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The SARS-CoV-2 pandemic has heightened concerns about immunological protection, especially for individuals with inborn errors of immunity (IEI). While COVID-19 vaccines elicit strong immune responses in healthy individuals, their effectiveness in IEI patients remains unclear, particularly against new viral variants and vaccine formulations. This uncertainty has led to anxiety, prolonged self-isolation, and repeated vaccinations with uncertain benefits among IEI patients. Despite some level of immune response from vaccination, the definition of protective immunity in IEI individuals is still unknown. Given their susceptibility to severe COVID-19, strategies such as immunoglobulin replacement therapy (IgRT) and monoclonal antibodies have been employed to provide passive immunity, and protection against both current and emerging variants. This review examines the efficacy of COVID-19 vaccines and antibody-based therapies in IEI patients, their capacity to recognize viral variants, and the necessary advances required for the ongoing protection of people with IEIs. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic kidney disease on haemodialysis (HD) were given priority COVID-19 vaccination due to increased disease risk. The immune response to COVID-19 vaccination in patients on HD was diminished compared to healthy individuals in 2-dose studies. This study aimed to evaluate seroconversion rate, neutralizing antibody (nAB) levels and longitudinal antibody dynamics to 3-dose heterologous vaccination against COVID-19 in a cohort of HD patients compared to healthy controls and assess patient factors associated with antibody levels. Methods: This study was a case–control longitudinal evaluation of nAB dynamics in 74 HD patients compared to 37 healthy controls in a low/middle income setting. Corresponding samples were obtained from the two cohorts at time-points (TP) 1–1-month post 2nd dose of AZD1222 vaccine, TP2- 4 months post 2nd dose, TP4- 2 weeks post 3rd dose with BNT162b2 vaccine, TP5-5 months post 3rd dose and TP6-12 months post 3rd dose. Additional data is available at TP0- pre 2nd dose and TP3- 6 months post 2nd dose in HC and HD cohorts respectively. Anti-SARS-CoV-2 nAB were detected using Genscript cPassTM pseudoviral neutralization kit. Demographic and clinical details were obtained using an interviewer administered questionnaire. Results: Cohorts were gender matched while mean age of the HD cohort was 54.1yrs (vs HCs mean age, 42.6yrs, p < 0.05). Percentage seroconverted and mean/median antibody level (MAB) in the HD cohort vs HCs at each sampling point were, TP1-83.7% vs 100% (p < 0.05), MAB-450 IU/ml vs 1940 IU/ml (p < 0.0001); TP2-71.4% vs 100%, (p < 0.001), MAB- 235 IU/ml vs 453 IU/ml, (p < 0.05); TP4-95.2% vs 100% (p > 0.05), MAB-1029 IU/ml vs 1538 IU/ml (p < 0.0001); TP5-100% vs 100%, MAB-1542 IU/ml vs 1741IU/ml (p > 0.05); TP6-100% vs 100%, MAB-1961 IU/ml vs 2911 IU/ml (p > 0.05). At TP2, patients aged < 60 years (p < 0.001) were associated with maintaining seropositivity compared to patients > 60 years. Conclusion: Two dose vaccination of haemodialysis patients provided poor nAB levels which improved markedly following 3rd dose vaccination, the effect of which was long- lasting with high nAB levels in both patients and controls detectable at 1 year follow-up. [ABSTRACT FROM AUTHOR]

About four years have passed since the detection of the first cases of COVID-19 in China. During this lethal pandemic, millions of people have lost their lives around the world. Since the first waves of COVID-19 infection, various pharmacotherapeutic agents have been examined in the management of COVID-19. Despite all these efforts in pharmacotherapy, drug repurposing, and design and development of new drugs, multiple organ involvement and various complications occurred during COVID-19. Some of these complications became chronic and long-lasting which led to the "long COVID" syndrome appearance. Therefore, the best way to eradicate this pandemic is prophylaxis through mass vaccination. In this regard, various vaccine platforms including inactivated vaccines, nucleic acid-based vaccines (mRNA and DNA vaccines), adenovirus-vectored vaccines, and protein-based subunit vaccines have been designed and developed to prevent or reduce COVID-19 infection, hospitalization, and mortality rates. In this focused review, at first, the most commonly reported clinical presentations of COVID-19 during these four years have been summarized. In addition, different therapeutic regimens and their latest status in COVID-19 management have been listed. Furthermore, the "long COVID" and related signs, symptoms, and complications have been mentioned. At the end, the effectiveness of available COVID-19 vaccines with different platforms against early SARS-CoV-2 variants and currently circulating variants of interest (VOI) and the necessity of booster vaccine shots have been summarized and discussed in more detail. [ABSTRACT FROM AUTHOR]

Coronaviruses are a large family of enveloped RNA viruses found in numerous animal species. They are well known for their ability to cross species barriers and have been transmitted from bats or intermediate hosts to humans on several occasions. Four of the seven human coronaviruses (hCoVs) are responsible for approximately 20% of common colds (hCoV-229E, -NL63, -OC43, -HKU1). Two others (SARS-CoV-1 and MERS-CoV) cause severe and frequently lethal respiratory syndromes but have only spread to very limited extents in the human population. In contrast the most recent human hCoV, SARS-CoV-2, while exhibiting intermediate pathogenicity, has a profound impact on public health due to its enormous spread. In this review, we discuss which initial features of the SARS-CoV-2 Spike protein and subsequent adaptations to the new human host may have helped this pathogen to cause the COVID-19 pandemic. Our focus is on host forces driving changes in the Spike protein and their consequences for virus infectivity, pathogenicity, immune evasion and resistance to preventive or therapeutic agents. In addition, we briefly address the significance and perspectives of broad-spectrum therapeutics and vaccines. [ABSTRACT FROM AUTHOR]

Background: Since the beginning of SARS-CoV-2 pandemic, numerous variants have emerged as a result of mutations occurring in earlier strains. A number of these variants have been linked with waves of widespread infections. The importance of the Variants of Concern (VOCs) lies in increased transmissibility, morbidity, and mortality, as well as escaping detection by conventional methods and resistance to treatment and vaccines. Aim of this study: Our aim is to screen for the presence of six SARS-CoV-2 variants in Egypt, for better understanding of its epidemiology during the epidemic. Methods: In this study, 2650 SARS-Cov-2 RNA positive nasopharyngeal specimens were collected at the Reference Laboratory of Egyptian University Hospitals (RLEUH) during the period from December 2020 through October 2021. All the samples were subjected to AllPlex SARSCoV-2 Master assay, Variant I, II and Novaplex Variant IV Assays. Six VOCs could be detected by this method, which are alpha, beta, gamma, delta, delta plus and epsilon. Results: According to our data, the most detected variant was delta variant comprising 1308 (49%) of the cases. This was followed by alpha variant 121 (5%), delta plus 57 (2%) and gamma 8 (0.3%). 1156 (44%) of the cases were designated as other variants. Beta and epsilon variants were not detected in our study. Conclusions: Our data show that multiplex PCR assays are helpful in the characterization of the genomic epidemiology of SARSCOV-2. Although the new generation sequencing remains the gold standard for surveillance of variants, AllPlexTM Assays can provide a rapid and affordable option. [ABSTRACT FROM AUTHOR]

Since the COVID-19 outbreak, the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) virus has evolved into variants with varied infectivity. Vaccines developed against COVID-19 infection have boosted immunity, but there is still uncertainty on how long the immunity from natural infection or vaccination will last. The present study attempts to outline the present level of information about the contagiousness and spread of SARS-CoV-2 variants of interest and variants of concern (VOCs). The keywords like COVID-19 vaccine types, VOCs, universal vaccines, bivalent, and other relevant terms were searched in NCBI, Science Direct, and WHO databases to review the published literature. The review provides an integrative discussion on the current state of knowledge on the type of vaccines developed against SARS-CoV-2, the safety and efficacy of COVID-19 vaccines concerning the VOCs, and prospects of novel universal, chimeric, and bivalent mRNA vaccines efficacy to fend off existing variants and other emerging coronaviruses. Genomic variation can be quite significant, as seen by the notable differences in impact, transmission rate, morbidity, and death during several human coronavirus outbreaks. Therefore, understanding the amount and characteristics of coronavirus genetic diversity in historical and contemporary strains can help researchers get an edge over upcoming variants. [ABSTRACT FROM AUTHOR]

The continuous emergence of SARS-CoV-2 variants has led to a protracted global COVID-19 pandemic with significant impacts on public health and global economy. While there are currently available SARS-CoV-2 vaccines and therapeutics, most of the FDA-approved antiviral agents directly target viral proteins. However, inflammation is the initial immune pathogenesis induced by SARS-CoV-2 infection, there is still a need to find additional agents that can control the virus in the early stages of infection to alleviate disease progression for the next pandemic. Here, we find that both the spike protein and its receptor CD147 are crucial for inducing inflammation by SARS-CoV-2 in THP-1 monocytic cells. Moreover, we find that 3-epi-betulin, isolated from Daphniphyllum glaucescens, reduces the level of proinflammatory cytokines induced by SARS-CoV-2, consequently resulting in a decreased viral RNA accumulation and plaque formation. In addition, 3-epi-betulin displays a broad-spectrum inhibition of entry of SARS-CoV-2 pseudoviruses, including Alpha (B.1.1.7), Eplison (B.1.429), Gamma (P1), Delta (B.1.617.2) and Omicron (BA.1). Moreover, 3-epi-betulin potently inhibits SARS-CoV-2 infection with an EC50 of <20 μM in Calu-3 lung epithelial cells. Bioinformatic analysis reveals the chemical interaction between the 3-epi-betulin and the spike protein, along with the critical amino acid residues in the spike protein that contribute to the inhibitory activity of 3-epi-betulin against virus entry. Taken together, our results suggest that 3-epi-betulin exhibits dual effect: it reduces SARS-CoV-2-induced inflammation and inhibits virus entry, positioning it as a potential antiviral agent against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Even with its endemic transition, the COVID-19 pandemic remains a public health threat, particularly in the light of emerging variants of concern (VoCs) and the need for pandemic preparedness in the future. In November 2021, the SARS-CoV-2 VoC Omicron emerged and its subvariants BA.1, BA.2 and BA.5 became predominant. Although the protease inhibitor Paxlovid® and the polymerase inhibitors Molnupiravir and Remdesivir were approved as specific antiviral treatment options for COVID-19 patients in the early stages after infection, effective prophylactically acting substances without adverse effects are not available yet. In a recent study, we demonstrated that iota-carrageenan, a sulfated polysaccharide extracted from red seaweed, efficiently inhibits the replication of the SARS-CoV-2 Wuhan Type and the VoCs Alpha, Beta, Gamma and Delta. Now, we extended this study by investigating the antiviral effects of iota-, lambda- and kappa-carrageenans on the VoC Omicron subvariants BA.1, BA.2 and BA.5. Using a VoC Omicron BA.1 spike pseudotyped murine leukemia virus (BA.1 MLVOMVLP) as well as patient-derived SARS-CoV-2 Omicron isolates BA.1, BA.2 and BA.5 (SARS-CoV-2OM BA.1, SARS-CoV-2OM BA.2 and SARS-CoV-2OM BA.5), we demonstrate that iota-carrageenan exhibits similar antiviral activity against all analyzed Omicron subvariants. As with other VoCs shown before, the biologically inert iota-carrageenan was more efficient than kappa- and lambda-carrageenan. Altogether, these results confirm that, independent of the current and potential future variants, the physical barrier provided by iota-carrageenan might be applicable for prophylaxis and early treatment of SARS-CoV-2 infections. [ABSTRACT FROM AUTHOR]

The world is presently in crisis facing an outbreak of a health-threatening microorganism known as COVID-19, responsible for causing uncommon viral pneumonia in humans. The virus was first reported in Wuhan, China, in early December 2019, and it quickly became a global concern due to the pandemic. Challenges in this regard have been compounded by the emergence of several variants such as B.1.1.7, B.1.351, P1, and B.1.617, which show an increase in transmission power and resistance to therapies and vaccines. Ongoing researches are focused on developing and manufacturing standard treatment strategies and effective vaccines to control the pandemic. Despite developing several vaccines such as Pfizer/BioNTech and Moderna approved by the U.S. Food and Drug Administration (FDA) and other vaccines in phase 4 clinical trials, preventive measures are mandatory to control the COVID-19 pandemic. In this review, based on the latest findings, we will discuss different types of drugs as therapeutic options and confirmed or developing vaccine candidates against SARS-CoV-2. We also discuss in detail the challenges posed by the variants and their effect on therapeutic and preventive interventions. [ABSTRACT FROM AUTHOR]

The COVID‐19 pandemic exerted complex pressures on the nephrology community. Despite multiple prior reviews on acute peritoneal dialysis during the pandemic, the effects of COVID‐19 on maintenance peritoneal dialysis patients remain underexamined. This review synthesizes and reports findings from 29 total cases of chronic peritoneal dialysis patients with COVID‐19, encompassing 3 case reports, 13 case series, and 13 cohort studies. When available, data for patients with COVID‐19 on maintenance hemodialysis are also discussed. Finally, we present a chronological timeline of evidence regarding the presence of SARS‐CoV‐2 in spent peritoneal dialysate and explore trends in telehealth as they relate to peritoneal dialysis patients during the pandemic. We conclude that the COVID‐19 pandemic has underscored the efficacy, flexibility, and utility of peritoneal dialysis. [ABSTRACT FROM AUTHOR]

Although the chief of the World Health Organization (WHO) has declared the end of the coronavirus disease 2019 (COVID-19) as a global health emergency, the disease is still a global threat. To be able to manage such pandemics in the future, it is necessary to develop proper strategies and opportunities to protect human life. The data on the SARS-CoV-2 virus must be continuously analyzed, and the possibilities of mutation and the emergence of new, more infectious variants must be anticipated, as well as the options of using different preventive and therapeutic techniques. This is because the fast development of severe acute coronavirus 2 syndrome (SARS-CoV-2) variants of concern have posed a significant problem for COVID-19 pandemic control using the presently available vaccinations. This review summarizes data on the SARS-CoV-2 variants that are responsible for severe COVID-19 and the clinical efficacy of the most commonly used vaccines in clinical practice. The consequences after the disease (long COVID or post-COVID conditions) continue to be the subject of studies and research, and affect social and economic life worldwide. [ABSTRACT FROM AUTHOR]

In 1918 many countries, but not Spain, were fighting World War I. Spanish press could report about the diffusion and severity of a new infection without censorship for the first-time, so that this pandemic is commonly defined as "Spanish flu", even though Spain was not its place of origin. "Spanish flu" was one of the deadliest pandemics in history and has been frequently compared with the coronavirus disease (COVID)-19 pandemic. These pandemics share similarities, being both caused by highly variable and transmissible respiratory RNA viruses, and diversity, represented by diagnostics, therapies, and especially vaccines, which were made rapidly available for COVID-19, but not for "Spanish flu". Most comparison studies have been carried out in the first period of COVID-19, when these resources were either not yet available or their use had not long started. Conversely, we wanted to analyze the role that the advanced diagnostics, anti-viral agents, including monoclonal antibodies, and innovative COVID-19 vaccines, may have had in the pandemic containment. Early diagnosis, therapies, and anti-COVID-19 vaccines have markedly reduced the pandemic severity and mortality, thus preventing the collapse of the public health services. However, their influence on the reduction of infections and re-infections, thus on the transition from pandemic to endemic condition, appears to be of minor relevance. The high viral variability of influenza and coronavirus may probably be contained by the development of universal vaccines, which are not easy to be obtained. The only effective weapon still remains the disease prevention, to be achieved with the reduction of promiscuity between the animal reservoirs of these zoonotic diseases and humans. [ABSTRACT FROM AUTHOR]

The severity of COVID-19 is a result of the complex interplay between various branches of the immune system. However, our understanding of the role of neutralizing antibodies and the activation of cellular immune response in COVID-19 pathogenesis remains limited. In this study, we investigated neutralizing antibodies in patients with mild, moderate, and severe COVID-19, analyzing their cross-reactivity with the Wuhan and Omicron variants. We also assessed the activation of the immune response by measuring serum cytokines in patients with mild, moderate, and severe COVID-19. Our findings suggest the early activation of neutralizing antibodies in moderate COVID-19 compared to mild cases. We also observed a strong correlation between the cross-reactivity of neutralizing antibodies to the Omicron and Wuhan variants and the severity of the disease. In addition, we found that Th1 lymphocyte activation was present in mild and moderate cases, while inflammasomes and Th17 lymphocytes were activated in severe COVID-19. In conclusion, our data indicate that the early activation of neutralizing antibodies is evident in moderate COVID-19, and there is a strong correlation between the cross-reactivity of neutralizing antibodies and the severity of the disease. Our findings suggest that the Th1 immune response may play a protective role, while inflammasome and Th17 activation may be involved in severe COVID-19. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic caused by SARS-CoV-2, new waves have been associated with new variants and have the potential to escape vaccinations. Therefore, it is useful to conduct retrospective genomic surveillance research. Herein, we present a detailed analysis of 88 SARS-CoV-2 genomes belonging to samples taken from COVID-19 patients from October 2020 to April 2021 at the "Reina Sofía" Hospital (Murcia, Spain) focused to variant appeared later. The results at the mentioned stage show the turning point since the 20E (EU1) variant was still prevalent (71.6%), but Alpha was bursting to 14.8%. Concern mutations have been found in 5 genomes classified as 20E (EU1), which were not characteristic of this still little evolved variant. Most of those mutations are found in the spike protein, namely Δ69–70, E484K, Q675H and P681H. However, a relevant deletion in ORF1a at positions 3675–3677 was also identified. These mutations have been reported in many later SARS-CoV-2 lineages, including Omicron. Taken together, our data suggest that preferential emergence mutations could already be present in the early converging evolution. Aside from this, the molecular information has been contrasted with clinical data. Statistical analyses suggest that the correlation between age and severity criteria is significantly higher in the viral samples with more accumulated changes. [ABSTRACT FROM AUTHOR]

Background: Mathematical models to forecast the risk trend of the COVID-19 pandemic timely are of great significance to control the pandemic, but the requirement of manual operation and many parameters hinders their efficiency and value for application. This study aimed to establish a convenient and prompt one for monitoring emerging infectious diseases online and achieving risk assessment in real time. Methods: The Optimized Moving Average Prediction Limit (Op-MAPL) algorithm model analysed real-time COVID-19 data online and was validated using the data of the Delta variant in India and the Omicron in the United States. Then, the model was utilized to determine the infection risk level of the Omicron in Shanghai and Beijing. Results: The Op-MAPL model can predict the epidemic peak accurately. The daily risk ranking was stable and predictive, with an average accuracy of 87.85% within next 7 days. Early warning signals were issued for Shanghai and Beijing on February 28 and April 23, 2022, respectively. The two cities were rated as medium–high risk or above from March 27 to April 20 and from April 24 to May 5, indicating that the pandemic had entered a period of rapid increase. After April 21 and May 26, the risk level was downgraded to medium and became stable by the algorithm, indicating that the pandemic had been controlled well and mitigated gradually. Conclusions: The Op-MAPL relies on nothing but an indicator to assess the risk level of the COVID-19 pandemic with different data sources and granularities. This forward-looking method realizes real-time monitoring and early warning effectively to provide a valuable reference to prevent and control infectious diseases. [ABSTRACT FROM AUTHOR]

Since the end of 2020, multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) have emerged and spread worldwide. Tracking their evolution has been a challenge due to the huge number of positive samples and limited capacities of whole-genome sequencing. Two in-house variant-screening RT-PCR assays were successively designed in our laboratory in order to detect specific known mutations in the spike region and to rapidly detect successively emerging VOCs. The first one (RT-PCR#1) targeted the 69–70 deletion and the N501Y substitution simultaneously, whereas the second one (RT-PCR#2) targeted the E484K, E484Q, and L452R substitutions simultaneously. To evaluate the analytical performance of these two RT-PCRs, 90 negative and 30 positive thawed nasopharyngeal swabs were retrospectively analyzed, and no discordant results were observed. Concerning the sensitivity, for RT-PCR#1, serial dilutions of the WHO international standard SARS-CoV-2 RNA, corresponding to the genome of an Alpha variant, were all detected up to 500 IU/mL. For RT-PCR#2, dilutions of a sample harboring the E484K substitution and of a sample harboring the L452R and E484Q substitutions were all detected up to 1000 IU/mL and 2000 IU/mL, respectively. To evaluate the performance in a real-life hospital setting, 1308 and 915 profiles of mutations, obtained with RT-PCR#1 and RT-PCR#2, respectively, were prospectively compared to next-generation sequencing (NGS) data. The two RT-PCR assays showed an excellent concordance with the NGS data, with 99.8% for RT-PCR#1 and 99.2% for RT-PCR#2. Finally, for each mutation targeted, the clinical sensitivity, the clinical specificity and the positive and negative predictive values showed excellent clinical performance. Since the beginning of the SARS-CoV-2 pandemic, the emergence of variants—impacting the disease's severity and the efficacy of vaccines and therapies—has forced medical analysis laboratories to constantly adapt to the strong demand for screening them. Our data showed that in-house RT-PCRs are useful and adaptable tools for monitoring such rapid evolution and spread of SARS-CoV-2 VOCs. [ABSTRACT FROM AUTHOR]

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued, with the persistent emergence of variants of concern (VOCs). Therefore, this study aimed to track the genomic evolution of SARS-CoV-2 strains by sequencing the spike protein for 29 months, which accounted for the majority of the COVID-19 pandemic period. A total of 109 swabs from patients with confirmed coronavirus disease 2019 (COVID-19) infection were randomly collected between March 2020 and July 2022. After genomic sequencing, we analyzed the naming systems and phylogenetic trees. Five surge peaks of COVID-19 cases have been reported in South Korea, resulting in 14,000,000 cumulative confirmed cases and 17,000 deaths. Among the sequenced samples, 34 wild-type strains and 75 VOCs, including 4 Alpha, 33 Delta, 2 Epsilon, and 36 Omicron VOCs, were identified. Omicron strains were comprised of 8 BA.1.1 (21 K), 27 BA.2 (21 L), and 1 BA.2.12.1 (22C). Phylogenetic analysis of the identified isolates and representative sequences of SARS-CoV-2 strains revealed clusters that presented the WHO VOCs. Specific or unique mutations for each VOC waxed and waned according to the variant waves. Our findings allowed recognition of the overall trends of SARS-CoV-2 isolates, which implicated replication advantage, immune evasion, and disease management. [ABSTRACT FROM AUTHOR]

The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has globally devastated public health, the economies of many countries and quality of life universally. The recent emergence of immune-escaped variants and scenario of vaccinated individuals being infected has raised the global concerns about the effectiveness of the current available vaccines in transmission control and disease prevention. Given the high rate mutation of SARS-CoV-2, an efficacious vaccine targeting against multiple variants that contains virus-specific epitopes is desperately needed. An immunoinformatics approach is gaining traction in vaccine design and development due to the significant reduction in time and cost of immunogenicity studies and increasing reliability of the generated results. It can underpin the development of novel therapeutic methods and accelerate the design and production of peptide vaccines for infectious diseases. Structural proteins, particularly spike protein (S), along with other proteins have been studied intensively as promising coronavirus vaccine targets. Numbers of promising online immunological databases, tools and web servers have widely been employed for the design and development of next generation COVID-19 vaccines. This review highlights the role of immunoinformatics in identifying immunogenic peptides as potential vaccine targets, involving databases, and prediction and characterization of epitopes which can be harnessed for designing future coronavirus vaccines. [ABSTRACT FROM AUTHOR]

The immune response elicited by the current COVID-19 vaccinations declines with time, especially among the immunocompromised population. Furthermore, the emergence of novel SARS-CoV-2 variants, particularly the Omicron variant, has raised serious concerns about the efficacy of currently available vaccines in protecting the most vulnerable people. Several studies have reported that vaccinated people get breakthrough infections amid COVID-19 cases. So far, five variants of concern (VOCs) have been reported, resulting in successive waves of infection. These variants have shown a variable amount of resistance towards the neutralising antibodies (nAbs) elicited either through natural infection or the vaccination. The spike (S) protein, membrane (M) protein, and envelope (E) protein on the viral surface envelope and the N-nucleocapsid protein in the core of the ribonucleoprotein are the major structural vaccine target proteins against COVID-19. Among these targets, S Protein has been extensively exploited to generate effective vaccines against COVID-19. Hence, amid the emergence of novel variants of SARS-CoV-2, we have discussed their impact on currently available vaccines. We have also discussed the potential roles of S Protein in the development of novel vaccination approaches to contain the negative consequences of the variants' emergence and acquisition of mutations in the S Protein of SARS-CoV-2. Moreover, the implications of SARS-CoV-2's structural proteins were also discussed in terms of their variable potential to elicit an effective amount of immune response. [ABSTRACT FROM AUTHOR]

Mutations allow viruses to continuously evolve by changing their genetic code to adapt to the hosts they infect. It is an adaptive and evolutionary mechanism that helps viruses acquire characteristics favoring their survival and propagation. The COVID-19 pandemic declared by the WHO in March 2020 is caused by the SARS-CoV-2 virus. The non-stop adaptive mutations of this virus and the emergence of several variants over time with characteristics favoring their spread constitute one of the biggest obstacles that researchers face in controlling this pandemic. Understanding the mutation mechanism allows for the adoption of anticipatory measures and the proposal of strategies to control its propagation. In this study, we focus on the mutations of this virus, and we propose the SARSMutOnto ontology to model SARS-CoV-2 mutations reported by Pango researchers. A detailed description is given for each mutation. The genes where the mutations occur and the genomic structure of this virus are also included. The sub-lineages and the recombinant sub-lineages resulting from these mutations are additionally represented while maintaining their hierarchy. We developed a Python-based tool to automatically generate this ontology from various published Pango source files. At the end of this paper, we provide some examples of SPARQL queries that can be used to exploit this ontology. SARSMutOnto might become a 'wet bench' machine learning tool for predicting likely future mutations based on previous mutations. [ABSTRACT FROM AUTHOR]

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Since early 2020, the world has been embroiled in an ongoing viral pandemic with SARS‐CoV‐2 and emerging variants resulting in mass morbidity and an estimated 6 million deaths globally. The scientific community pivoted rapidly, providing unique and innovative means to identify infected individuals, technologies to evaluate immune responses to infection and vaccination, and new therapeutic strategies to treat infected individuals. Never before has immunology been so critically at the forefront of combatting a global pandemic. It has now become evident that not just antibody responses, but formation and durability of immune memory cells following vaccination are associated with protection against severe disease from SARS‐CoV‐2 infection. Furthermore, the emergence of variants of concern (VoC) highlight the need for immunological markers to quantify the protective capacity of Wuhan‐based vaccines. Thus, harnessing and modulating the immune response is key to successful vaccination and treatment of disease. We here review the latest knowledge about immune memory generation and durability following natural infection and vaccination, and provide insights into the attributes of immune memory that may protect from emerging variants. [ABSTRACT FROM AUTHOR]

An important unmet need revealed by the COVID-19 pandemic is the near-real-time identification of potentially fitness-altering mutations within rapidly growing SARS-CoV-2 lineages. Although powerful molecular sequence analysis methods are available to detect and characterize patterns of natural selection within modestly sized gene-sequence datasets, the computational complexity of these methods and their sensitivity to sequencing errors render them effectively inapplicable in large-scale genomic surveillance contexts. Motivated by the need to analyze new lineage evolution in near-real time using large numbers of genomes, we developed the Rapid Assessment of Selection within CLades (RASCL) pipeline. RASCL applies state of the art phylogenetic comparative methods to evaluate selective processes acting at individual codon sites and across whole genes. RASCL is scalable and produces automatically updated regular lineage-specific selection analysis reports: even for lineages that include tens or hundreds of thousands of sampled genome sequences. Key to this performance is (i) generation of automatically subsampled high quality datasets of gene/ORF sequences drawn from a selected "query" viral lineage; (ii) contextualization of these query sequences in codon alignments that include high-quality "background" sequences representative of global SARS-CoV-2 diversity; and (iii) the extensive parallelization of a suite of computationally intensive selection analysis tests. Within hours of being deployed to analyze a novel rapidly growing lineage of interest, RASCL will begin yielding JavaScript Object Notation (JSON)-formatted reports that can be either imported into third-party analysis software or explored in standard web-browsers using the premade RASCL interactive data visualization dashboard. By enabling the rapid detection of genome sites evolving under different selective regimes, RASCL is well-suited for near-real-time monitoring of the population-level selective processes that will likely underlie the emergence of future variants of concern in measurably evolving pathogens with extensive genomic surveillance. [ABSTRACT FROM AUTHOR]

The vaccine weapon has resulted in being essential in fighting the COVID-19 outbreak, but it is not fully preventing infection due to an alarming spreading of several identified variants of concern. In fact, the recent emergence of variants has pointed out how the SARS-CoV-2 pandemic still represents a global health threat. Moreover, oral antivirals also develop resistance, supporting the need to find new targets as therapeutic tools. However, cocktail therapy is useful to reduce drug resistance and maximize vaccination efficacy. Natural products and metal-drug-based treatments have also shown interesting antiviral activity, representing a valid contribution to counter COVID-19 outbreak. This report summarizes the available evidence which supports the use of approved drugs and further focuses on significant clinical trials that have investigated the safety and efficacy of repurposing drugs and new molecules in different COVID-19 phenotypes. To date, there are many individuals vulnerable to COVID-19 exhibiting severe symptoms, thus characterizing valid therapeutic strategies for better management of the disease is still a challenge. [ABSTRACT FROM AUTHOR]

As of now, the COVID-19 pandemic has become uncontrolled and is spreading widely throughout the world. Additionally, new variants of the mutated viral variants have been found in some countries that are more dangerous than the original strain. Even vaccines cannot produce complete protective immunity against the newer strains of SARS-CoV-2. Due to such a dreadful situation, lots of fear and depression have been created among the public. People are looking for the treatment of the disease at any cost and there is a race in the market to provide treatment and make money, whether it is effective or not! In such a condition, many fraud products, remedies, and myths have come into the market, which is falsely claimed to be effective for the disease and can harm the patients. Hence, FDA has banned such products and remedies. In this review, we have compiled all such fraudulent and pseudosciences identified for COVID-19. Currently, in the pandemic time, health agencies are approving the repurposed medicines based on the small-scale clinical data for emergency uses that become ineffective (most of the cases) after large randomized clinical studies. Proper vigilance strategies need to be defined by the regulatory agencies of the nation and routine awareness programs shall be arranged for educating the people and healthcare workers on routine updates. [ABSTRACT FROM AUTHOR]

This paper provides a comprehensive summary of evidence to explore and position the role of serology testing in the context of coronavirus disease 19 (COVID-19) immunization and policy response in the Asia-Pacific (APAC) region. The document builds on a review of academic literature and existing policies followed by a process of discussion, validation, and feedback by a group of six experts. Six countries and territories—Australia, Hong Kong, India, Indonesia, Thailand, and Taiwan—were sampled to highlight the differing contexts and scenarios in the region. The review includes an overview of (1) the impact of the COVID-19 pandemic, including the emergence of Variants of Concern (VOCs), especially Omicron, (2) the introduction of immunization, (3) the available testing options and potential use of serology testing, (4) the landscape of guidelines and recommendations for their use, and (5) the barriers and challenges to implementing serology testing as a tool to support COVID-19 immunization. Based on the findings, the co-authors propose a set of recommendations to resolve knowledge gaps, to include the use of serology testing as part of the policy response, and to ensure adequate means of implementation. This paper's target audience includes members of the academic community, medical societies, health providers and practitioners, and decision-makers. [ABSTRACT FROM AUTHOR]

Over the past two years, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused hundreds of millions of infections, resulting in an unprecedented pandemic of coronavirus disease 2019 (COVID-19). As the virus spreads through the population, ongoing mutations and adaptations are being discovered. There is now substantial clinical evidence that demonstrates the SARS-CoV-2 variants have stronger transmissibility and higher virulence compared to the wild-type strain of SARS-CoV-2. Hence, development of vaccines against SARS-CoV-2 variants to boost individual immunity has become essential. However, current treatment options are limited for COVID-19 caused by the SARS-CoV-2 variants. In this review, we describe current distribution, variation, biology, and clinical features of COVID-19 caused by SARS-CoV-2 variants (including Alpha (B.1.1.7 Lineage) variant, Beta (B.1.351 Lineage) variant, Gamma (P.1 Lineage) variant, Delta (B.1.617.2 Lineage) variant, and Omicron (B.1.1.529 Lineage) variant and others. In addition, we review currently employed vaccines in clinical or preclinical phases as well as potential targeted therapies in an attempt to provide better preventive and treatment strategies for COVID-19 caused by different SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]

Social distancing measures are proposed as the primary strategy to curb the spread of the COVID-19 pandemic. Therefore, identifying situations where these protocols are violated has implications for curtailing the spread of the disease and promoting a sustainable lifestyle. This paper proposes a novel computer vision-based system to analyze CCTV footage to provide a threat level assessment of COVID-19 spread. The system strives to holistically interpret the information in CCTV footage spanning multiple frames to recognize instances of various violations of social distancing protocols, across time and space, as well as identification of group behaviors. This functionality is achieved primarily by utilizing a temporal graph-based structure to represent the information of the CCTV footage and a strategy to holistically interpret the graph and quantify the threat level of the given scene. The individual components are evaluated in a range of scenarios, and the complete system is tested against human expert opinion. The results reflect the dependence of the threat level on people, their physical proximity, interactions, protective clothing, and group dynamics, with a system performance of 76% accuracy. [ABSTRACT FROM AUTHOR]

The ongoing COVID-19 outbreak, initially identified in Wuhan, China, has impacted people all over the globe and new variants of concern continue to threaten hundreds of thousands of people. The delta variant (first reported in India) is currently classified as one of the most contagious variants of SARS-CoV-2. It is estimated that the transmission rate of delta variant is 225% times faster than the alpha variant, and it is causing havoc worldwide (especially in the USA, UK, and South Asia). The mutations found in the spike protein of delta variant make it more infective than other variants in addition to ruining the global efficacy of available vaccines. In the current study, an in silico reverse vaccinology approach was applied for multi-epitope vaccine construction against the spike protein of delta variant, which could induce an immune response against COVID-19 infection. Non-toxic, highly conserved, non-allergenic and highly antigenic B-cell, HTL, and CTL epitopes were identified to minimize adverse effects and maximize the efficacy of chimeric vaccines that could be developed from these epitopes. Finally, V1 vaccine construct model was shortlisted and 3D modeling was performed by refinement, docking against HLAs and TLR4 protein, simulation and in silico expression. In silico evaluation showed that the designed chimeric vaccine could elicit an immune response (i.e., cell-mediated and humoral) identified through immune simulation. This study could add to the efforts of overcoming global burden of COVID-19 particularly the variants of concern. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 pandemic, reported for the first time at the end of 2019 in the city of Wuhan (China), has spread worldwide in three years; it lead to the infection of more than 500 million people and about six million dead. SARS-CoV-2 has proved to be very dangerous for human health. Therefore, several efforts have been made in studying this virus. In a short time, about one year, the mechanisms of SARS-CoV-2 infection and duplication and its physiological effect on human have been pointed out. Moreover, different vaccines against it have been developed and commercialized. To date, more than 11 billion doses have been inoculated all over the world. Since the beginning of the pandemic, SARS-CoV-2 has evolved; it has done so by accumulating mutations in the genome, generating new virus versions showing different characteristics, and which have replaced the pre-existing variants. In general, it has been observed that the new variants show an increased infectivity and cause milder symptoms. The latest isolated Omicron variants contain more than 50 mutations in the whole genome and show an infectivity 10-folds higher compared to the wild-type strain. Here, we analyse the SARS-CoV-2 variants from a phylogenetic point of view and hypothesize a future scenario for SARS-CoV-2, by following its evolution to date. [ABSTRACT FROM AUTHOR]

Our understanding of the immune responses that follow SARS-CoV-2 infection and vaccination has progressed considerably since the COVID-19 pandemic was first declared on the 11th of March in 2020. Recovery from infection is associated with the development of protective immune responses, although over time these become less effective against new emerging SARS-CoV-2 variants. Consequently, reinfection with SARS-CoV-2 variants is not infrequent and has contributed to the ongoing pandemic. COVID-19 vaccines have had a tremendous impact on reducing infection and particularly the number of deaths associated with SARS-CoV-2 infection. However, waning of vaccine induced immunity plus the emergence of new variants has necessitated the use of boosters to maintain the benefits of vaccination in reducing COVID-19 associated deaths. Boosting is also beneficial for individuals who have recovered from COVID-19 and developed natural immunity, also enhancing responses immune responses to SARS-CoV-2 variants. This review summarizes our understanding of the immune responses that follow SARS-CoV-2 infection and vaccination, the risks of reinfection with emerging variants and the very important protective role vaccine boosting plays in both vaccinated and previously infected individuals. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 pandemic remains a major public health threat, especially due to newly emerging SARS-CoV-2 Variants of Concern (VoCs), which are more efficiently transmitted, more virulent, and more able to escape naturally acquired and vaccine-induced immunity. Recently, the protease inhibitor Paxlovid® and the polymerase inhibitor molnupiravir, both targeting mutant-prone viral components, were approved for high-risk COVID-19 patients. Nevertheless, effective therapeutics to treat COVID-19 are urgently needed, especially small molecules acting independently of VoCs and targeting genetically stable cellular pathways which are crucial for viral replication. Pamapimod is a selective inhibitor of p38 Mitogen-Activated Protein Kinase alpha (p38 MAPKα) that has been extensively clinically evaluated for the treatment of rheumatoid arthritis. Signaling via p38 has recently been described as a key pathway for the replication of SARS-CoV-2. Here, we reveal that the combination of pamapimod with pioglitazone, an anti-inflammatory and approved drug for the treatment of type 2 diabetes, possesses potent and synergistic activity to inhibit SARS-CoV-2 replication in vitro. Both drugs showed similar antiviral potency across several cultured cell types and similar antiviral activity against SARS-CoV-2 Wuhan type, and the VoCs Alpha, Beta, Gamma, Delta, and Omicron. These data support the combination of pamapimod and pioglitazone as a potential therapy to reduce duration and severity of disease in COVID-19 patients, an assumption currently evaluated in an ongoing phase II clinical study. [ABSTRACT FROM AUTHOR]

Since the start of SARS-CoV-2 pandemic, children aged ≤ 12 years have always been defined as underrepresented in terms of SARS-CoV-2 infections' frequency and severity. By correlating SARS-CoV-2 transmission dynamics with clinical and virological features in 612 SARS-CoV-2 positive patients aged ≤ 12 years, we demonstrated a sizeable circulation of different SARS-CoV-2 lineages over the four pandemic waves in paediatric population, sustained by local transmission chains. Age < 5 years, highest viral load, gamma and delta clades positively influence this local transmission. No correlations between COVID-19 manifestations and lineages or transmission chains are seen, except for a negative correlation between B.1.1.7 and hospitalization. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), which was classified as a pandemic in March 2020. As of 22 January 2022, globally more than 347 million cases of COVID-19 have been diagnosed, with 5.6 million deaths, making it the deadliest pandemic since the influenza pandemic in 1918. The clinical presentation of COVID-19-related illness spans from asymptomatic to mild respiratory symptoms akin to influenza infection to acute symptoms, including pneumonia necessitating hospitalisation and admission to intensive care units. COVID-19 starts in the upper respiratory tract and lungs but in severe cases can also involve the heart, blood vessels, brain, liver, kidneys and intestine. The increasing global health and economic burden of COVID-19 necessitates an urgent and global response. Understanding the functional characteristics and cellular tropism of SARS-CoV-2, and the pathogenesis that leads to multi-organ failure and death, has prompted an unprecedented adoption of organoid models. Successful drug discovery and vaccine development rely on pre-clinical models that faithfully recapitulate the viral life cycle and the host cell response to infection. Human stem cell-derived organoids fulfill these criteria. Here we highlight the role of organoids in the study of SARS-CoV-2 infection and modelling of COVID-19 pathogenesis. [ABSTRACT FROM AUTHOR]

Summary: The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is an emerging respiratory virus responsible for the ongoing coronavirus disease 19 (COVID‐19) pandemic. More than a year into this pandemic, the COVID‐19 fatigue is still escalating and takes hold of the entire world population. Driven by the ongoing geographical expansion and upcoming mutations, the COVID‐19 pandemic has taken a new shape in the form of emerging SARS‐CoV‐2 variants. These mutations in the viral spike (S) protein enhance the virulence of SARS‐CoV‐2 variants by improving viral infectivity, transmissibility and immune evasion abilities. Such variants have resulted in cluster outbreaks and fresh infection waves in various parts of the world with increased disease severity and poor clinical outcomes. Hence, the variants of SARS‐CoV‐2 pose a threat to human health and public safety. This review enlists the most recent updates regarding the presently characterized variants of SARS‐CoV‐2 recognized by the global regulatory health authorities (WHO, CDC). Based on the slender literature on SARS‐CoV‐2 variants, we collate information on the biological implications of these mutations on virus pathology. We also shed light on the efficacy of therapeutics and COVID‐19 vaccines against the emerging SARS‐CoV‐2 variants. [ABSTRACT FROM AUTHOR]

Background: The mayhem COVID-19 that was ushered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) was declared pandemic by the World Health Organization in March 2020. Since its initial outbreak in late 2019, the virus has affected hundreds of million adults in the world and killing millions in the process. After the approval of newly developed vaccines, severe challenges remain to manufacture and administer them to the adult population globally in quick time. However, we have witnessed several mutations of the virus leading to 'waves' of viral spread and mortality. WHO has categorized these mutations as variants of concern (VOCs) and variants of interest (VOIs). The mortality due to COVID-19 has also been associated with various comorbidities and improper immune response. This has created further complications in understanding the nature of the SARS-CoV2–host interaction that has fuelled doubts in the efficacy of the approved vaccines. Whether there is requirement of booster dose and whether the impending wave could affect the children are some of the hotly debated topics. Materials and Methods: A systematic literature review of PubMed, Medline, Scopus, Google Scholar was utilized to understand the nature of Delta variant and how it alters our T-cell responses and cytokine production and neutralizes vaccine-generated antibodies. Conclusion: In this review, we discuss the variants of SARS-CoV2 with specific focus on the Delta variant. We also specifically review the T-cell response against the virus and bring a narrative of various factors that may hold the key to fight against this marauding virus. [ABSTRACT FROM AUTHOR]

Most of us have never faced a pandemic before. The World Health Organization declared the 2019 novel coronavirus infectious disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus), a pandemic by March 11th, 2020. Today, this illness has reported more than 5'331,019 fatalities worldwide (December 17th, 2021). The COVID-19 pandemic has posed an unprecedented global challenge and put the academic community on "the spot." The following mini-review reports how the MS community improved the understanding of the SARS-CoV-2 virus pathophysiology while developing diagnostic procedures to complement the PCR-based approaches. For example, MS researchers identified the interaction sites between the SARS-CoV-2 virus and their hosts; this new knowledge is critical for developing antiviral drugs. MS researchers also realized that COVID-19 should be considered a systemic disease and not just a respiratory illness since its metabolic, lipidomic, and proteomic profile reflects four different clinical disorders: 1) acute inflammatory response, 2) a cardiovascular disease, 3) a prediabetic/diabetes and 4) liver dysfunction. Furthermore, MS researchers put forth the knowledge that the metabolic and lipidomic profile of several patients remained altered after being discharged, thus hinting at the scientific basis for the long COVID syndrome. [ABSTRACT FROM AUTHOR]

Since the rapid onset of the COVID‐19 or SARS‐CoV‐2 pandemic in the world in 2019, extensive studies have been conducted to unveil the behavior and emission pattern of the virus in order to determine the best ways to diagnosis of virus and thereof formulate effective drugs or vaccines to combat the disease. The emergence of novel diagnostic and therapeutic techniques considering the multiplicity of reports from one side and contradictions in assessments from the other side necessitates instantaneous updates on the progress of clinical investigations. There is also growing public anxiety from time to time mutation of COVID‐19, as reflected in considerable mortality and transmission, respectively, from delta and Omicron variants. We comprehensively review and summarize different aspects of prevention, diagnosis, and treatment of COVID‐19. First, biological characteristics of COVID‐19 were explained from diagnosis standpoint. Thereafter, the preclinical animal models of COVID‐19 were discussed to frame the symptoms and clinical effects of COVID‐19 from patient to patient with treatment strategies and in‐silico/computational biology. Finally, the opportunities and challenges of nanoscience/nanotechnology in identification, diagnosis, and treatment of COVID‐19 were discussed. This review covers almost all SARS‐CoV‐2‐related topics extensively to deepen the understanding of the latest achievements (last updated on January 11, 2022). [ABSTRACT FROM AUTHOR]

In the two years since the SARS-CoV-2 pandemic started, it has caused over 5 million deaths and 400 million infected cases, and the world continues to be on high alert for COVID-19. Among the variants of interest and concern of SARS-CoV-2, the current Omicron (B.1.1.529) and stealth Omicron (BA.2) raised serious concerns due to rapid rates of infection caused by numerous mutations in the spike protein, which could escape from the antibody-mediated neutralization and increase the risk of reinfections. Hence, this work aims to describe the most relevant mutations in the SARS-CoV-2 spike protein, discuss vaccine against variant of concerns, describe rare adverse events after COVID-19 vaccination, introduce the most available promising COVID-19 vaccine candidates, and provide few perspectives of the future variants. [ABSTRACT FROM AUTHOR]

Background Although mRNA-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines report >90% efficacy, breakthrough infections occur. Little is known about their effectiveness against SARS-CoV-2 variants, including the highly prevalent B.1.427/B.1.429 variant. Methods In this quality improvement project, we collected demographic and clinical information from post-vaccine SARS-CoV-2 cases (PVSCs), defined as healthcare personnel (HCP) with positive SARS-CoV-2 nucleic acid amplification test after receiving ≥1 vaccine dose. Available specimens were tested for L452R, N501Y, and E484K mutations using reverse-transcription polymerase chain reaction. Mutation prevalence was compared among unvaccinated, early post-vaccinated (≤14 days after dose 1), partially vaccinated (positive test >14 days after dose 1 and <14 days after dose 2), and fully vaccinated (>14 days after dose 2) PVSCs. Results From December 2020 to April 2021, ≥23 090 HCP received ≥1 dose of an mRNA-based SARS-CoV-2 vaccine, and 660 HCP cases of SARS-CoV-2 occurred, of which 189 were PVSCs. Among the PVSCs, 114 (60.3%), 49 (25.9%), and 26 (13.8%) were early post-vaccination, partially vaccinated, and fully vaccinated, respectively. Of 261 available samples from vaccinated and unvaccinated HCP, 103 (39.5%), including 42 PVSCs (36.5%), had the L452R mutation presumptive of B.1.427/B.1.429. When adjusted for community prevalence of B.1.427/B.1.429, PVSCs did not have significantly elevated risk of B.1.427/B.1.429 compared with unvaccinated HCP. Conclusions Most PVSCs occurred prior to expected onset of full, vaccine-derived immunity. Presumptive B.1.427/B.1.429 was not more prevalent in post-vaccine cases than in unvaccinated SARS-CoV-2 HCP. Continued infection control measures, particularly <14 days post-vaccination, and continued variant surveillance in PVSCs are imperative to control future SARS-CoV-2 surges. [ABSTRACT FROM AUTHOR]

SARS-CoV-2, a newly emerging coronavirus that caused the COVID-19 epidemic, has been spreading quickly throughout the world. Despite immunization and some fairly effective therapeutic regimens, SARS-CoV-2 has been ravaging patients, health workers, and the economy. SARS-CoV-2 mutates and evolves to adapt to its host as a result of extreme selection pressure. As a consequence, new SARS-CoV-2 variants have emerged, some of which are classified as variants of concern (VOC) because they exhibit greater transmissibility, cause more-severe disease, are better able to escape immunity, or cause higher mortality than the original Wuhan strain. Here, we introduce these VOCs and review their characteristics, such as transmissibility, immune escape, mortality risk, and diagnostics. [ABSTRACT FROM AUTHOR]

Extensive glycosylation of the spike protein of severe acute respiratory syndrome coronavirus 2 virus not only shields the major part of it from host immune responses, but glycans at specific sites also act on its conformation dynamics and contribute to efficient host receptor binding, and hence infectivity. As variants of concern arise during the course of the coronavirus disease of 2019 pandemic, it is unclear if mutations accumulated within the spike protein would affect its site-specific glycosylation pattern. The Alpha variant derived from the D614G lineage is distinguished from others by having deletion mutations located right within an immunogenic supersite of the spike N-terminal domain (NTD) that make it refractory to most neutralizing antibodies directed against this domain. Despite maintaining an overall similar structural conformation, our mass spectrometry-based site-specific glycosylation analyses of similarly produced spike proteins with and without the D614G and Alpha variant mutations reveal a significant shift in the processing state of N -glycans on one specific NTD site. Its conversion to a higher proportion of complex type structures is indicative of altered spatial accessibility attributable to mutations specific to the Alpha variant that may impact its transmissibility. This and other more subtle changes in glycosylation features detected at other sites provide crucial missing information otherwise not apparent in the available cryogenic electron microscopy-derived structures of the spike protein variants. [ABSTRACT FROM AUTHOR]

Since the emergence of the first case of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), the viral genome has constantly undergone rapid mutations for better adaptation in the host system. These newer mutations have given rise to several lineages/ variants of the virus that have resulted in high transmission and virulence rates compared to the previously circulating variants. Owing to this, the overall caseload and related mortality have tremendously increased globally to > 233 million infections and > 4.7 million deaths as of Sept. 28th, 2021. SARS-CoV-2, Spike (S) protein binds to host cells by recognizing human angiotensin-converting enzyme 2 (hACE2) receptor. The viral S protein contains S1 and S2 domains that constitute the binding and fusion machinery, respectively. Structural analysis of viral S protein reveals that the virus undergoes conformational flexibility and dynamicity to interact with the hACE2 receptor. The SARS-CoV-2 variants and mutations might be associated with affecting the conformational plasticity of S protein, potentially linked to its altered affinity, infectivity, and immunogenicity. This review focuses on the current circulating variants of SARS-CoV-2 and the structure–function analysis of key S protein mutations linked with increased affinity, higher infectivity, enhanced transmission rates, and immune escape against this infection. [ABSTRACT FROM AUTHOR]

The progression of the COVID-19 pandemic has generated numerous emerging variants of SARS-CoV-2 on a global scale. These variants have gained evolutionary advantages, comprising high virulence and serious infectivity due to multiple spike glycoprotein mutations. As a reason, variants are demonstrating significant abilities to escape the immune responses of the host. The D614G mutation in the S-glycoprotein of SARS-CoV-2 variants has shown the most efficient interaction with the ACE2 receptor of the cells. This explicit mutation at amino acid position 614 (aspartic acid-to-glycine substitution) is the prime cause of infection and re-infection. It changes the conformation of RBD and cleavage patterns S-glycoprotein with higher stability, replication fitness, and fusion efficiencies. Therefore, this review aims to provide several crucial pieces of information associated with the D614 mutational occurrence of SARS-CoV-2 variants and their infectivity patterns. This review will also effectively emphasize the mechanism of action of D614G mutant variants, immune escape, and partial vaccine escape of this virus. Furthermore, the viral characteristic changes leading to the current global pandemic condition have been highlighted. Here, we have tried to illustrate a novel direction for future researchers to develop effective therapeutic approaches and counterweight strategies to minimize the spread of COVID-19. Key points • D614G mutation arises within the S-glycoprotein of significant SARS-CoV-2 variants. • The D614G mutation affects infection, re-infection, cleavage patterns of S-glycoprotein, and replication fitness of SARS-CoV-2 variants. • The D614G mutation influences the immunity and partial vaccine escape. [ABSTRACT FROM AUTHOR]

Background: We report a genomic surveillance of SARS-CoV-2 lineages circulating in Paraná, southern Brazil, from March 2020 to April 2021. Our analysis, based on 333 genomes, revealed that the first variants detected in the state of Paraná in March 2020 were the B.1.1.33 and B.1.1.28 variants. The variants B.1.1.28 and B.1.1.33 were predominant throughout 2020 until the introduction of the variant P.2 in August 2020 and a variant of concern (VOC), Gamma (P.1), in January 2021. The VOC Gamma, a ramification of the B.1.1.28 lineage first detected in Manaus (northern Brazil), has grown rapidly since December 2020 and was thought to be responsible for the deadly second wave of COVID-19 throughout Brazil. Methods: The 333 genomic sequences of SARS-CoV-2 from March 2020 to April 2021 were generated as part of the genomic surveillance carried out by Fiocruz in Brazil Genomahcov Fiocruz. SARS-CoV-2 sequencing was performed using representative samples from all geographic areas of Paraná. Phylogenetic analyses were performed using the 333 genomes also included other SARS-CoV-2 genomes from the state of Paraná and other states in Brazil that were deposited in the GISAID. In addition, the time-scaled phylogenetic tree was constructed with up to 3 random sequences of the Gamma variant from each state in Brazil in each month of 2021. In this analysis we also added the sequences identified as the B.1.1.28 lineage of the Amazonas state and and the Gamma-like-II (P.1-like-II) lineage identified in different regions of Brazil. Results: Phylogenetic analyses of the SARS-CoV-2 genomes that were previously classified as the VOC Gamma lineage by WHO/PANGO showed that some genomes from February to April 2021 branched in a monophyletic clade and that these samples grouped together with genomes recently described with the lineage Gamma-like-II. Additionally, a new mutation (E661D) in the spike (S) protein has been identified in nearly 10% of the genomes classified as the VOC Gamma from Paraná in March and April 2021.Finally, we analyzed the correlation between the lineage and the Gamma variant frequency, age group (patients younger or older than 60 years old) and the clinical data of 86 cases from the state of Paraná. Conclusions: Our results provided a reliable picture of the evolution of the SARS-CoV-2 pandemic in the state of Paraná characterized by the dominance of the Gamma strain, as well as a high frequencies of the Gamma-like-II lineage and the S:E661D mutation. Epidemiological and genomic surveillance efforts should be continued to unveil the biological relevance of the novel mutations detected in the VOC Gamma in Paraná. [ABSTRACT FROM AUTHOR]

The global pandemic of the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), places a heavy burden on global public health. Four SARS-CoV-2 variants of concern including B.1.1.7, B.1.351, B.1.617.2, and P.1, and two variants of interest including C.37 and B.1.621 have been reported to have potential immune escape, and one or more mutations endow them with worrisome epidemiologic, immunologic, or pathogenic characteristics. This review introduces the latest research progress on SARS-CoV-2 variants of interest and concern, key mutation sites, and their effects on virus infectivity, mortality, and immune escape. Moreover, we compared the effects of various clinical SARS-CoV-2 vaccines and convalescent sera on epidemic variants, and evaluated the neutralizing capability of several antibodies on epidemic variants. In the end, SARS-CoV-2 evolution strategies in different transmission stages, the impact of different vaccination strategies on SARS-CoV-2 immune escape, antibody therapy strategies and COVID-19 epidemic control prospects are discussed. This review will provide a systematic and comprehensive understanding of the secret of SARS-CoV-2 variants of interest/concern and immune escape. [ABSTRACT FROM AUTHOR]

COVID-19 pandemic remains an on-going global health and economic threat that has amassed millions of deaths. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of this disease and is constantly under evolutionary pressures that drive the modification of its genome which may represent a threat to the efficacy of current COVID-19 vaccines available. This article highlights the pressures that facilitate the rise of new SARS-CoV-2 variants and the key mutations of the viral spike protein – L452R, E484K, N501Y and D614G– that promote immune escape mechanism and warrant a cautionary point for clinical and public health responses in terms of re-infection, vaccine breakthrough infection and therapeutic values. [ABSTRACT FROM AUTHOR]

Safe and effective vaccines are available to face the global threat of the COVID-19 pandemic. In this article, we report on the clinical cases of two healthcare workers vaccinated with two doses of BNT162b2 vaccine who were infected by the same viral clade but had different clinical outcomes. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic continues to spread around the world and remains a major public health threat. Vaccine inefficiency, vaccination breakthroughs and lack of supply, especially in developing countries, as well as the fact that a non-negligible part of the population either refuse vaccination or cannot be vaccinated due to age, pre-existing illness or non-response to existing vaccines intensify this issue. This might also contribute to the emergence of new variants, being more efficiently transmitted, more virulent and more capable of escaping naturally acquired and vaccine-induced immunity. Hence, the need of effective and viable prevention options to reduce viral transmission is of outmost importance. In this study, we investigated the antiviral effect of iota-, lambda- and kappa-carrageenan, sulfated polysaccharides extracted from red seaweed, on SARS-CoV-2 Wuhan type and the spreading variants of concern (VOCs) Alpha, Beta, Gamma and Delta. Carrageenans as part of broadly used nasal and mouth sprays as well as lozenges have the potential of first line defense to inhibit the infection and transmission of SARS-CoV-2. Here, we demonstrate by using a SARS-CoV-2 spike pseudotyped lentivirus particles (SSPL) system and patient-isolated SARS-CoV-2 VOCs to infect transgenic A549ACE2/TMPRSS2 and Calu-3 human lung cells that all three carrageenan types exert antiviral activity. Iota-carrageenan exhibits antiviral activity with comparable IC50 values against the SARS-CoV-2 Wuhan type and the VOCs. Altogether, these results indicate that iota-carrageenan might be effective for prophylaxis and treatment of SARS-CoV-2 infections independent of the present and potentially future variants. [ABSTRACT FROM AUTHOR]