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1.
Turkish Journal of Biochemistry ; 47(5):656-664, 2022.
Article in English | EMBASE | ID: covidwho-2227748

ABSTRACT

Objectives: The aim is to investigate the usefulness of lactate dehydrogenase (LDH)/Albumin, LDH/Lymphocyte and LDH/Platelet ratios on the prognosis of coronavirus disease (COVID-19) Alpha (B.1.1.7) variant pneumonia. Method(s): A total of 113 patients who were diagnosed with COVID-19 pneumonia and 60 healthy control group were included in this study. The cases were divided into 2 as classic COVID-19 group, and COVID-19 B.1.1.7 variant group. Complete blood count (CBC) and biochemical parameters of the patients were analyzed retrospectively. Patients with COVID-19 B.1.1.7 variant group were also grouped according to the length of stay in the hospital and the days of hospitalization. Result(s): LDH/Albumin, LDH/Platelet, and LDH/Lymphocyte ratios were found to be higher in COVID-19 B.1.1.7 variant group when compared to the control group (p<0.001). The ferritin, neutrophils/lymphocyte (NLR) ratio, procalcitonin (PCT) and LDH/Albumin had the highest area under the curve (AUC) values in the COVID-19 B.1.1.7 variant group (0.950, 0.802, 0.759, and 0.742, respectively). Albumin, Lymphocytes and hemoglobin values were significantly higher in the COVID-19 B.1.1.7 variant group than in the classic COVID-19 group (p<0.05). Conclusion(s): LDH/Albumin and LDH/Lymphocyte ratios may be useful for clinicians in predicting the risk of progression to pneumonia in COVID-19 B.1.1.7 variant patients. Copyright © 2022 the author(s), published by De Gruyter.

2.
Turkish Journal of Biochemistry / Turk Biyokimya Dergisi ; : 1, 2022.
Article in English | Academic Search Complete | ID: covidwho-2022061

ABSTRACT

The aim is to investigate the usefulness of lactate dehydrogenase (LDH)/Albumin, LDH/Lymphocyte and LDH/Platelet ratios on the prognosis of coronavirus disease (COVID-19) Alpha (B.1.1.7) variant pneumonia.A total of 113 patients who were diagnosed with COVID-19 pneumonia and 60 healthy control group were included in this study. The cases were divided into 2 as classic COVID-19 group, and COVID-19 B.1.1.7 variant group. Complete blood count (CBC) and biochemical parameters of the patients were analyzed retrospectively. Patients with COVID-19 B.1.1.7 variant group were also grouped according to the length of stay in the hospital and the days of hospitalization.LDH/Albumin, LDH/Platelet, and LDH/Lymphocyte ratios were found to be higher in COVID-19 B.1.1.7 variant group when compared to the control group (p<0.001). The ferritin, neutrophils/lymphocyte (NLR) ratio, procalcitonin (PCT) and LDH/Albumin had the highest area under the curve (AUC) values in the COVID-19 B.1.1.7 variant group (0.950, 0.802, 0.759, and 0.742, respectively). Albumin, Lymphocytes and hemoglobin values were significantly higher in the COVID-19 B.1.1.7 variant group than in the classic COVID-19 group (p<0.05).LDH/Albumin and LDH/Lymphocyte ratios may be useful for clinicians in predicting the risk of progression to pneumonia in COVID-19 B.1.1.7 variant patients. [ FROM AUTHOR] Copyright of Turkish Journal of Biochemistry / Turk Biyokimya Dergisi is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

3.
BMC Infect Dis ; 22(1): 713, 2022 Aug 29.
Article in English | MEDLINE | ID: covidwho-2021249

ABSTRACT

BACKGROUND: Variant of concern (VOC) SARS-CoV-2 alpha variant (B.1.1.7) was the dominant strain in the Netherlands between March 2021-June 2021. We describe three primary school outbreaks due to the alpha variant using whole genome sequencing with evidence of large-scale transmission among children, teachers and their household contacts. METHOD: All outbreaks described were investigated by the South Limburg Public Health Service, the Netherlands. A case was defined as an individual with a real-time polymerase chain reaction test or antigen test positive for SARS-CoV-2. Whole genome sequencing was performed on random samples from at least one child and one teacher of each affected class. RESULTS: Peak attack rates in classes were 53%, 33% and 39%, respectively. Specific genotypes were identified for each school across a majority of affected classes. Attack rates were high among staff members, likely to promote staff-to-children transmission. Cases in some classes were limited to children, indicating child-to-child transmission. At 39%, the secondary attack rate (SAR) in household contacts of infected children was remarkably high, similar to SAR in household contacts of staff members (42%). SAR of household contacts of asymptomatic children was only 9%. CONCLUSION: Our findings suggest increased transmissibility of the alpha variant in children compared to preceding non-VOC variants, consistent with a substantial rise in the incidence of cases observed in primary schools and children aged 5-12 since the alpha variant became dominant in March 2021. Lack of mandatory masking, insufficient ventilation and lack of physical distancing also probably contributed to the school outbreaks. The rise of the delta variant (B.1.617.2) since July 2021 which is estimated to be 55% more transmissible than the alpha variant, provides additional urgency to adequate infection prevention in school settings.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Disease Outbreaks , Humans , Netherlands/epidemiology , SARS-CoV-2/genetics , Schools , Whole Genome Sequencing
4.
Children (Basel) ; 9(5)2022 May 03.
Article in English | MEDLINE | ID: covidwho-1820186

ABSTRACT

BACKGROUND: The Delta (B.1.617.2) SARS-CoV-2 variant was the predominant UK circulating strain between May and November 2021. We investigated whether COVID-19 from Delta infection differed from infection with previous variants in children. METHODS: Through the prospective COVID Symptom Study, 109,626 UK school-aged children were proxy-reported between 28 December 2020 and 8 July 2021. We selected all symptomatic children who tested positive for SARS-CoV-2 and were proxy-reported at least weekly, within two timeframes: 28 December 2020 to 6 May 2021 (Alpha (B.1.1.7), the main UK circulating variant) and 26 May to 8 July 2021 (Delta, the main UK circulating variant), with all children unvaccinated (as per national policy at the time). We assessed illness profiles (symptom prevalence, duration, and burden), hospital presentation, and presence of long (≥28 day) illness, and calculated odds ratios for symptoms presenting within the first 28 days of illness. RESULTS: 694 (276 younger (5-11 years), 418 older (12-17 years)) symptomatic children tested positive for SARS-CoV-2 with Alpha infection and 706 (227 younger and 479 older) children with Delta infection. Median illness duration was short with either variant (overall cohort: 5 days (IQR 2-9.75) with Alpha, 5 days (IQR 2-9) with Delta). The seven most prevalent symptoms were common to both variants. Symptom burden over the first 28 days was slightly greater with Delta compared with Alpha infection (in younger children, 3 (IQR 2-5) symptoms with Alpha, 4 (IQR 2-7) with Delta; in older children, 5 (IQR 3-8) symptoms with Alpha, 6 (IQR 3-9) with Delta infection ). The odds of presenting several symptoms were higher with Delta than Alpha infection, including headache and fever. Few children presented to hospital, and long illness duration was uncommon, with either variant. CONCLUSIONS: COVID-19 in UK school-aged children due to SARS-CoV-2 Delta strain B.1.617.2 resembles illness due to the Alpha variant B.1.1.7., with short duration and similar symptom burden.

5.
Virus Evol ; 8(1): veac020, 2022.
Article in English | MEDLINE | ID: covidwho-1806583

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continue to emerge, and their identification is important for the public health response to coronavirus disease 2019 (COVID-19). Genomic sequencing provides robust information but may not always be accessible, and therefore, mutation-based polymerase chain reaction (PCR) approaches can be used for rapid identification of known variants. International travelers arriving in Karachi between December 2020 and February 2021 were tested for SARS-CoV-2 by PCR. A subset of positive samples was tested for S-gene target failure (SGTF) on TaqPathTM COVID-19 (Thermo Fisher Scientific) and for mutations using the GSD NovaType SARS-CoV-2 (Eurofins Technologies) assays. Sequencing was conducted on the MinION platform (Oxford Nanopore Technologies). Bayesian phylogeographic inference was performed integrating the patients' travel history information. Of the thirty-five COVID-19 cases screened, thirteen had isolates with SGTF. The travelers transmitted infection to sixty-eight contact cases. The B.1.1.7 lineage was confirmed through sequencing and PCR. The phylogenetic analysis of sequence data available for six cases included four B.1.1.7 strains and one B.1.36 and B.1.1.212 lineage isolate. Phylogeographic modeling estimated at least three independent B.1.1.7 introductions into Karachi, Pakistan, originating from the UK. B.1.1.212 and B.1.36 were inferred to be introduced either from the UK or the travelers' layover location. We report the introduction of SARS-CoV-2 B.1.1.7 and other lineages in Pakistan by international travelers arriving via different flight routes. This highlights SARS-CoV-2 transmission through travel, importance of testing, and quarantine post-travel to prevent transmission of new strains, as well as recording detailed patients' metadata. Such results help inform policies on restricting travel from destinations where new highly transmissible variants have emerged.

6.
J Infect Chemother ; 28(7): 998-1000, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1763841

ABSTRACT

We describe a case of probable prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Alpha(B.1.1.7) variant shedding for 221 days from the diagnosis, in a healthy 20-year-old Japanese pregnant woman with a normal delivery. To our knowledge, this is the longest duration of SARS-CoV-2 shedding reported in an immunocompetent individual to date.


Subject(s)
COVID-19 , Pregnancy Complications, Infectious , Adult , COVID-19/diagnosis , Female , Humans , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnant Women , RNA, Viral , SARS-CoV-2 , Virus Shedding , Young Adult
7.
Comput Struct Biotechnol J ; 19: 6140-6156, 2021.
Article in English | MEDLINE | ID: covidwho-1734314

ABSTRACT

We exploited a multi-scale microscopy imaging toolbox to address some major issues related to SARS-CoV-2 interactions with host cells. Our approach harnesses both conventional and super-resolution fluorescence microscopy and easily matches the spatial scale of single-virus/cell checkpoints. After its validation through the characterization of infected cells and virus morphology, we leveraged this toolbox to reveal subtle issues related to the entry phase of SARS-CoV-2 variants in Vero E6 cells. Our results show that in Vero E6 cells the B.1.1.7 strain (aka Alpha Variant of Concern) is associated with much faster kinetics of endocytic uptake compared to its ancestor B.1.177. Given the cell-entry scenario dominated by the endosomal "late pathway", the faster internalization of B.1.1.7 could be directly related to the N501Y mutation in the S protein, which is known to strengthen the binding of Spike receptor binding domain with ACE2. Remarkably, we also directly observed the central role of clathrin as a mediator of endocytosis in the late pathway of entry. In keeping with the clathrin-mediated endocytosis, we highlighted the non-raft membrane localization of ACE2. Overall, we believe that our fluorescence microscopy-based approach represents a fertile strategy to investigate the molecular features of SARS-CoV-2 interactions with cells.

8.
Math Biosci Eng ; 19(4): 3591-3596, 2022 02 07.
Article in English | MEDLINE | ID: covidwho-1704200

ABSTRACT

In this work, we report a large-scale synchronized replacement pattern of the Alpha (B.1.1.7) variant by the Delta (B.1.617.2) variant of SARS-COV-2. We argue that this phenomenon is associated with the invasion timing and the transmissibility advantage of the Delta (B.1.617.2) variant. Alpha (B.1.1.7) variant skipped some countries/regions, e.g. India and neighboring countries/regions, which could have led to a mild first wave before the invasion of the Delta (B.1.617.2) variant, in term of reported COVID-deaths per capita.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Humans , India/epidemiology , Pandemics , SARS-CoV-2/genetics
9.
Clin Infect Dis ; 74(3): 407-415, 2022 02 11.
Article in English | MEDLINE | ID: covidwho-1684538

ABSTRACT

BACKGROUND: How severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity varies with viral load is incompletely understood. Whether rapid point-of-care antigen lateral flow devices (LFDs) detect most potential transmission sources despite imperfect clinical sensitivity is unknown. METHODS: We combined SARS-CoV-2 testing and contact tracing data from England between 1 September 2020 and 28 February 2021. We used multivariable logistic regression to investigate relationships between polymerase chain reaction (PCR)-confirmed infection in contacts of community-diagnosed cases and index case viral load, S gene target failure (proxy for B.1.1.7 infection), demographics, SARS-CoV-2 incidence, social deprivation, and contact event type. We used LFD performance to simulate the proportion of cases with a PCR-positive contact expected to be detected using 1 of 4 LFDs. RESULTS: In total, 231 498/2 474 066 (9%) contacts of 1 064 004 index cases tested PCR-positive. PCR-positive results in contacts independently increased with higher case viral loads (lower cycle threshold [Ct] values), for example, 11.7% (95% confidence interval [CI] 11.5-12.0%) at Ct = 15 and 4.5% (95% CI 4.4-4.6%) at Ct = 30. B.1.1.7 infection increased PCR-positive results by ~50%, (eg, 1.55-fold, 95% CI 1.49-1.61, at Ct = 20). PCR-positive results were most common in household contacts (at Ct = 20.1, 8.7% [95% CI 8.6-8.9%]), followed by household visitors (7.1% [95% CI 6.8-7.3%]), contacts at events/activities (5.2% [95% CI 4.9-5.4%]), work/education (4.6% [95% CI 4.4-4.8%]), and least common after outdoor contact (2.9% [95% CI 2.3-3.8%]). Contacts of children were the least likely to test positive, particularly following contact outdoors or at work/education. The most and least sensitive LFDs would detect 89.5% (95% CI 89.4-89.6%) and 83.0% (95% CI 82.8-83.1%) of cases with PCR-positive contacts, respectively. CONCLUSIONS: SARS-CoV-2 infectivity varies by case viral load, contact event type, and age. Those with high viral loads are the most infectious. B.1.1.7 increased transmission by ~50%. The best performing LFDs detect most infectious cases.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19 Testing , Child , Family Characteristics , Humans , Viral Load
10.
Iranian Journal of Medical Microbiology ; 15(5):592-605, 2021.
Article in English | Scopus | ID: covidwho-1592666

ABSTRACT

Background and Aim: SARS-CoV-2 is the causative agent of Coronavirus 2019 or COVID-19 in the world. Novel coronavirus disease is a respiratory disease. To date, there have been challenges in the treatment for COVID-19 and emerged new variants like UK B1.1.7. Accordingly, an effective prevention regime is needed for this infection, which covers most variants. The purpose of this research was to predict the conserved epitopes of Spike and Nucleocapsid proteins from SARS-CoV-2 for the design of a novel coronavirus 2019 multi-epitope vaccine using in silico tools. Materials and Methods: Computational analysis and immunoinformatics approaches include identification of potential conserve epitopes and selection of epitopes based on allergenicity, toxicity, antigenicity, and molecular docking were used for epitope prediction and screening. In the next step, selected segments of the epitopes were attached by the suitable linkers. Finally, Maltese-bound protein (MBP) as an adjuvant was added to the novel vaccine structure. The secondary and third structures of the designed multi-epitope vaccine were predicted via immunoinformatics algorithms. Predicted structure refined and validated for attaining best stability. In the end, immunoinformatics evaluation, molecular docking, and molecular dynamics were performed to confirm vaccine efficiency. Codon optimization and in silico cloning were done to ensure the expression yield of the novel multi-epitope vaccine in the target host. Results: This study showed that our data support the suggestion that the designed vaccine could induce immune responses against SARS-CoV-2 variants. Conclusion: The structure designed had acceptable quality with software reviews. Further in vitro and in vivo experiments are needed to confirm the safety and immunogenicity of the candidate vaccine. © 2021. All Rights Reserved.

12.
Aging (Albany NY) ; 13(23): 24931-24942, 2021 12 12.
Article in English | MEDLINE | ID: covidwho-1573020

ABSTRACT

Since the Coronavirus 19 (COVID-19) pandemic, several SARS-CoV-2 variants of concern (SARS-CoV-2 VOC) have been reported. The B.1.1.7 variant has been associated with increased mortality and transmission risk. Furthermore, cluster and possible co-infection cases could occur in the next influenza season or COVID-19 pandemic wave, warranting efficient diagnosis and treatment decision making. Here, we aimed to detect SARS-CoV-2 and other common respiratory viruses using multiplex RT-PCR developed on the LabTurbo AIO 48 open system. We performed a multicenter study to evaluate the performance and analytical sensitivity of the LabTurbo AIO 48 system for SARS-CoV-2, influenza A/B, and respiratory syncytial virus (RSV) using 652 nasopharyngeal swab clinical samples from patients. The LabTurbo AIO 48 system demonstrated a sensitivity of 9.4 copies/per PCR for N2 of SARS-CoV-2; 24 copies/per PCR for M of influenza A and B; and 24 copies/per PCR for N of RSV. The assay presented consistent performance in the multicenter study. The multiplex RT-PCR applied on the LabTurbo AIO 48 open platform provided highly sensitive, robust, and accurate results and enabled high-throughput detection of B.1.1.7, influenza A/B, and RSV with short turnaround times. Therefore, this automated molecular diagnostic assay could enable streamlined testing if COVID-19 becomes a seasonal disease.


Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , Influenza, Human/diagnosis , Multiplex Polymerase Chain Reaction/methods , Respiratory Syncytial Virus Infections/diagnosis , Adult , Aged , COVID-19/virology , Female , Humans , Influenza A virus/genetics , Influenza A virus/isolation & purification , Influenza, Human/virology , Influenzavirus B/genetics , Influenzavirus B/isolation & purification , Male , Middle Aged , Respiratory Syncytial Virus Infections/virology , Respiratory Syncytial Viruses/genetics , Respiratory Syncytial Viruses/isolation & purification , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Sensitivity and Specificity , Young Adult
13.
Microbiol Spectr ; 9(3): e0088421, 2021 12 22.
Article in English | MEDLINE | ID: covidwho-1532978

ABSTRACT

This study evaluates the performance of the PanBio COVID-19 antigen (Ag) test as part of a hospital infection control policy. Hospital staff was encouraged to get tested for COVID-19 when presenting with SARS-CoV-2-related symptoms. In a period of approximately 5 months, a steady decline in the performance of the Ag test was noted, epidemiologically coinciding with the rise of the SARS-CoV-2 B.1.1.7 (alpha) variant of concern (VOC) in the Netherlands. This led to the hypothesis that the diagnostic performance of the PanBio COVID-19 Ag test was influenced by the infecting viral variant. The results show a significantly lower sensitivity of the PanBio COVID-19 Ag test in persons infected with the B.1.1.7 (alpha) variant of SARS-CoV-2 in comparison with that in persons infected with non-B.1.1.7 variants, also after adjustment for viral load. IMPORTANCE Antigen tests for COVID-19 are widely used for rapid identification of COVID-19 cases, for example, for access to schools, festivals, and travel. There are several FDA- and CE-cleared tests on the market. Their performance has been evaluated mainly on the basis of infections by the classical variant of the causing virus, SARS-CoV-2. This paper provides evidence that the performance of one of the most widely used antigen tests detects significantly fewer cases of COVID-19 by the alpha variant than by the classical variants of SARS-CoV-2. This means that the role of antigen tests needs to be reevaluated in regions where other variants of SARS-CoV-2 predominate.


Subject(s)
Antigens, Viral/immunology , COVID-19 Serological Testing/methods , COVID-19/diagnosis , COVID-19/immunology , SARS-CoV-2/classification , Antibodies, Viral/analysis , Diagnostic Tests, Routine , Humans , Netherlands , SARS-CoV-2/isolation & purification , Sensitivity and Specificity , Viral Load
14.
J Mark Access Health Policy ; 9(1): 2002008, 2021.
Article in English | MEDLINE | ID: covidwho-1522061

ABSTRACT

OBJECTIVE: This study aims at investigating associations between COVID-19 mortality and SARS-COV-2 variants spread during the second wave of COVID-19 pandemic in Europe. METHODS: For 38 European countries, data on numbers of COVID-19 deaths, SARS-COV-2 variants spread through time using Nextstrain classification, demographic and health characteristics were collected. Cumulative number of COVID-19 deaths and height of COVID-19 daily deaths peak during the second wave of the pandemic were considered as outcomes. Pearson correlations and multivariate generalized linear models with selection algorithms were used. RESULTS: The average proportion of B.1.1.7 variant was found to be a significant predictor of cumulative COVID-19 deaths within two months before the peak and between 1 January-25 February 2021, as well as of the deaths peak height considering proportions during the second wave and the pre-peak period. The average proportion of EU2 variant (S:477 N) was a significant predictor of cumulative COVID-19 deaths in the pre-peak period. CONCLUSIONS: Our findings suggest that spread of a new variant of concern B.1.1.7 had a significant impact on mortality during the second wave of COVID-19 pandemic in Europe and that proportions of EU2 and B.1.1.7 variants were associated with increased mortality in the initial phase of that wave.

15.
Cureus ; 13(10): e19140, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1504372

ABSTRACT

Coronavirus disease 2019 (COVID-19) cluster with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.7 variant occurred between April 10, 2021, and May 26, 2021, at Japan Community Health Care Organization (JCHO) Sapporo Hokushin Hospital in Sapporo, Japan. We found that the four infected staff members accounted for 5.3% of all 75 infected persons, approximately one of 10 the percentage of other Japanese hospitals that experienced disease clusters caused by wild-type SARS-CoV-2 until January 2021. Furthermore, none of the infected staff developed COVID-19. Nationwide vaccination began in February 2021, when wild-type SARS-CoV-2 infection remained prevalent in Japan. During March-May, Sapporo had already experienced an explosive increase in SARS-CoV-2 B.1.1.7 cases. JCHO Sapporo Hokushin Hospital started optional vaccination for staff members using BNT162b2. The first inoculations occurred between February 22, 2021, and April 28, 2021, and the second between March 15, 2021, and May 7, 2021. This is the first report that BNT162b2 might reduce B.1.1.7 variant transmission in Japanese population.

16.
Int J Infect Dis ; 114: 112-114, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1499944

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic. Diagnostic testing for SARS-CoV-2 has continuously been challenged due to several variants with diverse spike (S) and nucleocapsid (N) protein mutations []. SARS-CoV-2 variant proliferation potentially affects N protein-targeted rapid antigen testing. In this study, rapid antigen and reverse transcription PCR (RT-PCR) tests were performed simultaneously in patients with suspected coronavirus disease 2019 (COVID-19). Direct whole genome sequencing was performed to determine the N protein variations, and the viral assemblies were uploaded to GISAID. The genomes were then compared with those of global virus strains from GISAID. These isolates belonged to the B.1.1.7 variant, exhibiting several amino acid substitutions, including D3L, R203K, G204R, and S235F N protein mutations. The T135I mutation was also identified in one variant case in which the rapid antigen test and RT-PCR test were discordantly negative and positive, respectively. These findings suggest that the variants undetected by the Panbio COVID-19 rapid antigen test may be due to the T135I mutation in the N protein, posing a potential diagnostic risk for commercially available antigen tests. Hence, we recommend concomitant paired rapid antigen tests and molecular diagnostic methods to detect SARS-CoV-2. False-negative results could be rapidly corrected using confirmatory RT-PCR results to prevent future COVID-19 outbreaks.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Mutation , Nucleocapsid/genetics , Sensitivity and Specificity
17.
Virus Res ; 303: 198522, 2021 10 02.
Article in English | MEDLINE | ID: covidwho-1447221

ABSTRACT

The B.1.1.7 SARS-CoV-2 strain that has emerged in the UK in early December presents seven mutations and three deletions on S-protein structure that could lead to a more infective strain. The P681H mutation in the "PRRAR" furin cleavage site might affect the binding affinity to furin enzyme and hence its infectivity. Therefore, in this study, various structural bioinformatics approaches were used to model the S-protein structure with the B.1.1.7 variant amino acid substitutions and deletions. In addition to modelling the binding of furin to the cleavage site of the wild-type and the B.1.1.7 variant. Conclusively the B.1.1.7 variant resulted in dynamic stability, conformational changes and variations in binding energies in the S-protein structure, resulting in a more favourable binding of furin enzyme to the SARS-CoV-2 S-protein.


Subject(s)
Furin/metabolism , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/metabolism , Binding Sites , Furin/chemistry , Models, Molecular , Molecular Docking Simulation , Molecular Dynamics Simulation , Mutation , Protein Binding , Protein Conformation , SARS-CoV-2/chemistry , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/genetics
18.
Public Health ; 198: 230-237, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1392532

ABSTRACT

OBJECTIVES: This study aimed at estimating the real-life impact of vaccination on COVID-19 mortality, with adjustment for SARS-CoV-2 variants spread and other factors across Europe and Israel. STUDY DESIGN: Time series analysis. METHODS: Time series analysis of the daily number of COVID-19 deaths was performed using non-linear Poisson mixed regression models. Variables such as variants' frequency, demographics, climate, health, and mobility characteristics of thirty-two countries between January 2020 and April 2021 were considered as potentially relevant adjustment factors. RESULTS: The analysis revealed that vaccination efficacy in terms of protection against deaths was 72%, with a lower reduction of the number of deaths for B.1.1.7 vs non-B.1.1.7 variants (70% and 78%, respectively). Other factors significantly related to mortality were arrivals at airports, mobility change from the prepandemic level, and temperature. CONCLUSIONS: Our study confirms a strong effectiveness of COVID-19 vaccination based on real-life public data, although lower than expected from clinical trials. This suggests the absence of indirect protection for non-vaccinated individuals. Results also show that vaccination effectiveness against mortality associated with the B.1.1.7 variant is slightly lower than that with other variants. Lastly, this analysis confirms the role of mobility reduction, within and between countries, as an effective way to reduce COVID-19 mortality and suggests the possibility of seasonal variations in COVID-19 incidence.


Subject(s)
COVID-19 , COVID-19 Vaccines , Europe/epidemiology , Humans , Israel/epidemiology , SARS-CoV-2 , Vaccination
19.
Environ Sci Technol ; 55(17): 11756-11766, 2021 09 07.
Article in English | MEDLINE | ID: covidwho-1358335

ABSTRACT

Since its first identification in the United Kingdom in late 2020, the highly transmissible B.1.1.7 variant of SARS-CoV-2 has become dominant in several countries raising great concern. We developed a duplex real-time RT-qPCR assay to detect, discriminate, and quantitate SARS-CoV-2 variants containing one of its mutation signatures, the ΔHV69/70 deletion, and used it to trace the community circulation of the B.1.1.7 variant in Spain through the Spanish National SARS-CoV-2 Wastewater Surveillance System (VATar COVID-19). The B.1.1.7 variant was detected earlier than clinical epidemiological reporting by the local authorities, first in the southern city of Málaga (Andalucía) in week 20_52 (year_week), and multiple introductions during Christmas holidays were inferred in different parts of the country. Wastewater-based B.1.1.7 tracking showed a good correlation with clinical data and provided information at the local level. Data from wastewater treatment plants, which reached B.1.1.7 prevalences higher than 90% for ≥2 consecutive weeks showed that 8.1 ± 2.0 weeks were required for B.1.1.7 to become dominant. The study highlights the applicability of RT-qPCR-based strategies to track specific mutations of variants of concern as soon as they are identified by clinical sequencing and their integration into existing wastewater surveillance programs, as a cost-effective approach to complement clinical testing during the COVID-19 pandemic.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Pandemics , Wastewater
20.
Microbiol Spectr ; 9(1): e0027321, 2021 09 03.
Article in English | MEDLINE | ID: covidwho-1341310

ABSTRACT

The SARS-CoV-2 B.1.1.7 variant has increased sharply in numbers worldwide and is reported to be more contagious than the nonvariant. Little is known regarding the detailed clinical features of B.1.1.7 variant infection. Data on 74 COVID-19 cases from two outbreaks in two districts of Beijing, China were extracted from a cloud database, including 41 cases from Shunyi District (Shunyi B.1.470 group) and 33 from Daxing (Daxing B.1.1.7 group) from December 25, 2020 to January 17, 2021. We conducted a comparison of the clinical characteristics. Seven clinical indicators of the Daxing B.1.1.7 group were significantly higher than those of the Shunyi group, including the proportion with fever over 38°C, the levels of C-reactive protein (CRP), serum amyloid A (SAA), creatine kinase (CK), d-dimer (DD), and CD4+ T lymphocytes (CD4+ T), and the proportion with ground-glass opacity (GGO) in the lung (P values of ≤0.05). After adjusting for age, B.1.1.7 variant infection was a risk factor for elevated CRP (P = 0·045), SAA (P = 0·011), CK (P = 0·034), and CD4+ T (P = 0.029) and for the presence of GGO (P = 0.005). The median threshold cycle (CT) value of reverse transcriptase quantitative PCR (RT-qPCR) tests of the N gene target in the Daxing B.1.1.7 group was significantly lower (P = 0.036) than that in the Shunyi B.1.470 group. Clinical features, including a more serious inflammatory response, pneumonia, and a possibly higher viral load, were detected in the cases infected with B.1.1.7 SARS-CoV-2. The B.1.1.7 variant may have increased pathogenicity. IMPORTANCE The SARS-CoV-2 B.1.1.7 variant, which was first identified in the United Kingdom, has increased sharply in numbers worldwide and was reported to be more contagious than the nonvariant. To our knowledge, no studies investigating the detailed clinical features of COVID-19 cases infected with the B.1.1.7 variant have been published. Local epidemics have rarely occurred in China, but occasionally, a small clustered outbreak triggered by an imported SARS-CoV-2 strain with only one chain of transmission could happen. From late 2020 to early 2021, two clustered COVID-19 outbreaks occurred in Beijing, one of which was caused by the B.1.1.7 variant. The COVID-19 patients from the two outbreaks received similar clinical tests, diagnoses, and treatments. We found that the B.1.1.7 variant infection could lead to a more serious inflammatory response, acute response process, more severe pneumonia, and probably higher viral loads. This therefore implies that the B.1.1.7 variant may have increased pathogenicity.


Subject(s)
COVID-19/epidemiology , COVID-19/virology , Disease Outbreaks , SARS-CoV-2/classification , SARS-CoV-2/genetics , Adult , CD4-Positive T-Lymphocytes , China/epidemiology , Cohort Studies , Female , Humans , Lung/virology , Male , Middle Aged , Prospective Studies , Risk Factors , Viral Load , Whole Genome Sequencing
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