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Hengkrawit K, Thananon J, Telapol K, Chiewchalermsri C. Clinical Characteristics and Outcomes of Hospitalized COVID-19 Patients with Different Variants of SARS-CoV-2 in a Tertiary Care Hospital, Thailand. Trop Med Infect Dis 2024; 9:266. [PMID: 39591272 PMCID: PMC11598002 DOI: 10.3390/tropicalmed9110266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Revised: 10/29/2024] [Accepted: 10/31/2024] [Indexed: 11/28/2024] Open
Abstract
The different strains of SARS-CoV-2 were detected and labeled in 2021. Each strain differs in both clinical symptoms and severity. Previous studies found different clinical symptoms and treatment outcomes between outbreak waves; however, data in Southeast Asia were limited. This study collected data of hospitalized COVID-19 patients from a Tertiary hospital in Thailand between January 2020 and December 2023 and analyzed patients' data in each outbreak wave using Pearson's chi-square. A total of 1084 inpatients were included for analysis. The median age was 64 (IQR, 0.4-100) years. The patients were hospitalized in predominantly Alpha (22.78%), Delta (21.68%), and Omicron (5.07%) periods of the virus outbreak. The largest age group was elderly (over 65 years old) in all three variant of concern (VOC) periods; 82.65% of the patients had comorbidities, including 58.5% hypertension, 46.5% dyslipidemia, and 42.0% diabetes mellitus (DM). The study found pneumonia at 67.53%, septic shock at 4.61%, acute respiratory distress syndrome (ARDS) at 2.86%, and congestive heart failure at 0.83% in all age groups with no significant difference between outbreak periods. The overall mortality rate was 16.14%. A total of 75% of deaths occurred in patients over 65 years old. The mortality rates in each VOC period were 20.0% Delta, 19.83% Alpha, and 13.23% Omicron. In the elderly group, the mortality rates were Delta 15.32%, Alpha 11.75%, and Omicron 10.88%. The Omicron VOC was less severe than other variants, particularly in the elderly (≥65 years). There were no significant differences in the younger (<65 years) age group. The elderly still had more severe symptoms and the highest mortality rates in every wave of outbreak.
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Affiliation(s)
- Kitchawan Hengkrawit
- Department of Pediatrics, Panyananthaphikkhu Chonprathan Medical Center, Srinakharinwirot University, Nonthaburi 11120, Thailand;
| | - Juthamas Thananon
- Department of Radiology, Panyananthaphikkhu Chonprathan Medical Center, Srinakharinwirot University, Nonthaburi 11120, Thailand;
| | - Kritakarn Telapol
- Department of Obstetrics and Gynecology, Panyananthaphikkhu Chonprathan Medical Center, Srinakharinwirot University, Nonthaburi 11120, Thailand
| | - Chirawat Chiewchalermsri
- Department of Medicine, Panyananthaphikkhu Chonprathan Medical Center, Srinakharinwirot University, Nonthaburi 11120, Thailand
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2
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Erkihun M, Ayele B, Asmare Z, Endalamaw K. Current Updates on Variants of SARS-CoV- 2: Systematic Review. Health Sci Rep 2024; 7:e70166. [PMID: 39502131 PMCID: PMC11534727 DOI: 10.1002/hsr2.70166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2023] [Revised: 06/11/2024] [Accepted: 07/29/2024] [Indexed: 11/08/2024] Open
Abstract
Background Coronavirus disease 2019 is caused by the severe acute respiratory syndrome coronavirus 2, which has become a pandemic. Severe acute respiratory syndrome coronavirus 2 is an enveloped, unsegmented, positive-sense, single-stranded RNA virus that belongs to the family Coronaviridae. Aim The objective of this review is to conduct a qualitative analysis of the current updates on epidemiology, evolution, and vaccine variants for SARS-CoV-2. Method The search strategy was done from the database based on the PRISMA criteria for qualitative analysis of this review. Literature on variants of severe acute respiratory syndrome coronavirus 2, published in English in the last 5 years (2019-2023), were included. From 179 a total of 105 articles were reviewed, searched, and retrieved from the electronic databases PubMed. The search was done using keywords like COVID-19, SARS-CoV-2, variants, mutations, and vaccines, and articles were managed using EndNote X8 software. The scope of view for this review was the course of the pandemic by emerging variants and how man is struggling to overcome this sudden pandemic through vaccines. The narrative skeleton was constructed based on the article's scope of view. Result From the parent severe acute respiratory syndrome coronavirus 2, many variants emerged during the course of this pandemic. They are mainly categorized into two variants: variants of interest and variants of concern based on the impact on public health. The World Health Organization leveled five variants: Alpha (strain B.1.1.7), Beta (strain B.1.351), Gamma (strain P.1), Delta (strain B.1.617.2), and Omicron (B.1.1.529). Conclusions It is crucial to stay informed about the latest developments in the understanding of SARS-CoV-2 variants, as new variants can emerge and impact the course of the pandemic. Health authorities and researchers continuously have to monitor and study these variants to assess their characteristics, transmissibility, severity, and the effectiveness of vaccines against them. One has to always refer to the latest information from reputable health journals or organizations for the most up-to-date and accurate details on COVID-19 variants.
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Affiliation(s)
- Mulat Erkihun
- Department of Medical Laboratory Sciences, School of Health Sciences, College of Medicine and Health SciencesDebre Tabor UniversityDebre TaborEthiopia
| | - Bayu Ayele
- Laboratory Service UnitFelege Hiwot Comprehensive Specialized HospitalBahir DarEthiopia
| | - Zelalem Asmare
- Department of Medical Laboratory Sciences, College of Health SciencesWoldia UniversityWoldiaEthiopia
| | - Kirubel Endalamaw
- Department of Diagnostic Laboratory at Shegaw Motta General HospitalMotta TownEthiopia
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3
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Al-Qazzaz NK, Aldoori AA, Ali SHBM, Ahmad SA. Automatic COVID-19 Detection from Chest X-ray using Deep MobileNet Convolutional Neural Network. ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY. ANNUAL INTERNATIONAL CONFERENCE 2024; 2024:1-5. [PMID: 40039689 DOI: 10.1109/embc53108.2024.10781897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/06/2025]
Abstract
As the COVID-19 pandemic has put a strain on healthcare systems around the world, accurate and rapid virus detection has become increasingly important. Lung issues caused by COVID-19 can be detected using a chest X-ray (CXR). In order to automatically determine whether or not a patient's CXR data are consistent with COVID-19, this work provides a deep learning transfer learning MobileNetV2 model for constructing such a computational tool. In order to automatically learn and extract important information from CXR images, deep learning employs a Convolutional Neural Network (CNN) firstly by using pre-trained MobileNetV2 for classification. The second step was to use a support vector machine (SVM) classifier on the data gathered from the 'global average pooling2d 1' layer. When using transfer learning with deep learning (DL) pre-trained MobileNetV2 CNN model and SVM classifier, we were able to increase accuracy from 92.28% using the baseline model to 93.2%. Using a combination of MobileNetV2 features and SVM classifiers proved to be the most effective method for identifying COVID-19, non-COVID lung opacity, and normal. These findings provide credence to using deep processing algorithms to improve the discrimination of COVID-19, non-COVID, and lung opacity patients from healthy controls.
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Ghildiyal T, Rai N, Mishra Rawat J, Singh M, Anand J, Pant G, Kumar G, Shidiki A. Challenges in Emerging Vaccines and Future Promising Candidates against SARS-CoV-2 Variants. J Immunol Res 2024; 2024:9125398. [PMID: 38304142 PMCID: PMC10834093 DOI: 10.1155/2024/9125398] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 11/10/2023] [Accepted: 12/18/2023] [Indexed: 02/03/2024] Open
Abstract
Since the COVID-19 outbreak, the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) virus has evolved into variants with varied infectivity. Vaccines developed against COVID-19 infection have boosted immunity, but there is still uncertainty on how long the immunity from natural infection or vaccination will last. The present study attempts to outline the present level of information about the contagiousness and spread of SARS-CoV-2 variants of interest and variants of concern (VOCs). The keywords like COVID-19 vaccine types, VOCs, universal vaccines, bivalent, and other relevant terms were searched in NCBI, Science Direct, and WHO databases to review the published literature. The review provides an integrative discussion on the current state of knowledge on the type of vaccines developed against SARS-CoV-2, the safety and efficacy of COVID-19 vaccines concerning the VOCs, and prospects of novel universal, chimeric, and bivalent mRNA vaccines efficacy to fend off existing variants and other emerging coronaviruses. Genomic variation can be quite significant, as seen by the notable differences in impact, transmission rate, morbidity, and death during several human coronavirus outbreaks. Therefore, understanding the amount and characteristics of coronavirus genetic diversity in historical and contemporary strains can help researchers get an edge over upcoming variants.
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Affiliation(s)
- Tanmay Ghildiyal
- Department of Microbial Biotechnology, Panjab University, Chandigarh, India
| | - Nishant Rai
- Department of Biotechnology, Graphic Era Deemed to be University, Dehradun, India
| | - Janhvi Mishra Rawat
- Department of Biotechnology, Graphic Era Deemed to be University, Dehradun, India
| | - Maargavi Singh
- Department of Instrumentation and Control Engineering, Manipal Institute of Technology, Manipal, Karnataka, India
| | - Jigisha Anand
- Department of Biotechnology, Graphic Era Deemed to be University, Dehradun, India
| | - Gaurav Pant
- Department of Microbiology, Graphic Era Deemed to be University, Dehradun, India
| | - Gaurav Kumar
- Department of Microbiology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, India
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5
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Adam A, Kalveram B, Chen JYC, Yeung J, Rodriguez L, Singh A, Shi PY, Xie X, Wang T. A single-dose of intranasal vaccination with a live-attenuated SARS-CoV-2 vaccine candidate promotes protective mucosal and systemic immunity. NPJ Vaccines 2023; 8:160. [PMID: 37863935 PMCID: PMC10589337 DOI: 10.1038/s41541-023-00753-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2023] [Accepted: 09/26/2023] [Indexed: 10/22/2023] Open
Abstract
An attenuated SARS-CoV-2 virus with modified viral transcriptional regulatory sequences and deletion of open-reading frames 3, 6, 7 and 8 (∆3678) was previously reported to protect hamsters from SARS-CoV-2 infection and transmission. Here we report that a single-dose intranasal vaccination of ∆3678 protects K18-hACE2 mice from wild-type or variant SARS-CoV-2 challenge. Compared with wild-type virus infection, the ∆3678 vaccination induces equivalent or higher levels of lung and systemic T cell, B cell, IgA, and IgG responses. The results suggest ∆3678 as an attractive mucosal vaccine candidate to boost pulmonary immunity against SARS-CoV-2.
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Affiliation(s)
- Awadalkareem Adam
- Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA
- Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX, USA
| | - Birte Kalveram
- Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA
| | - John Yun-Chung Chen
- Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA
| | - Jason Yeung
- Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA
| | - Leslie Rodriguez
- Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA
| | - Ankita Singh
- Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA
| | - Pei-Yong Shi
- Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX, USA.
- Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
- Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
- Sealy Institute for Drug Discovery, University of Texas Medical Branch, Galveston, TX, USA.
- Sealy Center for Structural Biology & Molecular Biophysics, University of Texas Medical Branch, Galveston, TX, USA.
| | - Xuping Xie
- Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
- Sealy Institute for Drug Discovery, University of Texas Medical Branch, Galveston, TX, USA.
| | - Tian Wang
- Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
- Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX, USA.
- Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, USA.
- Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
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6
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Parums DV. Editorial: A Rapid Global Increase in COVID-19 is Due to the Emergence of the EG.5 (Eris) Subvariant of Omicron SARS-CoV-2. Med Sci Monit 2023; 29:e942244. [PMID: 37654205 PMCID: PMC10478578 DOI: 10.12659/msm.942244] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Accepted: 08/21/2023] [Indexed: 09/02/2023] Open
Abstract
A new variant of SARS-CoV-2 has currently achieved global domination. EG.5 (Eris) was first reported by the World Health Organization (WHO) on February 17, 2023, and designated as a variant under monitoring (VUM) on July 19, 2023. EG.5 (Eris), and its sublineages, EG.5.1, EG.5.1.1, and EG.5.2, is a descendent lineage of XBB.1.9.2, which has the same spike amino acid profile as XBB.1.5 (Kraken). However, EG.5 (Eris) has an additional F456L amino acid mutation in the spike protein compared to these parent subvariants, and the subvariant EG.5.1 has another spike mutation, Q52H. Following risk evaluation by the WHO, EG.5 (Eris) and its sublineages were designated as a variant of interest (VOI) on August 8, 2023. In the US, the Centers for Disease Control and Prevention (CDC) provides two-weekly monitoring data on the incidence and mortality from COVID-19 and SARS-CoV-2 variants. The most recent CDC data for August 19, 2023, showed an increase in cases in the past two weeks, with hospitalizations for COVID-19 increasing by 14.3% and mortality from COVID-19 rising by 8.3%. In the US, the most common COVID-19 cases have been due to three new SARS-CoV-2 Omicron variants: EG.5 (Eris) (20.6%); FL.1.5.1 (Fornax) (13.3%); and XBB.1.16 (Arcturus) (10.7%). This Editorial aims to highlight the importance of rapid virus genomic sequencing and continued global SARS-CoV-2 surveillance to identify rapidly emerging SARS-CoV-2 Omicron variants, such as EG.5 (Eris).
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Affiliation(s)
- Dinah V. Parums
- Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA, e-mail:
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7
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Bhattacharjee MJ, Bhattacharya A, Kashyap B, Taw MJ, Li WH, Mukherjee AK, Khan MR. Genome analysis of SARS-CoV-2 isolates from a population reveals the rapid selective sweep of a haplotype carrying many pre-existing and new mutations. Virol J 2023; 20:201. [PMID: 37658381 PMCID: PMC10474745 DOI: 10.1186/s12985-023-02139-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Accepted: 07/24/2023] [Indexed: 09/03/2023] Open
Abstract
To understand the mechanism underlying the evolution of SARS-CoV-2 in a population, we sequenced 92 viral genomes from Assam, India. Analysis of these and database sequences revealed a complete selective sweep of a haplotype in Assam carrying 13 pre-existing variants, including a high leap in frequency of a variant on ORF8, which is involved in immune evasion. A comparative study between sequences of same lineage and similar time frames in and outside Assam showed that 10 of the 13 pre-existing variants had a frequency ranging from 96 to 99%, and the remaining 3 had a low frequency outside Assam. Using a phylogenetic approach to infer sequential occurrences of variants we found that the variant Phe120del on ORF8, which had a low frequency (1.75%) outside Assam, is at the base of the phylogenetic tree of variants and became totally fixed (100%) in Assam population. Based on this observation, we inferred that the variant on ORF8 had a selective advantage, so it carried the haplotype to reach the100% frequency. The haplotype also carried 32 pre-existing variants at a frequency from 1.00 to 80.00% outside Assam. Those of these variants that are more closely linked to the S-protein locus, which often carries advantageous mutations and is tightly linked to the ORF8 locus, retained higher frequencies, while the less tightly linked variants showed lower frequencies, likely due to recombination among co- circulating variants in Assam. The ratios of non-synonymous substitutions to synonymous substitutions suggested that some genes such as those coding for the S-protein and non-structural proteins underwent positive selection while others were subject to purifying selection during their evolution in Assam. Furthermore, we observed negative correlation of the Ct value of qRT-PCR of the patients with abundant ORF6 transcripts, suggesting that ORF6 can be used as a marker for estimating viral titer. In conclusion, our in-depth analysis of SARS-CoV-2 genomes in a regional population reveals the mechanism and dynamics of viral evolution.
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Affiliation(s)
- Maloyjo Joyraj Bhattacharjee
- Division of Life Science, Institute of Advanced Study in Science and Technology, Paschim Boragaon, Guwahati, Assam, 781035, India
| | - Anupam Bhattacharya
- Division of Life Science, Institute of Advanced Study in Science and Technology, Paschim Boragaon, Guwahati, Assam, 781035, India
| | - Bhaswati Kashyap
- Division of Life Science, Institute of Advanced Study in Science and Technology, Paschim Boragaon, Guwahati, Assam, 781035, India
| | - Manash Jyoti Taw
- Department of Microbiology, Gauhati Medical College and Hospital, Guwahati, Assam, 781032, India
| | - Wen-Hsiung Li
- Biodiversity Research Center, Academia Sinica, 11529, Taipei, Taiwan.
- Department of Ecology and Evolution, University of Chicago, Chicago, IL, 60637, USA.
| | - Ashis K Mukherjee
- Division of Life Science, Institute of Advanced Study in Science and Technology, Paschim Boragaon, Guwahati, Assam, 781035, India.
| | - Mojibur Rohman Khan
- Division of Life Science, Institute of Advanced Study in Science and Technology, Paschim Boragaon, Guwahati, Assam, 781035, India.
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8
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Haddrell A, Otero-Fernandez M, Oswin H, Cogan T, Bazire J, Tian J, Alexander R, Mann JFS, Hill D, Finn A, Davidson AD, Reid JP. Differences in airborne stability of SARS-CoV-2 variants of concern is impacted by alkalinity of surrogates of respiratory aerosol. J R Soc Interface 2023; 20:20230062. [PMID: 37340783 PMCID: PMC10282576 DOI: 10.1098/rsif.2023.0062] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Accepted: 05/30/2023] [Indexed: 06/22/2023] Open
Abstract
The mechanistic factors hypothesized to be key drivers for the loss of infectivity of viruses in the aerosol phase often remain speculative. Using a next-generation bioaerosol technology, we report measurements of the aero-stability of several SARS-CoV-2 variants of concern in aerosol droplets of well-defined size and composition at high (90%) and low (40%) relative humidity (RH) upwards of 40 min. When compared with the ancestral virus, the infectivity of the Delta variant displayed different decay profiles. At low RH, a loss of viral infectivity of approximately 55% was observed over the initial 5 s for both variants. Regardless of RH and variant, greater than 95% of the viral infectivity was lost after 40 min of being aerosolized. Aero-stability of the variants correlate with their sensitivities to alkaline pH. Removal of all acidic vapours dramatically increased the rate of infectivity decay, with 90% loss after 2 min, while the addition of nitric acid vapour improved aero-stability. Similar aero-stability in droplets of artificial saliva and growth medium was observed. A model to predict loss of viral infectivity is proposed: at high RH, the high pH of exhaled aerosol drives viral infectivity loss; at low RH, high salt content limits the loss of viral infectivity.
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Affiliation(s)
- Allen Haddrell
- School of Chemistry, Cantock's Close, University of Bristol, Bristol, UK
| | | | - Henry Oswin
- School of Chemistry, Cantock's Close, University of Bristol, Bristol, UK
| | - Tristan Cogan
- Bristol Veterinary School, University of Bristol, Langford House, Langford, Bristol, UK
| | - James Bazire
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK
| | - Jianghan Tian
- School of Chemistry, Cantock's Close, University of Bristol, Bristol, UK
| | - Robert Alexander
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK
| | - Jamie F. S. Mann
- Bristol Veterinary School, University of Bristol, Langford House, Langford, Bristol, UK
| | - Darryl Hill
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK
| | - Adam Finn
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK
- School of Population Health Sciences, University of Bristol, Bristol, UK
| | - Andrew D. Davidson
- School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK
| | - Jonathan P. Reid
- School of Chemistry, Cantock's Close, University of Bristol, Bristol, UK
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9
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Parums DV. Editorial: The XBB.1.5 ('Kraken') Subvariant of Omicron SARS-CoV-2 and its Rapid Global Spread. Med Sci Monit 2023; 29:e939580. [PMID: 36722047 PMCID: PMC9901170 DOI: 10.12659/msm.939580] [Citation(s) in RCA: 32] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
In November 2021, the World Health Organization (WHO) first identified the Omicron variant of SARS-CoV-2, B.1.1.529, as a variant of concern (VOC). By early 2022, the Omicron variant and its five lineages, BA.1, BA.2, BA.3, BA.4. and BA.5, had become the predominant cause of COVID-19 in most countries. The Omicron XBB.1.5 subvariant is a sublineage of the XBB variant, a recombinant of two BA.2 sublineages, with the F486P mutation in the spike protein that increases infectivity due to increased binding affinity to the angiotensin-converting enzyme 2 (ACE2) receptor. On the week ending 21 January 2023, the XBB.1.5 subvariant caused 49.1% of cases of COVID-19 in the US. The rapid rise in the prevalence of this subvariant may be explained by immune escape to previous infection or vaccines, spike mutations in F486P, and increased affinity for the ACE2 receptor. Also, current booster vaccines may not provide adequate protection from infection from this subvariant, which has been named by the media as the 'Kraken' subvariant. This Editorial aims to present the current status of the XBB.1.5 subvariant of Omicron SARS-CoV-2 and the reasons for, and implications of, its rapid global spread.
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Affiliation(s)
- Dinah V. Parums
- Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, USA
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10
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Idowu AO, Omosun YO, Igietseme JU, Azenabor AA. The COVID-19 pandemic in sub-Saharan Africa: The significance of presumed immune sufficiency. Afr J Lab Med 2023; 12:1964. [PMID: 36756213 PMCID: PMC9900247 DOI: 10.4102/ajlm.v12i1.1964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Accepted: 10/24/2022] [Indexed: 02/04/2023] Open
Abstract
A novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in China in 2019 and later ignited a global pandemic. Contrary to expectations, the effect of the pandemic was not as devastating to Africa and its young population compared to the rest of the world. To provide insight into the possible reasons for the presumed immune sufficiency to coronavirus disease 2019 (COVID-19) in Africa, this review critically examines literature published from 2020 onwards on the dynamics of COVID-19 infection and immunity and how other prevalent infectious diseases in Africa might have influenced the outcome of COVID-19. Studies characterising the immune response in patients with COVID-19 show that the correlates of protection in infected individuals are T-cell responses against the SARS-CoV-2 spike protein and neutralising titres of immunoglobin G and immunoglobin A antibodies. In some other studies, substantial pre-existing T-cell reactivity to SARS-CoV-2 was detected in many people from diverse geographical locations without a history of exposure. Certain studies also suggest that innate immune memory, which offers protection against reinfection with the same or another pathogen, might influence the severity of COVID-19. In addition, an initial analysis of epidemiological data showed that COVID‑19 cases were not severe in some countries that implemented universal Bacillus Calmette-Guerin (BCG) vaccination policies, thus supporting the potential of BCG vaccination to boost innate immunity. The high burden of infectious diseases and the extensive vaccination campaigns previously conducted in Africa could have induced specific and non-specific protective immunity to infectious pathogens in Africans.
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Affiliation(s)
- Abel O Idowu
- Department of Pharmaceutical Microbiology and Biotechnology, Faculty of Pharmacy, College of Medicine, University of Lagos, Lagos, Nigeria
| | - Yusuf O Omosun
- Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, Georgia, United States
| | - Joseph U Igietseme
- Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, Georgia, United States
- Centers for Disease Control and Prevention (CDC), Atlanta, Georgia, United States
| | - Anthony A Azenabor
- Department of Pharmaceutical Microbiology and Biotechnology, Faculty of Pharmacy, College of Medicine, University of Lagos, Lagos, Nigeria
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11
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Xu K, Lei W, Kang B, Yang H, Wang Y, Lu Y, Lv L, Sun Y, Zhang J, Wang X, Yang M, Dan M, Wu G. A novel mRNA vaccine, SYS6006, against SARS-CoV-2. Front Immunol 2023; 13:1051576. [PMID: 36685587 PMCID: PMC9849951 DOI: 10.3389/fimmu.2022.1051576] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2022] [Accepted: 12/14/2022] [Indexed: 01/07/2023] Open
Abstract
The development of vaccines that can efficiently prevent the infection of SARS-CoV-2 is necessary to fight the COVID-19 epidemic. mRNA vaccine has been proven to induce strong humoral and cellular immunity against SARS-CoV-2. Here, we studied the immunogenicity and protection efficacy of a novel mRNA vaccine SYS6006. High expression of mRNA molecules in 293T cells was detected. The initial and boost immunization with a 21-day interval was determined as an optimal strategy for SYS6006. Two rounds of immunization with SYS6006 were able to induce the neutralizing antibodies against the SARS-CoV-2 wild-type (WT) strain, and Delta and Omicron BA.2 variants in mice or non-human primates (NHPs). A3rd round of vaccination could further enhance the titers of neutralization against Delta and Omicron variants. In vitro ELISpot assay showed that SYS6006 could induce memory B cell and T cell immunities specifically against SARS-CoV-2 in mice. FACS analysis indicated that SYS6006 successfully induced SARS-CoV-2-specific activation of T follicular helper cell (Tfh) and Th1 cell, and did not induce CD4+Th2 response in NHPs. SYS6006 vaccine could significantly reduce the viral RNA loads and prevent lung lesions in Delta variant infected hACE2 transgenic mice. Therefore, SYS6006 could provide significant immune protection against SARS-CoV-2.
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Affiliation(s)
- Ke Xu
- National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Wenwen Lei
- National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Bin Kang
- CSPC Pharmaceutical Group Co., Ltd., Shijiazhuang, Hebei, China
- State Key Laboratory of Novel Pharmaceutical Preparations and Excipients, CSPC Pharmaceutical Group Co., Ltd., Shijiazhuang, Hebei, China
| | - Hanyu Yang
- CSPC Pharmaceutical Group Co., Ltd., Shijiazhuang, Hebei, China
- State Key Laboratory of Novel Pharmaceutical Preparations and Excipients, CSPC Pharmaceutical Group Co., Ltd., Shijiazhuang, Hebei, China
| | - Yajuan Wang
- CSPC Pharmaceutical Group Co., Ltd., Shijiazhuang, Hebei, China
- State Key Laboratory of Novel Pharmaceutical Preparations and Excipients, CSPC Pharmaceutical Group Co., Ltd., Shijiazhuang, Hebei, China
| | - Yanli Lu
- CSPC Pharmaceutical Group Co., Ltd., Shijiazhuang, Hebei, China
- State Key Laboratory of Novel Pharmaceutical Preparations and Excipients, CSPC Pharmaceutical Group Co., Ltd., Shijiazhuang, Hebei, China
| | - Lu Lv
- CSPC Pharmaceutical Group Co., Ltd., Shijiazhuang, Hebei, China
- State Key Laboratory of Novel Pharmaceutical Preparations and Excipients, CSPC Pharmaceutical Group Co., Ltd., Shijiazhuang, Hebei, China
| | - Yufei Sun
- CSPC Pharmaceutical Group Co., Ltd., Shijiazhuang, Hebei, China
- State Key Laboratory of Novel Pharmaceutical Preparations and Excipients, CSPC Pharmaceutical Group Co., Ltd., Shijiazhuang, Hebei, China
| | - Jing Zhang
- National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Xiaolin Wang
- CSPC Pharmaceutical Group Co., Ltd., Shijiazhuang, Hebei, China
- State Key Laboratory of Novel Pharmaceutical Preparations and Excipients, CSPC Pharmaceutical Group Co., Ltd., Shijiazhuang, Hebei, China
| | - Mengjie Yang
- National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
| | - Mo Dan
- CSPC Pharmaceutical Group Co., Ltd., Shijiazhuang, Hebei, China
- State Key Laboratory of Novel Pharmaceutical Preparations and Excipients, CSPC Pharmaceutical Group Co., Ltd., Shijiazhuang, Hebei, China
| | - Guizhen Wu
- National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
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12
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COVID-19 diagnostics: Molecular biology to nanomaterials. Clin Chim Acta 2023; 538:139-156. [PMID: 36403665 PMCID: PMC9673061 DOI: 10.1016/j.cca.2022.11.017] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 11/11/2022] [Accepted: 11/14/2022] [Indexed: 11/21/2022]
Abstract
The SARS-CoV-2 pandemic has claimed around 6.4 million lives worldwide. The disease symptoms range from mild flu-like infection to life-threatening complications. The widespread infection demands rapid, simple, and accurate diagnosis. Currently used methods include molecular biology-based approaches that consist of conventional amplification by RT-PCR, isothermal amplification-based techniques such as RT-LAMP, and gene editing tools like CRISPR-Cas. Other methods include immunological detection including ELISA, lateral flow immunoassay, chemiluminescence, etc. Radiological-based approaches are also being used. Despite good analytical performance of these current methods, there is an unmet need for less costly and simpler tests that may be performed at point of care. Accordingly, nanomaterial-based testing has been extensively pursued. In this review, we discuss the currently used diagnostic techniques for SARS-CoV-2, their usefulness, and limitations. In addition, nanoparticle-based approaches have been highlighted as another potential means of detection. The review provides a deep insight into the current diagnostic methods and future trends to combat this deadly menace.
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Neamtu A, Mocci F, Laaksonen A, Barroso da Silva FL. Towards an optimal monoclonal antibody with higher binding affinity to the receptor-binding domain of SARS-CoV-2 spike proteins from different variants. Colloids Surf B Biointerfaces 2023; 221:112986. [PMID: 36375294 PMCID: PMC9617679 DOI: 10.1016/j.colsurfb.2022.112986] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 09/13/2022] [Accepted: 10/27/2022] [Indexed: 11/13/2022]
Abstract
A highly efficient and robust multiple scales in silico protocol, consisting of atomistic Molecular Dynamics (MD), coarse-grain (CG) MD, and constant-pH CG Monte Carlo (MC), has been developed and used to study the binding affinities of selected antigen-binding fragments of the monoclonal antibody (mAbs) CR3022 and several of its here optimized versions against 11 SARS-CoV-2 variants including the wild type. Totally 235,000 mAbs structures were initially generated using the RosettaAntibodyDesign software, resulting in top 10 scored CR3022-like-RBD complexes with critical mutations and compared to the native one, all having the potential to block virus-host cell interaction. Of these 10 finalists, two candidates were further identified in the CG simulations to be the best against all SARS-CoV-2 variants. Surprisingly, all 10 candidates and the native CR3022 exhibited a higher affinity for the Omicron variant despite its highest number of mutations. The multiscale protocol gives us a powerful rational tool to design efficient mAbs. The electrostatic interactions play a crucial role and appear to be controlling the affinity and complex building. Studied mAbs carrying a more negative total net charge show a higher affinity. Structural determinants could be identified in atomistic simulations and their roles are discussed in detail to further hint at a strategy for designing the best RBD binder. Although the SARS-CoV-2 was specifically targeted in this work, our approach is generally suitable for many diseases and viral and bacterial pathogens, leukemia, cancer, multiple sclerosis, rheumatoid, arthritis, lupus, and more.
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Affiliation(s)
- Andrei Neamtu
- Department of Physiology, "Grigore T. Popa" University of Medicine and Pharmacy of Iasi, Str. Universitatii nr. 16, 700051 Iasi, România; TRANSCEND Centre - Regional Institute of Oncology (IRO) Iasi, Str. General Henri Mathias Berthelot, Nr. 2-4 Iași, România
| | - Francesca Mocci
- University of Cagliari, Department of Chemical and Geological Sciences, Campus Monserrato, SS 554 bivio per Sestu, 09042 Monserrato, Italy
| | - Aatto Laaksonen
- Centre of Advanced Research in Bionanoconjugates and Biopolymers, PetruPoni Institute of Macromolecular Chemistry Aleea Grigore Ghica-Voda, 41 A, 700487 Iasi, Romania; University of Cagliari, Department of Chemical and Geological Sciences, Campus Monserrato, SS 554 bivio per Sestu, 09042 Monserrato, Italy; Department of Materials and Environmental Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden; State Key Laboratory of Materials-Oriented and Chemical Engineering, Nanjing Tech University, Nanjing 210009, PR China; Department of Engineering Sciences and Mathematics, Division of Energy Science, Luleå University of Technology, SE-97187 Luleå, Sweden
| | - Fernando L Barroso da Silva
- Universidade de São Paulo, Departamento de Ciências Biomoleculares, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Av. café, s/no - campus da USP, BR-14040-903 Ribeirão Preto, SP, Brazil; Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC 27695, USA.
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14
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Leneva IA, Smirnova DI, Kartashova NP, Gracheva AV, Ivanina AV, Glubokova EA, Korchevaya ER, Pancratov AA, Trunova GV, Khokhlova VA, Svitich OA, Zverev VV, Faizuloev EB. [Comparative study of Wuhan-like and omicron-like variants of SARS-CoV-2 in experimental animal models]. Vopr Virusol 2022; 67:439-449. [PMID: 36515289 DOI: 10.36233/0507-4088-135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Indexed: 12/05/2022]
Abstract
INTRODUCTION The variability of SARS-CoV-2 appeared to be higher than expected, the emergence of new variants raises concerns. The aim of the work was to compare the pathogenicity of the Wuhan and BA.1.1/Omicron variants in BALB/c mice and Syrian hamsters. MATERIALS AND METHODS The study used strains of SARS-CoV-2: Dubrovka phylogenetically close to Wuhan-Hu-1, and LIA phylogenetically close to Omicron, BALB/c mice, transgenic mice B6.Cg-Tg(K18-ACE2)2Prlmn/HEMI Hemizygous for Tg(K18-ACE2)2Prlmn, Syrian golden hamsters. Animals were infected intranasally, pathogenicity was estimated by a complex of clinical, pathomorphological and virological methods. RESULTS Comparative studies of SARS-CoV-2 Dubrovka and LIA strains on animal models demonstrated their heterogeneous pathogenicity. In parallel infection of BALB/c mice with Dubrovka and LIA variants, the infection proceeded without serious clinical signs and lung damage. Infection with the LIA strain resulted to a systemic disease with a high concentration of viral RNA in the lungs and brain tissues of animals. The presence of viral RNA in mice infected with the Dubrovka strain was transient and undetectable in the lungs by day 7 post-infection. Unlike the mouse model, in hamsters, the Dubrovka strain had a greater pathogenicity than the LIA strain. In hamsters infected with the Dubrovka strain lung lesions were more significant, and the virus spread through organs, in particular in brain tissue, was observed. In hamsters infected with the LIA strain virus was not detected in brain tissue. CONCLUSION The study of various variants of SARS-CoV-2 in species initially unsusceptible to SARS-CoV-2 infection is important for monitoring zoonotic reservoirs that increase the risk of spread of new variants in humans.
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Affiliation(s)
- I A Leneva
- Mechnikov Research Institute of Vaccines and Sera, Department of Virology
| | - D I Smirnova
- Mechnikov Research Institute of Vaccines and Sera, Department of Virology
| | - N P Kartashova
- Mechnikov Research Institute of Vaccines and Sera, Department of Virology
| | - A V Gracheva
- Mechnikov Research Institute of Vaccines and Sera, Department of Virology
| | - A V Ivanina
- Mechnikov Research Institute of Vaccines and Sera, Department of Virology
| | - E A Glubokova
- Mechnikov Research Institute of Vaccines and Sera, Department of Virology
| | - E R Korchevaya
- Mechnikov Research Institute of Vaccines and Sera, Department of Virology
| | - A A Pancratov
- Herzen Moscow Research Institute of Oncology of the Ministry of Health of Russia
| | - G V Trunova
- Herzen Moscow Research Institute of Oncology of the Ministry of Health of Russia
| | - V A Khokhlova
- Herzen Moscow Research Institute of Oncology of the Ministry of Health of Russia
| | - O A Svitich
- Mechnikov Research Institute of Vaccines and Sera, Department of Virology
| | - V V Zverev
- Mechnikov Research Institute of Vaccines and Sera, Department of Virology
| | - E B Faizuloev
- Mechnikov Research Institute of Vaccines and Sera, Department of Virology
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15
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Wang C, Li Y, Pan Y, Zhou L, Zhang X, Wei Y, Guo F, Shu Y, Gao J. Clinical and immune response characteristics among vaccinated persons infected with SARS-CoV-2 delta variant: a retrospective study. J Zhejiang Univ Sci B 2022; 23:899-914. [PMID: 36379610 PMCID: PMC9676093 DOI: 10.1631/jzus.b2200054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2022] [Accepted: 06/12/2022] [Indexed: 11/22/2022]
Abstract
OBJECTIVES This study aimed to observe the clinical and immune response characteristics of vaccinated persons infected with the delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Yangzhou, China. METHODS We extracted the medical data of 129 patients with delta-variant infection who were admitted to Northern Jiangsu People's Hospital (Yangzhou, China) between August and September, 2021. The patients were grouped according to the number of vaccine doses received into an unvaccinated group: a one-dose group and a two-dose group. The vaccine used was SARS-CoV-2-inactivated vaccine developed by Sinovac. We retrospectively analyzed the patients' epidemiological, clinical, laboratory, and imaging data. RESULTS Almost all patients with delta-variant infection in Yangzhou were elderly, and patients with severe/critical illness were over 70 years of age. The rates of severe/critical illness (P=0.006), fever (P=0.025), and dyspnea (P=0.045) were lower in the two-dose group than in the unvaccinated group. Compared to the unvaccinated group, the two-dose group showed significantly higher lymphocyte counts and significantly lower levels of C-reactive protein (CRP), interleukin-6 (IL-6), and D-dimer during hospitalization and a significantly higher positive rate of immunoglobulin G (IgG) antibodies at admission (all P<0.05). The cumulative probabilities of hospital discharge and negative virus conversion were also higher in the two-dose group than in the unvaccinated group (P<0.05). CONCLUSIONS Two doses of the SARS-CoV-2-inactivated vaccine were highly effective at limiting symptomatic disease and reducing immune response, while a single dose did not seem to be effective.
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Affiliation(s)
- Cunjin Wang
- Department of Anesthesiology, Northern Jiangsu People's Hospital, Yangzhou 225001, China
- Clinical Medical College, Yangzhou University, Yangzhou 225001, China
| | - Yong Li
- Department of Anesthesiology, Northern Jiangsu People's Hospital, Yangzhou 225001, China
- Clinical Medical College, Yangzhou University, Yangzhou 225001, China
| | - Yuchen Pan
- Department of Neurology, Jiangsu Provincial Corps Hospital, Chinese People's Armed Police Force, Yangzhou 225000, China
| | - Luojing Zhou
- Clinical Medical College, Yangzhou University, Yangzhou 225001, China
| | - Xi Zhang
- Clinical Medical College, Yangzhou University, Yangzhou 225001, China
- Department of Traditional Chinese Medicine, Northern Jiangsu People's Hospital, Yangzhou 225001, China
| | - Yan Wei
- Department of Anesthesiology, Northern Jiangsu People's Hospital, Yangzhou 225001, China
- Clinical Medical College, Yangzhou University, Yangzhou 225001, China
| | - Fang Guo
- Department of Anesthesiology, Northern Jiangsu People's Hospital, Yangzhou 225001, China
- Clinical Medical College, Yangzhou University, Yangzhou 225001, China
| | - Yusheng Shu
- Clinical Medical College, Yangzhou University, Yangzhou 225001, China.
- Department of Cardiothoracic Surgery, Northern Jiangsu People's Hospital, Yangzhou 225001, China.
| | - Ju Gao
- Department of Anesthesiology, Northern Jiangsu People's Hospital, Yangzhou 225001, China.
- Clinical Medical College, Yangzhou University, Yangzhou 225001, China.
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16
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Khamadi SA, Opanda S, Symekher SL, Limbaso SK, Langat S, Cirindi JK, Mwangi M, Mwikwabe N, Okeyo S, Koskei E, Mutisya J, Owaka S, Nyunja A, Koka H, Wadegu M, Chitechi E, Achilla R, Majanja JM, Kanyara L, Amukoye E, Bulimo W. Whole-genome sequence analysis reveals the circulation of multiple SARS-CoV-2 variants of concern in Nairobi and neighboring counties, Kenya between March and July 2021. Virol J 2022; 19:178. [PMID: 36348341 PMCID: PMC9640859 DOI: 10.1186/s12985-022-01895-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 10/05/2022] [Indexed: 11/10/2022] Open
Abstract
The emergence and rapid spread of SARS-CoV-2 variants of concern (VOC) have been linked to new waves of COVID-19 epidemics occurring in different regions of the world. The VOC have acquired adaptive mutations that have enhanced virus transmissibility, increased virulence, and reduced response to neutralizing antibodies. Kenya has experienced six waves of COVID-19 epidemics. In this study, we analyzed 64 genome sequences of SARS-CoV-2 strains that circulated in Nairobi and neighboring counties, Kenya between March 2021 and July 2021. Viral RNA was extracted from RT-PCR confirmed COVID-19 cases, followed by sequencing using the ARTIC network protocol and Oxford Nanopore Technologies. Analysis of the sequence data was performed using different bioinformatics methods. Our analyses revealed that during the study period, three SARS-CoV-2 variants of concern (VOC) circulated in Nairobi and nearby counties in Kenya. The Alpha (B.1.1.7) lineage predominated (62.7%), followed by Delta (B.1.617.2, 35.8%) and Beta (B.1.351, 1.5%). Notably, the Alpha (B.1.1.7) VOC were most frequent from March 2021 to May 2021, while the Delta (B.1.617.2) dominated beginning June 2021 through July 2021. Sequence comparisons revealed that all the Kenyan viruses were genetically similar to those that circulated in other regions. Although the majority of Kenyan viruses clustered together in their respective phylogenetic lineages/clades, a significant number were interspersed among foreign strains. Between March and July 2021, our study's findings indicate the prevalence of multiple lineages of SAR-CoV-2 VOC in Nairobi and nearby counties in Kenya. The data suggest that the recent increase in SARS-CoV-2 infection, particularly in Nairobi and Kenya as a whole, is attributable to the introduction and community transmission of SARS-CoV-2 VOC among the populace. In conclusion, the findings provide a snapshot of the SARS-CoV-2 variants that circulated in Kenya during the study period.
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Affiliation(s)
- Samoel Ashimosi Khamadi
- Centre for Virus Research, Kenya Medical Research Institute (KEMRI), P.O. Box 54628-00200, Nairobi, Kenya
| | - Silvanos Opanda
- Centre for Virus Research, Kenya Medical Research Institute (KEMRI), P.O. Box 54628-00200, Nairobi, Kenya
| | - Samwel Lifumo Symekher
- Centre for Virus Research, Kenya Medical Research Institute (KEMRI), P.O. Box 54628-00200, Nairobi, Kenya
| | - Samson Konongoi Limbaso
- Centre for Virus Research, Kenya Medical Research Institute (KEMRI), P.O. Box 54628-00200, Nairobi, Kenya
| | - Solomon Langat
- Centre for Virus Research, Kenya Medical Research Institute (KEMRI), P.O. Box 54628-00200, Nairobi, Kenya
| | - Josyline Kaburi Cirindi
- Centre for Biotechnology Research and Development, Kenya Medical Research Institute (KEMRI), Nairobi, Kenya
| | - Milkah Mwangi
- Centre for Biotechnology Research and Development, Kenya Medical Research Institute (KEMRI), Nairobi, Kenya
| | - Nicholas Mwikwabe
- Centre for Traditional Medicine and Drug Research, Kenya Medical Research Institute (KEMRI), Nairobi, Kenya
| | - Seth Okeyo
- Centre for Virus Research, Kenya Medical Research Institute (KEMRI), P.O. Box 54628-00200, Nairobi, Kenya
| | - Edith Koskei
- Centre for Virus Research, Kenya Medical Research Institute (KEMRI), P.O. Box 54628-00200, Nairobi, Kenya
| | - James Mutisya
- Centre for Virus Research, Kenya Medical Research Institute (KEMRI), P.O. Box 54628-00200, Nairobi, Kenya
| | - Samwel Owaka
- Centre for Virus Research, Kenya Medical Research Institute (KEMRI), P.O. Box 54628-00200, Nairobi, Kenya
| | - Albert Nyunja
- Centre for Virus Research, Kenya Medical Research Institute (KEMRI), P.O. Box 54628-00200, Nairobi, Kenya
| | - Hellen Koka
- Centre for Virus Research, Kenya Medical Research Institute (KEMRI), P.O. Box 54628-00200, Nairobi, Kenya
| | - Meshack Wadegu
- Centre for Virus Research, Kenya Medical Research Institute (KEMRI), P.O. Box 54628-00200, Nairobi, Kenya
| | - Esther Chitechi
- Centre for Virus Research, Kenya Medical Research Institute (KEMRI), P.O. Box 54628-00200, Nairobi, Kenya
| | - Rachel Achilla
- Centre for Virus Research, Kenya Medical Research Institute (KEMRI), P.O. Box 54628-00200, Nairobi, Kenya
| | - Janet Masitsa Majanja
- Centre for Virus Research, Kenya Medical Research Institute (KEMRI), P.O. Box 54628-00200, Nairobi, Kenya
| | - Lucy Kanyara
- Centre for Virus Research, Kenya Medical Research Institute (KEMRI), P.O. Box 54628-00200, Nairobi, Kenya
| | - Evans Amukoye
- Centre for Respiratory Diseases Research, Kenya Medical Research Institute (KEMRI), Nairobi, Kenya
| | - Wallace Bulimo
- Centre for Virus Research, Kenya Medical Research Institute (KEMRI), P.O. Box 54628-00200, Nairobi, Kenya.
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Kumari R, Lim JW, Sullivan MR, Malampy R, Baush C, Smolina I, Robin H, Demidov VV, Ugolini GS, Auclair JR, Konry T. A Novel Rolling Circle Amplification-Based Detection of SARS-CoV-2 with Multi-Region Padlock Hybridization. Diagnostics (Basel) 2022; 12:diagnostics12092252. [PMID: 36140653 PMCID: PMC9497765 DOI: 10.3390/diagnostics12092252] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2022] [Revised: 09/09/2022] [Accepted: 09/11/2022] [Indexed: 11/16/2022] Open
Abstract
SARS-CoV-2 has remained a global health burden, primarily due to the continuous evolution of different mutant strains. These mutations present challenges to the detection of the virus, as the target genes of qPCR, the standard diagnostic method, may possess sequence alterations. In this study, we develop an isothermal one-step detection method using rolling circle amplification (RCA) for SARS-CoV-2. This novel strategy utilizes a multi-padlock (MP-RCA) approach to detect viral-RNA via a simplified procedure with the reliable detection of mutated strains over other procedures. We designed 40 padlock-based probes to target different sequences across the SARS-CoV-2 genome. We established an optimal one-step isothermal reaction protocol utilizing a fluorescent output detected via a plate reader to test a variety of padlock combinations. This method was tested on RNA samples collected from nasal swabs and validated via PCR. S-gene target failure (SGTF)-mutated strains of SARS-CoV-2 were included. We demonstrated that the sensitivity of our assay was linearly proportional to the number of padlock probes used. With the 40-padlock combination the MP-RCA assay was able to correctly detect 45 out 55 positive samples (81.8% efficiency). This included 10 samples with SGTF mutations which we were able to detect as positive with 100% efficiency. We found that the MP-RCA approach improves the sensitivity of the MP-RCA assay, and critically, allows for the detection of SARS-CoV-2 variants with SGTF. Our method offers the simplicity of the reaction and requires basic equipment compared to standard qPCR. This method provides an alternative approach to overcome the challenges of detecting SARS-CoV-2 and other rapidly mutating viruses.
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Affiliation(s)
- Rajesh Kumari
- Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA
| | - Ji Won Lim
- Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA
| | - Matthew Ryan Sullivan
- Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA
| | - Rachel Malampy
- Life Science Testing Center, Northeastern University, Burlington, MA 01803, USA
| | - Connor Baush
- Life Science Testing Center, Northeastern University, Burlington, MA 01803, USA
| | | | - Howard Robin
- LJ Pathology Consultants, La Jolla, CA 92037, USA
| | - Vadim V. Demidov
- Biotechnology & Pharmaceuticals Group, Global Prior Art, Inc., Boston, MA 02109, USA
| | - Giovanni Stefano Ugolini
- Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA
| | | | - Tania Konry
- Department of Pharmaceutical Sciences, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA
- Correspondence:
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18
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Barroso da Silva FL, Giron CC, Laaksonen A. Electrostatic Features for the Receptor Binding Domain of SARS-COV-2 Wildtype and Its Variants. Compass to the Severity of the Future Variants with the Charge-Rule. J Phys Chem B 2022; 126:6835-6852. [PMID: 36066414 DOI: 10.1021/acs.jpcb.2c04225] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Electrostatic intermolecular interactions are important in many aspects of biology. We have studied the main electrostatic features involved in the interaction of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein with the human receptor Angiotensin-converting enzyme 2 (ACE2). As the principal computational tool, we have used the FORTE approach, capable to model proton fluctuations and computing free energies for a very large number of protein-protein systems under different physical-chemical conditions, here focusing on the RBD-ACE2 interactions. Both the wild-type and all critical variants are included in this study. From our large ensemble of extensive simulations, we obtain, as a function of pH, the binding affinities, charges of the proteins, their charge regulation capacities, and their dipole moments. In addition, we have calculated the pKas for all ionizable residues and mapped the electrostatic coupling between them. We are able to present a simple predictor for the RBD-ACE2 binding based on the data obtained for Alpha, Beta, Gamma, Delta, and Omicron variants, as a linear correlation between the total charge of the RBD and the corresponding binding affinity. This "RBD charge rule" should work as a quick test of the degree of severity of the coming SARS-CoV-2 variants in the future.
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Affiliation(s)
- Fernando L Barroso da Silva
- Departamento de Ciências Biomoleculares, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. café, s/no-campus da USP, BR-14040-903 Ribeirão Preto, SP, Brazil.,Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina 27695, United States
| | - Carolina Corrêa Giron
- Departamento de Ciências Biomoleculares, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. café, s/no-campus da USP, BR-14040-903 Ribeirão Preto, SP, Brazil.,Hospital de Clínicas, Universidade Federal do Triângulo Mineiro, Av. Getúlio Guaritá, 38025-440 Uberaba, MG, Brazil
| | - Aatto Laaksonen
- Department of Materials and Environmental Chemistry, Arrhenius Laboratory, Stockholm University, SE-106 91 Stockholm, Sweden.,State Key Laboratory of Materials-Oriented and Chemical Engineering, Nanjing Tech University, Nanjing, 210009, P. R. China.,Centre of Advanced Research in Bionanoconjugates and Biopolymers, Petru Poni Institute of Macromolecular Chemistry, Aleea Grigore Ghica-Voda, 41A, 700487 Iasi, Romania.,Department of Engineering Sciences and Mathematics, Division of Energy Science, Luleå University of Technology, SE-97187 Luleå, Sweden.,Department of Chemical and Geological Sciences, Campus Monserrato, University of Cagliari, SS 554 bivio per Sestu, 09042 Monserrato, Italy
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19
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Churiso G, Diriba K, Girma H, Tafere S. Laboratory Findings in Different Disease Status of COVID-19 Admitted Patients at Dilla University Referral Hospital Treatment Center, South Ethiopia. Infect Drug Resist 2022; 15:4307-4320. [PMID: 35965852 PMCID: PMC9373995 DOI: 10.2147/idr.s370907] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Accepted: 08/01/2022] [Indexed: 01/09/2023] Open
Abstract
Background Millions were infected and many were dying because of the coronavirus disease 2019, since its emergence. The patients experience asymptomatic, mild, moderate, severe and critical disease with varying signs and symptoms. Decreased lymphocytes and abnormal liver and renal function tests are common among COVID-19 patients. Severe and critical cases show higher number of white blood cells, and neutrophils. However, studies showed different laboratory findings in different disease status. Therefore, this study investigated laboratory findings of COVID-19 admitted patients at Dilla University Referral Hospital treatment center, South Ethiopia. Methods A retrospective study design was conducted on 220 patients confirmed by real time polymerase chain reaction, and admitted to Dilla University Referral Hospital treatment center from September 2020 to July 2021. Data were collected from the patients’ record, and analyzed by GraphPad Prism version 8.0.1.244 software. Descriptive statistics were used to analyze the frequency while independent t-test was used to compare means of each parameter for each disease status. Results Of the 220 study cases, 120 (54.5%) were severe, 89 (40.5%) were moderate and 11 (5.0%) were mild. One hundred forty (71.1%) of the 197 laboratory tested cases, 87 (77.7%) of severe, and 49 (64.5%) of the moderate cases had neutrophils above normal range. However, 134 (68.0%) of them, 82 (73.2%) of severe and 49 (64.5%) of moderate cases showed decreased lymphocyte level. Most of the cases showed an increased level of aspartate transaminase, alanine transaminase, alkaline phosphatase, total bilirubin, and total calcium. There was statistically significant mean neutrophils (p=0.04), number of white blood cells (p= 0.02), and creatinine level (p=0.00) difference between severe and mild cases. Conclusion Most of the severe COVID-19 patients showed increased neutrophils, liver function tests; and decreased lymphocytes; suggesting higher inflammation and lymphopenia. Therefore, patients with severe and critical disease status require close follow-up.
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Affiliation(s)
- Gemechu Churiso
- Department of Medical Laboratory Sciences, Dilla University, Dilla, Ethiopia
| | - Kuma Diriba
- Department of Medical Laboratory Sciences, Dilla University, Dilla, Ethiopia
| | - Henok Girma
- Ohio State University, Global One Health Initiative, Dilla, Ethiopia
| | - Soressa Tafere
- COVID-19 Treatment Center, Dilla University, Dilla, Ethiopia
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20
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Xu X, Deng Y, Ding J, Zheng X, Li S, Liu L, Chui HK, Poon LLM, Zhang T. Real-time allelic assays of SARS-CoV-2 variants to enhance sewage surveillance. WATER RESEARCH 2022; 220:118686. [PMID: 35679788 PMCID: PMC9148393 DOI: 10.1016/j.watres.2022.118686] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/19/2022] [Revised: 05/25/2022] [Accepted: 05/27/2022] [Indexed: 05/21/2023]
Abstract
To effectively control the ongoing outbreaks of fast-spreading SARS-CoV-2 variants, there is an urgent need to add rapid variant detection and discrimination methods to the existing sewage surveillance systems established worldwide. We designed eight assays based on allele-specific RT-qPCR for real-time allelic discrimination of eight SARS-CoV-2 variants (Alpha, Beta, Gamma, Delta, Omicron, Lambda, Mu, and Kappa) in sewage. In silico analysis of the designed assays for identifying SARS-CoV-2 variants using more than four million SARS-CoV-2 variant sequences yielded ∼100% specificity and >90% sensitivity. All assays could sensitively discriminate and quantify target variants at levels as low as 10 viral RNA copy/µL with minimal cross-reactivity to the corresponding nontarget genotypes, even for sewage samples containing mixtures of SARS-CoV-2 variants with differential abundances. Integration of this method into the routine sewage surveillance in Hong Kong successfully identified the Beta variant in a community sewage. Complete concordance was observed between the results of viral whole-genome sequencing and those of our novel assays in sewage samples that contained exclusively the Delta variant discharged by a clinically diagnosed COVID-19 patient living in a quarantine hotel. Our assays in this method also provided real-time discrimination of the newly emerging Omicron variant in sewage two days prior to clinical test results in another quarantine hotel in Hong Kong. These novel allelic discrimination assays offer a rapid, sensitive, and specific way for detecting multiple SARS-CoV-2 variants in sewage and can be directly integrated into the existing sewage surveillance systems.
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Affiliation(s)
- Xiaoqing Xu
- Environmental Microbiome Engineering and Biotechnology Lab, Center for Environmental Engineering Research, Department of Civil Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China
| | - Yu Deng
- Environmental Microbiome Engineering and Biotechnology Lab, Center for Environmental Engineering Research, Department of Civil Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China
| | - Jiahui Ding
- Environmental Microbiome Engineering and Biotechnology Lab, Center for Environmental Engineering Research, Department of Civil Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China
| | - Xiawan Zheng
- Environmental Microbiome Engineering and Biotechnology Lab, Center for Environmental Engineering Research, Department of Civil Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China
| | - Shuxian Li
- Environmental Microbiome Engineering and Biotechnology Lab, Center for Environmental Engineering Research, Department of Civil Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China
| | - Lei Liu
- Environmental Microbiome Engineering and Biotechnology Lab, Center for Environmental Engineering Research, Department of Civil Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China
| | - Ho-Kwong Chui
- Environmental Protection Department, The Government of Hong Kong SAR, Tamar, Hong Kong SAR, China
| | - Leo L M Poon
- School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Sassoon Road, Hong Kong SAR, China
| | - Tong Zhang
- Environmental Microbiome Engineering and Biotechnology Lab, Center for Environmental Engineering Research, Department of Civil Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China.
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21
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Flores-Alanis A, Delgado G, Espinosa-Camacho LF, Rodríguez-Gómez F, Cruz-Rangel A, Sandner-Miranda L, Cravioto A, Morales-Espinosa R. Two Years of Evolutionary Dynamics of SARS-CoV-2 in Mexico, With Emphasis on the Variants of Concern. Front Microbiol 2022; 13:886585. [PMID: 35865920 PMCID: PMC9294468 DOI: 10.3389/fmicb.2022.886585] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 06/07/2022] [Indexed: 01/09/2023] Open
Abstract
Background The advance of the COVID-19 pandemic and spread of SARS-CoV-2 around the world has generated the emergence of new genomic variants. Those variants with possible clinical and therapeutic implications have been classified as variants of concern (VOCs) and variants of interest (VOIs). Objective This study aims to describe the COVID-19 pandemic and build the evolutionary and demographic dynamics of SARS-CoV-2 populations in Mexico, with emphasis on VOCs. Methods 30,645 complete genomes of SARS-CoV-2 from Mexico were obtained from GISAID databases up to January 25, 2022. A lineage assignment and phylogenetic analysis was completed, and demographic history for Alpha, Gamma, Delta and Omicron VOCs, and the Mexican variant (B.1.1.519) was performed. Results 148 variants were detected among the 30,645 genomes analyzed with the Delta variant being the most prevalent in the country, representing 49.7% of all genomes. Conclusion The COVID-19 pandemic in Mexico was caused by several introductions of SARS-CoV-2, mainly from the United States of America and Europe, followed by local transmission. Regional molecular epidemiological surveillance must implement to detect emergence, introductions and spread of new variants with biologically important mutations.
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Affiliation(s)
- Alejandro Flores-Alanis
- Laboratorio de Genómica Bacteriana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Gabriela Delgado
- Laboratorio de Genómica Bacteriana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Luis F. Espinosa-Camacho
- Laboratorio de Genómica Bacteriana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Flor Rodríguez-Gómez
- Laboratorio de Análisis de la Biodiversidad y Genómica, Departamento de Bioingeniería Traslacional, Centro Universitario de Ciencias Exactas e Ingenierías, Universidad de Guadalajara, Guadalajara, Mexico
| | - Armando Cruz-Rangel
- Laboratorio de Bioquímica de Enfermedades Crónicas, Instituto Nacional de Medicina Genómica, Mexico City, Mexico
| | - Luisa Sandner-Miranda
- Laboratorio de Genómica Bacteriana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Alejandro Cravioto
- Laboratorio de Genómica Bacteriana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico
| | - Rosario Morales-Espinosa
- Laboratorio de Genómica Bacteriana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico
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22
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Lino A, Cardoso MA, Martins‐Lopes P, Gonçalves HMR. Omicron - The new SARS-CoV-2 challenge? Rev Med Virol 2022; 32:e2358. [PMID: 35445774 PMCID: PMC9111063 DOI: 10.1002/rmv.2358] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Revised: 04/02/2022] [Accepted: 04/04/2022] [Indexed: 01/05/2023]
Abstract
SARS-CoV-2 virus has infected nearly 300 M people worldwide and has been associated with over 6 M deaths by March 2022. Since the virus emergence in December 2019 in Wuhan, several new mutations have been described. The World Health Organization has developed a working name for these emerging variants according to their impact on the worldwide population. In this context a high alert has been paid to variants of concern (VOC) due to their high infectiousness and transmissibility patterns. The most recent VOC, Omicron (B.1.1.529), has become dominant in the shortest time ever and has placed Europe under an overwhelming and unprecedented number of new cases. This variant has numerous mutations in regions that are associated with higher transmissibility, stronger viral binding, affinity and antibody escape. Moreover, the mutations and deletions present in the spike protein suggest that the SARS-CoV-2 specific attachment inhibitors may not be the best option for Omicron therapy. Omicron is the dominant variant circulating worldwide and, at the end of February 2022, it was responsible for nearly all sequences reported to GISAID. Omicron is made up of several sublineages, where the most common are BA.1 and BA.2 (or Nextstrain clade 21K and 21L, respectively). At a global level, it is possible to say that the proportion of BA.2 has been increasing relative to BA.1 and in some countries it has been replacing it at high rates. In order to better assess the Omicron effectiveness on antibody escape, spread and infectious ability it is of the highest relevance to maintain a worldwide tight surveillance. Even though this variant has been associated with a lower death rate, it is important to highlight that the number of people becoming infected is concerning and that further unpredictable mutations may emerge as the number of infected people rises.
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Affiliation(s)
- A. Lino
- BioISI ‐ Biosystems & Integrative Sciences InstituteFaculty of SciencesUniversity of LisbonLisbonPortugal
| | - M. A. Cardoso
- REQUIMTEInstituto Superior de Engenharia do PortoPortoPortugal
| | - P. Martins‐Lopes
- BioISI ‐ Biosystems & Integrative Sciences InstituteFaculty of SciencesUniversity of LisbonLisbonPortugal
- Department of Genetics and Biotechnology (DGB)University of Trás‐os‐Montes e Alto Douro (UTAD)Vila RealPortugal
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23
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A simulation of geographic distribution for the emergence of consequential SARS-CoV-2 variant lineages. Sci Rep 2022; 12:9999. [PMID: 35705624 PMCID: PMC9199467 DOI: 10.1038/s41598-022-14308-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Accepted: 06/06/2022] [Indexed: 11/08/2022] Open
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has been facilitated by the intermittent emergence of consequential variant strains. This study evaluated the geographic disproportionality in the detection of consequential variant lineages across countries. As of November 2021, a total of 40 potentially consequential SARS-CoV-2 variant lineages have been identified. One-hundred repeated simulations that randomly produced consequential variants from overall COVID-19 cases worldwide were performed to evaluate the presence of geographical disproportion in the occurrence of consequential variant outbreaks. Both the total number of reported COVID-19 cases and the number of reported genome sequences in each country showed weak positive correlations with the number of detected consequential lineages in each country. The simulations suggest the presence of geographical disproportion in the occurrence of consequential variant outbreaks. Based on the random occurrence of consequential variants among COVID-19 cases, identified consequential variants occurred more often than expected in the United Kingdom and Africa, whereas they occurred less in other European countries and the Middle East. Simulations of the occurrence of consequential variants by assuming a random occurrence among all COVID-19 cases suggested the presence of biogeographic disproportion. Further studies enrolling unevaluated crucial biogeographical factors are needed to determine the factors underlying the suggested disproportionality.
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24
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Abstract
A fast and highly specific detection of COVID-19 infections is essential in managing the virus dissemination networks. The most relevant technologies developed for SARS-CoV-2 detection, along with their advantages and limitations, will be presented and fully explored. Additionally, some of the newest and emerging COVID-19 diagnosis tools, such as biosensing platforms, will also be introduced. Considering the extreme relevance that all these technologies assume in pandemic control, it is of the utmost relevance to have an intrinsic knowledge of the parameters that need to be taken into consideration before choosing the most adequate test for a particular situation. Moreover, the new variants of the virus and their potential impact on the detection method’s effectiveness will be discussed. In order to better manage the pandemic, it is essential to maintain continuous research into the SARS-CoV-2 genome and updated genomic surveillance at the global level. This will allow for timely detection of new mutations and viral variants, which may affect the performance of COVID-19 detection tests.
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25
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Hoteit R, Yassine HM. Biological Properties of SARS-CoV-2 Variants: Epidemiological Impact and Clinical Consequences. Vaccines (Basel) 2022; 10:919. [PMID: 35746526 PMCID: PMC9230982 DOI: 10.3390/vaccines10060919] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 05/18/2022] [Accepted: 05/21/2022] [Indexed: 02/06/2023] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus that belongs to the coronavirus family and is the cause of coronavirus disease 2019 (COVID-19). As of May 2022, it had caused more than 500 million infections and more than 6 million deaths worldwide. Several vaccines have been produced and tested over the last two years. The SARS-CoV-2 virus, on the other hand, has mutated over time, resulting in genetic variation in the population of circulating variants during the COVID-19 pandemic. It has also shown immune-evading characteristics, suggesting that vaccinations against these variants could be potentially ineffective. The purpose of this review article is to investigate the key variants of concern (VOCs) and mutations of the virus driving the current pandemic, as well as to explore the transmission rates of SARS-CoV-2 VOCs in relation to epidemiological factors and to compare the virus's transmission rate to that of prior coronaviruses. We examined and provided key information on SARS-CoV-2 VOCs in this study, including their transmissibility, infectivity rate, disease severity, affinity for angiotensin-converting enzyme 2 (ACE2) receptors, viral load, reproduction number, vaccination effectiveness, and vaccine breakthrough.
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Affiliation(s)
- Reem Hoteit
- Clinical Research Institute, Faculty of Medicine, American University of Beirut, Beirut 110236, Lebanon;
| | - Hadi M. Yassine
- Biomedical Research Center and College of Health Sciences-QU Health, Qatar University, Doha 2713, Qatar
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26
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Siqueira PC, Cola JP, Comerio T, Sales CMM, Maciel EL. Herd immunity threshold for SARS-CoV-2 and vaccination effectiveness in Brazil. J Bras Pneumol 2022; 48:e20210401. [PMID: 35649044 PMCID: PMC8836627 DOI: 10.36416/1806-3756/e20210401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Affiliation(s)
- Priscila C Siqueira
- . Programa de Pós Graduação em Saúde Coletiva, Universidade Federal do Espírito Santo, Vitória (ES), Brasil.,. Laboratório de Epidemiologia, Universidade Federal do Espirito Santo, Vitória (ES), Brasil
| | - João P Cola
- . Programa de Pós Graduação em Saúde Coletiva, Universidade Federal do Espírito Santo, Vitória (ES), Brasil.,. Laboratório de Epidemiologia, Universidade Federal do Espirito Santo, Vitória (ES), Brasil
| | - Tatiane Comerio
- . Laboratório de Epidemiologia, Universidade Federal do Espirito Santo, Vitória (ES), Brasil.,. Prefeitura Municipal de Vitória, Secretaria Municipal de Saúde, Vitória (ES), Brasil
| | - Carolina M M Sales
- . Programa de Pós Graduação em Saúde Coletiva, Universidade Federal do Espírito Santo, Vitória (ES), Brasil.,. Laboratório de Epidemiologia, Universidade Federal do Espirito Santo, Vitória (ES), Brasil
| | - Ethel L Maciel
- . Programa de Pós Graduação em Saúde Coletiva, Universidade Federal do Espírito Santo, Vitória (ES), Brasil.,. Laboratório de Epidemiologia, Universidade Federal do Espirito Santo, Vitória (ES), Brasil
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27
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Tarrés-Freixas F, Trinité B, Pons-Grífols A, Romero-Durana M, Riveira-Muñoz E, Ávila-Nieto C, Pérez M, Garcia-Vidal E, Perez-Zsolt D, Muñoz-Basagoiti J, Raïch-Regué D, Izquierdo-Useros N, Andrés C, Antón A, Pumarola T, Blanco I, Noguera-Julián M, Guallar V, Lepore R, Valencia A, Urrea V, Vergara-Alert J, Clotet B, Ballana E, Carrillo J, Segalés J, Blanco J. Heterogeneous Infectivity and Pathogenesis of SARS-CoV-2 Variants Beta, Delta and Omicron in Transgenic K18-hACE2 and Wildtype Mice. Front Microbiol 2022; 13:840757. [PMID: 35602059 PMCID: PMC9114491 DOI: 10.3389/fmicb.2022.840757] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 03/29/2022] [Indexed: 02/05/2023] Open
Abstract
The emerging SARS-CoV-2 variants of concern (VOCs) may display enhanced transmissibility, more severity and/or immune evasion; however, the pathogenesis of these new VOCs in experimental SARS-CoV-2 models or the potential infection of other animal species is not completely understood. Here we infected K18-hACE2 transgenic mice with B.1, B.1.351/Beta, B.1.617.2/Delta and BA.1.1/Omicron isolates and demonstrated heterogeneous infectivity and pathogenesis. B.1.351/Beta variant was the most pathogenic, while BA.1.1/Omicron led to lower viral RNA in the absence of major visible clinical signs. In parallel, we infected wildtype (WT) mice and confirmed that, contrary to B.1 and B.1.617.2/Delta, B.1.351/Beta and BA.1.1/Omicron can infect them. Infection in WT mice coursed without major clinical signs and viral RNA was transient and undetectable in the lungs by day 7 post-infection. In silico modeling supported these findings by predicting B.1.351/Beta receptor binding domain (RBD) mutations result in an increased affinity for both human and murine ACE2 receptors, while BA.1/Omicron RBD mutations only show increased affinity for murine ACE2.
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Affiliation(s)
| | - Benjamin Trinité
- IrsiCaixa AIDS Research Institute, Can Ruti Campus, UAB, Badalona, Spain
| | - Anna Pons-Grífols
- IrsiCaixa AIDS Research Institute, Can Ruti Campus, UAB, Badalona, Spain
| | | | - Eva Riveira-Muñoz
- IrsiCaixa AIDS Research Institute, Can Ruti Campus, UAB, Badalona, Spain
| | - Carlos Ávila-Nieto
- IrsiCaixa AIDS Research Institute, Can Ruti Campus, UAB, Badalona, Spain
| | - Mónica Pérez
- Unitat mixta d’investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB), Bellaterra, Spain
- IRTA, Programa de Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB), Bellaterra, Spain
| | | | - Daniel Perez-Zsolt
- IrsiCaixa AIDS Research Institute, Can Ruti Campus, UAB, Badalona, Spain
| | | | - Dàlia Raïch-Regué
- IrsiCaixa AIDS Research Institute, Can Ruti Campus, UAB, Badalona, Spain
| | - Nuria Izquierdo-Useros
- IrsiCaixa AIDS Research Institute, Can Ruti Campus, UAB, Badalona, Spain
- Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain
- CIBER Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Cristina Andrés
- Respiratory Virus Unit, Department of Microbiology, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Andrés Antón
- Respiratory Virus Unit, Department of Microbiology, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
| | - Tomàs Pumarola
- Respiratory Virus Unit, Department of Microbiology, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Hospital Universitari, Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain
| | | | - Marc Noguera-Julián
- IrsiCaixa AIDS Research Institute, Can Ruti Campus, UAB, Badalona, Spain
- CIBER Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
- University of Vic–Central University of Catalonia (UVic-UCC), Vic, Spain
| | - Victor Guallar
- Barcelona Supercomputing Center, Barcelona, Spain
- Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain
| | | | - Alfonso Valencia
- Barcelona Supercomputing Center, Barcelona, Spain
- Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain
| | - Victor Urrea
- IrsiCaixa AIDS Research Institute, Can Ruti Campus, UAB, Badalona, Spain
| | - Júlia Vergara-Alert
- Unitat mixta d’investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB), Bellaterra, Spain
- IRTA, Programa de Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB), Bellaterra, Spain
| | - Bonaventura Clotet
- IrsiCaixa AIDS Research Institute, Can Ruti Campus, UAB, Badalona, Spain
- University of Vic–Central University of Catalonia (UVic-UCC), Vic, Spain
| | - Ester Ballana
- IrsiCaixa AIDS Research Institute, Can Ruti Campus, UAB, Badalona, Spain
- Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain
| | - Jorge Carrillo
- IrsiCaixa AIDS Research Institute, Can Ruti Campus, UAB, Badalona, Spain
- Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain
- CIBER Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Joaquim Segalés
- Unitat mixta d’investigació IRTA-UAB en Sanitat Animal, Centre de Recerca en Sanitat Animal (CReSA), Campus de la Universitat Autònoma de Barcelona (UAB), Bellaterra, Spain
- Departament de Sanitat i Anatomia Animals, Facultat de Veterinària, Universitat Autònoma de Barcelona (UAB), Campus de la UAB, Bellaterra, Spain
| | - Julià Blanco
- IrsiCaixa AIDS Research Institute, Can Ruti Campus, UAB, Badalona, Spain
- Germans Trias i Pujol Research Institute (IGTP), Badalona, Spain
- CIBER Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
- University of Vic–Central University of Catalonia (UVic-UCC), Vic, Spain
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28
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Sokhansanj BA, Rosen GL. Mapping Data to Deep Understanding: Making the Most of the Deluge of SARS-CoV-2 Genome Sequences. mSystems 2022; 7:e0003522. [PMID: 35311562 PMCID: PMC9040592 DOI: 10.1128/msystems.00035-22] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/27/2022] [Indexed: 12/22/2022] Open
Abstract
Next-generation sequencing has been essential to the global response to the COVID-19 pandemic. As of January 2022, nearly 7 million severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequences are available to researchers in public databases. Sequence databases are an abundant resource from which to extract biologically relevant and clinically actionable information. As the pandemic has gone on, SARS-CoV-2 has rapidly evolved, involving complex genomic changes that challenge current approaches to classifying SARS-CoV-2 variants. Deep sequence learning could be a potentially powerful way to build complex sequence-to-phenotype models. Unfortunately, while they can be predictive, deep learning typically produces "black box" models that cannot directly provide biological and clinical insight. Researchers should therefore consider implementing emerging methods for visualizing and interpreting deep sequence models. Finally, researchers should address important data limitations, including (i) global sequencing disparities, (ii) insufficient sequence metadata, and (iii) screening artifacts due to poor sequence quality control.
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Affiliation(s)
- Bahrad A. Sokhansanj
- Drexel University, Ecological and Evolutionary Signal-Processing and Informatics Laboratory, Department of Electrical & Computer Engineering, College of Engineering, Philadelphia, Pennsylvania, USA
| | - Gail L. Rosen
- Drexel University, Ecological and Evolutionary Signal-Processing and Informatics Laboratory, Department of Electrical & Computer Engineering, College of Engineering, Philadelphia, Pennsylvania, USA
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29
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Jaspe RC, Zambrano JL, Hidalgo M, Sulbarán Y, Loureiro CL, Moros ZC, Garzaro DJ, Liprandi F, Rangel HR, Pujol FH. Detection of the Omicron variant of SARS-CoV-2 by restriction analysis targeting the mutations K417N and N440K of the spike protein. INVESTIGACIÓN CLÍNICA 2022. [DOI: 10.54817/ic.v63n1a08] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
By the end of 2021, the Omicron variant of concern (VOC) emerges in South Africa. This variant caused immediate concern, due to the explosive increase in cases associated with it and the large number of mutations it exhibits. In this study, the restriction sites that allow detecting the mutations K417N and N440K in the Spike gene are described. This analysis allows us to propose a rapid method for the identification of cases infected with the Omicron variant. We show that the proposed methodology can contribute to provide more information on the prevalence and rapid detection of cases of this new VOC.
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Affiliation(s)
- Rossana C Jaspe
- Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela
| | - José Luis Zambrano
- Laboratorio de Biología de Virus, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela
| | - Mariana Hidalgo
- Laboratorio de Inmunoparasitología, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela
| | - Yoneira Sulbarán
- Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela
| | - Carmen L Loureiro
- Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela
| | - Zoila C Moros
- Laboratorio de Biología de Virus, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela
| | - Domingo J Garzaro
- Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela
| | - Ferdinando Liprandi
- Laboratorio de Biología de Virus, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela
| | - Héctor R Rangel
- Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela
| | - Flor H Pujol
- Laboratorio de Virología Molecular, Centro de Microbiología y Biología Celular, Instituto Venezolano de Investigaciones Científicas, Caracas, Venezuela
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30
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Churiso G, Diriba K, Girma H, Tafere S. Clinical Features and Time to Recovery of Admitted COVID-19 Cases at Dilla University Referral Hospital Treatment Center, South Ethiopia. Infect Drug Resist 2022; 15:795-806. [PMID: 35281575 PMCID: PMC8904438 DOI: 10.2147/idr.s356606] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2022] [Accepted: 02/15/2022] [Indexed: 12/23/2022] Open
Abstract
Background Since coronavirus disease 2019 emergence, millions were infected and many were dying because of the virus. Clinical features and time to recovery of admitted clients vary across settings. Therefore showing clinical features and recovery time from COVID-19 in a different setting is necessary to design appropriate treatment and preventive measures. So, this study attempted to investigate the clinical features and time to recovery of admitted clients to Dilla University Referral Hospital treatment center, Ethiopia. Methods A retrospective study design was conducted in 220 patients confirmed by real time polymerase chain reaction and admitted to Dilla University Referral Hospital treatment center from September 2020 to July 2021. Data were collected from the patients' record. Data entry was done by an Epi-Info version 7.2.1.0 and analyzed by Statistical Package for the Social Sciences version 25 software. Descriptive statistics were used for clinical features, and median time to recovery was computed by using Kaplan-Meier. Results Common clinical features were cough 209 (95%), shortness of breath 153 (69.5%), fever 133 (60.5%), headache 75 (34.1%), easy fatigue 68 (30.9%), joint pain 56 (25.5%), tachypnea 197 (89.5%), hypoxia 95 (43.2%), and tachycardia 83 (37.7%). The overall median recovery time for admitted cases was 5 days. There was significant difference between recovery probability of severe and moderate cases, severe and mild cases (p=0.00), who had normal body temperature and hypothermic (p=0.05), who had normal breathing rate and bradypnea patients (p= 0.014). Conclusion COVID-19 patients frequently show cough, shortness of breath, fever, headache, easy fatigue and joint pain. Median time to recovery was 5 days. Having a normal body temperature, normal breathing rate, and severe disease status had statistically significant association with median recovery time. So, close follow up is required for client admitted with severe disease.
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Affiliation(s)
- Gemechu Churiso
- Department of Medical Laboratory Sciences, Dilla University, Dilla, Ethiopia
| | - Kuma Diriba
- Department of Medical Laboratory Sciences, Dilla University, Dilla, Ethiopia
| | - Henok Girma
- Ohio State University, Global One Health Initiative, Dilla, Ethiopia
| | - Soressa Tafere
- COVID-19 Treatment Center, Dilla University, Dilla, Ethiopia
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Karattuthodi MS, Chandrasekher D, Panakkal LM, C S, Salman M, E MS, Fasil M, A M M, Reji M. Pharmacist-directed Sputnik V (GAM-COVID-VAC) surveillance program: a prospective observational study in Southern India. J Basic Clin Physiol Pharmacol 2022; 0:jbcpp-2021-0345. [PMID: 35172420 DOI: 10.1515/jbcpp-2021-0345] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 01/26/2022] [Indexed: 06/14/2023]
Abstract
OBJECTIVES The study underwent to evaluate the adverse events, the incidence of COVID-19 and the participant's attitude and perception towards the vaccine following Sputnik V administration through an active surveillance program. METHODS The prospective observational study was conducted four months in the Sputnik V vaccination center that enrolled 700 participants. Sociodemographic details, medical histories, COVID-19 incidences and adverse events following immunization (AEFI) of each sample were collected through face-to-face interviews and a telephonic feedback system. A self-prepared and validated questionnaire addressed their acceptances and perceptions towards the vaccination drive. RESULTS Our study reported 42.1% of AEFIs after the first dose and 9.1% after the second. Fever, pain at the injection site, body pain, headache and fatigue were predominant, while dizziness and diarrhoea were rare. However, AEFIs were not influenced by the presence of comorbidities (p > 0.05). On the other hand, there were limited post immunization (1.8%) COVID-19 patients and that too with minor severity (p < 0.01). Our participants were overall satisfied with the Sputnik V immunization. However, those presented with AEFIs on the consecutive three days depicted slightly declined gratification (p < 0.05). CONCLUSIONS Our pharmacist-directed surveillance program on Sputnik V showed fewer events of AEFIs and negligible occurrence of COVID19 following immunization. Moreover, the population had appreciable attitude and positive perceptions towards Sputnik V vaccination.
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Affiliation(s)
- Mohammed Salim Karattuthodi
- Department of Pharmacy Practice, Al Shifa College of Pharmacy, Kerala University of Health Sciences, Kizhattoor, Kerala, India
| | - Dilip Chandrasekher
- Department of Pharmacy Practice, Al Shifa College of Pharmacy, Kerala University of Health Sciences, Kizhattoor, Kerala, India
| | - Linu Mohan Panakkal
- Department of Pharmacy Practice, Al Shifa College of Pharmacy, Kerala University of Health Sciences, Kizhattoor, Kerala, India
| | - Shinu C
- Department of Pharmacy Practice, Al Shifa College of Pharmacy, Kerala University of Health Sciences, Kizhattoor, Kerala, India
| | - Mohammed Salman
- Department of Pharmacy Practice, Al Shifa College of Pharmacy, Kerala University of Health Sciences, Kizhattoor, Kerala, India
| | - Muhammad Swabeeh E
- Department of Pharmacy Practice, Al Shifa College of Pharmacy, Kerala University of Health Sciences, Kizhattoor, Kerala, India
| | - Mohamed Fasil
- Department of Pharmacy Practice, Al Shifa College of Pharmacy, Kerala University of Health Sciences, Kizhattoor, Kerala, India
| | - Mohammad A M
- Department of Pharmacy Practice, Al Shifa College of Pharmacy, Kerala University of Health Sciences, Kizhattoor, Kerala, India
| | - Monika Reji
- Department of Pharmacy Practice, Al Shifa College of Pharmacy, Kerala University of Health Sciences, Kizhattoor, Kerala, India
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Parra-Lucares A, Segura P, Rojas V, Pumarino C, Saint-Pierre G, Toro L. Emergence of SARS-CoV-2 Variants in the World: How Could This Happen? Life (Basel) 2022; 12:194. [PMID: 35207482 PMCID: PMC8879166 DOI: 10.3390/life12020194] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 01/23/2022] [Accepted: 01/25/2022] [Indexed: 12/12/2022] Open
Abstract
The COVID-19 pandemic has had a significant global impact, with more than 280,000,000 people infected and 5,400,000 deaths. The use of personal protective equipment and the anti-SARS-CoV-2 vaccination campaigns have reduced infection and death rates worldwide. However, a recent increase in infection rates has been observed associated with the appearance of SARS-CoV-2 variants, including the more recently described lineage B.1.617.2 (Delta variant) and lineage B.1.1.529/BA.1 (Omicron variant). These new variants put the effectiveness of international vaccination at risk, with the appearance of new outbreaks of COVID-19 throughout the world. This emergence of new variants has been due to multiple predisposing factors, including molecular characteristics of the virus, geographic and environmental conditions, and the impact of social determinants of health that favor the genetic diversification of SARS-CoV-2. We present a literature review on the most recent information available on the emergence of new variants of SARS-CoV-2 in the world. We analyzed the biological, geographical, and sociocultural factors that favor the development of these variants. Finally, we evaluate the surveillance strategies for the early detection of new variants and prevent their distribution outside these regions.
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Affiliation(s)
- Alfredo Parra-Lucares
- Division of Critical Care Medicine, Department of Medicine, Hospital Clínico Universidad de Chile, 8380456 Santiago, Chile; (A.P.-L.); (V.R.)
| | - Paula Segura
- Department of Anatomic Pathology, Hospital Clínico Universidad de Chile, 8380456 Santiago, Chile;
| | - Verónica Rojas
- Division of Critical Care Medicine, Department of Medicine, Hospital Clínico Universidad de Chile, 8380456 Santiago, Chile; (A.P.-L.); (V.R.)
- Centro de Investigación Clínica Avanzada, Hospital Clínico Universidad de Chile, 8380456 Santiago, Chile
| | - Catalina Pumarino
- School of Medicine, Faculty of Medicine, Universidad de Chile, 8380456 Santiago, Chile;
| | - Gustavo Saint-Pierre
- Microbiology Unit, Clinical Laboratory, Hospital Clínico Universidad de Chile, 8380456 Santiago, Chile;
| | - Luis Toro
- Centro de Investigación Clínica Avanzada, Hospital Clínico Universidad de Chile, 8380456 Santiago, Chile
- Division of Nephrology, Department of Medicine, Hospital Clínico Universidad de Chile, 8380456 Santiago, Chile
- Critical Care Unit, Clínica Las Condes, 7591047 Santiago, Chile
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Islam S, Islam T, Islam MR. New Coronavirus Variants are Creating More Challenges to Global Healthcare System: A Brief Report on the Current Knowledge. CLINICAL PATHOLOGY (THOUSAND OAKS, VENTURA COUNTY, CALIF.) 2022; 15:2632010X221075584. [PMID: 35141522 PMCID: PMC8819824 DOI: 10.1177/2632010x221075584] [Citation(s) in RCA: 77] [Impact Index Per Article: 25.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/05/2021] [Accepted: 01/05/2022] [Indexed: 12/16/2022]
Abstract
The coronavirus is naturally mutating over time and producing new variants. Some of them are more contagious and destructive than previous strains. Also, some variants are capable of therapeutic escaping. Earlier SARS-CoV-2 variants proved that some are supercritical, and newly mutated strains are creating new challenges to the global healthcare systems. Here we aimed to evaluate different coronavirus variants and associated challenges for healthcare systems. We searched for information online and on the PubMed, Scopus, and Embase databases. We found the wild-type virus is more sensitive for neutralization and more controllable than newer variants. The Delta and Omicron variants are more highly transmissible than Alpha, Beta, and Gamma variants. Also, few strains are resistant to neutralization. Therefore, there is a chance of reinfection among the vaccinated population. The transmissibility and resistance of the recently identified Omicron variant is still unclear. The Delta variant is the most dangerous among all variants due to its high transmissibility, disease severity, and mortality rate. For poor and developing countries, oxygen supply, medication, vaccination, and device supply are challenging during epidemic waves. Slowing down the transmission, mass vaccination, vaccine redesign, re-compiling action plans, and following safety guidelines can be effective solutions to the new challenges.
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Affiliation(s)
| | | | - Md. Rabiul Islam
- Department of Pharmacy, University of Asia Pacific,
Dhaka, Bangladesh
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34
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Islam S, Islam T, Islam MR. New Coronavirus Variants are Creating More Challenges to Global Healthcare System: A Brief Report on the Current Knowledge. CLINICAL PATHOLOGY (THOUSAND OAKS, VENTURA COUNTY, CALIF.) 2022. [PMID: 35141522 DOI: 10.1177/2632010x2210755846] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 03/06/2023]
Abstract
The coronavirus is naturally mutating over time and producing new variants. Some of them are more contagious and destructive than previous strains. Also, some variants are capable of therapeutic escaping. Earlier SARS-CoV-2 variants proved that some are supercritical, and newly mutated strains are creating new challenges to the global healthcare systems. Here we aimed to evaluate different coronavirus variants and associated challenges for healthcare systems. We searched for information online and on the PubMed, Scopus, and Embase databases. We found the wild-type virus is more sensitive for neutralization and more controllable than newer variants. The Delta and Omicron variants are more highly transmissible than Alpha, Beta, and Gamma variants. Also, few strains are resistant to neutralization. Therefore, there is a chance of reinfection among the vaccinated population. The transmissibility and resistance of the recently identified Omicron variant is still unclear. The Delta variant is the most dangerous among all variants due to its high transmissibility, disease severity, and mortality rate. For poor and developing countries, oxygen supply, medication, vaccination, and device supply are challenging during epidemic waves. Slowing down the transmission, mass vaccination, vaccine redesign, re-compiling action plans, and following safety guidelines can be effective solutions to the new challenges.
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Affiliation(s)
- Salsabil Islam
- Department of Pharmacy, University of Asia Pacific, Dhaka, Bangladesh
| | - Towhidul Islam
- Department of Pharmacy, University of Asia Pacific, Dhaka, Bangladesh
| | - Md Rabiul Islam
- Department of Pharmacy, University of Asia Pacific, Dhaka, Bangladesh
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Jacob Machado D, White RA, Kofsky J, Janies DA. Fundamentals of genomic epidemiology, lessons learned from the coronavirus disease 2019 (COVID-19) pandemic, and new directions. ANTIMICROBIAL STEWARDSHIP & HEALTHCARE EPIDEMIOLOGY : ASHE 2021; 1:e60. [PMID: 36168505 PMCID: PMC9495640 DOI: 10.1017/ash.2021.222] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Accepted: 10/15/2021] [Indexed: 04/19/2023]
Abstract
The coronavirus disease 2019 (COVID-19) pandemic was one of the significant causes of death worldwide in 2020. The disease is caused by severe acute coronavirus syndrome (SARS) coronavirus 2 (SARS-CoV-2), an RNA virus of the subfamily Orthocoronavirinae related to 2 other clinically relevant coronaviruses, SARS-CoV and MERS-CoV. Like other coronaviruses and several other viruses, SARS-CoV-2 originated in bats. However, unlike other coronaviruses, SARS-CoV-2 resulted in a devastating pandemic. The SARS-CoV-2 pandemic rages on due to viral evolution that leads to more transmissible and immune evasive variants. Technology such as genomic sequencing has driven the shift from syndromic to molecular epidemiology and promises better understanding of variants. The COVID-19 pandemic has exposed critical impediments that must be addressed to develop the science of pandemics. Much of the progress is being applied in the developed world. However, barriers to the use of molecular epidemiology in low- and middle-income countries (LMICs) remain, including lack of logistics for equipment and reagents and lack of training in analysis. We review the molecular epidemiology literature to understand its origins from the SARS epidemic (2002-2003) through influenza events and the current COVID-19 pandemic. We advocate for improved genomic surveillance of SARS-CoV and understanding the pathogen diversity in potential zoonotic hosts. This work will require training in phylogenetic and high-performance computing to improve analyses of the origin and spread of pathogens. The overarching goals are to understand and abate zoonosis risk through interdisciplinary collaboration and lowering logistical barriers.
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Affiliation(s)
- Denis Jacob Machado
- University of North Carolina at Charlotte, College of Computing and Informatics, Department of Bioinformatics and Genomics, Charlotte, North Carolina
| | - Richard Allen White
- University of North Carolina at Charlotte, College of Computing and Informatics, Department of Bioinformatics and Genomics, Charlotte, North Carolina
- University of North Carolina at Charlotte, North Carolina Research Campus (NCRC), Kannapolis, North Carolina
| | - Janice Kofsky
- University of North Carolina at Charlotte, College of Computing and Informatics, Department of Bioinformatics and Genomics, Charlotte, North Carolina
| | - Daniel A. Janies
- University of North Carolina at Charlotte, College of Computing and Informatics, Department of Bioinformatics and Genomics, Charlotte, North Carolina
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Parums DV. Editorial: SARS-CoV-2 Vaccine Responses and Breakthrough COVID-19. Med Sci Monit 2021; 27:e935624. [PMID: 34848673 PMCID: PMC8647456 DOI: 10.12659/msm.935624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
In 2021, data from global disease monitoring and infection surveillance programs have shown that vaccination programs have reduced the incidence of SARS-CoV-2 infection and hospitalization and mortality rates. Currently, the US Centers for Disease Control and Prevention (CDC) identifies a fully vaccinated individual as being ≥14 days after the completion of all the recommended doses of a COVID-19 vaccine that has been authorized by the US Food and Drug Administration (FDA). A partially vaccinated individual is <14 days following primary vaccination or has not completed the vaccination program. Clinical studies and data on the vaccine status of populations have identified breakthrough COVID-19 cases in fully vaccinated individuals at 14 or more days after completing the recommended dose of an authorized SARS-CoV-2 vaccine. This Editorial presents an update on what has been learned in the past year on SARS-CoV-2 vaccine responses and breakthrough COVID-19.
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Affiliation(s)
- Dinah V Parums
- Scientific Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA
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Tao K, Tzou PL, Nouhin J, Gupta RK, de Oliveira T, Kosakovsky Pond SL, Fera D, Shafer RW. The biological and clinical significance of emerging SARS-CoV-2 variants. Nat Rev Genet 2021; 22:757-773. [PMID: 34535792 PMCID: PMC8447121 DOI: 10.1038/s41576-021-00408-x] [Citation(s) in RCA: 680] [Impact Index Per Article: 170.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/28/2021] [Indexed: 12/13/2022]
Abstract
The past several months have witnessed the emergence of SARS-CoV-2 variants with novel spike protein mutations that are influencing the epidemiological and clinical aspects of the COVID-19 pandemic. These variants can increase rates of virus transmission and/or increase the risk of reinfection and reduce the protection afforded by neutralizing monoclonal antibodies and vaccination. These variants can therefore enable SARS-CoV-2 to continue its spread in the face of rising population immunity while maintaining or increasing its replication fitness. The identification of four rapidly expanding virus lineages since December 2020, designated variants of concern, has ushered in a new stage of the pandemic. The four variants of concern, the Alpha variant (originally identified in the UK), the Beta variant (originally identified in South Africa), the Gamma variant (originally identified in Brazil) and the Delta variant (originally identified in India), share several mutations with one another as well as with an increasing number of other recently identified SARS-CoV-2 variants. Collectively, these SARS-CoV-2 variants complicate the COVID-19 research agenda and necessitate additional avenues of laboratory, epidemiological and clinical research.
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Affiliation(s)
- Kaiming Tao
- Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA, USA
| | - Philip L Tzou
- Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA, USA
| | - Janin Nouhin
- Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA, USA
| | - Ravindra K Gupta
- Cambridge Institute for Therapeutic Immunology and Infectious Diseases, University of Cambridge, Cambridge, UK
| | - Tulio de Oliveira
- KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), University of KwaZulu-Natal, Durban, South Africa
| | | | - Daniela Fera
- Department of Chemistry and Biochemistry, Swarthmore College, Swarthmore, PA, USA
| | - Robert W Shafer
- Division of Infectious Diseases, Department of Medicine, Stanford University, Stanford, CA, USA.
- Department of Pathology, Stanford University, Stanford, CA, USA.
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Khandelwal N, Chander Y, Kumar R, Nagori H, Verma A, Mittal P, T R, Kamboj S, Verma SS, Khatreja S, Pal Y, Gulati BR, Tripathi BN, Barua S, Kumar N. Studies on Growth Characteristics and Cross-Neutralization of Wild-Type and Delta SARS-CoV-2 From Hisar (India). Front Cell Infect Microbiol 2021; 11:771524. [PMID: 34888260 PMCID: PMC8650692 DOI: 10.3389/fcimb.2021.771524] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2021] [Accepted: 11/02/2021] [Indexed: 11/28/2022] Open
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly evolved to generate several antigenic variants. These variants have raised concerns whether pre-existing immunity to vaccination or prior infection would be able to protect against the newly emerging SARS-CoV-2 variants or not. We isolated SARS-CoV-2 from the coronavirus disease 2019 (COVID-19)-confirmed patients in the beginning of the first (April/May 2020) and second (April/May 2021) waves of COVID-19 in India (Hisar, Haryana). Upon complete nucleotide sequencing, the viruses were found to be genetically related with wild-type (WT) and Delta variants of SARS-CoV-2, respectively. The Delta variant of SARS-CoV-2 produced a rapid cytopathic effect (24-36 h as compared to 48-72 h in WT) and had bigger plaque size but a shorter life cycle (~6 h as compared to the ~8 h in WT). Furthermore, the Delta variant achieved peak viral titers within 24 h as compared to the 48 h in WT. These evidence suggested that the Delta variant replicates significantly faster than the WT SARS-CoV-2. The virus neutralization experiments indicated that antibodies elicited by vaccination are more efficacious in neutralizing the WT virus but significantly less potent against the Delta variant. Our findings have implications in devising suitable vaccination, diagnostic and therapeutic strategies, besides providing insights into understanding virus replication and transmission.
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Affiliation(s)
- Nitin Khandelwal
- Virology Laboratory, National Centre for Veterinary Type Cultures, ICAR-National Research Centre on Equines, Hisar, India
| | - Yogesh Chander
- Virology Laboratory, National Centre for Veterinary Type Cultures, ICAR-National Research Centre on Equines, Hisar, India
| | - Ram Kumar
- Virology Laboratory, National Centre for Veterinary Type Cultures, ICAR-National Research Centre on Equines, Hisar, India
| | - Himanshu Nagori
- Virology Laboratory, National Centre for Veterinary Type Cultures, ICAR-National Research Centre on Equines, Hisar, India
| | - Assim Verma
- Virology Laboratory, National Centre for Veterinary Type Cultures, ICAR-National Research Centre on Equines, Hisar, India
| | - Priyasi Mittal
- Virology Laboratory, National Centre for Veterinary Type Cultures, ICAR-National Research Centre on Equines, Hisar, India
| | - Riyesh T
- Virology Laboratory, National Centre for Veterinary Type Cultures, ICAR-National Research Centre on Equines, Hisar, India
| | | | | | | | - Yash Pal
- Virology Laboratory, National Centre for Veterinary Type Cultures, ICAR-National Research Centre on Equines, Hisar, India
| | - Baldev R Gulati
- Virology Laboratory, National Centre for Veterinary Type Cultures, ICAR-National Research Centre on Equines, Hisar, India
| | - Bhupendra N Tripathi
- Virology Laboratory, National Centre for Veterinary Type Cultures, ICAR-National Research Centre on Equines, Hisar, India
| | - Sanjay Barua
- Virology Laboratory, National Centre for Veterinary Type Cultures, ICAR-National Research Centre on Equines, Hisar, India
| | - Naveen Kumar
- Virology Laboratory, National Centre for Veterinary Type Cultures, ICAR-National Research Centre on Equines, Hisar, India
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Parums DV. Editorial: First Full Regulatory Approval of a COVID-19 Vaccine, the BNT162b2 Pfizer-BioNTech Vaccine, and the Real-World Implications for Public Health Policy. Med Sci Monit 2021; 27:e934625. [PMID: 34483336 PMCID: PMC8434768 DOI: 10.12659/msm.934625] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
In the past 18 months, accelerated vaccine development to prevent or reduce the severity of coronavirus disease 2019 (COVID-19) has resulted in rapid global emergency regulatory approvals, including the US Food and Drug Administration (FDA) emergency use authorization (EUA) approvals. On August 23, 2021, the US FDA gave the first full regulatory approval for a COVID-19 vaccine and approved the Pfizer-BioNTech COVID-19 vaccine (Comirnaty) for individuals 16 years and older. In the US, there is a continued EUA for individuals aged 12–15 years of age. Also, the EUA includes the administration of a third or booster dose in immunocompromised individuals at increased risk for severe COVID-19. This Editorial aims to present an update on the first COVID-19 vaccine to receive full regulatory approval, the Pfizer-BioNTech vaccine, and the implications for real-world public health during the global COVID-19 pandemic and increasing concerns for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern.
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Affiliation(s)
- Dinah V Parums
- Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA
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Parums DV. Editorial: Reporting Clinical Trials with Important Modifications Due to Extenuating Circumstances, Including the COVID-19 Pandemic: CONSERVE 2021. Med Sci Monit 2021; 27:e934514. [PMID: 34456331 PMCID: PMC8415037 DOI: 10.12659/msm.934514] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
During 2020 and 2021, the COVID-19 pandemic has resulted in interruptions and cancellations of clinical trials and has delayed drug development in all areas except SARS-CoV-2 vaccine development. A further concern is the need to rapidly share anonymized datasets and improve opportunities to conduct randomized clinical trials (RCTs) in low-resource developing countries, particularly for oncology trials and for other infectious diseases. The Consolidated Standards of Reporting Trials (CONSORT) 2010 and the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2013 currently guide the reporting of trial protocols and completed RCTs, respectively. Extenuating circumstances or unavoidable situations may occur that are beyond the control of study sponsors and investigators. On June 21, 2021, the CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstance (CONSERVE) was published. The scope of CONSERVE 2021 includes modifications that have substantive implications for the feasibility, ethical conduct, scientific content, and study analysis. This Editorial aims to provide the background to CONSERVE 2021 and show how these guidelines may reduce the number of clinical trials currently being paused or discontinued due to the COVID-19 pandemic, particularly in poorly resourced and developing countries.
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Affiliation(s)
- Dinah V Parums
- Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA
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Sütlüoğlu H, Özdemir Ö. May mesenchymal stem cell transplantation be a solution for COVID-19 induced cytokine storm? World J Transplant 2021; 11:344-355. [PMID: 34447671 PMCID: PMC8371495 DOI: 10.5500/wjt.v11.i8.344] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 06/16/2021] [Accepted: 08/10/2021] [Indexed: 02/06/2023] Open
Abstract
The recently emergent disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), transmitted by droplets and aerosols, was named coronavirus disease 2019 (COVID-19) by World Health Organization. Predominantly, the disease progress is asymptomatic or mild, but one-fifth of the patients advance to severe or critical illness. In severe COVID-19 patients, type-2 T helper cells release numerous cytokines; this excessive immune response is named as cytokine storm. The cytokine storm, which is the hallmark of the COVID-19 induced by the disease and aggravates due to lack of proper immune response, similar to SARS and Middle East respiratory syndrome (MERS), and the disease status may progress forward to acute respiratory distress syndrome (ARDS), systemic inflammatory response syndrome, multi-organ dysfunction syndrome, and death. Mesenchymal stromal cell transplantation is up-and-coming in treating many diseases such as HIV, hepatitis B, influenza, coronavirus diseases (SARS, MERS), lung injuries, and ARDS. Upon closer inspection on respiratory diseases, COVID-19, influenza, SARS, and MERS have similarities in pathogenesis, especially cytokine and immune response profiles. These comparable features in terms of the cytokine storm will provide hints for the treatment of COVID-19.
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Affiliation(s)
- Hüseyin Sütlüoğlu
- Faculty of Medicine, Sakarya University, Adapazarı 54100, Sakarya, Turkey
| | - Öner Özdemir
- Division of Pediatric Allergy and Immunology, Sakarya University Medical Faculty, Adapazarı 54100, Sakarya, Turkey
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Parums DV. Editorial: Post-Exposure Prophylactic Neutralizing Monoclonal Antibodies to SARS-CoV-2 for Individuals at High Risk for COVID-19. Med Sci Monit 2021; 27:e934393. [PMID: 34393218 PMCID: PMC8378223 DOI: 10.12659/msm.934393] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Regulatory authorities, including the US Food and Drug Administration (FDA), have accelerated diagnostic and therapeutic approvals during the coronavirus disease 2019 (COVID-19) pandemic. Accelerated clinical development and approvals have resulted in vaccine programs for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, some individuals remain at high risk for the progression of COVID-19. In the US, the FDA has given Emergency Use Authorization (EUA) for two neutralizing therapeutic monoclonal antibody 'cocktails,' casirivimab and imdevimab (REGEN-COV), bamlanivimab and etesevimab, and one monotherapy, bamlanivimab, for prophylactic post-exposure therapy in individuals at high risk of progressing to severe COVID-19. Preclinical and clinical studies showed consistent effectiveness of REGEN-COV against current variants of SARS-CoV-2. On 21st November 2020, the FDA approved an initial EUA for REGEN-COV to treat mild to moderate COVID-19 in adults and in children 12 years or older with exposure to SARS-CoV-2 at high risk for progression to severe COVID-19. On 30th July 2021, the FDA updated its EUA for REGEN-COV for emergency use as post-exposure prophylactic to prevent COVID-19 progression in adults and children aged 12 years or older. This Editorial aims to provide an update on accelerated regulatory authorization for post-exposure prophylactic neutralizing monoclonal antibodies to SARS-CoV-2 for individuals at high risk for COVID-19.
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Affiliation(s)
- Dinah V Parums
- Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA
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Parums DV. Editorial: Tocilizumab, a Humanized Therapeutic IL-6 Receptor (IL-6R) Monoclonal Antibody, and Future Combination Therapies for Severe COVID-19. Med Sci Monit 2021; 27:e933973. [PMID: 34276042 PMCID: PMC8299871 DOI: 10.12659/msm.933973] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2021] [Accepted: 07/12/2021] [Indexed: 12/15/2022] Open
Abstract
Vaccinated, non-vaccinated, and immunosuppressed individuals will continue to be infected with SARS-CoV-2. Therefore, there is a priority to develop treatments that reduce the severity of COVID-19 in patients who require hospital admission. Interleukin-6 (IL-6) is a proinflammatory cytokine. In 2011, a humanized monoclonal antibody to the IL-6 receptor (IL-6R), tocilizumab, was approved by the US Food and Drug Administration (FDA) for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, giant cell arteritis, and Castleman's disease. In 2017, tocilizumab was approved to treat chimeric antigen receptor (CAR) T-cell therapy-induced cytokine release syndrome (CRS). In 2021, the results of the REMAP-CAP clinical trial (NCT02735707) and the COVID-19 Therapy (RECOVERY) clinical trial (NCT04381936) supported FDA Emergency Use Authorization (EUA) for tocilizumab to treat hospitalized patients with moderate and severe COVID-19. Monoclonal antibodies are currently in clinical development or undergoing clinical trials to treat COVID-19. Further clinical trials will provide safety and efficacy data on targeting IL-6 and IL-6R and provide rationales for more personalized combination treatments to control the systemic effects of SARS-CoV-2 infection in hospitalized patients with moderate and severe COVID-19. This Editorial aims to present the background to the recent authorization of tocilizumab, a humanized therapeutic monoclonal antibody to the IL-6 receptor (IL-6R), for hospitalized patients with moderate and severe COVID-19 and future combination therapies.
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Affiliation(s)
- Dinah V Parums
- Science Editor, Medical Science Monitor, International Scientific Information, Inc., Mellville, NY, USA
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Parums DV. Editorial: Maternal SARS-CoV-2 Infection and Pregnancy Outcomes from Current Global Study Data. Med Sci Monit 2021; 27:e933831. [PMID: 34219126 PMCID: PMC8268975 DOI: 10.12659/msm.933831] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Accepted: 07/02/2021] [Indexed: 12/18/2022] Open
Abstract
During the global COVID-19 pandemic, data from clinical studies, systematic review, and population registry data have shown that when compared with non-pregnant women, SARS-CoV-2 infection in pregnancy is associated with a small increase in risk to the mother. Large cohort studies and registry data collected from 2020 have included the US Surveillance for Emerging Threats to Mothers and Babies Network (SET-NET), COVI-PREG, the UK and Global Pregnancy and Neonatal Outcomes in COVID-19 (PAN-COVID) study, the American Academy of Pediatrics (AAP) Section on Neonatal-Perinatal Medicine (SONPM) National Perinatal COVID-19 Registry, the Swedish Pregnancy Register, and the Canadian Surveillance of COVID-19 in Pregnancy (CANCOVID-Preg) registry. Recently published data have shown that most maternal infections with SARS-CoV-2 occur during the third trimester and result in a small increase in hospital admission, admission to the intensive care unit (ICU), mechanical ventilation, preterm birth, and increased cesarean sections in mothers infected with SARS-CoV-2. However, currently approved vaccines given in pregnancy result in an immune response to current SARS-CoV-2 variants. Transplacental transmission of SARS-CoV-2 to the fetus can occur, but the immediate and long-term effects on the newborn infant remain unclear. Therefore, women who are pregnant or planning a pregnancy should be managed according to current clinical guidelines with timely vaccination to prevent infection with SARS-CoV-2. This Editorial summarizes what is currently known about maternal SARS-CoV-2 infection and pregnancy outcomes from multinational studies.
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Affiliation(s)
- Dinah V Parums
- Science Editor, Medical Science Monitor, International Scientific Information, Inc., Mellville, NY, USA
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