SARS-CoV-2 variants, immune escape, COVID-19 vaccine, and therapeutic strategies.
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ABSTRACT:
SUBMITTER: Que H
PROVIDER: S-EPMC9638196 | biostudies-literature | 2022 Nov
REPOSITORIES: biostudies-literature
Publications
SARS-CoV-2 variants, immune escape, COVID-19 vaccine, and therapeutic strategies.
Que Haiying H Chen Li L Wei Xiawei X
Science China. Life sciences 20221103 2
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Project description:The COVID-19 pandemic caused by SARS-CoV-2 is associated with a lower fatality rate than its SARS and MERS counterparts. However, the rapid evolution of SARS-CoV-2 has given rise to multiple variants with varying pathogenicity and transmissibility, such as the Delta and Omicron variants. Individuals with advanced age or underlying comorbidities, including hypertension, diabetes and cardiovascular diseases, are at a higher risk of increased disease severity. Hence, this has resulted in an urgent need for the development of better therapeutic and preventive approaches. This review describes the origin and evolution of human coronaviruses, particularly SARS-CoV-2 and its variants as well as sub-variants. Risk factors that contribute to disease severity and the implications of co-infections are also considered. In addition, various antiviral strategies against COVID-19, including novel and repurposed antiviral drugs targeting viral and host proteins, as well as immunotherapeutic strategies, are discussed. We critically evaluate strategies of current and emerging vaccines against SARS-CoV-2 and their efficacy, including immune evasion by new variants and sub-variants. The impact of SARS-CoV-2 evolution on COVID-19 diagnostic testing is also examined. Collectively, global research and public health authorities, along with all sectors of society, need to better prepare against upcoming variants and future coronavirus outbreaks.
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Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of the coronavirus disease 2019 (COVID-19) pandemic, which has been a topic of major concern for global human health. The challenge to restrain the COVID-19 pandemic is further compounded by the emergence of several SARS-CoV-2 variants viz. B.1.1.7 (Alpha), B.1.351 (Beta), P1 (Gamma) and B.1.617.2 (Delta), which show increased transmissibility and resistance towards vaccines and therapies. Importantly, there is convincing evidence of increased susceptibility to SARS-CoV-2 infection among individuals with dysregulated immune response and comorbidities. Herein, we provide a comprehensive perspective regarding vulnerability of SARS-CoV-2 infection in patients with underlying medical comorbidities. We discuss ongoing vaccine (mRNA, protein-based, viral vector-based, etc.) and therapeutic (monoclonal antibodies, small molecules, plasma therapy, etc.) modalities designed to curb the COVID-19 pandemic. We also discuss in detail, the challenges posed by different SARS-CoV-2 variants of concern (VOC) identified across the globe and their effects on therapeutic and prophylactic interventions.
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Project description:COVID-19 pandemic caused by SARS-CoV-2 globally impacted the humanity causing tragic outcomes; costing millions of lives, destroying economies and demolishing public health infrastructures. The emergence of vaccines using various ingenious approaches in less than a year was deemed the light at the end of the tunnel. However, recent emergence of variants of SARS-CoV-2 in several parts of the world revealed that another hurdle is ahead in the fight against COVID-19. This review will highlight how SARS-CoV-2 mutations, creating different virus variants could potentially impact virus pathogenesis as well as different therapy approaches and vaccine design.
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Project description:More than a year after the SARS-CoV-2 pandemic, the Coronavirus disease 19 (COVID-19) is still a major global challenge for scientists to understand the different dimensions of infection and find ways to prevent, treat, and develop a vaccine. On January 30, 2020, the world health organization (WHO) officially announced this new virus as an international health emergency. While many biological and mechanisms of pathogenicity of this virus are still unclear, it seems that cytokine storm resulting from an immune response against the virus is considered the main culprit of the severity of the disease. Despite many global efforts to control the SARS-CoV-2, several problems and challenges have been posed in controlling the COVID-19 infection. These problems include the various mutations, the emergence of variants with high transmissibility, the short period of immunity against the virus, the possibility of reinfection in people improved, lack of specific drugs, and problems in the development of highly sensitive and specific vaccines. In this review, we summarized the results of the current trend and the latest research studies on the characteristics of the structure and genome of the SARS-CoV- 2, new mutations and variants of SARS-CoV-2, pathogenicity, immune response, virus diagnostic tests, potential treatment, and vaccine candidate.
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Project description:ACE2 on epithelial cells is the SARS-CoV-2 entry receptor. Single-cell RNA-sequencing data derived from two COVID-19 cohorts revealed that MAP4K3/GLK-positive epithelial cells were increased in patients. SARS-CoV-2-induced GLK overexpression in epithelial cells correlated with COVID-19 severity and vesicle secretion. GLK overexpression induced the epithelial cell-derived exosomes containing ACE2; the GLK-induced exosomes transported ACE2 proteins to recipient cells, facilitating pseudovirus infection. Consistently, ACE2 proteins were increased in the serum exosomes from another COVID-19 cohort. Remarkably, SARS-CoV-2 spike protein stimulated GLK, and GLK stabilized ACE2 in epithelial cells. Mechanistically, GLK phosphorylated ACE2 at two serine residues (Ser776, Ser783), leading to dissociation of ACE2 from its E3 ligase UBR4. Reduction of UBR4-induced Lys48-linked ubiquitination at three lysine residues (Lys26, Lys112, Lys114) of ACE2 prevented its degradation. Furthermore, SARS-CoV-2 pseudovirus or live virus infection in humanized ACE2 mice induced GLK and ACE2 protein levels, as well as ACE2-containing exosomes. Collectively, ACE2 stabilization by SARS-CoV-2-induced MAP4K3/GLK may contribute to the pathogenesis of COVID-19.
| S-SCDT-EMM-2022-15904 | biostudies-other
Project description:Coronavirus Disease 2019 (COVID-19) has been the most severe public health challenge in this century. Two years after its emergence, the rapid development and deployment of effective COVID-19 vaccines have successfully controlled this pandemic and greatly reduced the risk of severe illness and death associated with COVID-19. However, due to its ability to rapidly evolve, the SARS-CoV-2 virus may never be eradicated, and there are many important new topics to work on if we need to live with this virus for a long time. To this end, we hope to provide essential knowledge for researchers who work on the improvement of future COVID-19 vaccines. In this review, we provided an up-to-date summary for current COVID-19 vaccines, discussed the biological basis and clinical impact of SARS-CoV-2 variants and subvariants, and analyzed the effectiveness of various vaccine booster regimens against different SARS-CoV-2 strains. Additionally, we reviewed potential mechanisms of vaccine-induced severe adverse events, summarized current studies regarding immune correlates of protection, and finally, discussed the development of next-generation vaccines.
| S-EPMC9569411 | biostudies-literature
Project description:Fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) energize the COVID-19 pandemic. While viral infections elicit a conserved immune response, it is not known whether SARS-CoV-2 variants, which display reduced neutralizing activity by vaccine-elicited antibodies, prompt specific genomic immune responses. To test this, we generated and investigated the transcriptomes in PBMCs from hospitalized patients infected with either the Alpha variant (n=36) or with the Alpha variant that had acquired the E484K escape mutation (Alpha+E484K) (n=13). We identified a gene module preferentially activated in patients infected with the Alpha+E484K variant and in patients infected with the Alpha (n=9) and Gamma (n=3) variants that also carry by the E484K escape mutation. The E484K signature was enriched for genes preferentially expressed in monocytes and linked to severe viral infection. However, both cohorts had undergone similar treatments and no differences in disease severity were reported suggesting that this signature reflects a variant response and does not necessarily associate with disease outcome. Additionally, longitudinal transcriptome analyses revealed a more persistent retention of immune signatures in Alpha+E484K patients throughout the entire course of COVID-19 disease and convalescence. While the OAS1 Neanderthal mutation has been linked to a milder COVID-19 pathology, we did not identify significant immune transcriptomes differences in the 25 patients homozygous for this mutation. Our study offers insights into distinct molecular immune responses elicited by SARS-CoV-2 variants carrying the E484K escape mutation throughout the COVID-19 disease.
2022-02-23 | GSE190680 | GEO
Project description:Although most mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome are expected to be either deleterious and swiftly purged or relatively neutral, a small proportion will affect functional properties and may alter infectivity, disease severity or interactions with host immunity. The emergence of SARS-CoV-2 in late 2019 was followed by a period of relative evolutionary stasis lasting about 11 months. Since late 2020, however, SARS-CoV-2 evolution has been characterized by the emergence of sets of mutations, in the context of 'variants of concern', that impact virus characteristics, including transmissibility and antigenicity, probably in response to the changing immune profile of the human population. There is emerging evidence of reduced neutralization of some SARS-CoV-2 variants by postvaccination serum; however, a greater understanding of correlates of protection is required to evaluate how this may impact vaccine effectiveness. Nonetheless, manufacturers are preparing platforms for a possible update of vaccine sequences, and it is crucial that surveillance of genetic and antigenic changes in the global virus population is done alongside experiments to elucidate the phenotypic impacts of mutations. In this Review, we summarize the literature on mutations of the SARS-CoV-2 spike protein, the primary antigen, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets.
| S-EPMC8167834 | biostudies-literature
Project description:The origin of SARS-CoV-2 variants of concern remains unclear. Here, we test whether intra-host virus evolution during persistent infections could be a contributing factor by characterizing the long-term SARS-CoV-2 infection dynamics in an immunosuppressed kidney transplant recipient. Applying RT-qPCR and next-generation sequencing (NGS) of sequential respiratory specimens, we identify several mutations in the viral genome late in infection. We demonstrate that a late viral isolate exhibiting genome mutations similar to those found in variants of concern first identified in UK, South Africa, and Brazil, can escape neutralization by COVID-19 antisera. Moreover, infection of susceptible mice with this patient's escape variant elicits protective immunity against re-infection with either the parental virus and the escape variant, as well as high neutralization titers against the alpha and beta SARS-CoV-2 variants, B.1.1.7 and B.1.351, demonstrating a considerable immune control against such variants of concern. Upon lowering immunosuppressive treatment, the patient generated spike-specific neutralizing antibodies and resolved the infection. Our results suggest that immunocompromised patients could be a source for the emergence of potentially harmful SARS-CoV-2 variants.
| S-EPMC8568958 | biostudies-literature
Project description:BackgroundOmicron's high transmissibility and variability present new difficulties for COVID-19 vaccination prevention and therapy. In this article, we analyzed the sensitivity of vaccine-induced antibodies as well as the effect of booster vaccinations against Omicron sublineages.MethodsWe looked for Randomized Controlled Trials and cohort studies that reported the COVID-19 vaccines against Omicron sublineages up to 28 July 2022 through PubMed, the Cochrane Library, EMBASE, and Web of Science. Quantitative synthesis was carried out using Stata 16.0 and RevMa5.3, then the serum NT50 and antibody sensitivity to neutralize Omicron sublineages were assessed before and after booster vaccination. This study was registered with PROSPERO number CRD42022350477.ResultsThis meta-analysis included 2138 patients from 20 studies, and the booster vaccination against Omicron sublineages showed a significant difference compared to 2 dosage: BA.1/BA.1.1 (SMD = 0.80, 95% CI: 0.75-0.85, P = 0.00), BA.2/BA.2.12.1 (SMD = 0.77, 95% CI: 0.69-0.85, P = 0.00), BA.3 (SMD = 0.91, 95% CI: 0.83-1.0, P = 0.00), and BA.4/5 (SMD = 0.77, 95% CI: 0.60-0.94, P = 0.00). The sensitivity of vaccines-induced antibodies decreased by at least 5-folds after booster vaccination, particularly in the case of BA.4/5 which had the most notable decline in vaccine effectiveness.ConclusionAfter the booster vaccination, the NT50 and the neutralization ability of vaccine-induced antibodies increased, but the susceptibility of antibodies decreased compared with the control virus, which may be a clue for future Omicron sublineages prevention.
| S-EPMC10652597 | biostudies-literature