Omicron Variant Escapes Therapeutic Monoclonal Antibodies (mAbs) Including Recently Released Evusheld®, Contrary to 8 Prior Main Variant of Concern (VOC).
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ABSTRACT:
SUBMITTER: Boschi C
PROVIDER: S-EPMC9402686 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
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Omicron Variant Escapes Therapeutic Monoclonal Antibodies (mAbs) Including Recently Released Evusheld®, Contrary to 8 Prior Main Variant of Concern (VOC).
Boschi Céline C Colson Philippe P Bancod Audrey A Moal Valérie V La Scola Bernard B
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20220801 1
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Project description:BackgroundOmicron (B.1.1.529), a variant of SARS-CoV-2 is currently spreading globally as a dominant strain. Due to multiple mutations at its Spike protein, including 15 amino acid substitutions at the receptor binding domain (RBD), Omicron is a variant of concern (VOC) and capable of escaping vaccine generated immunity. So far, no specific treatment regime is suggested for this VOC.MethodsThe three-dimensional structure of the Spike RBD domain of Omicron variant was constructed by incorporating 15 amino acid substitutions to the Native Spike (S) structure and structural changes were compared that of the Native S. Seven phytochemicals namely Allicin, Capsaicin, Cinnamaldehyde, Curcumin, Gingerol, Piperine, and Zingeberene were docked with Omicron S protein and Omicron S-hACE2 complex. Further, molecular dynamic simulation was performed between Crcumin and Omicron S protein to evaluate the structural stability of the complex in the physiological environment and compared with that of the control drug Chloroquine.ResultsCurcumin, among seven phytochemicals, was found to have the most substantial inhibitory potential with Omicron S protein. Further, it was found that curcumin could disrupt the Omicron S-hACE2 complex. The molecular dynamic simulation demonstrated that Curcumin could form a stable structure with Omicron S in the physiological environment.ConclusionTo conclude, Curcumin can be considered as a potential therapeutic agent against the highly infectious Omicron variant of SARS-CoV-2.
| S-EPMC9044632 | biostudies-literature
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| S-EPMC9111213 | biostudies-literature
Project description:Millions have died due to the COVID-19 pandemic. The irrepressible propensity of the pandemic, which was highlighted by the outbreak of the Delta variant, should not be underestimated. The Omicron SARS-CoV-2 variant is thought to have originated from Africa. Sequences of the omicron variant show that it carries the highest number of point mutations detected in a betacoronavirus. High hospitalization numbers due to the Omicron variant has retriggered precautionary restrictions and border closures even in countries which have attained herd immunity by mass vaccinations. Surveillance systems for accurate screening of the Omicron variant are needed to guide implementation of hygiene principles and restrictions. Development of vaccines against the variants is important as the pandemic evolves. Whether Omicron is the last variant depends on the success of the local and global public-health strategies against SARS-CoV-2.
| S-EPMC8768426 | biostudies-literature
Project description:Since the initial report of the severe acute respiratory syndrome (SARS CoV-2) in Wuhan, China, in 2019, the virus has constantly mutated, resulting in the appearance of novel variants. In December 2020, the B.1.617.2 (delta) variant concern (VOC) was first reported in India, and rapidly spread around the globe, is now the main brand in the United Kingdom, and it has grown dramatically. Here we present the clinical features and laboratory findings of the first case of B. 1.617.2 (delta) variant concern (VOC) in Iraq. A 6-year-old female child presented with severe abdominal pain, headache, severe vomiting, and diarrhea, runny nose, alerted mental status, loss of appetite, and fever. The patient was diagnosed with COVID-19 delta variant B.1.617.2 by RT-PCR. The patient was treated by administration of glucose saline 4% for 3 days, ceftriaxone vial 1 mg every 12 h for 6 days, and an acetaminophen bottle on a need to prevent fever followed by a Flagyl bottle every 24 h for 3 days. Vaccination and prevention the spread of the virus and against it are important preventive approaches for delta variant. Sore throat, runny nose, headache, and vomiting, diarrhea are the major clinical features of the delta variant. This was followed by an elevation of the leukocyte WBC, and blood platelets. To reduce the impact of new delta variant B.1.617.2 infection; handwashing, wearing a double mask, avoiding crowded and closed settings, social distancing, lockdown, and ensuring good ventilation are major significant options against this variant.
| S-EPMC8416700 | biostudies-literature
Project description:The emergence of recombinant viruses is a threat to public health, as recombination may integrate variant-specific features that together result in escape from treatment or immunity. The selective advantages of recombinant SARS-CoV-2 isolates over their parental lineages remain unknown. We identified a Delta-Omicron (AY.45-BA.1) recombinant in an immunosuppressed transplant recipient treated with monoclonal antibody Sotrovimab. The single recombination breakpoint is located in the spike N-terminal domain adjacent to the Sotrovimab binding site. While Delta and BA.1 are sensitive to Sotrovimab neutralization, the Delta-Omicron recombinant is highly resistant. To our knowledge, this is the first described instance of recombination between circulating SARS-CoV-2 variants as a functional mechanism of resistance to treatment and immune escape.
| S-EPMC9937133 | biostudies-literature
Project description:The SARS-CoV-2 omicron variant is recent member of variant of concerns that confer neutralizing antibodies and escape immune system due to harboring more than 40 mutations. Current evidences suggest two dosages SARS-CoV-2 vaccine dose not efficient protects against new variants of SARS-CoV-2; however, recent studies declare that the third booster vaccination can elicit higher antibodies concentration as well as cross-reaction between neutralizing antibodies and new SARS-CoV-2 variants. On the other hand, although a third booster vaccination seems to be benefit in some immunocompromised patients such as recipients of solid-organ transplants or hemodialysis patients, but in other immunosuppressed patients, for instance patients with B cell lymphoproliferative disease partially respond to SARS-CoV-2. Herein, we evaluate the effectiveness of the third booster vaccination against Omicron variant using comprehensive literature review.
| S-EPMC9259195 | biostudies-literature
Project description:Background Pre-exposure prophylaxis for COVID-19 with tixagevimab/cilgavimab (T/C) received Emergency Use Authorization (EUA) based on results of a clinical trial conducted prior to the emergence of the Omicron variant. The clinical effectiveness of T/C has not been well described in the Omicron era. We examined the incidence of symptomatic illness and hospitalizations among T/C recipients when Omicron accounted for virtually all local cases. Methods Through retrospective electronic medical record chart review, we identified patients who received T/C between January 1 –July 31, 2022 within our quaternary referral health system. We determined the incidence of symptomatic COVID-19 infections and hospitalizations due to or presumed to be caused by early Omicron variants before and after receiving T/C (pre-T/C and post-T/C). Chi square and Mann-Whitney Wilcoxon two-sample tests were used to examine differences between the characteristics of those who got COVID-19 before or after T/C prophylaxis, and rate ratios (RR) and 95% confidence intervals (CI) were calculated to assess differences in hospitalization rates for the two groups. Results Of 1295 T/C recipients, 105 (8.1%) developed symptomatic COVID-19 infection before receiving T/C, and 102 (7.9%) developed symptomatic disease after receiving it. Of the 105 patients who developed symptomatic infection pre-T/C, 26 (24.8%) were hospitalized, compared with six of the 102 patients (5.9%) who were diagnosed with COVID-19 post-T/C (RR = 0.24; 95% CI = 0.10–0.55; p = 0.0002). Seven of the 105 (6.7%) patients infected pre-T/C, but none of the 102 infected post-T/C required ICU care. No COVID-related deaths occurred in either group. The majority of COVID-19 cases among those infected pre-T/C treatment occurred during the Omicron BA.1 surge, while the majority of post-T/C cases occurred when Omicron BA.5 was predominant. In both groups, having at least one dose of vaccine strongly protected against hospitalization (pre-T/C group RR = 0.31, 95% CI = 0.17–0.57, p = 0.02; post-T/C group RR = 0.15; 95% CI = 0.03–0.94; p = 0.04). Conclusion We identified COVID-19 infections after T/C prophylaxis. Among patients who received T/C at our institution, COVID-19 Omicron cases occurring after T/C were one-fourth as likely to require hospitalization compared to those with Omicron prior to T/C. However, due to the presence of changing vaccine coverage, multiple therapies, and changing variants, the effectiveness of T/C in the Omicron era remains difficult to assess.
| S-EPMC10138227 | biostudies-literature
Project description:The emergence of the SARS-CoV-2 variant of concern Omicron (Pango lineage B.1.1.529), first identified in Botswana and South Africa, may compromise vaccine effectiveness and lead to re-infections1. Here we investigated Omicron escape from neutralization by antibodies from South African individuals vaccinated with Pfizer BNT162b2. We used blood samples taken soon after vaccination from individuals who were vaccinated and previously infected with SARS-CoV-2 or vaccinated with no evidence of previous infection. We isolated and sequence-confirmed live Omicron virus from an infected person and observed that Omicron requires the angiotensin-converting enzyme 2 (ACE2) receptor to infect cells. We compared plasma neutralization of Omicron relative to an ancestral SARS-CoV-2 strain and found that neutralization of ancestral virus was much higher in infected and vaccinated individuals compared with the vaccinated-only participants. However, both groups showed a 22-fold reduction in vaccine-elicited neutralization by the Omicron variant. Participants who were vaccinated and had previously been infected exhibited residual neutralization of Omicron similar to the level of neutralization of the ancestral virus observed in the vaccination-only group. These data support the notion that reasonable protection against Omicron may be maintained using vaccination approaches.
| S-EPMC8866126 | biostudies-literature
Project description:Since WHO announced the COVID-19 pandemic in March 2020, SARS-CoV-2 has undergone several mutations, with the most recent variant first identified in South Africa in November 2021, the SARS-CoV-2 variant of concern (VOC B.1.1.529) named by WHO as Omicron. To date, it has undergone more mutations compared to previous SARS-CoV-2 variants, particularly, in the S gene that encodes the spike protein, which can cause S gene target failure in some PCR kits. Since its discovery, the Omicron variant has caused a sharp rise in COVID-19 cases worldwide and was responsible for a record of 15 million new COVID-19 cases reported globally in a single week, although this may be an underestimate. Since January 2022, Omicron subvariants with variable genetic characteristics, BA.1, BA.1.1, BA.2, BA.3, BA.4, BA.5, and BA.2.12.2 have been identified, with several countries reporting BA.1.1 was the major subvariant (27.42%), followed by BA.2 (25.19%). At the begining of May 2022, BA.2.12.1 mostly (42%) was detected in the United States. Like adults, the clinical manifestations of the Omicron variant in children are similar to the previous variants consisting of fever, cough, vomiting, breathing difficulties, and diarrhea, with some reports on croup-like symptoms and seizures. Though it presents apparently milder disease than the Delta variant, it is significantly more contagious and has caused more hospitalizations, especially in unvaccinated children younger than 5 years and unvaccinated or incompletely vaccinated adults. However, there is insufficient evidence yet to distinguish the Omicron variant from the other variants based solely on the clinical manifestations, therefore, this review presents a brief literature review of the most current evidence and data related to Omicron.
| S-EPMC9378986 | biostudies-literature
Project description:Emerging strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19) pandemic, that show increased transmission fitness and/or immune evasion are classified as "variants of concern" (VOCs). Recently, a SARS-CoV-2 variant first identified in November 2021 in South Africa has been recognized as a fifth VOC, termed "Omicron." What makes this VOC so alarming is the high number of changes, especially in the viral Spike protein, and accumulating evidence for increased transmission efficiency and escape from neutralizing antibodies. In an amazingly short time, the Omicron VOC has outcompeted the previously dominating Delta VOC. However, it seems that the Omicron VOC is overall less pathogenic than other SARS-CoV-2 VOCs. Here, we provide an overview of the mutations in the Omicron genome and the resulting changes in viral proteins compared to other SARS-CoV-2 strains and discuss their potential functional consequences.
| S-EPMC8941872 | biostudies-literature