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1.
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.)

2.
Front Med (Lausanne) ; 9: 869818, 2022.
Article in English | MEDLINE | ID: covidwho-2009875

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is believed to have originated in Wuhan City, Hubei Province, China, in December 2019. Infection with this highly dangerous human-infecting coronavirus via inhalation of respiratory droplets from SARS-CoV-2 carriers results in coronavirus disease 2019 (COVID-19), which features clinical symptoms such as fever, dry cough, shortness of breath, and life-threatening pneumonia. Several COVID-19 waves arose in Taiwan from January 2020 to March 2021, with the largest outbreak ever having a high case fatality rate (CFR) (5.95%) between May and June 2021. In this study, we identified five 20I (alpha, V1)/B.1.1.7/GR SARS-CoV-2 (KMUH-3 to 7) lineage viruses from COVID-19 patients in this largest COVID-19 outbreak. Sequence placement analysis using the existing SARS-CoV-2 phylogenetic tree revealed that KMUH-3 originated from Japan and that KMUH-4 to KMUH-7 possibly originated via local transmission. Spike mutations M1237I and D614G were identified in KMUH-4 to KMUH-7 as well as in 43 other alpha/B.1.1.7 sequences of 48 alpha/B.1.1.7 sequences deposited in GISAID derived from clinical samples collected in Taiwan between 20 April and July. However, M1237I mutation was not observed in the other 12 alpha/B.1.1.7 sequences collected between 26 December 2020, and 12 April 2021. We conclude that the largest COVID-19 outbreak in Taiwan between May and June 2021 was initially caused by the alpha/B.1.1.7 variant harboring spike D614G + M1237I mutations, which was introduced to Taiwan by China Airlines cargo crew members. To our knowledge, this is the first documented COVID-19 outbreak caused by alpha/B.1.1.7 variant harboring spike M1237I mutation thus far. The largest COVID-19 outbreak in Taiwan resulted in 13,795 cases and 820 deaths, with a high CFR, at 5.95%, accounting for 80.90% of all cases and 96.47% of all deaths during the first 2 years. The high CFR caused by SARS-CoV-2 alpha variants in Taiwan can be attributable to comorbidities and low herd immunity. We also suggest that timely SARS-CoV-2 isolation and/or sequencing are of importance in real-time epidemiological investigations and in epidemic prevention. The impact of G614G + M1237I mutations in the spike gene on the SARS-CoV-2 virus spreading as well as on high CFR remains to be elucidated.

3.
Virus Evolution ; 8(2), 2022.
Article in English | Web of Science | ID: covidwho-1997081

ABSTRACT

Retrospective evaluation of past waves of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic is key for designing optimal interventions against future waves and novel pandemics. Here, we report on analysing genome sequences of SARS-CoV-2 from the first two waves of the epidemic in 2020 in Hungary, mirroring a suppression and a mitigation strategy, respectively. Our analysis reveals that the two waves markedly differed in viral diversity and transmission patterns. Specifically, unlike in several European areas or in the USA, we have found no evidence for early introduction and cryptic transmission of the virus in the first wave of the pandemic in Hungary. Despite the introduction of multiple viral lineages, extensive community spread was prevented by a timely national lockdown in March 2020. In sharp contrast, the majority of the cases in the much larger second wave can be linked to a single transmission lineage of the pan-European B.1.160 variant. This lineage was introduced unexpectedly early, followed by a 2-month-long cryptic transmission before a soar of detected cases in September 2020. Epidemic analysis has revealed that the dominance of this lineage in the second wave was not associated with an intrinsic transmission advantage. This finding is further supported by the rapid replacement of B.1.160 by the alpha variant (B.1.1.7) that launched the third wave of the epidemic in February 2021. Overall, these results illustrate how the founder effect in combination with the cryptic transmission, instead of repeated international introductions or higher transmissibility, can govern viral diversity.

4.
Extreme Medicine ; - (1):5-11, 2022.
Article in English | Scopus | ID: covidwho-1989067

ABSTRACT

The emergence of novel SARS-CoV-2 genetic variants with increased transmissivity and reduced antibody neutralization efficiency is a threat to global public health. Reverse transcription polymerase chain reaction (RT-PCR) with the use of fluorescent probes, which make it possible to detect the single nucleotide substitutions, is a technique suitable for screening the SARS-CoV-2 RNA-containing samples for the already known functionally significant mutations in the S-gene, identification of which allows to define and differentiate the most epidemiologically significant genetic variants. The study was aimed to develop an assay for the large-scale monitoring of the spread of the SARS-CoV-2 top-priority variants. Based on the whole-genome alignment of the SARS-CoV-2 sequences, deposited in the GISAID database, primers and LNA-modified probes were selected to detect mutations in the S gene, typical for the Alpha, Beta/Gamma and Delta variants of concern (VOC). The developed reagent kit for detection of the key mutations in the SARS-CoV-2 S gene by the real time RT-PCR has good analytical and diagnostic characteristics and was authorized as a medical device (reagent) for in vitro use. The results of detecting the VOC and the key mutations with the use of the developed reagent kit were consistent with the data of the whole genome sequencing of 1,500 SARS-CoV-2 RNA samples. The developed reagent kit and the subsequent SARS-CoV-2 RNA sequencing assay used to perform the epidemiological monitoring of SARS-CoV-2 variants made it possible to promptly report the emergence of the Delta genetic variant in Russia, and to trace the dynamic changes in the prevalence of Delta in Moscow Region in April-September 2021. © 2022 Obstetrics, Gynecology and Reproduction. All rights reserved.

5.
Journal of Microbiology, Immunology and Infection ; 2022.
Article in English | ScienceDirect | ID: covidwho-1983504

ABSTRACT

Background /Purpose: Clinical characteristics of patients in the first community outbreak of coronavirus disease 2019 (COVID-19) by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant B.1.1.7 in Taiwan have not been characterized. Methods SARS-CoV-2 positive specimens from inpatients between May 7 and June 15 in 2021were screen for SARS-CoV-2 B.1.1.7 lineage by VirSNiP assay. Clinical characteristics were reviewed and compared to those from Feb 1 to April 30, 2020 and from Jan 1 to March 31, 2022. Results One hundred forty-one inpatients from May 7 to June 15, 2021 infected with SARS-CoV-2 B.1.1.7 lineage were included. The major presenting symptoms were fever (88.7%) and cough (59.6%). Incidence of relevant complications including pulmonary embolism, simultaneous infections with bacteria, virus, and fungi were 0.7%, 12.8%, 13.5%, and 2.1%, respectively. Old age, high Charlson comorbidity index, short of breath, and initial critical illness were independently associated with 28-day mortality (all p < 0.05). In comparison to COVID-19 inpatients from Feb 1 to April 30, 2020, patients from the outbreak by SARS-CoV-2 B.1.1.7 lineage were older, more severe in disease condition, higher mortality but less obvious initial presenting symptoms. After implementation of nationwide vaccination campaign in the next half year of 2021, COVID-19 inpatients from Jan 1 to March 31 in 2022 indicated less severe diseases than those infected with SARS-CoV-2 B.1.1.7 lineage. Conclusion COVID-19 inpatients by SARS-CoV-2 variant B.1.1.7 with old age, multiple comorbidities, and more severe disease conditions were associated with increased mortality. Vaccination for this vulnerable populations may be helpful.

6.
Jpn J Infect Dis ; 2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1969762

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019, is spreading globally. In general, the viral genome becomes undetectable within a couple of weeks after infection. Herein, we report a case of long-term detection of the SARS-CoV-2 genome from the same individual for 106 days. Whole genome sequencing was performed on specimens taken at the onset of the disease and at 2 months after onset, and the B.1.1.7 lineage was detected in both samples. Comparison of the full-length sequences revealed a single-base difference and no amino acid mutations. This is the first case in Japan where the virus was detected over a long time, and the full-length sequences were compared.

7.
Journal of Hazardous Materials Advances ; : 100140, 2022.
Article in English | ScienceDirect | ID: covidwho-1966586

ABSTRACT

The coronavirus known as COVID-19, which causes pandemics, is causing a global epidemic at a critical stage today. Furthermore, novel mutations in the SARS-CoV-2 spike protein have been discovered in an entirely new strain, impacting the clinical and epidemiological features of COVID-19. Variants of these viruses can increase the transmission in wastewater, lead to reinfection, and reduce immunity provided by monoclonal antibodies and vaccinations. According to the research, a large quantity of viral RNA was discovered in wastewater, suggesting that wastewater can be a crucial source of epidemiological data and health hazards. The purpose of this paper is to introduce a few basic concepts regarding wastewater surveillance as a starting point for comprehending COVID-19′s epidemiological aspects. Next, the observation of Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), and Omicron (B.1.1.529) in wastewater is discussed in detail. Secondly, the essential information for the initial, primary, and final treating sewage in SARS-CoV-2 is introduced. Following that, a thorough examination is provided to highlight the newly developed methods for eradicating SARS-CoV-2 using a combination of solar water disinfection (SODIS) and ultraviolet radiation A (UVA (315-400 nm)), ultraviolet radiation B (UVB (280-315 nm)), and ultraviolet radiation C (UVC (100-280 nm)) processes. SARS-CoV-2 eradication requires high temperatures (above 56°C) and UVC. However, SODIS technologies are based on UVA and operate at cooler temperatures (less than 45°C). Hence, it is not appropriate for sewage treatment (or water consumption) to be conducted using SODIS methods in the current pandemic. Finally, SARS-CoV-2 may be discovered in sewage utilizing the wastewater-based epidemiology (WBE) monitoring method.

8.
Future Microbiol ; 17: 1125-1131, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1963285

ABSTRACT

Aim: To evaluate the accuracy of two PCR-based techniques for detecting SARS-CoV-2 variant Alpha (B.1.1.7). Materials & methods: A multicenter prospective cohort with 1137 positive specimens from Slovenia was studied. A mutation-based assay (rTEST-COVID-19 qPCR B.1.1.7 assay) and amplification curve pattern analysis of the Allplex SARS-CoV-2 assay were compared with whole-genome sequencing. Results: SARS-CoV-2 variant Alpha was detected in 155 samples (13.6%). Sensitivity and specificity were 98.1 and 98.0%, respectively, for the rTEST-COVID-19 qPCR B.1.1.7 assay and 97.4 and 97.5%, respectively, for amplification curve pattern analysis. Conclusion: The good analytical performance of both methods was confirmed for the preliminary identification of SARS-CoV-2 variant Alpha. This cost-effective principle for screening SARS-CoV-2 populations is also applicable to other emerging variants and may help to conserve some whole-genome sequencing resources.

9.
Front Immunol ; 13: 812606, 2022.
Article in English | MEDLINE | ID: covidwho-1902974

ABSTRACT

Background: B.1.1.7 (alpha) and B.1.617.2 (delta) variants of concern for SARS-CoV-2 have been reported to have differential infectivity and pathogenicity. Difference in recovery patterns across these variants and the interaction with vaccination status has not been reported in population-based studies. Objective: The objective of this research was to study the length of stay and temporal trends in RT-PCR cycle times (Ct) across alpha and delta variants of SARS-CoV-2 between vaccinated and unvaccinated individuals. Methods: Participants consisted of patients admitted to national COVID-19 treatment facilities if they had a positive RT-PCR test for SARS-CoV-2, and analysis of variants was performed (using whole genome sequencing). Information on vaccination status, age, sex, cycle times (Ct) for four consecutive RT-PCR tests conducted during hospital stay, and total length of hospital stay for each participant were ascertained from electronic medical records. Results: Patients infected with the delta variant were younger (mean age = 35years vs 39 years for alpha, p<0.001) and had lesser vaccination coverage (54% vs 72% for alpha, p<0.001). RT-PCR Ct values were similar for both variants at the baseline test; however by the fourth test, delta variant patients had significantly lower Ct values (27 vs 29, p=0.05). Length of hospital stay was higher in delta variant patients in vaccinated (3 days vs 2.9 days for alpha variant) as well as in unvaccinated patients (5.2 days vs 4.4 days for alpha variant, p<0.001). Hazards of hospital discharge after adjusting for vaccination status, age, and sex was higher for alpha variant infections (HR=1.2, 95% CI: 1.01-1.41, p=0.029). Conclusion: Patients infected with the delta variant of SARS-CoV-2 were found to have a slower recovery as indicated by longer length of stay and higher shedding of the virus compared to alpha variant infections, and this trend was consistent in both vaccinated and unvaccinated patients.


Subject(s)
COVID-19/virology , SARS-CoV-2/pathogenicity , Adult , Age Factors , Bahrain/epidemiology , COVID-19/epidemiology , COVID-19/prevention & control , Female , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , SARS-CoV-2/genetics , Vaccination/statistics & numerical data
10.
IJID Reg ; 3: 106-113, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1899827

ABSTRACT

Background: : SARS-CoV-2 variants have been emerging and are shown to increase transmissibility, pathogenicity, and decreased vaccine efficacies. The objective of this study was to determine the distribution, prevalence, and dynamics of SARS-CoV-2 variants circulating in Brazzaville, the Republic of Congo (ROC). Methods: : Between December 2020 and July 2021, a total of n=600 oropharyngeal specimens collected in the community were tested for COVID-19. Of the samples tested, 317 (53%) were SARS-CoV-2 positive. All samples that had a threshold of Ct <30 (n=182) were sequenced by next-generation sequencing (NGS), and all complete sequenced genomes were submitted to GISAID; lineages were assigned using pangolin nomenclature and a phylogenetic tree was reconstructed. In addition, the global prevalence of the predominant lineages was analysed using data from GISAID and Outbreak databases. Results: : A total of 15 lineages circulated with B.1.214.2 (26%), B.1.214.1 (19%) and B.1.620 (18%) being predominant. The variants of concern (VOC) alpha (B.1.1.7) (6%) and for the first time in June delta (B.1.617.2) (4%) were observed. In addition, the B.1.214.1 lineage first reported from ROC was observed to be spreading locally and regionally. Phylogenetic analysis suggests that the B.1.620 variant (VUM) under observation may have originated from either Cameroon or the Central African Republic. SARS-CoV-2 lineages were heterogeneous, with the densely populated districts of Poto-Poto and Moungali likely the epicenter of spread. Conclusion: : Longitudinal monitoring and molecular surveillance across time and space are critical to understanding viral phylodynamics, which could have important implications for transmissibility and impact infection prevention and control measures.

11.
Comb Chem High Throughput Screen ; 2022 Jun 07.
Article in English | MEDLINE | ID: covidwho-1892471

ABSTRACT

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), affects the lower respiratory tract by binding to angiotensin-converting enzyme 2 (ACE2) via its S-protein. Recent emerging SARS-CoV-2 variants from the United Kingdom (B.1.1.7) and South Africa (501Y.V2) are spreading worldwide at an alarming rate. The new variants have manifested amino acid substitution K417N, E484K and N501Y on the RBD domain that binds to ACE2. As such, these mutations may influence the binding of the S-protein to ACE2 and affect viral entry into the host cell. Methods In this study, we modelled the amino acids substitutions on the S-protein and utilised HADDOCK server to assess the S-protein RBD domain binding with ACE2. Additionally, we calculated the binding affinity of ACE2 to S-protein WT, B.1.1.7 and 501Y.V2 variants using Molecular Mechanics-Generalized Born Surface Area (MM/GBSA). Results We demonstrate that the S-protein of both variants possesses higher binding affinity to ACE2 than WT, with the South African 501Y.V2 is a more infective strain than the B.1.1.7 that originated in the United Kingdom. Conclusion The South African 501Y.V2 variant presents three amino acid substitutions that changed the H-bonding network resulting in a higher affinity to ACE2, indicating that the 501Y.V2 strain is more infective than the B.1.1.7 strain.

12.
Future Virol ; 2022 May.
Article in English | MEDLINE | ID: covidwho-1887076

ABSTRACT

Aim: SARS-CoV-2 variants of concern (VOCs) carry signature mutations particularly in the spike protein. Most VOCs lineages that carry N501Y substitution have been reported to evade viral diagnostic tests and have impact on vaccine effectiveness. Therefore, monitoring the circulating variants represents a major requirement for a public health response worldwide. We aimed to investigate the prevalence of N501Y bearing SARS-CoV-2 samples in Northern Cyprus. Materials & methods: Reverse transcription quantitative PCR technique was used to identify N501Y mutation from 658 samples. Results: Our results indicate that the proportion of N501Y-bearing lineages increased significantly from January through May 2021 (45.2-75.5%) in the region. Conclusion: These results indicate that VOCs are dominant lineages in the country and highlight an alarming situation which require strict governmental measures to minimize COVID-19 morbidity and mortality.

13.
Viruses ; 14(6)2022 06 06.
Article in English | MEDLINE | ID: covidwho-1884382

ABSTRACT

In this report, we describe a national-scale monitoring of the SARS-CoV-2 (SC-2) variant dynamics in Israel, using multiple-time sampling of 13 wastewater treatment plants. We used a combination of inclusive and selective quantitative PCR assays that specifically identify variants A19/A20 or B.1.1.7 and tested each sample for the presence and relative viral RNA load of each variant. We show that between December 2020 and March 2021, a complete shift in the SC-2 variant circulation was observed, where the B.1.1.7 replaced the A19 in all examined test points. We further show that the normalized viral load (NVL) values and the average new cases per week reached a peak in January 2021 and then decreased gradually in almost all test points, in parallel with the progression of the national vaccination campaign, during February-March 2021. This study demonstrates the importance of monitoring SC-2 variant by using a combination of inclusive and selective PCR tests on a national scale through wastewater sampling, which is far more amendable for high-throughput monitoring compared with sequencing. This approach may be useful for real-time dynamics surveillance of current and future variants, such as the Omicron (BA.1, BA.2) and other variants.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , Humans , Israel/epidemiology , SARS-CoV-2/genetics , Waste Water
14.
Malta Medical Journal ; 34(1):1-3, 2022.
Article in English | EMBASE | ID: covidwho-1866047
15.
Clin Infect Dis ; 2022 May 25.
Article in English | MEDLINE | ID: covidwho-1864959

ABSTRACT

The emergence of new SARS-COV-2 variants is of public health concern in case of vaccine escape. Described are three patients with advanced HIV-1 and chronic SARS-CoV-2 infection in whom there is evidence of selection and persistence of novel mutations which are associated with increased transmissibility and immune escape.

16.
Tohoku J Exp Med ; 257(4): 273-281, 2022 Jul 14.
Article in English | MEDLINE | ID: covidwho-1855183

ABSTRACT

At the end of 2019, the world met with the coronavirus disease 2019 (COVID-19), which will affect all humanity. Later in the course, the genetic variants of SARS-CoV-2 have emerged, bringing new questions and concerns. This study investigated differences between patients infected with the B.1.1.7 (UK variant) and the B.1.617.2 (Delta variant) regarding patient complaints, intensive care unit (ICU) admission and stay time, intubation, severe disease, mortality rates, and laboratory parameters. Hospitalized 205 patients infected with B.1.1.7 and 207 patients infected with B.1.617.2 were included in the study. Laboratory parameters, admission complaints, and the percent saturation of oxygen in the blood (SpO2) were recorded on the same day as the diagnosis and clinical findings during their follow-up. Cough and fever were more common complaints in the B.1.1.7 infected group, whereas tiredness, joint pain, and gastrointestinal complaints were more frequent in patients infected with B.1.617.2. The B.1.617.2 infected group had higher severe disease, acute coronary syndrome (ACS), mortality rates, neutrophil, troponin, and ferritin levels. In conclusion, patients infected with B.1.617.2 had a higher risk of intubation, ACS, and mortality rates. Cough and fever were more common in B.1.1.7 infected group, whereas tiredness was more frequent in B.1.617.2 infected group. Vaccination with at least one dose of Pfizer-BioNTech or CoronaVac is independently associated with a decreased mortality risk caused by two variants (Odds Ratio 0.4).


Subject(s)
COVID-19 , SARS-CoV-2 , Cough , Fever , Humans , United Kingdom/epidemiology
17.
Clin Infect Dis ; 2022 May 06.
Article in English | MEDLINE | ID: covidwho-1831050

ABSTRACT

BACKGROUND: Vaccination may control the COVID-19 pandemic, including in nursing homes where many high-risk people live. We conducted extensive outbreak investigations. METHODS: We studied an outbreak at a nursing home in Switzerland where vaccination uptake of mRNA vaccines against SARS-CoV-2 was 82% among residents as of Jan 21/2021. After a vaccinated symptomatic HCW was diagnosed with COVID-19 on Feb 22, we did an outbreak investigations in house A (47 residents, 37 HCWs) using SARS-CoV-2-specific PCR in nasopharyngeal swabs. We performed whole-genome sequencing of SARS-CoV-2 and serological analyses. RESULTS: We identified 17 individuals with positive PCR tests; ten residents (five vaccinated) and seven HCWs (three vaccinated). Median age among residents was 86 years (interquartile range [IQR] 70-90) and 49 years (IQR 29-59) among HCWs. Among the five vaccinated residents, 60% had mild disease and had 40% no symptoms, whereas all five unvaccinated residents had mild to severe disease and two died. The vaccine effectiveness for the prevention of infection among the residents was 73.0% (95% Cl 24.7-90.1). The 12 available genomes were all alpha variants. Neutralizing titers were significantly higher in vaccinated individuals upon re-exposure (>1 week after diagnosis) than in vaccinated, unexposed HCWs (p=0.012). Transmission networks indicated four likely or possible transmissions from vaccinated to other individuals, and 12 transmission events from unvaccinated individuals. CONCLUSIONS: COVID-19 outbreaks can occur in nursing homes, including transmission from vaccinated persons to others. Outbreaks might occur silently, underlining the need for continued testing and basic infection control measures in these high-risk settings.

18.
Int J Pept Res Ther ; 28(1): 33, 2022.
Article in English | MEDLINE | ID: covidwho-1826702

ABSTRACT

The structural consequences of ongoing mutations on the SARS-CoV-2 spike-protein remains to be fully elucidated. These mutations could change the binding affinity between the virus and its target cell. Moreover, obtaining new mutations would also change the therapeutic efficacy of the designed drug candidates. To evaluate these consequences, 3D structure of a mutant spike protein was predicted and checked for stability, cavity sites, and residue depth. The docking analyses were performed between the 3D model of the mutated spike protein and the ACE2 protein and an engineered therapeutic ACE2 against COVID-19. The obtained results revealed that the N501Y substitution has altered the interaction orientation, augmented the number of interface bonds, and increased the affinity against the ACE2. On the other hand, the P681H mutation contributed to the increased cavity size and relatively higher residue depth. The binding affinity between the engineered therapeutic ACE2 and the mutant spike was significantly higher with a distinguished binding orientation. It could be concluded that the mutant spike protein increased the affinity, preserved the location, changed the orientation, and altered the interface amino acids of its interaction with both the ACE2 and its therapeutic engineered version. The obtained results corroborate the more aggressive nature of mutated SARS-CoV-2 due to their higher binding affinity. Moreover, designed ACe2-baased therapeutics would be still highly effective against covid-19, which could be the result of conserved nature of cellular ACE2. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10989-021-10346-1.

19.
Vaccines (Basel) ; 10(5)2022 Apr 29.
Article in English | MEDLINE | ID: covidwho-1820439

ABSTRACT

With the emergence and rapid spread of new pandemic variants, especially variants of concern (VOCs), the development of next-generation vaccines with broad-spectrum neutralizing activities is of great importance. In this study, SCTV01C, a clinical stage bivalent vaccine based on trimeric spike extracellular domain (S-ECD) of SARS-CoV-2 variants Alpha (B.1.1.7) and Beta (B.1.351) with a squalene-based oil-in-water adjuvant was evaluated in comparison to its two corresponding (Alpha and Beta) monovalent vaccines in mouse immunogenicity studies. The two monovalent vaccines induced potent neutralizing antibody responses against the antigen-matched variants, but drastic reductions in neutralizing antibody titers against antigen-mismatched variants were observed. In comparison, the bivalent vaccine SCTV01C induced relatively higher and broad-spectrum cross-neutralizing activities against various SARS-CoV-2 variants, including the D614G variant, VOCs (B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.1.529), variants of interest (VOIs) (C.37, B.1.621), variants under monitoring (VUMs) (B.1.526, B.1.617.1, B.1.429, C.36.3) and other variants (B.1.618, 20I/484Q). All three vaccines elicited potent Th1-biased T-cell immune responses. These results provide direct evidence that variant-based multivalent vaccines could play important roles in addressing the critical issue of reduced protective efficacy against the existing and emerging SARS-CoV-2 variants.

20.
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.

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