Cross neutralization of SARS-CoV-2 omicron subvariants after repeated doses of COVID-19 mRNA vaccines

We have measured the humoral response to messenger RNA (mRNA) vaccines in COVID-19 naïve and convalescent individuals. Third doses of mRNA COVID-19 vaccines induced a significant increase in potency and breadth of neutralization against SARS-CoV-2 variants of concern (VoC) including Omicron subvariants BA.1, BA.2, and BA.2.12.1, that were cross-neutralized at comparable levels and less for BA.4/5. This booster effect was especially important in naïve individuals that only after the third dose achieved a level that was comparable with that of vaccinated COVID-19 convalescents except for BA.4/5. Avidity of RBD-binding antibodies was also significantly increased in naïve individuals after the third dose, indicating an association between affinity maturation and cross neutralization of VoC. These results suggest that at least three antigenic stimuli by infection or vaccination with ancestral SARS-CoV-2 sequences are required to induce high avidity cross-neutralizing antibodies. Nevertheless, the circulation of new subvariants such as BA.4/5 with partial resistance to neutralization will have to be closely monitored and eventually consider for future vaccine developments.     

SARS-CoV-2 Omicron Variant of Concern: Everything You Wanted to Know about Omicron but Were Afraid to Ask

As soon as the first case of the omicron variant of severe acute respiratory syndrome coronavirus 2 was reported in November 2021, it quickly spread worldwide with the emergence of several subvariants. Compared to previous variants, omicron was heavily mutated, especially for those in the Spike (S) protein and its receptor-binding domain. These mutations allowed the viruses to evade immune responses (i.e., previous infections and vaccine-elicited) and increase in transmissibility. Although vaccine effectiveness is decreased for omicron, boosters remain effective for protecting against severe diseases. Also, bivalent vaccines have been developed to increase vaccine effectiveness. Interestingly, although omicron is highly infectious, it has less morbidity and mortality compared to previously identified variants, such as delta. Additionally, the mutations that allow the virus to evade immune responses also allow it to evade many of the monoclonal antibodies developed at the beginning of the pandemic for treatment. Here, we reviewed the omicron variant’s epidemiology, genetics, transmissibility, disease severity, and responsiveness to vaccine and treatments.     

SARS-CoV-2 Omicron variant (B.1.1.529): A concern with immune escape

Omicron, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant that is now spreading across the world, is the most altered version to emerge so far, with mutations comparable to changes reported in earlier variants of concern linked with increased transmissibility and partial resistance to vaccine-induced immunity. This article provides an overview of the SARS-CoV-2 variant Omicron (B.1.1.529) by reviewing the literature from major scientific databases. Although clear immunological and clinical data are not yet available, we extrapolated from what is known about mutations present in the Omicron variant of SARS-CoV-2 and offer preliminary indications on transmissibility, severity, and immune escape through existing research and databases.     

SARS-CoV-2, the pandemic coronavirus: Molecular and structural insights

The outbreak of a novel coronavirus associated with acute respiratory disease, called COVID-19, marked the introduction of the third spillover of an animal coronavirus (CoV) to humans in the last two decades. The genome analysis with various bioinformatics tools revealed that the causative pathogen (SARS-CoV-2) belongs to the subgenus Sarbecovirus of the genus Betacoronavirus, with highly similar genome as bat coronavirus and receptor-binding domain (RBD) of spike glycoprotein as Malayan pangolin coronavirus. Based on its genetic proximity, SARS-CoV-2 is likely to have originated from bat-derived CoV and transmitted to humans via an unknown intermediate mammalian host, probably Malayan pangolin. Further, spike protein S1/S2 cleavage site of SARS-CoV-2 has acquired polybasic furin cleavage site which is absent in bat and pangolin suggesting natural selection either in an animal host before zoonotic transfer or in humans following zoonotic transfer. In the current review, we recapitulate a preliminary opinion about the disease, origin and life cycle of SARS-CoV-2, roles of virus proteins in pathogenesis, commonalities, and differences between different corona viruses. Moreover, the crystal structures of SARS-CoV-2 proteins with unique characteristics differentiating it from other CoVs are discussed. Our review also provides comprehensive information on the molecular aspects of SARS-CoV-2 including secondary structures in the genome and protein–protein interactions which can be useful to understand the aggressive spread of the SARS-CoV-2. The mutations and the haplotypes reported in the SARS-CoV-2 genome are summarized to understand the virus evolution.     

Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine breakthrough infections: a multicentre cohort study

ObjectivesHighly effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed but variants of concerns are worrisome, especially B.1.617.2 (Delta) which has rapidly spread across the world. We aim to study if vaccination alters virological and serological kinetics in breakthrough infections.MethodsWe conducted a multicentre retrospective cohort study of patients in Singapore who had received a licensed mRNA vaccine and been admitted to hospital with B.1.617.2 SARS-CoV-2 infection. We compared clinical features, virological and serological kinetics (anti-nucleocapsid, anti-spike and surrogate virus neutralization titres) between fully vaccinated and unvaccinated individuals.ResultsOut of 218 individuals with B.1.617.2 infection, 84 received an mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and four received a non-mRNA vaccine. Despite significantly older age in the vaccine breakthrough group, only 2.8% (2/71) developed severe COVID-19 requiring oxygen supplementation compared with 53.1% (69/130) in the unvaccinated group (p < 0.001). Odds of severe COVID-19 following vaccination were significantly lower (adjusted odds ratio 0.07 95% CI 0.015–0.335, p 0.001). PCR cycle threshold values were similar between vaccinated and unvaccinated groups at diagnosis, but viral loads decreased faster in vaccinated individuals. Early, robust boosting of anti-spike protein antibodies was observed in vaccinated patients; however, these titres were significantly lower against B.1.617.2 than the wildtype vaccine strain.DiscussionThe mRNA vaccines are highly effective at preventing symptomatic and severe COVID-19 associated with B.1.617.2 infection. Vaccination is associated with faster decline in viral RNA load and a robust serological response. Vaccination remains a key strategy for control of the COVID-19 pandemic.     

COVID-19 multisystem inflammatory syndrome in three teenagers with confirmed SARS-CoV-2 infection

Coronavirus disease 2019 (COVID-19) is generally a relatively mild illness in children. An emerging disease entity coined as pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) has been reported recently, but is very rare and only affects a very small minority of children. Here we describe the clinical presentations and outcomes of three teenagers with serologically-confirmed SARS-CoV-2 infection admitted to a pediatric intensive care unit for PIMS-TS. Although their initial presentations were very similar, their COVID-19-related disease varied in severity.     

A comparison of the protective effect of vaccination and clinical features between the SARS-CoV-2 wild-type strain and Delta (B.1.617.2) variant

IntroductionThis study aimed to investigate the clinical features and vaccine effectiveness of patients with the SARS-CoV-2 wild-type strain and the Delta variant.MethodsWe retrospectively evaluated patients with the SARS-CoV-2 wild-type strain and the Delta variant.ResultsThe Delta-variant group showed a higher infection rate in minors, who had higher incidence of anosmia or dysgeusia and shorter incubation period. Unvaccinated patients had a 15.59-fold higher risk of severe classification than vaccinated patients. The viral clearance time was significantly shorter in the Delta-variant group.ConclusionsThe Delta-variant group show higher transmissibility, and vaccination reduces the incidence of severe classification and promotes viral clearance.     

SARS-CoV-2 Variants of Concern

Since the COVID-19 pandemic first began in December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has continuously evolved with many variants emerging across the world. These variants are categorized as the variant of interest (VOI), variant of concern (VOC), and variant under monitoring (VUM). As of September 15, 2021, there are four SARS-CoV-2 lineages designated as the VOC (alpha, beta, gamma, and delta variants). VOCs have increased transmissibility compared to the original virus, and have the potential for increasing disease severity. In addition, VOCs exhibit decreased susceptibility to vaccine-induced and infection-induced immune responses, and thus possess the ability to reinfect previously infected and recovered individuals. Given their ability to evade immune responses, VOC are less susceptible to monoclonal antibody treatments. VOCs can also impact the effectiveness of mRNA and adenovirus vector vaccines, although the currently authorized COVID-19 vaccines are still effective in preventing infection and severe disease. Current measures to reduce transmission as well as efforts to monitor and understand the impact of variants should be continued. Here, we review the molecular features, epidemiology, impact on transmissibility, disease severity, and vaccine effectiveness of VOCs.     

A potently neutralizing SARS-CoV-2 antibody inhibits variants of concern by utilizing unique binding residues in a highly conserved epitope

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Infectivity of pseudotyped SARS-CoV-2 variants of concern in different human cell types and inhibitory effects of recombinant spike protein and entry-related cellular factors

Since the report of the first COVID-19 case in 2019, SARS-CoV-2 variants of concern (VOCs) have continued to emerge, manifesting diverse infectivity, evasion of host immunity and pathology. While ACE2 is the predominant receptor of SARS-CoV-2, TMPRSS2, Kim-1, NRP-1, CD147, furin, CD209L, and CD26 have also been implicated as viral entry-related cofactors. To understand the variations in infectivity and pathogenesis of VOCs, we conducted infection analysis in human cells from different organ systems using pseudoviruses of VOCs including Alpha, Beta, Gamma, and Delta. Recombinant spike S1, RBD, ACE2, Kim-1, and NRP-1 proteins were tested for their ability to block infection to dissect their roles in SARS-CoV-2 entry into cells. Compared with wild type SARS-CoV-2 (WT), numerous VOCs had significant increases of infectivity across a wide spectrum of cell types. Recombinant ACE2 protein more effectively inhibited the infection of VOCs including Delta and Omicron (BA.1 and BA.2) than that of WT. Interestingly, recombinant S1, RBD, Kim-1, and NRP-1 proteins inhibited the infection of all pseudoviruses in a manner dependent on the levels of ACE2 expression in different cell types. These results provide insights into the diverse infectivity of SARS-CoV-2 VOCs, which might be helpful for managing the emergence of new VOCs.     

Genetic variants and source of introduction of SARS-CoV-2 in South America

After more than 4 months of the COVID-19 pandemics with genomic information of SARS-CoV-2 around the globe, there are more than 1000 complete genomes of this virus. We used 691 genomes from the GISAID database. Several studies have been reporting mutations and hotspots according to viral evolution. Our work intends to show and compare positions that have variants in 30 complete viral genomes from South American countries. We classified strains according to point alterations and portray the source where strains came into this region. Most viruses entered South America from Europe, followed by Oceania. Only Chilean isolates demonstrated a relationship with Asian isolates. Some changes in South American genomes are near to specific domains related to viral replication or the S protein. Our work contributes to the global understanding of which sort of strains are spreading throughout South America, and the differences among them according to the first isolates introduced to this region.     

Update on the omicron sub-variants BA.4 and BA.5

Several nations have recently begun to relax their public health protocols, particularly regarding the use of face masks when engaging in outdoor activities. This is because there has been a general trend towards fewer cases of coronavirus disease 2019 (COVID-19). However, new Omicron sub-variants (designated BA.4 and BA.5) have recently emerged. These two subvariants are thought to be the cause of an increase in COVID-19 cases in South Africa, the United States, and Europe. They have also begun to spread throughout Asia. They evolved from the Omicron lineage with characteristics that make them even more contagious and which allow them to circumvent immunity from a previous infection or vaccination. This article reviews a number of scientific considerations about these new variants, including their apparently reduced clinical severity.     

Temporal maturation of neutralizing antibodies in COVID-19 convalescent individuals improves potency and breadth to circulating SARS-CoV-2 variants

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Understanding evolution of SARS-CoV-2: A perspective from analysis of genetic diversity of RdRp gene

Coronavirus disease 2019 emerged as the first example of “Disease X”, a hypothetical disease of humans caused by an unknown infectious agent that was named as novel coronavirus and subsequently designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The origin of the outbreak at the animal market in Wuhan, China implies it as a case of zoonotic spillover. The study was designed to understand evolution of Betacoronaviruses and in particular diversification of SARS-CoV-2 using RNA dependent RNA polymerase (RdRp) gene, a stable genetic marker. Phylogenetic and population stratification analyses were carried out using maximum likelihood and Bayesian methods, respectively. Molecular phylogeny using RdRp showed that SARS-CoV-2 isolates cluster together. Bat-CoV isolate RaTG13 and Pangolin-CoVs are observed to branch off prior to SARS-CoV-2 cluster. While SARS-CoV form a single cluster, Bat-CoVs form multiple clusters. Population-based analyses revealed that both SARS-CoV-2 and SARS-CoV form separate clusters with no admixture. Bat-CoVs were found to have single and mixed ancestry and clustered as four sub-populations. Population-based analyses of Betacoronaviruses using RdRp revealed that SARS-CoV-2 is a homogeneous population. SARS-CoV-2 appears to have evolved from Bat-CoV isolate RaTG13, which diversified from a common ancestor from which Pangolin-CoVs have also evolved. The admixed Bat-CoV sub-populations indicate that bats serve as reservoirs harboring virus ensembles that are responsible for zoonotic spillovers such as SARS-CoV and SARS-CoV-2. The extent of admixed isolates of Bat-CoVs observed in population diversification studies underline the need for periodic surveillance of bats and other animal reservoirs for potential spillovers as a measure towards preparedness for emergence of zoonosis.     

A new SARS-CoV-2 variant with high lethality poorly detected by RT-PCR on nasopharyngeal samples: an observational study

ObjectivesIn early January 2021 an outbreak of nosocomial cases of coronavirus disease 2019 (COVID-19) emerged in Western France; RT-PCR tests were repeatedly negative on nasopharyngeal samples but positive on lower respiratory tract samples. Whole-genome sequencing (WGS) revealed a new variant, currently defining a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage B.1.616. In March, the WHO classified this as a ‘variant under investigation’ (VUI). We analysed the characteristics and outcomes of COVID-19 cases related to this new variant.MethodsClinical, virological, and radiological data were retrospectively collected from medical charts in the two hospitals involved. We enrolled those inpatients with: (a) positive SARS-CoV-2 RT-PCR on a respiratory sample, (b) seroconversion with anti-SARS-CoV-2 IgG/IgM, or (c) suggestive symptoms and typical features of COVID-19 on a chest CT scan. Cases were categorized as B.1.616, a variant of concern (VOC), or unknown.ResultsFrom 1st January to 24th March 2021, 114 patients fulfilled the inclusion criteria: B.1.616 (n = 39), VOC (n = 32), and unknown (n = 43). B.1.616-related cases were older than VOC-related cases (81 years, interquartile range (IQR) 73–88 versus 73 years, IQR 67–82, p < 0.05) and their first RT-PCR tests were rarely positive (6/39, 15% versus 31/32, 97%, p < 0.05). The B.1.616 variant was independently associated with severe disease (multivariable Cox model HR 4.0, 95%CI 1.5–10.9) and increased lethality (28-day mortality 18/39 (46%) for B.1.616 versus 5/32 (16%) for VOC, p = 0.006).ConclusionWe report a nosocomial outbreak of COVID-19 cases related to a new variant, B.1.616, which is poorly detected by RT-PCR on nasopharyngeal samples and is associated with high lethality.