Topic Editors

Dr. Joan Puig-Barberà
Vaccines Research Area FISABIO, 46020 Valencia, Spain
Dr. María Lourdes Guerrero
Departamento de Infectología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Tlalpan, Mexico
Prof. Dr. Anna Sominina
Research Institute of Influenza, Saint Petersburg, Russian
Dr. Svetlana V. Trushakova
D.I. Ivanovsky Institute of Virology FGBC “N.F., Gamaleya FRCEM” Ministry of Health of Russian Federation, Moscow, Russian
Dr. F. Xavier López-Labrador
Virology Laboratory, Genomics and Health Area, FISABIO - Center for Public Health Research, Generalitat Valenciana, Spain

Acute Respiratory Viruses Molecular Epidemiology

Abstract submission deadline
closed (31 August 2022)
Manuscript submission deadline
31 December 2022
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Topic Information

Dear Colleagues,

The COVID-19 pandemic has introduced the use of the molecular epidemiology of viral pathogens to support public health decision-making on the centre stage. Molecular epidemiology has been already central to influenza surveillance in the last ten years, to derive the influenza vaccine composition and interpret real-world vaccine effectiveness. The molecular epidemiology of other respiratory viruses is emerging as a tool to improve public health, providing insights into virus seasonality, age-related susceptibility, disease severity, viral load and transmission. Virus genome sequencing, combined with metadata, provides evidence not only for outbreak investigations, regional, national and international epidemiological trends, but also for the study of a potential viral escape to natural or vaccine-induced immunity. With the expanding scale of whole-genome pathogen sequencing, new analytical challenges arise regarding how and when to apply these technologies. We are looking for manuscripts on the molecular epidemiology of acute respiratory viruses that report the results of studies conducted prior to and during the current SARS-CoV-2 pandemic and the post-pandemic period. We aim to publish evidence on critical aspects of transmission, geographic dispersion, virulence, immune escape, and the impact on the effectiveness of available vaccines, diagnostics and therapeutics.

Dr. Joan Puig-Barberà
Dr. María Lourdes Guerrero
Prof. Dr. Anna Sominina
Dr. Svetlana V. Trushakova
Dr. F. Xavier López-Labrador
Topic Editors

Keywords

  • acute respiratory viruses / epidemiology*
  • acute respiratory viruses / genetics*
  • base sequence / genetics
  • clinical decision-making
  • disease outbreaks*
  • epidemiological monitoring*
  • genome, viral / genetics*
  • humans
  • molecular epidemiology / methods*
  • phylogenetic analyses
  • public health
  • RNA, viral / genetics*
  • viral load/methods
  • virulence
  • whole genome sequencing

Participating Journals

Journal Name Impact Factor CiteScore Launched Year First Decision (median) APC
COVID
covid
- - 2021 16.7 Days 1000 CHF Submit
International Journal of Molecular Sciences
ijms
6.208 6.9 2000 15.9 Days 2300 CHF Submit
Pathogens
pathogens
4.531 3.5 2012 16 Days 2200 CHF Submit
Toxins
toxins
5.075 6.6 2009 14.8 Days 2400 CHF Submit
Viruses
viruses
5.818 6.6 2009 16.9 Days 2400 CHF Submit

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Published Papers (21 papers)

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Article
Characterisation of RSV Fusion Proteins from South African Patients with RSV Disease, 2019 to 2020
Viruses 2022, 14(11), 2321; https://doi.org/10.3390/v14112321 - 22 Oct 2022
Abstract
Respiratory syncytial virus (RSV) is classified into RSV-A and RSV-B, which are further classified into genotypes based on variability in the G gene. The fusion (F) protein is highly conserved; however, variability within antigenic sites has been reported. This study aimed to characterise [...] Read more.
Respiratory syncytial virus (RSV) is classified into RSV-A and RSV-B, which are further classified into genotypes based on variability in the G gene. The fusion (F) protein is highly conserved; however, variability within antigenic sites has been reported. This study aimed to characterise F proteins from RSV strains detected in South Africa from 2019 to 2020. Patients of all ages, from whom respiratory samples were submitted to the National Health Laboratory Service at Charlotte Maxeke Johannesburg Academic Hospital, South Africa during 2019 to 2020, were included. Complete RSV F genes were amplified for next-generation sequencing. MEGA X software was used for phylogenetic analysis. The overall prevalence of RSV was 5.8% (101/1734). Among 101 RSV positive samples only 69.3% (70/101) were available for characterization of the RSV F protein gene. Among cases included for F gene characterisation, viral co-infections were observed in 50% (35/70) and 25.7% (18/70) were admitted to intensive care units (ICU). About 74.2% (23/31) of F gene sequences cluster with other African NA1/ON1 genotypes. At antigenic site I, the V384I mutation was replaced by V384T in South African strains. The S275F mutation was seen in a single South African strain. The N120 N-linked glycosylation site was present in 25.8% (8/31) of RSV-A F proteins described in this study. For the first time, we detected the rare S275F mutation that is associated with palivizumab resistance. Full article
(This article belongs to the Topic Acute Respiratory Viruses Molecular Epidemiology)
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Article
Epidemiological and Phylogeographic Study of Equid Herpesviruses in Tunisia
Pathogens 2022, 11(9), 1016; https://doi.org/10.3390/pathogens11091016 - 05 Sep 2022
Abstract
Equid herpesvirus (EHV) is a contagious viral disease affecting horses, causing illness characterized by respiratory symptoms, abortion and neurological disorders. It is common worldwide and causes severe economic losses to the equine industry. The present study was aimed at investigating the incidence of [...] Read more.
Equid herpesvirus (EHV) is a contagious viral disease affecting horses, causing illness characterized by respiratory symptoms, abortion and neurological disorders. It is common worldwide and causes severe economic losses to the equine industry. The present study was aimed at investigating the incidence of EHVs, the genetic characterization of Tunisian isolates and a spatiotemporal study, using 298 collected samples from diseased and clinically healthy horses. The global incidence of EHV infection was found to be about 71.81%. EHV2 and EHV5 were detected in 146 (48.99%) and 159 (53.35%) sampled horses, respectively. EHV1 was detected in 11 samples (3.69%); EHV4 was not detected. Co-infections with EHV1-EHV2, EHV1-EHV5 and EHV2-EHV5 were observed in 0.33%, 1.34% and 31.54% of tested horses, respectively. Phylogenetic analyses showed that gB of EHV2 and EHV5 displays high genetic diversity with a nucleotide sequence identity ranging from 88 to 100% for EHV2 and 97.5 to 100% for EHV5. Phylogeography suggested Iceland and USA as the most likely countries of origin of the Tunisian EHV2 and EHV5 isolates. These viruses detected in Tunisia seemed to be introduced in the 2000s. This first epidemiological and phylogeographic study is important for better knowledge of the evolution of equid herpesvirus infections in Tunisia. Full article
(This article belongs to the Topic Acute Respiratory Viruses Molecular Epidemiology)
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Article
From Alpha to Delta—Genetic Epidemiology of SARS-CoV-2 (hCoV-19) in Southern Poland
Pathogens 2022, 11(7), 780; https://doi.org/10.3390/pathogens11070780 - 08 Jul 2022
Abstract
In Poland, the first case of SARS-CoV-2 infection was confirmed in March 2020. Since then, many circulating virus lineages fueled rapid pandemic waves which inflicted a severe burden on the Polish healthcare system. Some of these lineages were associated with increased transmissibility and [...] Read more.
In Poland, the first case of SARS-CoV-2 infection was confirmed in March 2020. Since then, many circulating virus lineages fueled rapid pandemic waves which inflicted a severe burden on the Polish healthcare system. Some of these lineages were associated with increased transmissibility and immune escape. Mutations in the viral spike protein, which is responsible for host cell recognition and serves as the primary target for neutralizing antibodies, are of particular importance. We investigated the molecular epidemiology of the SARS-CoV-2 clades circulating in Southern Poland from February 2021 to August 2021. The 921 whole-genome sequences were used for variant identification, spike mutation, and phylogenetic analyses. The Pango B.1.1.7 was the dominant variant (n = 730, 89.68%) from March 2021 to July 2021. In July 2021, the B.1.1.7 was displaced by the B.1.617.2 lineage with 66.66% in July 2021 and 92.3% in August 2021 frequencies, respectively. Moreover, our results were compared with the sequencing available on the GISAID platform for other regions of Poland, the Czech Republic, and Slovakia. The analysis showed that the dominant variant in the analyzed period was B.1.1.7 in all countries and Southern Poland (Silesia). Interestingly, B.1.1.7 was replaced by B.1.617.2 earlier in Southern Poland than in the rest of the country. Moreover, in the Czech Republic and Slovakia, AY lineages were predominant at that time, contrary to the Silesia region. Full article
(This article belongs to the Topic Acute Respiratory Viruses Molecular Epidemiology)
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Article
Genomic Epidemiology of SARS-CoV-2 in Seychelles, 2020–2021
Viruses 2022, 14(6), 1318; https://doi.org/10.3390/v14061318 - 16 Jun 2022
Cited by 2
Abstract
Seychelles, an archipelago of 155 islands in the Indian Ocean, had confirmed 24,788 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the 31st of December 2021. The first SARS-CoV-2 cases in Seychelles were reported on the 14th of March 2020, but [...] Read more.
Seychelles, an archipelago of 155 islands in the Indian Ocean, had confirmed 24,788 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the 31st of December 2021. The first SARS-CoV-2 cases in Seychelles were reported on the 14th of March 2020, but cases remained low until January 2021, when a surge was observed. Here, we investigated the potential drivers of the surge by genomic analysis of 1056 SARS-CoV-2 positive samples collected in Seychelles between 14 March 2020 and 31 December 2021. The Seychelles genomes were classified into 32 Pango lineages, 1042 of which fell within four variants of concern, i.e., Alpha, Beta, Delta and Omicron. Sporadic cases of SARS-CoV-2 detected in Seychelles in 2020 were mainly of lineage B.1 (lineage predominantly observed in Europe) but this lineage was rapidly replaced by Beta variant starting January 2021, and which was also subsequently replaced by the Delta variant in May 2021 that dominated till November 2021 when Omicron cases were identified. Using the ancestral state reconstruction approach, we estimated that at least 78 independent SARS-CoV-2 introduction events occurred in Seychelles during the study period. The majority of viral introductions into Seychelles occurred in 2021, despite substantial COVID-19 restrictions in place during this period. We conclude that the surge of SARS-CoV-2 cases in Seychelles in January 2021 was primarily due to the introduction of more transmissible SARS-CoV-2 variants into the islands. Full article
(This article belongs to the Topic Acute Respiratory Viruses Molecular Epidemiology)
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Review
Potential Antiviral Strategy Exploiting Dependence of SARS-CoV-2 Replication on Lysosome-Based Pathway
Int. J. Mol. Sci. 2022, 23(11), 6188; https://doi.org/10.3390/ijms23116188 - 31 May 2022
Cited by 1
Abstract
The recent novel coronavirus (SARS-CoV-2) disease (COVID-19) outbreak created a severe public health burden worldwide. Unfortunately, the SARS-CoV-2 variant is still spreading at an unprecedented speed in many countries and regions. There is still a lack of effective treatment for moderate and severe [...] Read more.
The recent novel coronavirus (SARS-CoV-2) disease (COVID-19) outbreak created a severe public health burden worldwide. Unfortunately, the SARS-CoV-2 variant is still spreading at an unprecedented speed in many countries and regions. There is still a lack of effective treatment for moderate and severe COVID-19 patients, due to a lack of understanding of the SARS-CoV-2 life cycle. Lysosomes, which act as “garbage disposals” for nearly all types of eukaryotic cells, were shown in numerous studies to support SARS-CoV-2 replication. Lysosome-associated pathways are required for virus entry and exit during replication. In this review, we summarize experimental evidence demonstrating a correlation between lysosomal function and SARS-CoV-2 replication, and the development of lysosomal perturbation drugs as anti-SARS-CoV-2 agents. Full article
(This article belongs to the Topic Acute Respiratory Viruses Molecular Epidemiology)
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Article
Dynamics of Variants of Concern (VOC) of SARS-CoV-2 during the Different Waves of COVID-19 in Senegal
COVID 2022, 2(6), 691-702; https://doi.org/10.3390/covid2060052 - 30 May 2022
Abstract
Background: In Senegal, the incidence of SARS-CoV-2 evolved with four successive epidemic waves. The first wave started in March 2020 with low virus variability, whilst the second outbreak, which started in December 2020, was dominated by the Alpha variant. The third wave took [...] Read more.
Background: In Senegal, the incidence of SARS-CoV-2 evolved with four successive epidemic waves. The first wave started in March 2020 with low virus variability, whilst the second outbreak, which started in December 2020, was dominated by the Alpha variant. The third wave took place in June 2021, and the fourth at the end of November 2021. Our interest was to investigate the involvement of variants of concern during these four waves and to track the viral diversity of SARS-CoV-2. Methodology: During the four waves of the pandemic, 276,876 nasopharyngeal swabs were analyzed at the Institut de Recherche en Santé, de Surveillance Epidémiologique et de Formation (IRESSEF). Of these, 22,558 samples tested positive for SARS-CoV-2 by RT-PCR. Then, the virus genomes were sequenced in 817 positive samples using the ARTIC Network of Oxford Nanopore Technologies (ONT). In addition, 10% of the negative samples in RT-PCR new variants were also targeted for the detection of new and previously undescribed variants. Results: Our data have overall shown that the Senegalese strains are very similar to each other or closely related to other strains, such as Gambia, France etc. During the first wave, the most common clade found was 19A (67.5%) and a majority of the samples were of the B.1 (50%) lineage. We noted more diversity during the second wave where clade 20A (38.4%) was more frequent, followed by clade 20B (31.52%) and 20I (9.74%). At the level of lineages, we identified variants of concern as B.1.1.7 (9.74%) and B.1.617.2 (0.86%). In the third wave, we observed at the clade level with mainly 21A (32.63%) and 21J (16.84%). During the fourth wave at the end of November 2021, we mainly identified clade 21K Omicron variant 21K (B.1.1.529 and BA.1) (80.47%) and Delta variant (21A, 21J, and 21I) (AY.103, AY.122, AY.122.1, AY.26, AY.34, AY.36, AY.4, AY.48, AY.57, AY.61, and AY.87) (14.06%). Impact: SARS-CoV-2 diversity may affect the virus’s properties, such as how it spreads, disease severity, or the performance of vaccines, tools, or other public health and social measures. Therefore, such tracking of SARS-CoV-2 variants is not only of public interest, but also highlights the role some African institutes such as IRESSEF with surveillance capabilities through the real-time sequencing of SARS-CoV-2 genomes in the local context. Conclusion: In Senegal, the SARS-CoV-2 pandemic has disrupted the organization of the health system. IRESSEF contributed to put in place strategies to respond effectively to the expectations of medical authorities by providing them with data on the strains circulating in Senegal at each moment of the epidemic. Full article
(This article belongs to the Topic Acute Respiratory Viruses Molecular Epidemiology)
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Article
A Hierarchical Genotyping Framework Using DNA Melting Temperatures Applied to Adenovirus Species Typing
Int. J. Mol. Sci. 2022, 23(10), 5441; https://doi.org/10.3390/ijms23105441 - 13 May 2022
Abstract
Known genetic variation, in conjunction with post-PCR melting curve analysis, can be leveraged to provide increased taxonomic detail for pathogen identification in commercial molecular diagnostic tests. Increased taxonomic detail may be used by clinicians and public health decision-makers to observe circulation patterns, monitor [...] Read more.
Known genetic variation, in conjunction with post-PCR melting curve analysis, can be leveraged to provide increased taxonomic detail for pathogen identification in commercial molecular diagnostic tests. Increased taxonomic detail may be used by clinicians and public health decision-makers to observe circulation patterns, monitor for outbreaks, and inform testing practices. We propose a method for expanding the taxonomic resolution of PCR diagnostic systems by incorporating a priori knowledge of assay design and sequence information into a genotyping classification model. For multiplexed PCR systems, this framework is generalized to incorporate information from multiple assays to increase classification accuracy. An illustrative hierarchical classification model for human adenovirus (HAdV) species was developed and demonstrated ~95% cross-validated accuracy on a labeled dataset. The model was then applied to a near-real-time surveillance dataset in which deidentified adenovirus detected patient test data from 2018 through 2021 were classified into one of six adenovirus species. These results show a marked change in both the predicted prevalence for HAdV and the species makeup with the onset of the COVID-19 pandemic. HAdV-B decreased from a pre-pandemic predicted prevalence of up to 40% to less than 5% in 2021, while HAdV-A and HAdV-F species both increased in predicted prevalence. Full article
(This article belongs to the Topic Acute Respiratory Viruses Molecular Epidemiology)
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Article
Imported SARS-CoV-2 Variants of Concern Drove Spread of Infections across Kenya during the Second Year of the Pandemic
COVID 2022, 2(5), 586-598; https://doi.org/10.3390/covid2050044 - 05 May 2022
Cited by 2
Abstract
Using classical and genomic epidemiology, we tracked the COVID-19 pandemic in Kenya over 23 months to determine the impact of SARS-CoV-2 variants on its progression. SARS-CoV-2 surveillance and testing data were obtained from the Kenya Ministry of Health, collected daily from 306 health [...] Read more.
Using classical and genomic epidemiology, we tracked the COVID-19 pandemic in Kenya over 23 months to determine the impact of SARS-CoV-2 variants on its progression. SARS-CoV-2 surveillance and testing data were obtained from the Kenya Ministry of Health, collected daily from 306 health facilities. COVID-19-associated fatality data were also obtained from these health facilities and communities. Whole SARS-CoV-2 genome sequencing were carried out on 1241 specimens. Over the pandemic duration (March 2020–January 2022), Kenya experienced five waves characterized by attack rates (AR) of between 65.4 and 137.6 per 100,000 persons, and intra-wave case fatality ratios (CFR) averaging 3.5%, two-fold higher than the national average COVID-19 associated CFR. The first two waves that occurred before emergence of global variants of concerns (VoC) had lower AR (65.4 and 118.2 per 100,000). Waves 3, 4, and 5 that occurred during the second year were each dominated by multiple introductions each, of Alpha (74.9% genomes), Delta (98.7%), and Omicron (87.8%) VoCs, respectively. During this phase, government-imposed restrictions failed to alleviate pandemic progression, resulting in higher attack rates spread across the country. In conclusion, the emergence of Alpha, Delta, and Omicron variants was a turning point that resulted in widespread and higher SARS-CoV-2 infections across the country. Full article
(This article belongs to the Topic Acute Respiratory Viruses Molecular Epidemiology)
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Communication
SARS-CoV-2 Delta VOC in a Paucisymptomatic Dog, Italy
Pathogens 2022, 11(5), 514; https://doi.org/10.3390/pathogens11050514 - 26 Apr 2022
Abstract
Since the very beginning of the COVID-19 pandemic, SARS-CoV-2 detection has been described in several animal species. A total of 625 outbreaks in animals have been reported globally, affecting 17 species in 32 countries and the human source of infection has been recognized [...] Read more.
Since the very beginning of the COVID-19 pandemic, SARS-CoV-2 detection has been described in several animal species. A total of 625 outbreaks in animals have been reported globally, affecting 17 species in 32 countries and the human source of infection has been recognized including pet owners, zookeepers, and farmers. In this report, we describe the case of a paucisymptomatic dog in Italy infected with SARS-CoV-2 from a household with three confirmed human cases of COVID-19 living in Pesaro (Marche region, Italy). The dog showed high viral RNA titers in the nasal and oropharyngeal swabs. In the nasal swab, SARS-CoV-2 RNA lasted for a least a week. By sequencing, the strain was assigned to the AY.23 lineage (PANGO), one of the sub-lineages of the major SARS-CoV-2 Delta variant of concern (VOC). Although we did not process the swabs of the three human cases, we strongly suspect a human origin for the dog infection. In this regard, AY.23 sequences, although never released thus far in the Marche region, were detected in the neighboring regions. Our findings highlight once more the need for a One Health approach for SARS-CoV-2 surveillance, management, and control, thus preventing viral spillover from animals to humans. Full article
(This article belongs to the Topic Acute Respiratory Viruses Molecular Epidemiology)
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Review
The Cytokine Storm in COVID-19: The Strongest Link to Morbidity and Mortality in the Current Epidemic
COVID 2022, 2(5), 540-552; https://doi.org/10.3390/covid2050040 - 25 Apr 2022
Cited by 3
Abstract
COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. The clinical presentations of the SARS-CoV-2 infection are widely variable and treatment strategies for COVID-19 are dependent on the infection phase. Timing the right treatment for the right phase of this disease is [...] Read more.
COVID-19 is an infectious disease caused by the SARS-CoV-2 virus. The clinical presentations of the SARS-CoV-2 infection are widely variable and treatment strategies for COVID-19 are dependent on the infection phase. Timing the right treatment for the right phase of this disease is paramount, with correlations detected between the phase of the infection and the type of drug used to treat. The immune system activation following COVID-19 infection can further develop to a fulminant cytokine storm which can progress to acute respiratory distress syndrome. The inflammatory phase, or the hyperinflammation phase, is a later stage when patients develop acute respiratory distress syndrome (ARDS), sepsis, and kidney and other organ failure. In this stage, the virus is probably not necessary and all the damage is due to the immune system’s cytokine storm. Immunosuppressive or immunomodulatory agent administration is the major strategy in treating COVID-19 patients at this stage. On the other hand, immunodeficient patients who are treated with immunomodulator agents have attenuated immune systems that do not produce enough cytokines. Current data do not show an increased risk of severe COVID-19 in patients taking biologic therapies or targeted disease-modifying antirheumatic drugs. However, more comprehensive studies are needed to assess the effect of these medications, and whether they may actually be protective of the severe type of disease. Although medications for COVID-19 and for the cytokine storm are important, the main breakthrough in slowing down the pandemic was developing effective vaccines. These vaccines showed a dramatic result in reducing morbidity and mortality up to the Delta variant’s spread. However, the emergence of the new variant, Omicron, influenced the successful results we had before. This variant is more contagious but less dangerous than Delta. The aim now is to develop vaccines based on the Omicron and Delta immunogens in the future for broad protection against different variants. Full article
(This article belongs to the Topic Acute Respiratory Viruses Molecular Epidemiology)
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Brief Report
Recent Zoonotic Spillover and Tropism Shift of a Canine Coronavirus Is Associated with Relaxed Selection and Putative Loss of Function in NTD Subdomain of Spike Protein
Viruses 2022, 14(5), 853; https://doi.org/10.3390/v14050853 - 21 Apr 2022
Abstract
A canine coronavirus (CCoV) has now been reported from two independent human samples from Malaysia (respiratory, collected in 2017–2018; CCoV-HuPn-2018) and Haiti (urine, collected in 2017); these two viruses were nearly genetically identical. In an effort to identify any novel adaptations associated with [...] Read more.
A canine coronavirus (CCoV) has now been reported from two independent human samples from Malaysia (respiratory, collected in 2017–2018; CCoV-HuPn-2018) and Haiti (urine, collected in 2017); these two viruses were nearly genetically identical. In an effort to identify any novel adaptations associated with this apparent shift in tropism we carried out detailed evolutionary analyses of the spike gene of this virus in the context of related Alphacoronavirus 1 species. The spike 0-domain retains homology to CCoV2b (enteric infections) and Transmissible Gastroenteritis Virus (TGEV; enteric and respiratory). This domain is subject to relaxed selection pressure and an increased rate of molecular evolution. It contains unique amino acid substitutions, including within a region important for sialic acid binding and pathogenesis in TGEV. Overall, the spike gene is extensively recombinant, with a feline coronavirus type II strain serving a prominent role in the recombinant history of the virus. Molecular divergence time for a segment of the gene where temporal signal could be determined, was estimated at around 60 years ago. We hypothesize that the virus had an enteric origin, but that it may be losing that particular tropism, possibly because of mutations in the sialic acid binding region of the spike 0-domain. Full article
(This article belongs to the Topic Acute Respiratory Viruses Molecular Epidemiology)
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Commentary
Explain Again: Why Are We Vaccinating Young Children against COVID-19?
COVID 2022, 2(4), 492-500; https://doi.org/10.3390/covid2040036 - 12 Apr 2022
Cited by 1
Abstract
Public trust in governmental policies concerning public health measures is often now questioned. This is an acute problem with respect to vaccinations and particularly true regarding concerns around vaccination of children. Vaccination against COVID-19 is a particularly acute issue with many conspiracy theories [...] Read more.
Public trust in governmental policies concerning public health measures is often now questioned. This is an acute problem with respect to vaccinations and particularly true regarding concerns around vaccination of children. Vaccination against COVID-19 is a particularly acute issue with many conspiracy theories circulating. These can almost certainly be countered by a strong evidence base. However, what if a policy is not based on strong evidence but on a judgement call? There is a strong evidence base concerning the beneficial and lifesaving attributes of immunization of adult and particularly vulnerable elderly groups against COVID-19. But what about young children? Here the benefit of immunization is not borne out by any publicly available data and would appear to be led by opinion, not evidence. The language used and vague statements giving a public justification for childhood vaccination COVID-19 immunization could be interpreted as misleading. Given a prevailing mistrust of government public health mandates, could these policies discourage childhood immunization and cost lives of children from other diseases? Full article
(This article belongs to the Topic Acute Respiratory Viruses Molecular Epidemiology)
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Review
How Do Point Mutations Enhancing the Basic Character of the RBDs of SARS-CoV-2 Variants Affect Their Transmissibility and Infectivity Capacities?
Viruses 2022, 14(4), 783; https://doi.org/10.3390/v14040783 - 10 Apr 2022
Cited by 3
Abstract
The spread of SARS-CoV-2 variants in the population depends on their ability to anchor the ACE2 receptor in the host cells. Differences in the electrostatic potentials of the spike protein RBD (electropositive/basic) and ACE2 receptor (electronegative/acidic) play a key role in both the [...] Read more.
The spread of SARS-CoV-2 variants in the population depends on their ability to anchor the ACE2 receptor in the host cells. Differences in the electrostatic potentials of the spike protein RBD (electropositive/basic) and ACE2 receptor (electronegative/acidic) play a key role in both the rapprochement and the recognition of the coronavirus by the cell receptors. Accordingly, point mutations that result in an increase in electropositively charged residues, e.g., arginine and lysine, especially in the RBD of spike proteins in the SARS-CoV-2 variants, could contribute to their spreading capacity by favoring their recognition by the electronegatively charged ACE2 receptors. All SARS-CoV-2 variants that have been recognized as being highly transmissible, such as the kappa (κ), delta (δ) and omicron (o) variants, which display an enhanced electropositive character in their RBDs associated with a higher number of lysine- or arginine-generating point mutations. Lysine and arginine residues also participate in the enhanced RBD–ACE2 binding affinity of the omicron variant, by creating additional salt bridges with aspartic and glutamic acid residues from ACE2. However, the effects of lysine- and arginine-generating point mutations on infectivity is more contrasted, since the overall binding affinity of omicron RBD for ACE2 apparently results from some epistasis among the whole set of point mutations. Full article
(This article belongs to the Topic Acute Respiratory Viruses Molecular Epidemiology)
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Article
Transportin-3 Facilitates Uncoating of Influenza A Virus
Int. J. Mol. Sci. 2022, 23(8), 4128; https://doi.org/10.3390/ijms23084128 - 08 Apr 2022
Cited by 1
Abstract
Influenza A viruses (IAVs) are a major global health threat and in the future, may cause the next pandemic. Although studies have partly uncovered the molecular mechanism of IAV–host interaction, it requires further research. In this study, we explored the roles of transportin-3 [...] Read more.
Influenza A viruses (IAVs) are a major global health threat and in the future, may cause the next pandemic. Although studies have partly uncovered the molecular mechanism of IAV–host interaction, it requires further research. In this study, we explored the roles of transportin-3 (TNPO3) in IAV infection. We found that TNPO3-deficient cells inhibited infection with four different IAV strains, whereas restoration of TNPO3 expression in knockout (KO) cells restored IAV infection. TNPO3 overexpression in wild-type (WT) cells promoted IAV infection, suggesting that TNPO3 is involved in the IAV replication. Furthermore, we found that TNPO3 depletion restrained the uncoating in the IAV life cycle, thereby inhibiting the process of viral ribonucleoprotein (vRNP) entry into the nucleus. However, KO of TNPO3 did not affect the virus attachment, endocytosis, or endosomal acidification processes. Subsequently, we found that TNPO3 can colocalize and interact with viral proteins M1 and M2. Taken together, the depletion of TNPO3 inhibits IAV uncoating, thereby inhibiting IAV replication. Our study provides new insights and potential therapeutic targets for unraveling the mechanism of IAV replication and treating influenza disease. Full article
(This article belongs to the Topic Acute Respiratory Viruses Molecular Epidemiology)
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Article
Identification of Entry Inhibitors against Delta and Omicron Variants of SARS-CoV-2
Int. J. Mol. Sci. 2022, 23(7), 4050; https://doi.org/10.3390/ijms23074050 - 06 Apr 2022
Cited by 5
Abstract
Entry inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed to control the outbreak of coronavirus disease 2019 (COVID-19). This study developed a robust and straightforward assay that detected the molecular interaction between the receptor-binding domain (RBD) of viral spike [...] Read more.
Entry inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed to control the outbreak of coronavirus disease 2019 (COVID-19). This study developed a robust and straightforward assay that detected the molecular interaction between the receptor-binding domain (RBD) of viral spike protein and the angiotensin-converting enzyme 2 (ACE2) receptor in just 10 min. A drug library of 1068 approved compounds was used to screen for SARS-CoV2 entry inhibition, and 9 active drugs were identified as specific pseudovirus entry inhibitors. A plaque reduction neutralization test using authentic SARS-CoV-2 virus in Vero E6 cells confirmed that 2 of these drugs (Etravirine and Dolutegravir) significantly inhibited the infection of SARS-CoV-2. With molecular docking, we showed that both Etravirine and Dolutegravir are preferentially bound to primary ACE2-interacting residues on the RBD domain, implying that these two drug blocks may prohibit the viral attachment of SARS-CoV-2. We compared the neutralizing activities of these entry inhibitors against different pseudoviruses carrying spike proteins from alpha, beta, gamma, and delta variants. Both Etravirine and Dolutegravir showed similar neutralizing activities against different variants, with EC50 values between 4.5 to 5.8 nM for Etravirine and 10.2 to 22.9 nM for Dolutegravir. These data implied that Etravirine and Dolutegravir may serve as general spike inhibitors against dominant viral variants of SARS-CoV-2. Full article
(This article belongs to the Topic Acute Respiratory Viruses Molecular Epidemiology)
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Article
Exercising the Sanger Sequencing Strategy for Variants Screening and Full-Length Genome of SARS-CoV-2 Virus during Alpha, Delta, and Omicron Outbreaks in Hiroshima
Viruses 2022, 14(4), 720; https://doi.org/10.3390/v14040720 - 30 Mar 2022
Cited by 1
Abstract
This study aimed to exercise the Sanger sequencing strategy for screening of variants among confirmed COVID-19 cases and validate our strategy against NGS strains in Hiroshima retrieved from GISAID. A total of 660 samples from confirmed COVID-19 cases underwent screening for variants by [...] Read more.
This study aimed to exercise the Sanger sequencing strategy for screening of variants among confirmed COVID-19 cases and validate our strategy against NGS strains in Hiroshima retrieved from GISAID. A total of 660 samples from confirmed COVID-19 cases underwent screening for variants by Sanger-based partial sequencing to the targeted spike gene (nt22,735~nt23,532) using an in-house-developed primer set. The identification of variants was done by unique checkpoints of base nucleotide changes in the targeted spike gene. Moreover, we amplified one full-length genome using Sanger method and an in-house-developed primer library. Using NGS strains of the same sampling period from GISAID, a phylogenetic tree was constructed to examine the distribution pattern of variants in Hiroshima and to validate our Sanger method. The modified primer set provided 100% validation and 99.2% amplification. PANGO Lineage R.1 was detected in late in the third wave, followed by Alpha (B.1.1.7) domination in the fourth wave, Delta (B.1.617.2) domination in the fifth wave, and Omicron (B.1.1.529) domination in the sixth wave, and there was no significant difference in viral copies between variants (p = 0.09). The variants showed different transmission patterns, but the distribution of variants is consistent to that shown by the phylogenetic tree. The Sanger method also provided successful amplification of the full-length genome of the SARS-CoV-2 virus. Our Sanger sequencing strategy was useful for the screening of SASR-CoV-2 variants without the need for full-genome amplification. The modified primer set was validated to use universally, which allows an understanding of the variants’ distribution in real time and provides the evidence for policy-making and the formulation or modification of preventive strategies. Full article
(This article belongs to the Topic Acute Respiratory Viruses Molecular Epidemiology)
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Article
Emergence of Two Distinct SARS-CoV-2 Gamma Variants and the Rapid Spread of P.1-like-II SARS-CoV-2 during the Second Wave of COVID-19 in Santa Catarina, Southern Brazil
Viruses 2022, 14(4), 695; https://doi.org/10.3390/v14040695 - 27 Mar 2022
Cited by 3
Abstract
The western mesoregion of the state of Santa Catarina (SC), Southern Brazil, was heavily affected as a whole by the COVID-19 pandemic in early 2021. This study aimed to evaluate the dynamics of the SARS-CoV-2 virus spreading patterns in the SC state from [...] Read more.
The western mesoregion of the state of Santa Catarina (SC), Southern Brazil, was heavily affected as a whole by the COVID-19 pandemic in early 2021. This study aimed to evaluate the dynamics of the SARS-CoV-2 virus spreading patterns in the SC state from March 2020 to April 2021 using genomic surveillance. During this period, there were 23 distinct variants, including Beta and Gamma, among which the Gamma and related lineages were predominant in the second pandemic wave within SC. A regionalization of P.1-like-II in the Western SC region was observed, concomitant to the increase in cases, mortality, and the case fatality rate (CFR) index. This is the first evidence of the regionalization of the SARS-CoV-2 transmission in SC and it highlights the importance of tracking the variants, dispersion, and impact of SARS-CoV-2 on the public health systems. Full article
(This article belongs to the Topic Acute Respiratory Viruses Molecular Epidemiology)
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Article
An Upgrade on the Surveillance System of SARS-CoV-2: Deployment of New Methods for Genetic Inspection
Int. J. Mol. Sci. 2022, 23(6), 3143; https://doi.org/10.3390/ijms23063143 - 15 Mar 2022
Abstract
SARS-CoV-2 variants surveillance is a worldwide task that has been approached with techniques such as Next Generation Sequencing (NGS); however, this technology is not widely available in developing countries because of the lack of equipment and limited funding in science. An option is [...] Read more.
SARS-CoV-2 variants surveillance is a worldwide task that has been approached with techniques such as Next Generation Sequencing (NGS); however, this technology is not widely available in developing countries because of the lack of equipment and limited funding in science. An option is to deploy a RT-qPCR screening test which aids in the analysis of a higher number of samples, in a shorter time and at a lower cost. In this study, variants present in samples positive for SARS-CoV-2 were identified with a RT-qPCR mutation screening kit and were later confirmed by NGS. A sample with an abnormal result was found with the screening test, suggesting the simultaneous presence of two viral populations with different mutations. The DRAGEN Lineage analysis identified the Delta variant, but there was no information about the other three mutations previously detected. When the sequenced data was deeply analyzed, there were reads with differential mutation patterns, that could be identified and classified in terms of relative abundance, whereas only the dominant population was reported by DRAGEN software. Since most of the software developed to analyze SARS-CoV-2 sequences was aimed at obtaining the consensus sequence quickly, the information about viral populations within a sample is scarce. Here, we present a faster and deeper SARS-CoV-2 surveillance method, from RT-qPCR screening to NGS analysis. Full article
(This article belongs to the Topic Acute Respiratory Viruses Molecular Epidemiology)
Article
Emotional Distress and Associated Factors among the General Population during the COVID-19 Pandemic in China: A Nationwide Cross-Sectional Survey
COVID 2022, 2(3), 261-272; https://doi.org/10.3390/covid2030021 - 09 Mar 2022
Abstract
Objective: This study investigated emotional distress and associated factors among the general population in the aftermath of the COVID-19 lockdown in China. Design and sample: An online nationwide survey was conducted using a self-designed questionnaire, which included items related to demography, lifestyle, and [...] Read more.
Objective: This study investigated emotional distress and associated factors among the general population in the aftermath of the COVID-19 lockdown in China. Design and sample: An online nationwide survey was conducted using a self-designed questionnaire, which included items related to demography, lifestyle, and experience of emotional distress during the previous month of the pandemic period. A total of 10,545 respondents completed the survey. Results: Over 30% of participants reported experiencing one or more symptoms of emotional distress to a moderate or higher degree. Increased emotional distress was associated with COVID-19-related impact on diet (β = −1.106, 95% CI: −1.187 to −1.026, p < 0.001), experiencing food shortage (β = 1.334, 95% CI: 1.117 to 1.551, p < 0.001), lack of physical exercise (β = −0.845, 95% CI: −1.024 to −0.667, p < 0.001), younger age (β = −0.050, 95% CI: −0.062 to −0.039, p < 0.001), being a smoker (β = 0.852, 95% CI: 0.604 to 1.100, p < 0.001), lower education level (β = −0.524, 95% CI: −0.702 to −0.346, p < 0.001), and lack of medical insurance (β = −0.742, 95% CI: −1.012 to −0.473, p < 0.001). Emotional distress was negatively associated time spent sleeping (β = −0.020, 95% CI: −0.027 to −0.013, p < 0.001). Conclusion: The levels of emotional distress are high in the aftermath of the lockdown and associated with a number of demographic and lifestyle factors. Full article
(This article belongs to the Topic Acute Respiratory Viruses Molecular Epidemiology)
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Article
Differential Peripheral Blood Glycoprotein Profiles in Symptomatic and Asymptomatic COVID-19
Viruses 2022, 14(3), 553; https://doi.org/10.3390/v14030553 - 07 Mar 2022
Abstract
Glycosylation is the most common form of post-translational modification of proteins, critically affecting their structure and function. Using liquid chromatography and mass spectrometry for high-resolution site-specific quantification of glycopeptides coupled with high-throughput artificial intelligence-powered data processing, we analyzed differential protein glycoisoform distributions of [...] Read more.
Glycosylation is the most common form of post-translational modification of proteins, critically affecting their structure and function. Using liquid chromatography and mass spectrometry for high-resolution site-specific quantification of glycopeptides coupled with high-throughput artificial intelligence-powered data processing, we analyzed differential protein glycoisoform distributions of 597 abundant serum glycopeptides and nonglycosylated peptides in 50 individuals who had been seriously ill with COVID-19 and in 22 individuals who had recovered after an asymptomatic course of COVID-19. As additional comparison reference phenotypes, we included 12 individuals with a history of infection with a common cold coronavirus, 16 patients with bacterial sepsis, and 15 healthy subjects without history of coronavirus exposure. We found statistically significant differences, at FDR < 0.05, for normalized abundances of 374 of the 597 peptides and glycopeptides interrogated between symptomatic and asymptomatic COVID-19 patients. Similar statistically significant differences were seen when comparing symptomatic COVID-19 patients to healthy controls (350 differentially abundant peptides and glycopeptides) and common cold coronavirus seropositive subjects (353 differentially abundant peptides and glycopeptides). Among healthy controls and sepsis patients, 326 peptides and glycopeptides were found to be differentially abundant, of which 277 overlapped with biomarkers that showed differential expression between symptomatic COVID-19 cases and healthy controls. Among symptomatic COVID-19 cases and sepsis patients, 101 glycopeptide and peptide biomarkers were found to be statistically significantly abundant. Using both supervised and unsupervised machine learning techniques, we found specific glycoprotein profiles to be strongly predictive of symptomatic COVID-19 infection. LASSO-regularized multivariable logistic regression and K-means clustering yielded accuracies of 100% in an independent test set and of 96% overall, respectively. Our findings are consistent with the interpretation that a majority of glycoprotein modifications observed which are shared among symptomatic COVID-19 and sepsis patients likely represent a generic consequence of a severe systemic immune and inflammatory state. However, there are glycoisoform changes that are specific and particular to severe COVID-19 infection. These may be representative of either COVID-19-specific consequences or susceptibility to or predisposition for a severe course of the disease. Our findings support the potential value of glycoproteomic biomarkers in the biomedical understanding and, potentially, the clinical management of serious acute infectious conditions. Full article
(This article belongs to the Topic Acute Respiratory Viruses Molecular Epidemiology)
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Review
Biosensors for the Determination of SARS-CoV-2 Virus and Diagnosis of COVID-19 Infection
Int. J. Mol. Sci. 2022, 23(2), 666; https://doi.org/10.3390/ijms23020666 - 08 Jan 2022
Cited by 25
Abstract
Monitoring and tracking infection is required in order to reduce the spread of the coronavirus disease 2019 (COVID-19), induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To achieve this goal, the development and deployment of quick, accurate, and sensitive diagnostic methods are [...] Read more.
Monitoring and tracking infection is required in order to reduce the spread of the coronavirus disease 2019 (COVID-19), induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To achieve this goal, the development and deployment of quick, accurate, and sensitive diagnostic methods are necessary. The determination of the SARS-CoV-2 virus is performed by biosensing devices, which vary according to detection methods and the biomarkers which are inducing/providing an analytical signal. RNA hybridisation, antigen-antibody affinity interaction, and a variety of other biological reactions are commonly used to generate analytical signals that can be precisely detected using electrochemical, electrochemiluminescence, optical, and other methodologies and transducers. Electrochemical biosensors, in particular, correspond to the current trend of bioanalytical process acceleration and simplification. Immunosensors are based on the determination of antigen-antibody interaction, which on some occasions can be determined in a label-free mode with sufficient sensitivity. Full article
(This article belongs to the Topic Acute Respiratory Viruses Molecular Epidemiology)
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