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With the continuous emergence of coronavirus disease 2019 (COVID-19) waves, the scientific community has developed a vaccine that offers broad-spectrum protection at virus-targeted organs for inhibiting the transmission and protection of disease development. In the present study, a bivalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine containing receptor-binding domain (RBD) protein of spike from Wuhan-1 and omicron BA.1 loaded in nanoparticles, bivalent RBD NPs, was developed. The immunogenicity and protective efficacy of this vaccine candidate were evaluated using an in vivo model. Results showed that mice that received intranasal cGAMP-adjuvanted bivalent RBD-NPs vaccine elicited robust and durable antibody responses. The stimulated antibody broadly neutralized the ancestral strain and variants of concerns (delta and omicron BA.1) in the upper and lower respiratory tracts. Furthermore, the immunized mice developed T-cell response in their lung tissue. Importantly, intranasal immunization with this vaccine candidate efficiently protected mice from nasal infection caused by both Wuhan-1 and BA.1 viruses. Immunized mice that remained susceptible to nasal infection did not develop any symptoms. This is because activated responses in the nasal cavity significantly suppressed virus production. Another word is this nasal vaccine completely protected the mice from disease development and mortality. Therefore, the bivalent RBD vaccine platform has potential to be developed into an anti-SARS-CoV-2 universal vaccine. [ABSTRACT FROM AUTHOR]

Background: Estimation of the SARS-CoV-2 incubation time distribution is hampered by incomplete data about infection. We discuss two biases that may result from incorrect handling of such data. Notified cases may recall recent exposures more precisely (differential recall). This creates bias if the analysis is restricted to observations with well-defined exposures, as longer incubation times are more likely to be excluded. Another bias occurred in the initial estimates based on data concerning travellers from Wuhan. Only individuals who developed symptoms after their departure were included, leading to under-representation of cases with shorter incubation times (left truncation). This issue was not addressed in the analyses performed in the literature. Methods: We performed simulations and provide a literature review to investigate the amount of bias in estimated percentiles of the SARS-CoV-2 incubation time distribution. Results: Depending on the rate of differential recall, restricting the analysis to a subset of narrow exposure windows resulted in underestimation in the median and even more in the 95th percentile. Failing to account for left truncation led to an overestimation of multiple days in both the median and the 95th percentile. Conclusion: We examined two overlooked sources of bias concerning exposure information that the researcher engaged in incubation time estimation needs to be aware of. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID‐19) caused by the severe acute respiratory syndrome coronavirus 2n first appeared in Wuhan, China in 2019. Soon after, it was declared a pandemic by the World Health Organization. The health crisis imposed by a new virus and its rapid spread worldwide prompted the fast development of vaccines. For the first time in human history, two vaccines based on recombinant genetic material technology were approved for human use. These mRNA vaccines were applied in massive immunization programs around the world, followed by other vaccines based on more traditional approaches. Even though all vaccines were tested in clinical trials prior to their general administration, serious adverse events, usually of very low incidence, were mostly identified after application of millions of doses. Establishing a direct correlation (the cause‐effect paradigm) between vaccination and the appearance of adverse effects has proven challenging. This review focuses on the main adverse effects observed after vaccination, including anaphylaxis, myocarditis, vaccine‐induced thrombotic thrombocytopenia, Guillain–Barré syndrome, and transverse myelitis reported in the context of COVID‐19 vaccination. We highlight the symptoms, laboratory tests required for an adequate diagnosis, and briefly outline the recommended treatments for these adverse effects. The aim of this work is to increase awareness among healthcare personnel about the serious adverse events that may arise post‐vaccination. Regardless of the ongoing discussion about the safety of COVID‐19 vaccination, these adverse effects must be identified promptly and treated effectively to reduce the risk of complications. [ABSTRACT FROM AUTHOR]

The Omicron BA.5 variant of SARS-CoV-2 is known for its high transmissibility and its capacity to evade immunity provided by vaccine protection against the (original) Wuhan strain. In our prior research, we successfully produced the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein in an E. coli expression system. Extensive biophysical characterization indicated that, even without glycosylation, the RBD maintained native-like conformational and biophysical properties. The current study explores the immunogenicity and neutralization capacity of the E. coli-expressed Omicron BA.5 RBD using a mouse model. Administration of three doses of the RBD without any adjuvant elicited high titer antisera of up to 7.3 × 105 and up to 1.6 × 106 after a booster shot. Immunization with RBD notably enhanced the population of CD44+CD62L+ T cells, indicating the generation of T cell memory. The in vitro assays demonstrated the antisera's protective efficacy through significant inhibition of the interaction between SARS-CoV-2 and its human receptor, ACE2, and through potent neutralization of a pseudovirus. These findings underscore the potential of our E. coli-expressed RBD as a viable vaccine candidate against the Omicron variant of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Introduction: Convalescent plasma (CP) emerged as potential treatment for COVID-19 early in the pandemic. While efficacy in hospitalised patients has been lacklustre, CP may be beneficial at the first stages of disease. Despite multiple new variants emerging, no trials have involved analyses on variant-specific antibody titres of CP. Methods: We recruited hospitalised COVID-19 patients within 10 days of symptom onset and, employing a double-blinded approach, randomised them to receive 200 ml convalescent plasma with high (HCP) or low (LCP) neutralising antibody (NAb) titre against the ancestral strain (Wuhan-like variant) or placebo in 1:1:1 ratio. Primary endpoints comprised intubation, corticosteroids for symptom aggravation, and safety assessed as serious adverse events. For a pre-planned ad hoc analysis, the patients were regrouped by infused CP’s NAb titers to variants infecting the recipients i.e. by titres of homologous HCP (hHCP) or LCP (hLCP). Results: Of the 57 patients, 18 received HCP, 19 LCP and 20 placebo, all groups smaller than planned. No significant differences were found for primary endpoints. In ad hoc analysis, hHCPrecipients needed significantly less respiratory support, and appeared to be given corticosteroids less frequently (1/14; 7.1%) than those receiving hLCP (9/23; 39.1%) or placebo (8/20; 40%), (p = 0.077). Discussion: Our double-blinded, placebo-controlled CP therapy trial remained underpowered and does not allow any firm conclusions for early-stage hospitalised COVID-19 patients. Interestingly, however, regrouping by homologous – recipients’ variant-specific – CP titres suggested benefits for hHCP. We encourage similar re-analysis of ongoing/previous larger CP studies. [ABSTRACT FROM AUTHOR]

Background. In late 2019, several medical institutions in Wuhan, Hubei Province, China, reported cases of unexplained pneumonia. A novel coronavirus was isolated from human airway epithelial cells causing coronavirus disease-2019 (COVID-19). In recent years, many nonpharmaceutical interventions (NPIs) have been implemented to stop COVID-19 epidemic. This study aimed to explore the effect of NPIs on the circulation of avian influenza virus (AIV) in Wuhan. Materials and Methods. External environmental samples were collected and subjected to viral RNA extraction. Real-time quantitative polymerase chain reaction was used to detect the H5, H7, and H9 subtypes of AIV. Statistical analyses were performed using the chi-square test and binary logistic regression in SPSS 20.0 software. Results. A total of 2,451 external environmental samples were collected from seven districts from 2018 to 2022 in Wuhan, comprising 1,041 samples collected before COVID-19 and 1,410 samples after COVID-19. After COVID-19, the positive rate of AIV decreased significantly with the implementation of NPIs. The dominant subtype was the H9 subtype, followed by the H5 subtype. The positive rates of AIV in live poultry markets and poultry free-range sites were reduced significantly through the implementation of NPIs. Among the different sample types, higher positive rates of AIV were found in chopping boards, sewage, and cages. The positive rate of AIV was higher in trafficked source samples than that in autotrophic source samples. Conclusions. This study identified the characteristics of AIV in terms of different districts, surveillance sites, sample types, and bird sources in Wuhan. This study conducted a multifactorial analysis of the factors affecting AIV infection and provided a theoretical basis and guidance for the future prevention and control of AIV in Wuhan. [ABSTRACT FROM AUTHOR]

The complexity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its variants in lung cells can truly be characterized only at the tissue and protein levels among unique cell subtypes. However, in vivo data are limited due to lack of accessible human tissues. Using a transgenic mouse model of SARS-CoV-2 infection and flow cytometry, we provide in vivo novel insight at the protein level that the differential impact of SARS-CoV-2 (Wuhan strain) and its B.1.617.2 (Delta) and BA.1 (Omicron) variants on lung may be attributed to differential patterns of viral protein levels among ciliated airway cells, alveolar types 1 and 2 cells, immune cells, and endothelial lung cells. [ABSTRACT FROM AUTHOR]

Coronavirus disease of 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing outbreak, disrupting human life worldwide. Vaccine development was prioritized to obtain a biological substance for combating the viral pathogen and lessening disease severity. In vaccine production, biological origin and relevant materials must be carefully examined for potential contaminants in conformity with good manufacturing practice. Due to fast mutation, several SARS-CoV-2 variants and sublineages have been identified. Currently, most of COVID-19 vaccines are developed based on the protein sequence of the Wuhan wild type strain. New vaccines specific for emerging SARS-CoV-2 strains are continuously needed to tackle the incessant evolution of the virus. Therefore, in vaccine development and production, a reliable method to identify the nature of subunit vaccines is required to avoid cross-contamination. In this study, liquid chromatography-mass spectrometry using quadrupole-time of flight along with tryptic digestion was developed for distinguishing protein materials derived from different SARS-CoV-2 strains. After analyzing the recombinantly produced receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, nine characteristic peptides were identified with acceptable limits of detection. They can be used together to distinguish 14 SARS-CoV-2 strains, except Kappa and Epsilon. Plant-produced RBD-Fc protein derived from Omicron strains can be easily distinguished from the others with 4–5 unique peptides. Eventually, a peptide key was developed based on the nine peptides, offering a prompt and precise flowchart to facilitate SARS-CoV-2 strain identification in COVID-19 vaccine manufacturing. [ABSTRACT FROM AUTHOR]

After the outbreak of COVID-19 pandemic, devising an effective reverse logistics supply chain to clean up disaster medical waste is conducive to controlling and containing novel coronavirus transmission. Thus, the focus of this paper concentrates on multi-period multi-type disaster medical waste location-transportation integrated optimization problem with the concern of sustainability, which is formulated as a tri-objective mixed-integer programming model with the goals of maximizing total economic benefits, minimizing total carbon emissions and total potential social risks. Then, a real-world case from Wuhan using CPLEX solver is used to validate the developed model. Results indicate that constructing DMWTTSs with flexible capacity in different periods is encouraged to handle the sharply increasing disaster medical waste. The multi-period decision model outperforms the single-period one in disaster medical waste supply chains because the former has the capability of handling the uncertainties in the future periods. Increasingly, since the increase of budget doesn't always work well and social resources are limited, the estimation of minimum budget to obtain optimum overall performance is of great importance. [ABSTRACT FROM AUTHOR]

• Waning immunity and new variants necessitate next generation SARS-CoV-2 vaccines. • The M2SR platform has a clear safety and immunogenic profile in clinical testing. • Intranasal dual influenza/COVID-19 vaccine induces systemic and mucosal antibodies. • SARS-CoV-2 M2SR protects hamsters from SARS-CoV-2 infection and lung pathology. • Dual vaccine maintains immunogenicity to matched and drifted influenza strains. The COVID-19 pandemic has highlighted the need for mucosal vaccines as breakthrough infections, short-lived immune responses and emergence of new variants have challenged the efficacy provided by the first generation of vaccines against SARS-CoV-2 viruses. M2SR SARS-CoV-2, an M2-deleted single-replication influenza virus vector modified to encode the SARS-CoV-2 receptor binding domain, was evaluated following intranasal delivery in a hamster challenge model for protection against Wuhan SARS-CoV-2. An adjuvanted inactivated SARS-CoV-2 whole virus vaccine administered intramuscularly was also evaluated. The intranasal M2SR SARS-CoV-2 was more effective than the intramuscular adjuvanted inactivated whole virus vaccine in providing protection against SARS-CoV-2 challenge. M2SR SARS-CoV-2 elicited neutralizing serum antibodies against Wuhan and Omicron SARS-CoV-2 viruses in addition to cross-reactive mucosal antibodies. Furthermore, M2SR SARS-CoV-2 generated serum HAI and mucosal antibody responses against influenza similar to an H3N2 M2SR influenza vaccine. The intranasal dual influenza/COVID M2SR SARS-CoV-2 vaccine has the potential to provide protection against both influenza and COVID. [ABSTRACT FROM AUTHOR]

People living with HIV (PLWH) could be at risk of blunted immune responses to COVID-19 vaccination. We investigated factors associated with neutralizing antibody (NAb) responses against SARS-CoV-2 and variants of concern (VOCs), following two-dose and third booster monovalent COVID-19 mRNA vaccination in Japanese PLWH. NAb titers were assessed in polyclonal IgG fractions by lentiviral-based pseudovirus assays. Overall, NAb titers against Wuhan, following two-dose vaccination, were assessed in 82 PLWH on treatment, whereby 17/82 (20.73%) were classified as low-NAb participants. Within the low-NAb participants, the third booster vaccination enhanced NAb titers against Wuhan and VOCs, albeit to a significantly lower magnitude than the rest. In the multivariate analysis, NAb titers against Wuhan after two-dose vaccination correlated with age and days since vaccination, but not with CD4+ count, CD4+/CD8+ ratio, and plasma high-sensitivity C-Reactive protein (hsCRP). Interestingly, an extended analysis within age subgroups revealed NAb titers to correlate positively with the CD4+ count and negatively with plasma hsCRP in younger, but not older, participants. In conclusion, a third booster vaccination substantially enhances NAb titers, but the benefit may be suboptimal in subpopulations of PLWH exhibiting low titers at baseline. Considering clinical and immune parameters could provide a nuanced understanding of factors associated with vaccine responses in PLWH. [ABSTRACT FROM AUTHOR]

Oropharyngeal microbiomes play a significant role in the susceptibility and severity of COVID-19, yet the role of these microbiomes play for the development of COVID-19 Omicron variant have not been reported. A total of 791 pharyngeal swab samples were prospectively included in this study, including 297 confirmed cases of Omicron variant (CCO), 222 confirmed case of Omicron who recovered (CCOR), 73 confirmed cases of original strain (CCOS) and 199 healthy controls (HC). All samples completed MiSeq sequencing. The results showed that compared with HC, conditional pathogens increased in CCO, while acid-producing bacteria decreased. Based on six optimal oropharyngeal operational taxonomy units (OTUs), we constructed a marker microbial classifier to distinguish between patients with Omicron variant and healthy people, and achieved high diagnostic efficiency in both the discovery queue and the verification queue. At same time, we introduced a group of cross-age infection verification cohort and Omicron variant subtype XBB.1.5 branch, which can be accurately distinguished by this diagnostic model. We also analyzed the characteristics of oropharyngeal microbiomes in two subgroups of Omicron disease group—severity of infection and vaccination times, and found that the change of oropharyngeal microbiomes may affect the severity of the disease and the efficacy of the vaccine. In addition, we found that some genera with significant differences gradually increased or decreased with the recovery of Omicron variant infection. The results of Spearman analysis showed that 27 oropharyngeal OTUs were closely related to 6 clinical indexes in CCO and HC. Finally, we found that the Omicron variant had different characterization of oropharyngeal microbiomes from the original strain. Our research characterizes oropharyngeal microbiomes of Omicron variant cases and rehabilitation cases, successfully constructed and verified the non-invasive diagnostic model of Omicron variant, described the correlation between microbial OTUs and clinical indexes. It was found that the infection of Omicron variant and the infection of original strain have different characteristics of oropharyngeal microbiomes. Author summary: COVID-19, caused by the SARS-CoV-2 virus, was first discovered in Wuhan, Hubei Province, China in December 2019, causing a huge impact around the world. In the past three years, novel coronavirus has successively appeared many varieties through gene mutation, among which Omicron strain is the most popular variety. Studies have shown that the imbalance of microflora is closely related to the progress of novel coronavirus infection and the severity of clinical symptoms. In the previous study, we build database of oral-intestinal microbial metagenomics, immunome and metabolome of novel coronavirus Original Strain with mild, medium and severe clinical symptoms and healthy subjects, reveal the role and mechanism of the oral and intestinal microbiome in Original Strain infection and exacerbation, and build the model of susceptibility, severe warning and prognosis of Original Strain pneumonia which based on the microbiome-immunity-metabolism. Our research characterizes oropharyngeal microbiomes of Omicron variant cases and rehabilitation cases, successfully constructed and verified the non-invasive diagnostic model of Omicron variant. We also analyzed the characteristics of oropharyngeal microbiomes in two subgroups of Omicron disease group—severity of infection and vaccination times, and found that the change of oropharyngeal microbiomes may affect the severity of the disease and the efficacy of the vaccine. And we described the correlation between microbial OTUs and clinical indexes. At last, it was found that the infection of Omicron variant and the infection of original strain have different characteristics of oropharyngeal microbiomes. [ABSTRACT FROM AUTHOR]

The immune mechanisms of long coronavirus disease 2019 (COVID) are not yet fully understood. We aimed to investigate the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific memory immune responses in discharged COVID-19 patients with and without long COVID symptoms. In this cross-sectional study, we included 1041 hospitalized COVID-19 patients with the original virus strain in Wuhan (China) 12 months after initial infection. We simultaneously conducted a questionnaire survey and collected peripheral blood samples from the participants. Based on the presence or absence of long COVID symptoms during the follow-up period, we divided the patients into 2 groups: a long COVID group comprising 480 individuals and a convalescent group comprising 561 individuals. Both groups underwent virus-specific immunological analyses, including enzyme-linked immunosorbent assay, interferon-γ-enzyme-linked immune absorbent spot, and intracellular cytokine staining. At 12 months after infection, 98.5% (1026/1041) of the patients were found to be seropositive and 93.3% (70/75) had detectable SARS-CoV-2-specific memory T cells. The long COVID group had significantly higher levels of receptor binding domain (RBD)–immunoglobulin G (IgG) levels, presented as OD450 values, than the convalescent controls (0.40 ± 0.22 vs 0.37 ± 0.20; P =.022). The magnitude of SARS-CoV-2-specific T-cell responses did not differ significantly between groups, nor did the secretion function of the memory T cells. We did not observe a significant correlation between SARS-CoV-2-IgG and magnitude of memory T cells. This study revealed that long COVID patients had significantly higher levels of RBD-IgG antibodies when compared with convalescent controls. Nevertheless, we did not observe coordinated SARS-CoV-2-specific cellular immunity. As there may be multiple potential causes of long COVID, it is imperative to avoid adopting a "one-size-fits-all" approach to future treatment modalities. [ABSTRACT FROM AUTHOR]

Simple Summary: Coronaviruses are serious pathogens for both humans and animals. The name corona was designated because of the crown-like spikes on their surface. Currently, seven coronaviruses have been identified, such as 229E, NL63, OC43, HKU1, MERS-CoV, SARS-CoV, and SARS-CoV-2. Sometimes, animal coronaviruses infect humans and evolve due to genetic mutations, interspecies transmission, host adaptations, and favorable conditions. The main objective of this study was to analyze the genetic diversity and predict the emergence of new variants with novel properties. It has been reported that the spike protein gene plays an important role in host cell attachment and entry into host cells. The S gene has the highest mutation/deletion and is the most utilized target for vaccine/antiviral development. In this work, we discussed the genetic diversity, phylogenetic relationship, and recombination patterns of selected HCoVs with an emphasis on the newly emerged SARS-CoV-2 and MERS-CoV. The findings of this study showed that MERS-CoV and SARS-CoV-2 have significant sequence identities with the selected HCoVs. The phylogenetic and recombination results concluded that new variants may emerge in the future with novel properties that infect both humans and animals. This information will be helpful for global society to design and develop an effective vaccine and disease management strategy. Human coronaviruses (HCoVs) are seriously associated with respiratory diseases in humans and animals. The first human pathogenic SARS-CoV emerged in 2002–2003. The second was MERS-CoV, reported from Jeddah, the Kingdom of Saudi Arabia, in 2012, and the third one was SARS-CoV-2, identified from Wuhan City, China, in late December 2019. The HCoV-Spike (S) gene has the highest mutation/insertion/deletion rate and has been the most utilized target for vaccine/antiviral development. In this manuscript, we discuss the genetic diversity, phylogenetic relationships, and recombination patterns of selected HCoVs with emphasis on the S protein gene of MERS-CoV and SARS-CoV-2 to elucidate the possible emergence of new variants/strains of coronavirus in the near future. The findings showed that MERS-CoV and SARS-CoV-2 have significant sequence identity with the selected HCoVs. The phylogenetic tree analysis formed a separate cluster for each HCoV. The recombination pattern analysis showed that the HCoV-NL63-Japan was a probable recombinant. The HCoV-NL63-USA was identified as a major parent while the HCoV-NL63-Netherland was identified as a minor parent. The recombination breakpoints start in the viral genome at the 142 nucleotide position and end at the 1082 nucleotide position with a 99% CI and Bonferroni-corrected p-value of 0.05. The findings of this study provide insightful information about HCoV-S gene diversity, recombination, and evolutionary patterns. Based on these data, it can be concluded that the possible emergence of new strains/variants of HCoV is imminent. [ABSTRACT FROM AUTHOR]

Background: The infection that caused the pneumonia, the virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the source of coronavirus disease 2019 (COVID-19) is the source of the global pandemic. The pneumonia cases began in Wuhan, China in December 2019 and had no apparent reason. Essential inflammatory mediators Chemokines are necessary for an immune response to eliminate pathogens. However, the fundamental cause of hyper inflammation is their excessive release. Chemokines may be directly responsible for the acute respiratory illness syndrome in the current COVID-19 outbreak. Objective: The current study aimed to estimate hematological changes with immunogenic markers CD177, GNLY, and CXCR4 gene expression in COVID-19 patients, and compare these parameters among patients and healthy individuals. Materials and Methods: the study was conducted at Al-Yarmouk Teaching Hospital and Medical Teaching Laboratories. Finally, to detect the immune markers level in samples of patients, by RT-PCR. Results: the results revealed the gene expression results in patients with COVID-19 means Ct difference of CD177 (24.70) fold more than (10.5) elevated when compared with the mean of Ct control healthy group is (28.21) fold of gene expression is 1.00 of CD177 when our study showed increased gene expression the mean of GNLY Ct receptor was reached to (28.70 ng/L) with fold more than 15.0 in COVID-19 patients, while mean Ct in healthy control was (32.61 ng/L) with fold 1.00, the current study found mean CT of CXCR4 gene expression (31.2) with fold (1.1) compared with healthy control CT(31.3) fold of gene expression was (1.0). Conclusion: It was concluded that COVID-19 caused significant changes in many immunological parameters and found the titer of immune markers was higher in infection compared with control. [ABSTRACT FROM AUTHOR]

The global spread of the SARS-CoV-2 pandemic, originating in Wuhan, China, has had profound consequences on both health and the economy. Traditional alignment-based phylogenetic tree methods for tracking epidemic dynamics demand substantial computational power due to the growing number of sequenced strains. Consequently, there is a pressing need for an alignment-free approach to characterize these strains and monitor the dynamics of various variants. In this work, we introduce a swift and straightforward tool named GenoSig, implemented in C++. The tool exploits the Di and Tri nucleotide frequency signatures to delineate the taxonomic lineages of SARS-CoV-2 by employing diverse machine learning (ML) and deep learning (DL) models. Our approach achieved a tenfold cross-validation accuracy of 87.88% (± 0.013) for DL and 86.37% (± 0.0009) for Random Forest (RF) model, surpassing the performance of other ML models. Validation using an additional unexposed dataset yielded comparable results. Despite variations in architectures between DL and RF, it was observed that later clades, specifically GRA, GRY, and GK, exhibited superior performance compared to earlier clades G and GH. As for the continental origin of the virus, both DL and RF models exhibited lower performance than in predicting clades. However, both models demonstrated relatively higher accuracy for Europe, North America, and South America compared to other continents, with DL outperforming RF. Both models consistently demonstrated a preference for cytosine and guanine over adenine and thymine in both clade and continental analyses, in both Di and Tri nucleotide frequencies signatures. Our findings suggest that GenoSig provides a straightforward approach to address taxonomic, epidemiological, and biological inquiries, utilizing a reductive method applicable not only to SARS-CoV-2 but also to similar research questions in an alignment-free context. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is the cause of coronavirus disease 2019 (COVID-19); a severe respiratory distress that has emerged from the city of Wuhan, Hubei province, China during December 2019. COVID-19 is currently the major global health problem and the disease has now spread to most countries in the world. COVID-19 has profoundly impacted human health and activities worldwide. Genetic mutation is one of the essential characteristics of viruses. They do so to adapt to their host or to move to another one. Viral genetic mutations have a high potentiality to impact human health as these mutations grant viruses unique unpredicted characteristics. The difficulty in predicting viral genetic mutations is a significant obstacle in the field. Evidence indicates that SARS-CoV-2 has a variety of genetic mutations and genomic diversity with obvious clinical consequences and implications. In this review, we comprehensively summarized and discussed the currently available knowledge regarding SARS-CoV-2 outbreaks with a fundamental focus on the role of the viral proteins and their mutations in viral infection and COVID-19 progression. We also summarized the clinical implications of SARS-CoV-2 variants and how they affect the disease severity and hinder vaccine development. Finally, we provided a massive phylogenetic analysis of the spike gene of 214 SARS-CoV-2 isolates from different geographical regions all over the world and their associated clinical implications. [ABSTRACT FROM AUTHOR]

While the first infection of an emerging disease is often unknown, information on early cases can be used to date it. In the context of the COVID-19 pandemic, previous studies have estimated dates of emergence (e.g., first human SARS-CoV-2 infection, emergence of the Alpha SARS-CoV-2 variant) using mainly genomic data. Another dating attempt used a stochastic population dynamics approach and the date of the first reported case. Here, we extend this approach to use a larger set of early reported cases to estimate the delay from first infection to the Nth case. We first validate our framework by running our model on simulated data. We then apply our model using data on Alpha variant infections in the UK, dating the first Alpha infection at (median) August 21, 2020 (95% interpercentile range across retained simulations (IPR): July 23–September 5, 2020). Next, we apply our model to data on COVID-19 cases with symptom onset before mid-January 2020. We date the first SARS-CoV-2 infection in Wuhan at (median) November 28, 2019 (95% IPR: November 2–December 9, 2019). Our results fall within ranges previously estimated by studies relying on genomic data. Our population dynamics-based modelling framework is generic and flexible, and thus can be applied to estimate the starting time of outbreaks in contexts other than COVID-19. Author summary: While the first infection of an emerging disease is often unknown, information on early cases can be used to date it. In the context of the COVID-19 pandemic, previous studies have estimated dates of emergence of epidemic outbreaks (e.g., first human SARS-CoV-2 infection, emergence of the Alpha SARS-CoV-2 variant) using mainly genomic data. Another dating attempt used a population-level stochastic approach and the date of the first reported case. Here, we extend this generic and flexible approach to use a larger set of early reported cases to estimate the time elapsed between the first infection and the Nth case. Our model dates the first Alpha infection at around August 21, 2020, and the first SARS-CoV-2 infection in Wuhan at around November 28, 2019. Our findings fall within ranges previously estimated by studies relying on genomic data. [ABSTRACT FROM AUTHOR]

Background: The emergence of new SARS-CoV-2 variants and the waning of immunity raise concerns about vaccine effectiveness and protection against COVID-19. While antibody response has been shown to correlate with the risk of infection with the original variant and earlier variants of concern, the effectiveness of antibody-mediated protection against Omicron and the factors associated with protection remain uncertain. Methods: We evaluated antibody responses to SARS-CoV-2 spike (S) and nucleocapsid (N) antigens from Wuhan and variants of concern by Luminex and their role in preventing breakthrough infections 1 year after a third dose of mRNA vaccination, in a cohort of health care workers followed since the pandemic onset in Spain (N = 393). Data were analyzed in relation to COVID-19 history, demographic factors, comorbidities, vaccine doses, brand, and adverse events. Results: Higher levels of anti-S IgG and IgA to Wuhan, Delta, and Omicron were associated with protection against vaccine breakthroughs (IgG against Omicron S antigen HR, 0.06, 95%CI, 0.26–0.01). Previous SARS-CoV-2 infection was positively associated with antibody levels and protection against breakthroughs, and a longer time since last infection was associated with lower protection. In addition, priming with BNT162b2 followed by mRNA-1273 booster was associated with higher antibody responses than homologous mRNA-1273 vaccination. Conclusions: Data show that IgG and IgA induced by vaccines against the original strain or by hybrid immunization are valid correlates of protection against Omicron BA.1 despite immune escape and support the benefits of heterologous vaccination regimens to enhance antibodies and the prioritization of booster vaccination in individuals without recent infections. [ABSTRACT FROM AUTHOR]

Background: The emergence of new SARS-CoV-2 variants and the waning of immunity raise concerns about vaccine effectiveness and protection against COVID-19. While antibody response has been shown to correlate with the risk of infection with the original variant and earlier variants of concern, the effectiveness of antibody-mediated protection against Omicron and the factors associated with protection remain uncertain. Methods: We evaluated antibody responses to SARS-CoV-2 spike (S) and nucleocapsid (N) antigens from Wuhan and variants of concern by Luminex and their role in preventing breakthrough infections 1 year after a third dose of mRNA vaccination, in a cohort of health care workers followed since the pandemic onset in Spain (N = 393). Data were analyzed in relation to COVID-19 history, demographic factors, comorbidities, vaccine doses, brand, and adverse events. Results: Higher levels of anti-S IgG and IgA to Wuhan, Delta, and Omicron were associated with protection against vaccine breakthroughs (IgG against Omicron S antigen HR, 0.06, 95%CI, 0.26–0.01). Previous SARS-CoV-2 infection was positively associated with antibody levels and protection against breakthroughs, and a longer time since last infection was associated with lower protection. In addition, priming with BNT162b2 followed by mRNA-1273 booster was associated with higher antibody responses than homologous mRNA-1273 vaccination. Conclusions: Data show that IgG and IgA induced by vaccines against the original strain or by hybrid immunization are valid correlates of protection against Omicron BA.1 despite immune escape and support the benefits of heterologous vaccination regimens to enhance antibodies and the prioritization of booster vaccination in individuals without recent infections. [ABSTRACT FROM AUTHOR]

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with greater transmissibility or immune evasion properties has jeopardized the existing vaccine and antibody-based countermeasures. Here, we evaluated the efficacy of boosting pre-immune hamsters with protein nanoparticle vaccines (Novavax, Inc.) containing recombinant Prototype (Wuhan-1) or BA.5 S proteins against a challenge with the Omicron BA.5 variant of SARS-CoV-2. Serum antibody binding and neutralization titers were quantified before challenge, and viral loads were measured 3 days after challenge. Boosting with Prototype or BA.5 vaccine induced similar antibody binding responses against ancestral Wuhan-1 or BA.5 S proteins, and neutralizing activity of Omicron BA.1 and BA.5 variants. One and three months after vaccine boosting, hamsters were challenged with the Omicron BA.5 variant. Prototype and BA.5 vaccine-boosted hamsters had reduced viral infection in the nasal washes, nasal turbinates, and lungs compared to unvaccinated animals. Although no significant differences in virus load were detected between the Prototype and BA.5 vaccine-boosted animals, fewer breakthrough infections were detected in the BA.5-vaccinated hamsters. Thus, immunity induced by Prototype or BA.5 S protein nanoparticle vaccine boosting can protect against the Omicron BA.5 variant in the Syrian hamster model. [ABSTRACT FROM AUTHOR]

Introduction: The emergence of a new and highly pathogenic coronavirus (SARS-CoV-2) in Wuhan (China) and its spread worldwide has resulted in enormous social and economic losses. Amongst many proteins encoded by the SARS-CoV-2 genome, the main protease (Mpro) or chymotrypsin-like cysteine protease (3CLpro) and papain-like protease (PLpro) serve as attractive drug targets. Material and methods: We screened a library of 2267 natural compounds against Mpro and PLpro using high throughput virtual screening (HTVS). Fifty top-scoring compounds against each protein in HTVS were further evaluated by standard-precision (SP) docking. Compounds with SP docking energy of ≤ -8.0 kcal/mol against Mpro and ≤ -5.0 kcal/mol against PLpro were subjected to extra-precision (XP) docking. Finally, six compounds against each target proteins were identified and subjected to Prime/MM-GBSA free energy calculations. Compounds with the lowest Prime/MM-GBSA energy were subjected to molecular dynamics simulation to evaluate the stability of protein-ligand complexes. Results: Proanthocyanidin and rhapontin were identified as the most potent inhibitors of Mpro and PLpro, respectively. Analysis of protein-inhibitor interaction revealed that both protein-inhibitor complexes were stabilized by hydrogen bonding and hydrophobic interactions. Proanthocyanidin interacted with the catalytic residues (His41 and Cys145) of Mpro, while rhapontin contacted the active site residues (Trp106, His272, Asp286) of PLpro. The docking energies of proanthocyanidin and rhapontin towards their respective targets were -10.566 and -10.022 kcal/mol. Conclusions: This study's outcome may support application of proanthocyanidin and rhapontin as a scaffold to build more potent inhibitors with desirable drug-like properties. However, it requires further validation by in vitro and in vivo studies. [ABSTRACT FROM AUTHOR]

As there are limited data on B-cell epitopes for the nucleocapsid protein in SARS-CoV-2, we sought to identify the immunodominant regions within the N protein, recognized by patients with varying severity of natural infection with the Wuhan strain (WT), delta, omicron, and in those who received the Sinopharm vaccines, which is an inactivated, whole virus vaccine. Using overlapping peptides representing the N protein, with an in-house ELISA, we mapped the immunodominant regions within the N protein, in seronegative (n = 30), WT infected (n = 30), delta infected (n = 30), omicron infected + vaccinated (n = 20) and Sinopharm (BBIBP-CorV) vaccinees (n = 30). We then investigated the sensitivity and specificity of these immunodominant regions and analyzed their conservation with other SARS-CoV-2 variants of concern, seasonal human coronaviruses, and bat Sarbecoviruses. We identified four immunodominant regions aa 29–52, aa 155–178, aa 274–297, and aa 365–388, which were highly conserved within SARS-CoV-2 and the bat coronaviruses. The magnitude of responses to these regions varied based on the infecting SARS-CoV-2 variants, >80% of individuals gave responses above the positive cut-off threshold to many of the four regions, with some differences with individuals who were infected with different VoCs. These regions were found to be 100% specific, as none of the seronegative individuals gave any responses. As these regions were highly specific with high sensitivity, they have a potential to be used to develop diagnostic assays and to be used in development of vaccines. We identified four immunodominant regions within SARS-CoV-2 N protein, aa 29–52, aa 155–178, aa 274–297, and aa 365–388, were highly conserved within SARS-CoV-2 and the bat coronaviruses. As these regions were highly specific with high sensitivity, they have a potential to be used to develop diagnostic assays and to be used in development of vaccines. Graphical Abstract [ABSTRACT FROM AUTHOR]

Machine learning (ML) is a key focus in predicting protein mutations and aiding directed evolution. Research on potential virus variants is crucial for vaccine development. In this study, the machine learning software PyPEF was employed to conduct mutation analysis within the receptor-binding domain (RBD) of the Spike glycoprotein of SARS-CoV-2. Over 48,960,000 variants were predicted. Eight prospective variants that could surface in the future underwent modeling and molecular dynamics simulations. The study forecasts that the latest variant, ISOY2P5O1, may potentially emerge around 17 November 2023, with an approximate window of uncertainty of ±22 days. The ISOY8P5O2 variant displayed an increased binding capacity in the dry assay, with a total predicted binding energy of −110.306 kcal/mol. This represents an 8.25% enhancement in total binding energy compared to the original SARS-CoV-2 strain discovered in Wuhan (−101.892 kcal/mol). Reverse research confirmed the structural significance of mutation sites using ML models, particularly in the context of protein folding. The study validated regression methods (SVR, RF, and PLS) with different data structures. This study investigates the effectiveness of the "ML-Guided Design Correctly Predicts Combinatorial Effects Strategy" compared to the "ML-Guided Design Correctly Predicts Natural Evolution Prediction Strategy". To enhance machine learning, we created a timestamping algorithm and two auxiliary programs using advanced techniques to rapidly process extensive data, surpassing batch sequencing capabilities. This study not only advances machine learning in guiding protein evolution but also holds potential for forecasting future viruses and vaccine development. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 Omicron sub-variants BA.2.86 and JN.1 contain multiple mutations in the spike protein that were not present in previous variants of concern and Omicron sub-variants. Preliminary research suggests that these variants reduce the neutralizing capability of antibodies induced by vaccines, which is particularly significant for JN.1. This raises concern as many widely deployed COVID-19 vaccines are based on the spike protein of the ancestral Wuhan strain of SARS-CoV-2. While T cell responses have been shown to be robust against previous SARS-CoV-2 variants, less is known about the impact of mutations in BA.2.86 and JN.1 on T cell responses. We evaluate the effect of mutations specific to BA.2.86 and JN.1 on experimentally determined T cell epitopes derived from the spike protein of the ancestral Wuhan strain and the spike protein of the XBB.1.5 strain that has been recommended as a booster vaccine. Our data suggest that BA.2.86 and JN.1 affect numerous T cell epitopes in spike compared to previous variants; however, the widespread loss of T cell recognition against these variants is unlikely. [ABSTRACT FROM AUTHOR]

First described in December 2019 in Wuhan (China), COVID-19 disease rapidly spread worldwide, constituting the biggest pandemic in the last 100 years. Even if SARS-CoV-2, the agent responsible for COVID-19, is mainly associated with pulmonary injury, evidence is growing that this virus can affect many organs, including the heart and vascular endothelial cells, and cause haemostasis, CNS, and kidney and gastrointestinal tract abnormalities that can impact in the disease course and prognosis. In fact, COVID-19 may affect almost all the organs. Hence, SARS-CoV-2 is essentially a systemic infection that can present a large number of clinical manifestations, and it is variable in distribution and severity, which means it is potentially life-threatening. The goal of this comprehensive review paper in the series is to give an overview of non-pulmonary involvement in COVID-19, with a special focus on underlying pathophysiological mechanisms and clinical presentation. [ABSTRACT FROM AUTHOR]

The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infections that were first detected in Wuhan, China, at the end of 2019 led to the state of the global COVID-19 pandemic declared by the World Health Organization in March 2020. Thus, the world faces a new challenge to control the spread of the virus. The pandemic highlighted the need for rapid detection of infections that would be able to accurately screen the population much more rapidly and economically than the gold standard molecular biology-based tools such as quantitative real-time reverse transcription polymerase chain reaction. Such screening measures would be able to isolate infected individuals, including those showing no symptoms, and provide early treatments before more serious complications develop, thus allowing for the spread of infections to be better controlled without the implementation of socioeconomically crippling lockdowns. In this review, we present a comprehensive overview of the major advances in the use of electrolyte-gated field effect transistor-based biosensors for the detection of viruses, including their use for SARS-CoV-2 detection. We describe the main types of bioreceptors used for the detection of viruses in general and those used for COVID-19 in detail. [ABSTRACT FROM AUTHOR]

Introduction: The world has been badly affected by the spread of a novel virus known as Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) that was first reported in Wuhan, China back in December 2019. As the virus is transmitted through aerosol, respiratory droplets and close contact, hand hygiene and wearing mask are the most important preventive measures for COVID-19. Studies showed hand hygiene intervention improved compliances. This paper discussed the development of a hand hygiene intervention module, validation, usability and effectiveness reports. Methods: This study involved 5 stages; need analysis, module development, validation, usability and effectiveness studies. Need analysis and module development were carried out through brainstorming and literature search. The content was evaluated by three experts, whereas the usability was screened by four preschool teachers. The effectiveness of knowledge transfer was evaluated via pre and post intervention surveys. Results: The hand hygiene educational module received valuable comments from the content expert and the end-users (teachers). Knowledge score related to COVID-19 transmission, prevention and hand hygiene moments among pre-school children were significantly increased after the intervention. Conclusion: This module can be used to improve teaching method related to COVID-19 and hand hygiene. The 'learn and play' approach may increase excitement, thus make learning process enjoyable and memorable. [ABSTRACT FROM AUTHOR]

Simple Summary: The COVID-19 pandemic showcases the impact of mitigation and elimination strategies across the globe, including the development of effective vaccines, antiviral drugs and diagnostic tools. However, the virus changes rapidly over time. Consequently, control strategies have been limited by time-consuming experimental acquisition of three-dimensional atomic protein structures of the fast-developing mutant 'variants' of the virus, which remains an unviable strategy for fast and effective disease control. Here, we use AlphaFold2 to model the atomic structure of the ever-changing SARS-CoV-2 spike protein in silico. AlphaFold2 is an artificial intelligence (AI) deep learning computational tool capable of producing models at experimental resolution in only a few hours. Structural models for major Variants of Concern (Alpha, Delta, and Omicron) and latitude-delimited haplotypes, sets of genetically linked and highly prevalent mutations that impact the epidemic calendar of the virus, were compared to the structure of the reference Wuhan strain. We find that patterns of structural change triggered by seasonal haplotype diversification could help predict the changing face of the virus, understand seasonal behavior, and develop more resilient vaccines and drugs. The slow experimental acquisition of high-quality atomic structures of the rapidly changing proteins of the COVID-19 virus challenges vaccine and therapeutic drug development efforts. Fortunately, deep learning tools such as AlphaFold2 can quickly generate reliable models of atomic structure at experimental resolution. Current modeling studies have focused solely on definitions of mutant constellations of Variants of Concern (VOCs), leaving out the impact of haplotypes on protein structure. Here, we conduct a thorough comparative structural analysis of S-proteins belonging to major VOCs and corresponding latitude-delimited haplotypes that affect viral seasonal behavior. Our approach identified molecular regions of importance as well as patterns of structural recruitment. The S1 subunit hosted the majority of structural changes, especially those involving the N-terminal domain (NTD) and the receptor-binding domain (RBD). In particular, structural changes in the NTD were much greater than just translations in three-dimensional space, altering the sub-structures to greater extents. We also revealed a notable pattern of structural recruitment with the early VOCs Alpha and Delta behaving antagonistically by suppressing regions of structural change introduced by their corresponding haplotypes, and the current VOC Omicron behaving synergistically by amplifying or collecting structural change. Remarkably, haplotypes altering the galectin-like structure of the NTD were major contributors to seasonal behavior, supporting its putative environmental-sensing role. Our results provide an extensive view of the evolutionary landscape of the S-protein across the COVID-19 pandemic. This view will help predict important regions of structural change in future variants and haplotypes for more efficient vaccine and drug development. [ABSTRACT FROM AUTHOR]

The etiological agent of coronavirus disease (COVID-19) that emerged at the end of year 2019 was first reported in Wuhan, China and was found to be SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2). The massive COVID-19 waves were due to various variants. As per the reports of other study it was also found that Omicron variant spread faster than various other variant such as delta variant. Omicron has been reported from various countries and now from many states of India too. Therefore, keeping this in mind, this study was undertaken to study all the lineages of SARS-CoV-2 Omicron variant of disease COVID-19 that are circulating in the population of Uttarakhand with objective to study next generation sequencing of all the RT-PCR positive of SARS-CoV-2 and to find out all the lineages of the Omicron variant of SARS-CoV-2. This was a retrospective study conducted from 1st January 2022 to 30th September 2022. Next generation sequencing was performed on all the samples that were tested for COVID-19 by using Ion AmpliSeq kit on Ion Chef instrument. A total of 2149 samples were tested in which majority of samples belong to age group of 21-40 years. Males were affected more than females. BA.2 was found to be the predominant lineage of total of 46 lineages that were identified. Their mutations were also studied. We conclude that different variants of clade 21L, 22B, 22D and Omicron subvariant BA.2, BA.2.38 and BA.2.75 were the ones that were circulating amongst the population of Uttarakhand. The characteristic mutation that was found were T19I and V213G in NTD, S373P, S375F, T376A, and D405N in RBD. [ABSTRACT FROM AUTHOR]

The onset of the COVID-19 pandemic in late 2019 triggered an unprecedented global health crisis. Originating in Wuhan, China, the spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a worldwide upheaval, affecting every aspect of human life. As countries grappled with rising case counts, hospitalizations, and fatalities, the role of geospatial information and visualization in managing and understanding the pandemic became increasingly vital. This special issue of the Cartography and Geographic Information Science (CaGIS) Journal sought to explore the innovative and impactful ways in which geovisualization techniques have been employed to confront and elucidate the complexities of COVID-19. We describe significance and contribution of each paper that is part of the special issue, and avenues for new, exciting research around infectious diseases, keeping in mind that the research needs to be reproducible. [ABSTRACT FROM AUTHOR]

In late December 2019, a novel coronavirus, COVID −19 originated in Wuhan city of China, and significant improvement in not only the air quality but also the water quality. Therefore, the current study demonstrates the changes in water quality parameters of the Ghaggar river, Punjab, India. The variations in the water quality of the Ghaggar river have been examined during the pre-, during, and post-pandemic periods. The maximum temperature of the Ghaggar river for all monitoring stations was between 28 to 37°C during the pandemic period, whereas the maximum dissolved oxygen value varied from 3 to 7 mg/L. The maximum pH obtained from the monitoring stations was reported to be 7.7 to 8.0, except chhatbir monitoring station (7.6). The maximum biochemical oxygen demand for all monitoring stations was found to be between 18–53 mg/L. Strong positive correlations were observed between total coliform and fecal coliform for pre (0.76) and during (0.89) the pandemic periods. Similar significant positive correlations were recorded between BOD and conductivity for pre (0.75) and during (0.58) pandemic periods. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is an infectious viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged at the end of 2019. SARS-CoV-2 can be transmitted through droplets, aerosols, and fomites. Disinfectants such as alcohol, quaternary ammonium salts, and chlorine-releasing agents, including hypochlorous acid, are used to prevent the spread of SARS-CoV-2 infection. In the present study, we investigated the efficacy of ionless hypochlorous acid water (HOCl) in suspension and by spraying to inactivate SARSCoV-2. The virucidal efficacy of HOCl solution in tests against SARS-CoV-2 was evaluated as 50% tissue culture infectious dose. Although the presence of organic compounds influenced the virucidal efficacy, HOCl treatment for 20 s was significantly effective to inactivate Wuhan and Delta strains in the suspension test. HOCl atomization for several hours significantly reduced the SARS-CoV-2 attached to plastic plates. These results indicate that HOCl solution with elimination containing NaCl and other ions may have high virucidal efficacy against SARS-CoV-2. This study provides important information about the virucidal efficacy and use of HOCl solution. [ABSTRACT FROM AUTHOR]

The novel coronavirus, COVID-19, first identified in Wuhan, China, in December 2019, rapidly spread across the globe and resulted in significant public concern. In response, numerous countries have implemented guidelines aimed at promoting social distancing, limiting movement and gatherings, instituting lockdowns and curfews, and closing institutions. As a result, the media, including news releases, has become a primary source of information for many individuals (Laor & Lissitsa, 2022). The present study seeks to investigate differences between major television programs featured on public and commercial channels in Israel, utilizing the lens of framing theory. Specifically, twelve monologues broadcast simultaneously on both channels were analyzed to compare differences in content, topics, format, and accompanying visuals. The study's results indicate that both commercial and public channels exhibited similar behavior in shaping public opinion during the crisis period. Specifically, both channels displayed criticism of the government's conduct and utilized negative framing techniques while neglecting to provide space for popular voices. Nevertheless, certain distinctions between the commercial and public broadcasting spheres still persist, particularly in the realm of visual presentation, as some long-standing elements that typify each channel have endured over time. [ABSTRACT FROM AUTHOR]

The responsiveness/cross-binding of vaccine-induced memory B cells/MBCs to previous and emerging divergent SARS-CoV-2 variants (e.g., Omicron) is understudied. In this longitudinal study subjects receiving two or three doses of monovalent ancestral strain-containing COVID-19 mRNA vaccine were evaluated. In contrast to others, we observed significantly lower frequencies of MBCs reactive to the receptor-binding domain/RBD, the N-terminal domain/NTD, and the S1 of Omicron/BA.1, compared to Wuhan and Delta, even after a 3rd vaccine dose/booster. Our study is a proof of concept that MBC cross-reactivity to variants with greater sequence divergence from the vaccine strain may be overestimated and suggests that these variants may exhibit immune escape with reduced recognition by circulating pre-existing MBCs upon infection. [ABSTRACT FROM AUTHOR]

COVID-19, the Ecumenical Pandemic that hit Wuhan, Hubei Province, China, in 2019 has instigated an emergency situation all over the globe. Current scientific corroborations highlighted the role of zoonotic cross-over species transmission for the spread of the deadly virus SARSCoV2. The proposition of ABO blood grouping to susceptibility for various infectious diseases has been documented in the past since blood group antigens constitute polymorphic traits that are inherited among humans, therefore are frequent targets in epidemiological studies. Aim: To correlate the ABO blood group susceptibility to disease severity in COVID-19-positive cases among Indian populations. Objectives: Association of ABO blood group patterns to disease severity in COVID-19-positive cases. Materials and Methods: A cross-sectional, observational study design was conducted among 700 confirmed COVID-19-positive cases admitted to the tertiary health care center in Maharashtra, India. The data collected were subjected to statistical analysis. Results: Blood group 'A' positive was frequent (40%) in severe COVID-19 (E group) disease, and 'O' positive blood group was frequent in moderate COVID-19 disease (34.62%). Conclusion: ABO Blood grouping can be used as one of the efficient biomarker for COVID-19, thereby providing a new platform for therapeutic applications in the field of research. [ABSTRACT FROM AUTHOR]

The emergence of SARS-CoV-2 variants alters the efficacy of existing immunity towards the viral spike protein, whether acquired from infection or vaccination. Mutations that impact N -glycosylation of spike may be particularly important in influencing antigenicity, but their consequences are difficult to predict. Here, we compare the glycosylation profiles and antigenicity of recombinant viral spike of ancestral Wu-1 and the Gamma strain, which has two additional N -glycosylation sites due to amino acid substitutions in the N-terminal domain (NTD). We found that a mutation at residue 20 from threonine to asparagine within the NTD caused the loss of NTD-specific antibody COVA2-17 binding. Glycan site-occupancy analyses revealed that the mutation resulted in N -glycosylation switching to the new sequon at N20 from the native N17 site. Site-specific glycosylation profiles demonstrated distinct glycoform differences between Wu-1, Gamma, and selected NTD variant spike proteins, but these did not affect antibody binding. Finally, we evaluated the specificity of spike proteins against convalescent COVID-19 sera and found reduced cross-reactivity against some mutants, but not Gamma spike compared to Wuhan spike. Our results illustrate the impact of viral divergence on spike glycosylation and SARS-CoV-2 antibody binding profiles. [ABSTRACT FROM AUTHOR]

Since its discovery in Wuhan, China, in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly around the world with being declared a pandemic in March 2020 by the World Health Organization (WHO). Comorbidities are one of the most concerning clinical considerations for mortality. Materials and Methods: This was a retrospective observational study conducted at the All India Institute of Medical Sciences in Patna, Bihar, from June 2020 to December 2020. It included adult patients who succumbed to coronavirus disease 2019 (COVID-19) during this period, and their relevant information, such as demographic information hospital stay duration, haematological parameters and comorbidities, was gathered. Results: The mean age of the study group was 63.5 (11.8) years. Of 150 cases, 126 men (about 84 per cent) and 24 women were involved (16 per cent). In our study, hypertension (HTN) was shown to be the most frequent comorbidity at 68.7% (103/150), followed by diabetes mellitus (DM) at 61.3% (92/150). The most prevalent haematological disorder identified in our investigation was anaemia and leucocytosis. Conclusion: The categorisation of patients who would need extra measures including early hospitalisation, heightened monitoring and intense therapy would be made easier by identifying patient traits and conditions. [ABSTRACT FROM AUTHOR]

Vaccine-induced mucosal immunity and broad protective capacity against various severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants remain inadequate. Formyl peptide receptor-like 1 inhibitory protein (FLIPr), produced by Staphylococcus aureus, can bind to various Fcγ receptor subclasses. Recombinant lipidated FLIPr (rLF) was previously found to be an effective adjuvant. In this study, we developed a vaccine candidate, the recombinant Delta SARS-CoV-2 spike (rDS)-FLIPr fusion protein (rDS-F), which employs the property of FLIPr binding to various Fcγ receptors. Our study shows that rDS-F plus rLF promotes rDS capture by dendritic cells. Intranasal vaccination of mice with rDS-F plus rLF increases persistent systemic and mucosal antibody responses and CD4/CD8 T-cell responses. Importantly, antibodies induced by rDS-F plus rLF vaccination neutralize Delta, Wuhan, Alpha, Beta, and Omicron strains. Additionally, rDS-F plus rLF provides protective effects against various SARS-CoV-2 variants in hamsters by reducing inflammation and viral loads in the lung. Therefore, rDS-F plus rLF is a potential vaccine candidate to induce broad protective responses against various SARS-CoV-2 variants. IMPORTANCE Mucosal immunity is vital for combating pathogens, especially in the context of respiratory diseases like COVID-19. Despite this, most approved vaccines are administered via injection, providing systemic but limited mucosal protection. Developing vaccines that stimulate both mucosal and systemic immunity to address future coronavirus mutations is a growing trend. However, eliciting strong mucosal immune responses without adjuvants remains a challenge. In our study, we have demonstrated that using a recombinant severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) spike-formyl peptide receptor-like 1 inhibitory protein (FLIPr) fusion protein as an antigen, in combination with recombinant lipidated FLIPr as an effective adjuvant, induced simultaneous systemic and mucosal immune responses through intranasal immunization in mice and hamster models. This approach offered protection against various SARS-CoV-2 strains, making it a promising vaccine candidate for broad protection. This finding is pivotal for future broad-spectrum vaccine development. [ABSTRACT FROM AUTHOR]

BST2/Tetherin is a restriction factor with broad antiviral activity against enveloped viruses, including coronaviruses. Specifically, BST2 traps nascent particles to membrane compartments, preventing their release and spread. In turn, viruses have evolved multiple mechanisms to counteract BST2. Here, we examined the interactions between BST2 and SARS-CoV-2. Our study shows that BST2 reduces SARS-CoV-2 virion release. However, the virus uses the Spike (S) protein to downregulate BST2. This requires a physical interaction between S and BST2, which routes BST2 for lysosomal degradation in a Clathtin- and ubiquitination-dependent manner. By surveying different SARS-CoV-2 variants of concern (Alpha-Omicron), we found that Omicron is more efficient at counteracting BST2, and that mutations in S account for its enhanced anti-BST2 activity. Mapping analyses revealed that several surfaces in the extracellular region of BST2 are required for an interaction with the Spike, and that the Omicron variant has changed its patterns of association with BST2 to improve its counteraction. Therefore, our study suggests that, besides enhancing receptor binding and evasion of neutralizing antibodies, mutations accumulated in the Spike afford more efficient counteraction of BST2, which highlights that BST2 antagonism is important for SARS-CoV-2 infectivity and spread. Author summary: BST2/Tetherin is a potent antiviral factor that prevents the egress of multiple enveloped viruses. In turn, viruses have evolved mechanisms to circumvent this block. Here, we found that SARS-CoV-2 primarily uses the Spike protein to promote the lysosomal degradation of BST2, thus, removing it from sites of virion assembly and facilitating virus release. When analyzing several SARS-CoV-2 variants of concern, we found that Omicron is more efficient at counteracting BST2, to the point where its replication is barely impacted by this restriction factor. Subsequent studies identified mutations accumulated in the Omicron Spike as responsible for improving an interaction between Spike and BST2. However, the surfaces in BST2 required for this association differ between Wuhan and Omicron. Remarkably, increased Spike-BST2 binding is associated with enhanced BST2 downregulation. Therefore, these observations suggest that, in addition to enhancing receptor binding and immune evasion, mutations in the Spike afford more efficient counteraction of BST2, highlighting that BST2 antagonism is important for SARS-CoV-2 infectivity. [ABSTRACT FROM AUTHOR]

• Production of Gag-Spike VLPs using suspension serum-free HEK 293 cells. • Purification of VLPs by ultracentrifugation, tangential flow filtration and affinity chromatography. • Incorporation of SARS-CoV-2 components into Gag-Spike VLPs. • Evaluation of humoral and cellular responses to Gag-Spike VLPs through mouse studies. The virus-like particle (VLP) platform is a robust inducer of humoral and cellular immune responses; hence, it has been used in vaccine development for several infectious diseases. In the current work, VLPs carrying SARS-CoV-2 Spike (S) protein (Wuhan strain) with an HIV-1 Gag core were produced using suspension HEK 293SF-3F6 cells by transient transfection. The Gag was fused with green fluorescent protein (GFP) for rapid quantification of the VLPs. Five different versions of Gag-Spike VLPs (Gag-S-VLPs) consisting of Gag-S alone or combined with other SARS-CoV-2 components, namely Gag-S-Nucleocapsid (N), Gag-S-Matrix (M), Gag-S-Envelope (E), Gag-S-MEN, along with Gag alone were produced and processed by clarification, nuclease treatment, concentration by tangential flow filtration (TFF) and diafiltration. A pilot mouse study was performed to evaluate the immunogenicity of the Gag-S-VLPs through the measurement of the humoral and/or cellular responses against all the mentioned SARS-CoV-2 components. Antibody response to Spike was observed in all variants. The highest number of Spike-specific IFN-γ + T cells was detected with Gag-S-VLPs. No induction of antigen-specific cellular responses to M, N or E proteins were detected with any of the Gag-S, M, E/or N VLPs tested. Therefore, the Gag-S-VLP, by reason of consistently eliciting strong antigen-specific cellular and antibody responses, was selected for further evaluation. The purification process was improved by replacing the conventional centrifugation by serial microfiltration in the clarification step, followed by Spike-affinity chromatography to get concentrated VLPs with higher purity. Three different doses of Gag-S-VLP in conjunction with two adjuvants (Quil-A or AddaVax) were used to assess the dose-dependent antigen-specific cellular and antibody responses in mice. The Gag-S-VLP adjuvanted with Quil-A resulted in a stronger Spike-specific cellular response compared to that adjuvanted with AddaVax. A strong spike neutralisation activity was observed for all doses, independent of the adjuvant combination. [ABSTRACT FROM AUTHOR]

The COVID-19 is recognized as one of the deadly disease in the history of human life. It is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since its first case appeared in December 2019 in Wuhan, China, number of COVID-19 cases are still growing worldwide, till now number of confirmed COVID-19 cases reported globally are 594 million and number of fatalities are 6.29 million. It creates panic situation on every individual as well as put an extraordinary challenge on every country, especially on the health care system. The ruthlessness of the disease and its noxious complexities need development of suitable and effective drug on urgent basis to prevent as well as treat COVID-19. Though specific drug with proper efficacy is not yet found, a number of research and clinical trials are still going on to check the suitability and effectiveness of existing drug, i.e. repurposed drug to treat patients of COVID-19. In this article, repurposed drug—arbidol, baricitinib, favipiravir, galidesivir and ribavirin are reported by using Conceptual Density Functional Theory (CDFT) approach. Optimization energy, spin multiplicity, zero point energy correction, CDFT-based descriptors, optical and thermochemical properties of these repurposed drugs are computed and analysed. Result signify that favipiravir is the most reactive compound whereas ribavirin is found as the most stable among these molecular species. Favipiravir has the lowest thermal energy, heat capacity and entropy, whereas arbidol has the maximum thermal energy, heat capacity and entropy. There is an interesting correlation found between optimization energy, zero point energy correction, polarizability and thermochemical properties of these repurposed drugs. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is the reason for coronavirus disease 2019 (COVID-19), which was first diagnosed in Wuhan, China. COVID-19 has since led to a worldwide pandemic. SARS-CoV-2 infection increases the risk of thrombotic events, including ischemic strokes. There are limited data on ischemic stroke associated with COVID-19. The aim of our study was to determine the effects of SARS-CoV-2 infection on ischemic stroke. A total of 248 ischemic stroke and transient ischemic attack (TIA) patients hospitalized in our neurology intensive care and stroke units between March 2020 and January 2022 were retrospectively analyzed. Two hundred and five stroke patients were diagnosed with COVID-19- negative strokes. COVID-19-positive patients were first isolated from the relevant units, and neurological follow-up was performed. Forty-three patients who were diagnosed with COVID-19-related ischemic stroke and survived at the end of the isolation period were transferred and followed up in the neurology intensive care and stroke unit. Stroke classifications, vascular risk factors, clinical course, disease severity, laboratory parameters, recanalization treatment results, and mortality rates of ischemic strokes in patients with positive or negative COVID-19 infection were evaluated. COVID19-positive and COVID-19-negative stroke patients had similar characteristics of age, gender, vascular risk factors and stroke subtype. Cryptogenic stroke was the most common type of stroke in both groups. TIA and small vessel diseases were detected only in the COVID-19-negative group. COVID-19-positive stroke patients had lower lymphocyte counts and higher procalcitonin, troponin and fibrinogen levels. Ischemic strokes had similar clinical characteristics and did not show a different course or prognosis in COVID-19-positive and COVID-19-negative stroke patients. [ABSTRACT FROM AUTHOR]

Better understanding of social media uses in crisis situations can help improve disaster management by policy-makers, organizations, businesses, and members of the public. It can also build theoretical understanding of how social life and citizenship incorporate social media usage. This study tracks the evolution of public sentiment in Wuhan, China, during the first 12 weeks after the identification of COVID-19 on the Chinese microblogging platform Sina Weibo. Data consist of 133,079 original Sina Weibo posts dealing with the novel coronavirus. The relative prevalence of eight different emotion groups is traced longitudinally using the ROST Content Mining System and the Emotion Vocabulary of Dalian University of Technology. The study finds a progression from confusion/fear, to disappointment/frustration, to depression/anxiety, then finally to happiness/gratitude. It argues that this progression indexes the changing affective energies of digital medical citizenship, which in turn indicates the context for intervention in future crises. [ABSTRACT FROM AUTHOR]

In this study, a cost-effective sandwich ELISA test, based on polyclonal antibodies, for routine quantification SARS-CoV-2 nucleocapsid (N) protein was developed. The recombinant N protein was produced and used for the production of mice and rabbit antisera. Polyclonal N protein-specific antibodies served as capture and detection antibodies. The prototype ELISA has LOD 0.93 ng/mL and LOQ 5.3 ng/mL, with a linear range of 1.52–48.83 ng/mL. N protein heat pretreatment (56 °C, 1 h) decreased, while pretreatment with 1% Triton X-100 increased analytical ELISA sensitivity. The diagnostic specificity of ELISA was 100% (95% CI, 91.19–100.00%) and sensitivity was 52.94% (95% CI, 35.13–70.22%) compared to rtRT-PCR (Ct < 40). Profoundly higher sensitivity was obtained using patient samples mostly containing Wuhan-similar variants (Wuhan, alpha, and delta), 62.50% (95% CI, 40.59 to 81.20%), in comparison to samples mostly containing Wuhan-distant variants (Omicron) 30.00% (6.67–65.25%). The developed product has relatively high diagnostic sensitivity in relation to its analytical sensitivity due to the usage of polyclonal antibodies from two species, providing a wide repertoire of antibodies against multiple N protein epitopes. Moreover, the fast, simple, and inexpensive production of polyclonal antibodies, as the most expensive assay components, would result in affordable antigen tests. [ABSTRACT FROM AUTHOR]

Since the first few cases of pneumonia attributed to infection with the highly contagious novel coronavirus 2 (SARs-CoV-2) were detected in Wuhan, China, in December 2019, imaging has proven an invaluable diagnostic tool throughout the resulting global pandemic. This review describes the imaging features of severe pulmonary disease caused by SARs-CoV-2, named COVID-19 by the World Health Organization (WHO), particularly focussing on computed tomography (CT). CT plays an important role in understanding the pathology behind the progression of disease, as well as helping to identify the potential complications of COVID-19 pneumonia and recognising possible alternative or concurrent diagnoses. This review also focusses on follow-up imaging of survivors of COVID-19, which continues to contribute substantially to our understanding of the longer-term pulmonary changes in patients who have survived severe COVID-19 pneumonia. [ABSTRACT FROM AUTHOR]

Coronavirus infection disease-19 (COVID-19) is a worldwide catastrophic emergency that first appeared in late 2019, in Wuhan, China. COVID-19 is a multitropism disease that first affects lung tissue. However, extrapulmonary manifestations have been suspected from the first COVID-19 cases. The ocular signs and symptoms were from the early changes that occur during the course of the disease. Changes in the anterior eye segment have a relatively higher incidence than the posterior eye segment. Of which, conjunctivitis, COVID-19 pharyngioceratoconjuctivitis, iridocyclitis, corneal punctate epitheliopathy, and pathomorphological changes in the physio-anatomy of the anterior eye segment. The potential pathogenesis includes direct penetration of the virus into the eye (conjunctiva, lumbus, and cornea) or due to a systemic pathway through viremia, as well as due to autoimmune antibodies against the ocular structure (immune privilege). The presence of ocular manifestations of the external anterior fibrous layer suggests a mild course of the disease. [ABSTRACT FROM AUTHOR]

The coronavirus SARS-CoV-2 protects its RNA from being recognized by host immune responses by methylation of its 5' end, also known as capping. This process is carried out by two enzymes, non-structural protein 16 (NSP16) containing 2'-O-methyltransferase and NSP14 through its N7 methyltransferase activity, which are essential for the replication of the viral genome as well as evading the host's innate immunity. NSP10 acts as a crucial cofactor and stimulator of NSP14 and NSP16. To further understand the role of NSP10, we carried out a comprehensive analysis of >13 million globally collected whole-genome sequences (WGS) of SARS-CoV-2 obtained from the Global Initiative Sharing All Influenza Data (GISAID) and compared it with the reference genome Wuhan/WIV04/2019 to identify all currently known variants in NSP10. T12I, T102I, and A104V in NSP10 have been identified as the three most frequent variants and characterized using X-ray crystallography, biophysical assays, and enhanced sampling simulations. In contrast to other proteins such as spike and NSP6, NSP10 is significantly less prone to mutation due to its crucial role in replication. The functional effects of the variants were examined for their impact on the binding affinity and stability of both NSP14-NSP10 and NSP16-NSP10 complexes. These results highlight the limited changes induced by variant evolution in NSP10 and reflect on the critical roles NSP10 plays during the SARS-CoV-2 life cycle. These results also indicate that there is limited capacity for the virus to overcome inhibitors targeting NSP10 via the generation of variants in inhibitor binding pockets. [ABSTRACT FROM AUTHOR]