mer sets and are independent of the size of sets themselves. As another application, we show how our ideas can be applied in order to efficiently compute (an approximation of) k-mers that differ between two datasets, still using space only proportional to their number. We experimentally illustrate our results on both simulated and real data (SARS-CoV-2 and Streptococcus Pneumoniae genomes). © Yoshihiro Shibuya, Djamal Belazzougui, and Gregory Kucherov.

17.
J Med Entomol ; 59(6): 1853-1860, 2022 Nov 16.
Article in English | MEDLINE | ID: covidwho-2051479

ABSTRACT

Life remained far from normal as we completed the first year of the Covid-19 pandemic and entered a second year. Despite the challenges faced worldwide, together we continue to move the field of Medical Entomology forward. Here, I reflect on parallels between control of Covid-19 and vector-borne disease control, discuss the advantages and caveats of using new genotyping technologies for the study of invasive species, and proceed to highlight papers that were published between 2020 and 2021 with a focus on those related to mosquito surveillance and population genetics of mosquito vectors.


Subject(s)
COVID-19 , Vector Borne Diseases , Animals , Pandemics , Entomology , Mosquito Vectors
18.
Nature ; 2022 Oct 03.
Article in English | MEDLINE | ID: covidwho-2050304
19.
BMC Public Health ; 22(1): 1817, 2022 09 24.
Article in English | MEDLINE | ID: covidwho-2043123

ABSTRACT

BACKGROUND: Along with rapid diagnostic testing, contact tracing, and public health measures, an effective pandemic response incorporates genomics-based surveillance. Large-scale SARS-CoV-2 genome sequencing is a crucial component of the global response to COVID-19. Characterizing the state of genomics readiness among Canada's public health laboratories was necessary to inform strategic planning and deployment of capacity-building resources in the early stages of the pandemic. METHODS: We used a qualitative study design and focus group discussions, encompassing both technical and leadership perspectives, to perform an in-depth evaluation of the state of pathogen genomics readiness in Canada. RESULTS: We found substantial diversity in the state of readiness for SARS-CoV-2 genomic surveillance across Canada. Despite this variability, we identified common barriers and needs in the areas of specimen access, data flow and sharing, computing infrastructure, and access to highly qualified bioinformatics personnel. CONCLUSIONS: These findings enable the strategic prioritization and deployment of resources to increase Canada's ability to perform effective public health genomic surveillance for COVID-19 and prepare for future emerging infectious diseases. They also provide a unique qualitative research model for use in capacity building.


Subject(s)
COVID-19 , Public Health , COVID-19/diagnosis , COVID-19/epidemiology , Genomics , Humans , Laboratories , SARS-CoV-2/genetics
20.
Annals of Oncology ; 33:S594-S595, 2022.
Article in English | EMBASE | ID: covidwho-2041518

ABSTRACT

Background: Many patients fail to achieve a clinical benefit from ICI. Several scores have been developed to improve ICI candidates selection but it is uncertain which one better predicts patients’ outcome. Here, we performed a direct comparison of the most successful scores. Methods: This is a sub-analysis of the immunoblood prospective observational study that enrolled patients diagnosed with advanced solid tumors treated with ICI. Main clinicopathological data were retrieved from medical records and responses assessed according to RECIST 1.1 criteria. LIPI, RMH, PMH, dNLR, NLR, PIPO and GRIm scores were calculated. Receiving operator characteristics (ROC) curves and their area under curve (AUC) were used to predict PFS and durable clinical benefit (DCB;stable disease≥6 months or better). Associations with PFS, OS and DCB, where assessed with Cox and logistic regressions. Scores’ correlation was assessed with Spearman rho. Significance was set at p<0.05. Results: We recruited 155 patients (65% male, mean age 63). NSCLC (28%), colorectal (20%) breast (9%) H&N (6%) cancer and melanoma (6%) were the most frequent tumor types. Frequency of the high risk/bad outcome group of each score were: LIPI 13%, RMH 36%, PMH 54%, GRIm 14%, PIPO 6%, NLR 32% and dNRL 27%. Fair accuracy in identifying patients at higher risk of progression or mild accuracy in predicting DCB were observed for the RMH (AUC PFS: 0.7, 95%CI: 0.6-0.8;AUC DCB: 0.6, 0.5-0.8) and LIPI (AUC PFS: 0.7, 95%CI: 0.6-0.8;AUC: 0.6, 0.5-0.7) scores. All other scores provided poor/no accuracy. No significant difference was observed between RMH and LIPI AUC for PFS and DCB (both p>0.05). Additionally, only LIPI and RMH were associated with PFS (p=0.001;p<0.001), OS (p<0.001;p=0.001) and DCB (p=0.034;p=0.010) at univariate analyses. At multivariate analyses RMH and LIPI remained significantly associated with PFS (p=0.030;p=0.021) and OS (p=0.012;p<0.001). A strong correlation between both scores (rho=0.72, p<0.001) was observed. Conclusions: RMH and LIPI scores were sufficiently reliable in assessing the prognosis of patients with advanced solid tumors treated with ICI. They were superior to other analyzed scores in our population and highly correlated. Legal entity responsible for the study: Hospital Clinic y Provincial de Barcelona, Medical Oncology Department. Funding: Has not received any funding. Disclosure: J. Garcia-Corbacho: Financial Interests, Personal, Advisory Board, FGFR inhibitors implementation in clinical practice: Johnson & Johnson Pharmaceutical;Financial Interests, Institutional, Invited Speaker, Participation in clinical trials of the company as PI: Johnson and Johnson Pharmaceutical, Boehringer Ingelheim, Astellas, Cytomx, Incyte, Lilly, Menarini, Merck, Bayer, AstraZeneca, Amgen, Daiichi Sankyo. L. Mezquita: Financial Interests, Personal, Advisory Board: Takeda, AstraZeneca, Roche;Financial Interests, Personal, Invited Speaker: Roche, BMS, AstraZeneca, Takeda;Financial Interests, Personal, Research Grant, SEOM Beca Retorno 2019: BI;Financial Interests, Personal, Research Grant, ESMO TR Research Fellowship 2019: BMS;Financial Interests, Institutional, Research Grant, COVID research Grant: Amgen;Financial Interests, Institutional, Invited Speaker: Inivata, Stilla. N. Baste Rotllan: Non-Financial Interests, Advisory Role: Eisai, MSD, Merck Serono, BioNTech, Roche, BMS, Exelixis. A. Prat: Financial Interests, Personal, Invited Speaker: Roche;Financial Interests, Personal, Invited Speaker, Lecture fees: Novartis, Daiichi Sankyo;Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Novartis, Pfizer, BMS, Puma, Oncolytics Biotech, MSD, Guardant Health, Peptomyc;Financial Interests, Institutional, Invited Speaker, Clinical trials: Daiichi Sankyo;Financial Interests, Institutional, Other, Contracted research: Boehringer, Medica Scientia Inno. Research;Financial Interests, Personal, Advisory Board: AstraZeneca;Financial Interests, Personal, Invited Speaker, Leadership role: Reveal Genomics, SL.;Financial I terests, Personal, Stocks/Shares: Reveal Genomics, Oncolytics Biotech;Financial Interests, Personal, Royalties: Reveal Genomics;Financial Interests, Institutional, Invited Speaker: Roche, AstraZeneca, Novartis;Financial Interests, Personal and Institutional, Invited Speaker: Daiichi Sankyo;Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: SOLTI Foundation, Actitud Frente al Cáncer Foundation. All other authors have declared no conflicts of interest.

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