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1.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22269361

RESUMO

Emergence of the SARS-CoV-2 variant-of-concern (VOC) B.1.1.529 (Omicron) in late 2021 has raised alarm among scientific and health care communities due to a surprisingly large number of mutations in its spike protein. Public health surveillance indicates that the Omicron variant is significantly more contagious than the previously dominant VOC, B.1.617.2 (Delta). Several early reports demonstrated that Omicron exhibits a higher degree (~10-30-fold) of escape from antibody neutralization compared to earlier lineage variants. Therefore, it is critical to determine how well the second line of adaptive immunity, T cell memory, performs against Omicron in people following COVID-19 infection and/or vaccination. To that purpose, we analyzed a cohort (n=345 subjects) of two- or three- dose messenger RNA (mRNA) vaccine recipients and COVID-19 post infection subjects (including those receiving 2 doses of mRNA vaccine after infection), recruited to the CDC-sponsored AZ HEROES research study, alongside 32 pre-pandemic control samples. We report that T cell responses against Omicron spike peptides were largely preserved in all cohorts with established immune memory. IFN-gamma producing T cell responses remained equivalent to the response against the ancestral strain (WA1/2020), with some (<20%) loss in IL-2 single- or IL-2+IFN-gamma+ poly-functional responses. Three-dose vaccinated participants had similar responses to Omicron relative to convalescent or convalescent plus two-dose vaccinated groups and exhibited responses significantly higher than those receiving two mRNA vaccine doses. These results provide further evidence that a three-dose vaccine regimen benefits the induction of optimal functional T cell immune memory.

2.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22269161

RESUMO

Adopting an early doubling time of three days for the rate of new infections with the omicron mutant the temporal evolution of the omicron wave in different countries is predicted. The predictions are based on the susceptible-infectious-recovered/removed (SIR) epidemic compartment model with a constant stationary ratio k=mu(t)/a(t) between the infection (a(t)) and recovery (mu(t)) rate. The fixed early doubling time then uniquely relates the initial infection rate a0 to the ratio k, which therefore determines the full temporal evolution of the omicron waves. For each country three scenarios (optimistic, pessimistic, intermediate) are considered and the resulting pandemic parameters are calculated. These include the total number of infected persons, the maximum rate of new infections, the peak time and the maximum 7-day incidence per 100000 persons. Among the considered European countries Denmark has the smallest omicron peak time and the recently observed saturation of the 7-day incidence value at 2478 is in excellent agreement with the prediction in the optimistic scenario. For Germany we predict peak times of the omicron wave ranging from 32 to 38 and 45 days after the start of the omicron wave in the optimistic, intermediate and pessimistic scenario, respectively, with corresponding maximum SDI values of 7090, 13263 and 28911, respectively. Adopting Jan 1st, 2022 as the starting date our predictions implies that the maximum of the omicron wave is reached between Feb 1 and Feb 15, 2022. Rather similar values are predicted for Switzerland. Due to an order of magnitude smaller omicron hospitalization rate, due to the high percentage of vaccinated and boostered population, the German health system can cope with maximum omicron SDI value of 2800 which is about a factor 2.5 smaller than the maximum omicron SDI value 7090 in the optimistic case. By either reducing the duration of intensive care during this period of maximum, and/or by making use of the nonuniform spread of the omicron wave across Germany, it seems that the German health system can barely cope with the omicron wave avoiding triage decisions. The reduced omicron hospitalization rate also causes significantly smaller mortality rates compared to the earlier mutants in Germany. In the optimistic scenario one obtains for the total number of fatalities 7445 and for the maximum death rate 418 per day which are about one order of magnitude smaller than the beta fatality rate and total number.

4.
European physical journal plus ; 137(1), 2022.
Artigo em Inglês | EuropePMC | ID: covidwho-1615153

RESUMO

Omicron (B.1.1.529), a highly mutated SARS-CoV-2 variant, has emerged in the south of African continent in the November 2021. The spike protein of Omicron has 26 amino acid mutations, which makes it distinct from the other variants of concern. Researches are underway to know the virulence and transmission rate of Omicron variant. In this letter, the seven-day moving average of most affected Omicron variant countries Denmark, Germany, India, Netherlands, South Africa and UK has been investigated and compared with each other. Further, the seven-day average of daily positive Omicron cases of the prescribed countries has been predicted for the months of December 2021, January 2022 and February 2022 using the fractal interpolation method. Results elucidate that the curve of daily positive case follows the same pattern even though the new variant of concern, Omicron added in the existing variants.

6.
Pulse International ; 23(1):1-11, 2022.
Artigo em Inglês | Academic Search Complete | ID: covidwho-1615001
8.
Bdj in Practice ; 35(1):5-5, 2022.
Artigo em Inglês | EuropePMC | ID: covidwho-1614688
9.
Nature ; 2021 Dec 31.
Artigo em Inglês | MEDLINE | ID: covidwho-1616995

RESUMO

The Omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was initially identified in November of 2021 in South Africa and Botswana as well as in a sample from a traveler from South Africa in Hong Kong1,2. Since then, B.1.1.529 has been detected globally. This variant seems to be at least equally infectious than B.1.617.2 (Delta), has already caused super spreader events3 and has outcompeted Delta within weeks in several countries and metropolitan areas. B.1.1.529 hosts an unprecedented number of mutations in its spike gene and early reports have provided evidence for extensive immune escape and reduced vaccine effectiveness2,4-6. Here, we investigated the neutralizing and binding activity of sera from convalescent, mRNA double vaccinated, mRNA boosted, convalescent double vaccinated, and convalescent boosted individuals against wild type, B.1.351 and B.1.1.529 SARS-CoV-2 isolates. Neutralizing activity of sera from convalescent and double vaccinated participants was undetectable to very low against B.1.1.529 while neutralizing activity of sera from individuals who had been exposed to spike three or four times was maintained, albeit at significantly reduced levels. Binding to the B.1.1.529 receptor binding domain (RBD) and N-terminal domain (NTD) was reduced in convalescent not vaccinated individuals, but was mostly retained in vaccinated individuals.

10.
Nature ; 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: covidwho-1616994

RESUMO

The SARS-CoV-2 Omicron variant was first identified in November 2021 in Botswana and South Africa1-3. It has since then spread to many countries and is expected to rapidly become dominant worldwide. The lineage is characterized by the presence of about 32 mutations in the spike, located mostly in the N-terminal domain (NTD) and the receptor binding domain (RBD), which may enhance viral fitness and allow antibody evasion. Here, we isolated an infectious Omicron virus in Belgium, from a traveller returning from Egypt. We examined its sensitivity to 9 monoclonal antibodies (mAbs) clinically approved or in development4, and to antibodies present in 115 sera from COVID-19 vaccine recipients or convalescent individuals. Omicron was totally or partially resistant to neutralization by all mAbs tested. Sera from Pfizer or AstraZeneca vaccine recipients, sampled 5 months after complete vaccination, barely inhibited Omicron. Sera from COVID-19 convalescent patients collected 6 or 12 months post symptoms displayed low or no neutralizing activity against Omicron. Administration of a booster Pfizer dose as well as vaccination of previously infected individuals generated an anti-Omicron neutralizing response, with titers 6 to 23 fold lower against Omicron than against Delta. Thus, Omicron escapes most therapeutic monoclonal antibodies and to a large extent vaccine-elicited antibodies. Omicron remains however neutralized by antibodies generated by a booster vaccine dose.

11.
Nature ; 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: covidwho-1616993

RESUMO

The Omicron (B.1.1.529) variant of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) was only recently detected in southern Africa, but its subsequent spread has been extensive, both regionally and globally1. It is expected to become dominant in the coming weeks2, probably due to enhanced transmissibility. A striking feature of this variant is the large number of spike mutations3 that pose a threat to the efficacy of current COVID-19 (coronavirus disease 2019) vaccines and antibody therapies4. This concern is amplified by the findings from our study. We found B.1.1.529 to be markedly resistant to neutralization by serum not only from convalescent patients, but also from individuals vaccinated with one of the four widely used COVID-19 vaccines. Even serum from persons vaccinated and boosted with mRNA-based vaccines exhibited substantially diminished neutralizing activity against B.1.1.529. By evaluating a panel of monoclonal antibodies to all known epitope clusters on the spike protein, we noted that the activity of 17 of the 19 antibodies tested were either abolished or impaired, including ones currently authorized or approved for use in patients. In addition, we also identified four new spike mutations (S371L, N440K, G446S, and Q493R) that confer greater antibody resistance to B.1.1.529. The Omicron variant presents a serious threat to many existing COVID-19 vaccines and therapies, compelling the development of new interventions that anticipate the evolutionary trajectory of SARS-CoV-2.

12.
Nature ; 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: covidwho-1616992

RESUMO

The emergence of Omicron (Pango lineage B.1.1.529), first identified in Botswana and South Africa, may compromise vaccine effectiveness and lead to re-infections1. We investigated whether Omicron escapes antibody neutralization in South Africans vaccinated with Pfizer BNT162b2. We also investigated if Omicron requires the ACE2 receptor to infect cells. We isolated and sequence confirmed live Omicron virus from an infected person in South Africa and compared plasma neutralization of Omicron relative to an ancestral SARS-CoV-2 strain, observing that Omicron still required ACE2 to infect. For neutralization, blood samples were taken soon after vaccination from participants who were vaccinated and previously infected or vaccinated with no evidence of previous infection. Neutralization of ancestral virus was much higher in infected and vaccinated versus vaccinated only participants but both groups showed a 22-fold escape from vaccine elicited neutralization by the Omicron variant. However, in the previously infected and vaccinated group, the level of residual neutralization of Omicron was similar to the level of neutralization of ancestral virus observed in the vaccination only group. These data support the notion that, provided high neutralization capacity is elicited by vaccination/boosting approaches, reasonable effectiveness against Omicron may be maintained.

13.
Nature ; 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: covidwho-1616991

RESUMO

The recently emerged SARS-CoV-2 Omicron variant encodes 37 amino acid substitutions in the spike (S) protein, 15 of which are in the receptor-binding domain (RBD), thereby raising concerns about the effectiveness of available vaccines and antibody therapeutics. Here, we show that the Omicron RBD binds to human ACE2 with enhanced affinity, relative to the Wuhan-Hu-1 RBD, and binds to mouse ACE2. Marked reductions of plasma neutralizing activity were observed against Omicron compared to the ancestral pseudovirus for convalescent and vaccinated individuals, but this loss was less pronounced after a third vaccine dose. Most receptor-binding motif (RBM)-directed monoclonal antibodies (mAbs) lost in vitro neutralizing activity against Omicron, with only 3 out of 29 mAbs retaining unaltered potency, including the ACE2-mimicking S2K146 mAb1. Furthermore, a fraction of broadly neutralizing sarbecovirus mAbs neutralized Omicron through recognition of antigenic sites outside the RBM, including sotrovimab2, S2X2593 and S2H974. The magnitude of Omicron-mediated immune evasion marks a major SARS-CoV-2 antigenic shift. Broadly neutralizing mAbs recognizing RBD epitopes conserved among SARS-CoV-2 variants and other sarbecoviruses may prove key to controlling the ongoing pandemic and future zoonotic spillovers.

14.
Nature ; 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: covidwho-1616990

RESUMO

The SARS-CoV-2 B.1.1.529 variant (Omicron) contains 15 mutations on the receptor-binding domain (RBD). How Omicron would evade RBD neutralizing antibodies (NAbs) requires immediate investigation. Here, we used high-throughput yeast display screening1,2 to determine the RBD escaping mutation profiles for 247 human anti-RBD NAbs and showed that the NAbs could be unsupervised clustered into six epitope groups (A-F), which is highly concordant with knowledge-based structural classifications3-5. Strikingly, various single mutations of Omicron could impair NAbs of different epitope groups. Specifically, NAbs in Group A-D, whose epitope overlap with ACE2-binding motif, are largely escaped by K417N, G446S, E484A, and Q493R. Group E (S309 site)6 and F (CR3022 site)7 NAbs, which often exhibit broad sarbecovirus neutralizing activity, are less affected by Omicron, but still, a subset of NAbs are escaped by G339D, N440K, and S371L. Furthermore, Omicron pseudovirus neutralization showed that single mutation tolerating NAbs could also be escaped due to multiple synergetic mutations on their epitopes. In total, over 85% of the tested NAbs are escaped by Omicron. Regarding NAb drugs, the neutralization potency of LY-CoV016/LY-CoV555, REGN10933/REGN10987, AZD1061/AZD8895, and BRII-196 were greatly reduced by Omicron, while VIR-7831 and DXP-604 still function at reduced efficacy. Together, data suggest Omicron would cause significant humoral immune evasion, while NAbs targeting the sarbecovirus conserved region remain most effective. Our results offer instructions for developing NAb drugs and vaccines against Omicron and future variants.

15.
J Med Virol ; 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: covidwho-1616023

RESUMO

Due to the continuous emergence of multiple variants of severe acute respiratory syndrome cronavirus-2 (SARS-CoV-2), the Coronavirus disease (COVID-19) pandemic has caused severe morbidity and mortality worldwide in the last two years amidst waves of pandemic within the ongoing pandemic resulting into high global health concerns and adverse socioeconomics impacts. 1-4 Omicron, the recent highly mutated SARS-CoV-2 variant (B.1.1.529), classified as variant of concern (VoC) by WHO on 26 November 2021, is now becoming a dominant strain in several countries and a very massive surge in COVID-19 cases is being faced presently with nearly 300 million cumulative cases and 5.5 million deaths reported as of January 5, 2022 This article is protected by copyright. All rights reserved.

17.
Research ; 2021:4, 2021.
Artigo em Inglês | Web of Science | ID: covidwho-1614605

RESUMO

The spread of the latest SARS-CoV-2 variant Omicron is particularly concerning because of the large number of mutations present in its genome and lack of knowledge about how these mutations would affect the current SARS-CoV-2 vaccines and treatments. Here, by performing phylogenetic analysis using the Omicron spike (S) protein sequence, we found that the Omicron S protein presented the longest evolutionary distance in relation to the other SARS-CoV-2 variants. We predicted the structures of S, M, and N proteins of the Omicron variant using AlphaFold2 and investigated how the mutations have affected the S protein and its parts, S1 NTD and RBD, in detail. We found many amino acids on RBD were mutated, which may influence the interactions between the RBD and ACE2, while also showing the S309 antibody could still be capable of neutralizing Omicron RBD. The Omicron S1 NTD structures display significant differences from the original strain, which could lead to reduced recognition by antibodies resulting in potential immune escape and decreased effectiveness of the existing vaccines. However, this study of the Omicron variant was mainly limited to structural predictions, and these findings should be explored and verified by subsequent experiments. This study provided basic data of the Omicron protein structures that lay the groundwork for future studies related to the SARS-CoV-2 Omicron variant.

18.
Viruses ; 14(1), 2022.
Artigo em Inglês | EMBASE | ID: covidwho-1614001

RESUMO

Omicron, the most recent SARS-CoV-2 variant of concern (VOC), harbours multiple mutations in the spike protein that were not observed in previous VOCs. Initial studies suggest Omicron to substantially reduce the neutralizing capability of antibodies induced from vaccines and previous infection. However, its effect on T cell responses remains to be determined. Here, we assess the effect of Omicron mutations on known T cell epitopes and report data suggesting T cell responses to remain broadly robust against this new variant.

19.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22268821

RESUMO

We estimated the probability of undetected emergence of the SARS-CoV-2 Omicron variant in 25 low and middle-income countries (LMICs) prior to December 5, 2021. In nine countries, the risk exceeds 50%; in Turkey, Pakistan and the Philippines, it exceeds 99%. Risks are generally lower in the Americas than Europe or Asia.

20.
Preprint em Inglês | medRxiv | ID: ppmedrxiv-22268861

RESUMO

As part of an ongoing study assessing homologous and heterologous booster vaccines, following primary EUA series, we assessed neutralization of D614G and Omicron variants prior to and 28 days after boost. Subset analysis was done in six combinations (N = 10/group): four homologous primary-booster combinations included mRNA-1273 two-dose priming followed by boosting with 100-g or 50-g mRNA-1273, Ad26.COV2.S single-dose priming followed by Ad26.COV2.S booster and BNT162b2 two-dose priming followed by BNT162b2 boosting; and two heterologous primary-booster combinations: BNT162b2 followed by Ad26.COV2.S and Ad26.COV2.S followed by BNT162b2. Neutralizing antibody (Nab) titers to D614G on the day of boost (baseline) were detected in 85-100% of participants, with geometric mean titers (GMT) of 71-343 in participants who received an mRNA vaccine series versus GMTs of 35-41 in participants primed with Ad26.OV2.S. Baseline NAb titers to Omicron were detected in 50-90% of participants who received an mRNA vaccine series (GMT range 12.8-24.5) versus 20-25% among participants primed with Ad26.COV2.S. The booster dose increased the neutralizing GMT in most combinations to above 1000 for D614G and above 250 for Omicron by Day 29. Homologous prime-boost Ad26.COV2.S had the lowest NAb on Day 29 (D614G GMT 128 and Omicron GMT 45). Results were similar between age groups. Most homologous and heterologous boost combinations examined will increase humoral immunity to the Omicron variant.

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