scholarly journals Rapid, widespread, and preferential increase of SARS-CoV-2 B.1.1.7 variant in Houston, TX, revealed by 8,857 genome sequences

2021 ◽  
Author(s):  
James M. Musser ◽  
Randall J. Olsen ◽  
Paul A. Christensen ◽  
S. Wesley Long ◽  
Sishir Subedi ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Doubling Time ◽  
Spike Protein ◽  
Genome Sequences ◽  
Houston Area

Genetic variants of the SARS-CoV-2 virus have become of great interest worldwide because they have the potential to detrimentally alter the course of the SARS-CoV-2 pandemic, and disease in individual patients. We recently sequenced 20,453 SARS-CoV-2 genomes from patients with COVID-19 disease in metropolitan Houston (population 7 million), dating from March 2020 to early February 2021. We discovered that all major variants of concern or interest are circulating in the region. To follow up on this discovery, we analyzed 8,857 genome sequences from patients in eight Houston Methodist hospitals dispersed throughout the metroplex diagnosed from January 1, 2021 to March 7, 2021. This sample represents 94% of Houston Methodist cases and 4.8% of all reported cases in metropolitan Houston during this period. We discovered rapid, widespread, and preferential increase of the SARS-CoV-2 UK B.1.1.7 throughout the region. The estimated case doubling time in the Houston area is 6.9 days. None of the 648 UK B.1.1.7 samples identified had the E484K change in spike protein that can cause decreased recognition by antibodies.

scholarly journals Identification and trajectory of growth of concerning SARS-CoV-2 variants in Houston, Texas, January through April 2021 based on 11,568 genome sequences

2021 ◽  
Author(s):  
Randall James Olsen ◽  
Paul Christensen ◽  
Scott Wesley Long ◽  
Sishir Subedi ◽  
Parsa Hodjat ◽  
...  
Keyword(s):  
Amino Acid ◽  
Metropolitan Area ◽  
Genetic Variants ◽  
Threshold Value ◽  
Amino Acid Replacement ◽  
Spike Protein ◽  
Disease Course ◽  
Genome Sequences ◽  
Major Metropolitan Area ◽  
Houston Area

Genetic variants of the SARS-CoV-2 virus are of substantial concern because they can detrimentally alter the trajectory of the ongoing pandemic, and disease course in individual patients. Here we report genome sequences from 11,568 COVID-19 patients in the Houston Methodist healthcare system dispersed throughout the metroplex that were diagnosed from January 1, 2021 through April 30, 2021. This sample represents 94% of Houston Methodist cases and 4.6% of all reported cases in the metropolitan area during this period. The SARS-CoV-2 variant designated UK B.1.1.7 increased very rapidly, and now causes 75%-90% of all new cases in the Houston area. Five of the 2,543 B.1.1.7 genomes had an E484K change in spike protein. Compared with non-B.1.1.7 patients, individuals infected with B.1.1.7 had a significantly lower cycle threshold value (considered to be a proxy for higher virus load) and higher rate of hospitalization. Other variants (e.g., B.1.429, B.1.427, P.1, P.2, and R.1) also increased rapidly in frequency, although the magnitude was less than for B.1.1.7. We also identified 42 patients with a recently described R.1 variant that has an E484K amino acid replacement, and seven patients with the B.1.617 "India" variants. In the aggregate, our study shows the occurrence of a diverse array of concerning SARS-CoV-2 variants circulating in a major metropolitan area, documents B.1.1.7 as the major cause of new cases in Houston and heralds the arrival and spread of B.1.617 variants in the metroplex.

scholarly journals Human Milk Antibodies Against SARS-CoV-2: A Longitudinal Follow-Up Study

2021 ◽  
pp. 089033442110301
Author(s):  
Hannah G. Juncker ◽  
M. Romijn ◽  
Veerle N. Loth ◽  
Tom G. Caniels ◽  
Christianne J.M. de Groot ◽  
...  
Keyword(s):  
Human Milk ◽  
Clinical Symptoms ◽  
Immunoglobulin A ◽  
Spike Protein ◽  
Enzyme Linked Immunosorbent Assay ◽  
Follow Up Study ◽  
Lactating Mothers ◽  
Milk Antibodies ◽  
Over Time

Background: Human milk contains antibodies against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) following Coronavirus Disease 2019 (COVID-19). These antibodies may serve as protection against COVID-19 in infants. However, the evolution of these human milk antibodies over time is unclear. Research Aim: To elucidate the evolution of immunoglobulin A (IgA) against SARS-CoV-2 in human milk after a SARS-CoV-2 infection. Methods: This longitudinal follow-up study included lactating mothers ( N = 24) who had participated in the COVID MILK study. To assess the evolution of SARS-CoV-2 antibodies, serum and human milk samples were collected 14–143 days after the onset of clinical symptoms related to COVID-19. Enzyme-Linked ImmunoSorbent Assay was used to detect antibodies against the ectodomain of the SARS-CoV-2 spike protein. Results: SARS-CoV-2 antibodies remain present up to 5 months (143 days) in human milk after onset of COVID-19 symptoms. Overall, SARS-CoV-2 IgA in human milk seems to gradually decrease over time. Conclusion: Human milk from SARS-CoV-2 convalescent lactating mothers contains specific IgA antibodies against SARS-CoV-2 spike protein up to at least 5 months post-infection. Passive viral immunity can be transferred via human milk and may serve as protection for infants against COVID-19. Dutch Trial Register on May 1st, 2020, number: NL 8575, URL: https://www.trialregister.nl/trial/8575 .

scholarly journals Concurrent mutations in RNA-dependent RNA polymerase and spike protein emerged as the epidemiologically most successful SARS-CoV-2 variant

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sten Ilmjärv ◽  
Fabien Abdul ◽  
Silvia Acosta-Gutiérrez ◽  
Carolina Estarellas ◽  
Ioannis Galdadas ◽  
...  
Keyword(s):  
Rna Polymerase ◽  
Molecular Modelling ◽  
Spike Protein ◽  
Genome Sequences ◽  
Viral Polymerase ◽  
Rna Dependent Rna Polymerase ◽  
High Quality

AbstractThe D614G mutation in the Spike protein of the SARS-CoV-2 has effectively replaced the early pandemic-causing variant. Using pseudotyped lentivectors, we confirmed that the aspartate replacement by glycine in position 614 is markedly more infectious. Molecular modelling suggests that the G614 mutation facilitates transition towards an open state of the Spike protein. To explain the epidemiological success of D614G, we analysed the evolution of 27,086 high-quality SARS-CoV-2 genome sequences from GISAID. We observed striking coevolution of D614G with the P323L mutation in the viral polymerase. Importantly, the exclusive presence of G614 or L323 did not become epidemiologically relevant. In contrast, the combination of the two mutations gave rise to a viral G/L variant that has all but replaced the initial D/P variant. Our results suggest that the P323L mutation, located in the interface domain of the RNA-dependent RNA polymerase, is a necessary alteration that led to the epidemiological success of the present variant of SARS-CoV-2. However, we did not observe a significant correlation between reported COVID-19 mortality in different countries and the prevalence of the Wuhan versus G/L variant. Nevertheless, when comparing the speed of emergence and the ultimate predominance in individual countries, it is clear that the G/L variant displays major epidemiological supremacy over the original variant.

scholarly journals Molecular beacons allow specific RT-LAMP detection of B.1.1.7 variant SARS-CoV-2

2021 ◽  
Author(s):  
Scott Sherrill-Mix ◽  
Gregory D. Van Duyne ◽  
Frederic D. Bushman
Keyword(s):  
Genetic Variants ◽  
Molecular Beacons ◽  
Spike Protein ◽  
Detection Methods ◽  
Gene Encoding ◽  
Detection And Identification ◽  
Rapid Spread ◽  
The World ◽  
Primer Sets ◽  
Current Detection

AbstractOver the course of the COVID-19 pandemic, several SARS-CoV-2 genetic variants of concern have appeared and spread throughout the world. Detection and identification of these variants is important to understanding and controlling their rapid spread. Current detection methods for a particularly concerning variant, B.1.1.7, require expensive qPCR machines and depend on the absence of a signal rather than a positive indicator of variant presence. Here we report an assay using a pair of molecular beacons paired with reverse transcription loop mediated amplification to allow isothermal amplification from saliva to specifically detect B.1.1.7 and other variants which contain a characteristic deletion in the gene encoding the viral spike protein. This assay is specific, affordable and allows multiplexing with other SARS-CoV-2 LAMP primer sets.

scholarly journals Identification of novel genetic variants predisposing to familial oral squamous cell carcinomas

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Yaping Huang ◽  
Jizhi Zhao ◽  
Guogen Mao ◽  
Grace Sanghee Lee ◽  
Jia Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Genetic Variants ◽  
Autosomal Dominant ◽  
Tongue Cancer ◽  
Oral Tongue ◽  
Genome Sequences ◽  
The Family ◽  
Oral Tongue Cancer

AbstractOral squamous cell carcinoma (OSCC) is a common subtype of head and neck squamous cell carcinoma (HNSCC), but the pathogenesis underlying familial OSCCs is unknown. Here, we analyzed whole-genome sequences of a family with autosomal dominant expression of oral tongue cancer and identified proto-oncogenes VAV2 and IQGAP1 as the primary factors responsible for oral cancer in the family. These two genes are also frequently mutated in sporadic OSCCs and HNSCCs. Functional analysis revealed that the detrimental variants target tumorigenesis-associated pathways, thus confirming that these novel genetic variants help to establish a predisposition to familial OSCC.

scholarly journals Serological follow-up of SARS-CoV-2 asymptomatic subjects

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Gregorio Paolo Milani ◽  
◽  
Laura Dioni ◽  
Chiara Favero ◽  
Laura Cantone ◽  
...  
Keyword(s):  
Blood Sample ◽  
Nasal Swab ◽  
Severe Pneumonia ◽  
Spike Protein ◽  
Serum Antibodies ◽  
Follow Up Study ◽  
Asymptomatic Subjects ◽  
The University ◽  
Structured Questionnaire

AbstractSARS-CoV-2 symptoms are non-specific and can range from asymptomatic presentation to severe pneumonia. Asymptomatic subjects carrying SARS-CoV-2 often remain undiagnosed and it is still debated whether they develop immunoglobulins (Ig) and how long they persist. The aim of this study was to investigate the development and persistence of antibodies against SARS-CoV-2 in asymptomatic subjects infected by the virus. This follow-up study was performed on the 31 asymptomatic subjects who presented a positive nasal swab or serology against SARS-CoV-2 (Ig against Spike-RBD) in the first part of the UNICORN study (March 2020) aimed at attesting previous or current contacts with the virus in the personnel of the University of Milan. Eight weeks after the first Ig measure, these subjects were invited to donate a second blood sample for testing serum antibodies (IgM, IgG and total antibodies) and to fill-in a structured questionnaire. About 80% of asymptomatic subjects did not present circulating immunoglobulins against SARS-CoV-2 after 8 weeks from a positive nasal swab against the virus. Moreover, in more than 40% of these subjects, no Ig against SARS-CoV-2 were detected at any time. Finally, about two third of subjects with immunoglobulins at baseline did not present IgG against SARS-CoV-2 after 8 weeks. The majority of subjects who developed an asymptomatic SARS-CoV-2 infection do not present antibodies against the RBD-spike protein after 8 weeks of follow-up. These data should be taken into account for the interpretation of the serological evidences on SARS-CoV-2 that are emerging nowadays.

Utility of PSA doubling time in follow-up of untreated patients with localized prostate cancer

Urology ◽  
2002 ◽  
Vol 59 (5) ◽  
pp. 652-656 ◽  
Author(s):  
Andrew J Stephenson ◽  
Armen G Aprikian ◽  
Luis Souhami ◽  
Hassan Behlouli ◽  
Avrum I Jacobson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Doubling Time ◽  
Localized Prostate Cancer ◽  
Psa Doubling Time
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