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Transmission of SARS-CoV-2 Omicron VOC subvariants BA.1 and BA.2: Evidence from Danish Households
Transmission of SARS-CoV-2 Omicron VOC subvariants BA.1 and BA.2: Evidence from Danish Households
The Omicron SARS-CoV-2 variant of concern (VOC lineage B.1.1.529), which became dominant in many countries during early 2022, includes several subvariants with strikingly different genetic characteristics. Several countries, including Denmark, have observed the two Omicron subvariants: BA.1 and BA.2. In Denmark the latter has rapidly replaced the former as the dominant subvariant. Based on nationwide Danish data, we estimate the transmission dynamics of BA.1 and BA.2 following the spread of Omicron VOC within Danish households in late December 2021 and early January 2022. Among 8,541 primary household cases, of which 2,122 were BA.2, we identified a total of 5,702 secondary infections among 17,945 potential secondary cases during a 1-7 day follow-up period. The secondary attack rate (SAR) was estimated as 29% and 39% in households infected with Omicron BA.1 and BA.2, respectively. We found BA.2 to be associated with an increased susceptibility of infection for unvaccinated individuals (Odds Ratio (OR) 2.19; 95%-CI 1.58-3.04), fully vaccinated individuals (OR 2.45; 95%-CI 1.77-3.40) and booster-vaccinated individuals (OR 2.99; 95%-CI 2.11-4.24), compared to BA.1. We also found an increased transmissibility from unvaccinated primary cases in BA.2 households when compared to BA.1 households, with an OR of 2.62 (95%-CI 1.96-3.52). The pattern of increased transmissibility in BA.2 households was not observed for fully vaccinated and booster-vaccinated primary cases, where the OR of transmission was below 1 for BA.2 compared to BA.1. We conclude that Omicron BA.2 is inherently substantially more transmissible than BA.1, and that it also possesses immune-evasive properties that further reduce the protective effect of vaccination against infection, but do not increase its transmissibility from vaccinated individuals with breakthrough infections. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Frederik Plesner Lyngse: Independent Research Fund Denmark (Grant no. 9061-00035B.); Novo Nordisk Foundation (grant no. NNF17OC0026542); the Danish National Research Foundation through its grant (DNRF-134) to the Center for Economic Behavior and Inequality (CEBI) at the University of Copenhagen. Laust Hvas Mortensen is supported in part by grants from the Novo Nordisk Foundation (grant no. NNF17OC0027594, NNF17OC0027812). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was conducted using data from national registers only. According to Danish law, ethics approval is not needed for this type of research. All data management and analyses were carried out on the Danish Health Data Authority's restricted research servers with project number FSEID-00004942. The study only contains aggregated results and no personal data. The study is, therefore, not covered by the European General Data Protection Regulation (GDPR). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data used in this study are available under restricted access due to Danish data protection legislation. The data are available for research upon reasonable request to The Danish Health Data Authority and Statens Serum Institut and within the framework of the Danish data protection legislation and any required permission from Authorities. We performed no data collection or sequencing specifically for this study. Consensus genome data from the Danish cases are routinely shared publicly at GISAID (www.gisaid.org).
·medrxiv.org·
Transmission of SARS-CoV-2 Omicron VOC subvariants BA.1 and BA.2: Evidence from Danish Households
Historically High Excess Mortality During the COVID-19 Pandemic in Switzerland, Sweden, and Spain
Historically High Excess Mortality During the COVID-19 Pandemic in Switzerland, Sweden, and Spain
Background: Excess mortality quantifies the overall mortality impact of a pandemic. Mortality data have been accessible for many countries in recent decades, but few continuous data have been available for longer periods. Objective: To assess the historical dimension of the COVID-19 pandemic in 2020 for 3 countries with reliable death count data over an uninterrupted span of more than 100 years. Design: Observational study. Setting: Switzerland, Sweden, and Spain, which were militarily neutral and not involved in combat during either world war and have not been affected by significant changes in their territory since the end of the 19th century. Participants: Complete populations of these 3 countries. Measurements: Continuous series of recorded deaths (from all causes) by month from the earliest available year (1877 for Switzerland, 1851 for Sweden, and 1908 for Spain) were jointly modeled with annual age group–specific death and total population counts using negative binomial and multinomial models, which accounted for temporal trends and seasonal variability of prepandemic years. The aim was to estimate the expected number of deaths in a pandemic year for a nonpandemic scenario and the difference in observed and expected deaths aggregated over the year. Results: In 2020, the number of excess deaths recorded per 100 000 persons was 100 (95% credible interval [CrI], 60 to 135) for Switzerland, 75 (CrI, 40 to 105) for Sweden, and 155 (CrI, 110 to 195) for Spain. In 1918, excess mortality was 6 to 7 times higher. In all 3 countries, the peaks of monthly excess mortality in 2020 were greater than most monthly excess mortality since 1918, including many peaks due to seasonal influenza and heat waves during that period. Limitation: Historical vital statistics might be affected by minor completeness issues before the beginning of the 20th century. Conclusion: In 2020, the COVID-19 pandemic led to the second-largest infection-related mortality disaster in Switzerland, Sweden, and Spain since the beginning of the 20th century. Primary Funding Source: Foundation for Research in Science and the Humanities at the University of Zurich, Swiss National Science Foundation, and National Institute of Allergy and Infectious Diseases.
·acpjournals.org·
Historically High Excess Mortality During the COVID-19 Pandemic in Switzerland, Sweden, and Spain
Safety and immunogenicity of the SARS-CoV-2 ARCoV mRNA vaccine in Chinese adults: a randomised, double-blind, placebo-controlled, phase 1 trial
Safety and immunogenicity of the SARS-CoV-2 ARCoV mRNA vaccine in Chinese adults: a randomised, double-blind, placebo-controlled, phase 1 trial
Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 eligible participants were randomly assigned to receive five-dose levels of ARCoV or a placebo (20 per group). All participants received the first vaccination and 118 received the second dose. No serious adverse events were reported within 56 days after vaccination and the majority of adverse events were mild or moderate. Fever was the most common systemic adverse reaction (one [5%] of 20 in the 5 μg group, 13 [65%] of 20 in the 10 μg group, 17 [85%] of 20 in the 15 μg group, 19 [95%] of 20 in the 20 μg group, 16 [100%] of 16 in the 25 μg group; p0·0001). The incidence of grade 3 systemic adverse events were none (0%) of 20 in the 5 μg group, three (15%) of 20 in the 10 μg group, six (30%) of 20 in the 15 μg group, seven (35%) of 20 in the 20 μg group, five (31%) of 16 in the 25 μg group, and none (0%) of 20 in the placebo group (p=0·0013). As expected, the majority of fever resolved in the first 2 days after vaccination for all groups. The incidence of solicited systemic adverse events was similar after administration of ARCoV as a first or second vaccination. Humoral immune responses including anti-RBD IgG and neutralising antibodies increased significantly 7 days after the second dose and peaked between 14 and 28 days thereafter. Specific T-cell response peaked between 7 and 14 days after full vaccination. 15 μg induced the highest titre of neutralising antibodies, which was about twofold more than the antibody titre of convalescent patients with COVID-19.
·thelancet.com·
Safety and immunogenicity of the SARS-CoV-2 ARCoV mRNA vaccine in Chinese adults: a randomised, double-blind, placebo-controlled, phase 1 trial
Evidence for a role of phenotypic mutations in virus adaptation
Evidence for a role of phenotypic mutations in virus adaptation
Viruses interact extensively with the host molecular machinery, but the underlying mechanisms are poorly understood. Bacteriophage T7 recruits the small protein thioredoxin of the Escherichia coli host as an essential processivity factor for the viral DNA polymerase. We challenged the phage t …
·pubmed.ncbi.nlm.nih.gov·
Evidence for a role of phenotypic mutations in virus adaptation
Age-specific rate of severe and critical SARS-CoV-2 infections estimated with multi-country seroprevalence studies - 2021.07.29.21261282v2.full.pdf
Age-specific rate of severe and critical SARS-CoV-2 infections estimated with multi-country seroprevalence studies - 2021.07.29.21261282v2.full.pdf
Knowing the age-specific rates at which individuals infected with SARS-CoV-2 develop severe and critical disease is essential for designing public policy, for epidemic modeling, and for individual risk evaluation. In this study, we present the first estimates of these rates using multi-country serology studies, and data on hospital admissions and mortality from early to mid-2020. We integrated data from those sources using a Bayesian model that accounts for the high heterogeneity between data sources and for the uncertainty associated to the estimates reported from each data source. Our results show that the risk of severe and critical disease increases exponentially with age, but much less steeply than the risk of fatal illness. Importantly, the estimated rate of severe disease outcome in adolescents is between one and two orders of magnitude larger than the reported rate of vaccine side-effects, showing how these estimates are relevant for health policy. Finally, we validate our results by showing that they are in close agreement with the estimates obtained from an indirect method that uses reported infection fatality rates estimates and hospital mortality data.
·medrxiv.org·
Age-specific rate of severe and critical SARS-CoV-2 infections estimated with multi-country seroprevalence studies - 2021.07.29.21261282v2.full.pdf
Progressive Increase in Virulence of Novel SARS-CoV-2 Variants in Ontario, Canada - 2021.07.05.21260050v3.full.pdf
Progressive Increase in Virulence of Novel SARS-CoV-2 Variants in Ontario, Canada - 2021.07.05.21260050v3.full.pdf
Compared to non-VOC SARS-CoV-2 strains, the adjusted elevation in risk associated with N501Y-positive variants was 52% (43-62%) for hospitalization; 89% (67-116%) for ICU admission; and 51% (30-74%) for death. Increases with Delta variant were more pronounced: 108% (80-138%) for hospitalization; 234% (164-331%) for ICU admission; and 132% (47-230%) for death. Interpretation: The progressive increase in transmissibility and virulence of SARS-CoV-240 VOCs will result in a significantly larger, and more deadly, pandemic than would have occurred41 in the absence of VOC emergence.
·medrxiv.org·
Progressive Increase in Virulence of Novel SARS-CoV-2 Variants in Ontario, Canada - 2021.07.05.21260050v3.full.pdf
Synergism of TNF-α and IFN-γ Triggers Inflammatory Cell Death, Tissue Damage, and Mortality in SARS-CoV-2 Infection and Cytokine Shock Syndromes
Synergism of TNF-α and IFN-γ Triggers Inflammatory Cell Death, Tissue Damage, and Mortality in SARS-CoV-2 Infection and Cytokine Shock Syndromes
COVID-19 is characterized by excessive production of pro-inflammatory cytokines and acute lung damage associated with patient mortality. While multipl…
·sciencedirect.com·
Synergism of TNF-α and IFN-γ Triggers Inflammatory Cell Death, Tissue Damage, and Mortality in SARS-CoV-2 Infection and Cytokine Shock Syndromes
The interferon landscape along the respiratory tract impacts the severity of COVID-19
The interferon landscape along the respiratory tract impacts the severity of COVID-19
An in-depth analysis of IFNs in COVID-19 reveals differences in their roles based on anatomical location, viral load, age, and disease severity. In the upper respiratory tract, high levels of IFN-III are protective and result in mild disease in spite of higher SARS-CoV-2 viral burden, while the lower airways of patients with severe COVID-19 demonstrate elevated IFN-I and IFN-III, cell death, and a reduction in IFN-stimulated genes.
·cell.com·
The interferon landscape along the respiratory tract impacts the severity of COVID-19
Effectiveness of BNT162b2 and mRNA-1273 COVID-19 boosters against SARS-CoV-2 Omicron (B.1.1.529) infection in Qatar
Effectiveness of BNT162b2 and mRNA-1273 COVID-19 boosters against SARS-CoV-2 Omicron (B.1.1.529) infection in Qatar
BACKGROUND Waning of COVID-19 vaccine protection and emergence of SARS-CoV-2 Omicron (B.1.1.529) variant have expedited efforts to scale up booster vaccination. This study compared protection afforded by booster doses of the BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) vaccines, compared to the primary series of only two doses in Qatar, during a large, rapidly growing Omicron wave. METHODS In a population of 2,232,224 vaccinated persons with at least two doses, two matched, retrospective cohort studies were implemented to investigate effectiveness of booster vaccination against symptomatic SARS-CoV-2 infection and against COVID-19 hospitalization and death, up to January 9, 2022. Association of booster status with infection was estimated using Cox proportional-hazards regression models. RESULTS For BNT162b2, cumulative symptomatic infection incidence was 2.9% (95% CI: 2.8-3.1%) in the booster-dose cohort and 5.5% (95% CI: 5.3-5.7%) in the primary-series cohort, after 49 days of follow-up. Adjusted hazard ratio for symptomatic infection was 0.50 (95% CI: 0.47-0.53). Booster effectiveness relative to primary series was 50.1% (95% CI: 47.3-52.8%). For mRNA-1273, cumulative symptomatic infection incidence was 1.9% (95% CI: 1.7-2.2%) in the booster-dose cohort and 3.5% (95% CI: 3.2-3.9%) in the primary-series cohort, after 35 days of follow-up. The adjusted hazard ratio for symptomatic infection was 0.49 (95% CI: 0.43-0.57). Booster effectiveness relative to primary series was 50.8% (95% CI: 43.4-57.3%). There were fewer cases of severe COVID-19 in booster-dose cohorts than in primary-series cohorts, but cases of severe COVID-19 were rare in all cohorts. CONCLUSIONS mRNA booster vaccination is associated with modest effectiveness against symptomatic infection with Omicron. The development of a new generation of vaccines targeting a broad range of variants may be warranted. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The authors are grateful for institutional salary support from the Biomedical Research Program and the Biostatistics, Epidemiology, and Biomathematics Research Core, both at Weill Cornell Medicine-Qatar, as well as for institutional salary support provided by the Ministry of Public Health, Hamad Medical Corporation, and Sidra Medicine. The authors are also grateful for the Qatar Genome Programme and Qatar University Biomedical Research Center for institutional support for the reagents needed for the viral genome sequencing. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the article. Statements made herein are solely the responsibility of the authors. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Hamad Medical Corporation and Weill Cornell Medicine-Qatar Institutional Review Boards approved this retrospective study with waiver of informed consent. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The dataset of this study is a property of the Qatar Ministry of Public Health that was provided to the researchers through a restricted-access agreement that prevents sharing the dataset with a third party or publicly. Future access to this dataset can be considered through a direct application for data access to Her Excellency the Minister of Public Health (). Aggregate data are available within the manuscript and its Supplementary information.
·medrxiv.org·
Effectiveness of BNT162b2 and mRNA-1273 COVID-19 boosters against SARS-CoV-2 Omicron (B.1.1.529) infection in Qatar
Pressemitteilungen - Antikörper nach SARS-CoV-2-Infektion – neue Erkenntnisse über die Sensitivität und Nachweisdauer von Antikörpertests
Pressemitteilungen - Antikörper nach SARS-CoV-2-Infektion – neue Erkenntnisse über die Sensitivität und Nachweisdauer von Antikörpertests
Das Paul-Ehrlich-Institut hat in Zusammenarbeit mit der Universität Frankfurt am Main die Langzeit-Antikörperreaktion nach SARS-CoV-2-Infektion bei 828 Personen mit verschiedenen COVID-19-Schweregraden untersucht. Gemessen wurden bindende Antikörper gegen unterschiedliche SARS-CoV-2-Zielantigene, neutralisierende Antikörper und die Stärke der Antikörperbindung (Antikörperavidität). Sensitivität, Kinetik und Dauer des Antikörpernachweises waren abhängig von detektierter Antikörperklasse, Testdesign, Zielantigen des Anti-SARS-CoV-2-Antikörpertests sowie von Antikörperavidität und COVID-19-Schweregrad.
·pei.de·
Pressemitteilungen - Antikörper nach SARS-CoV-2-Infektion – neue Erkenntnisse über die Sensitivität und Nachweisdauer von Antikörpertests
Executive dysfunction following SARS-CoV-2 infection: A cross-sectional examination in a population-representative sample
Executive dysfunction following SARS-CoV-2 infection: A cross-sectional examination in a population-representative sample
Background Prior studies have documented reliable associations between SARS-CoV-2 infection and adverse cognitive impact in older adults. The current study sought to determine whether SARS-CoV-2 infection and COVID-19 symptom severity are associated with cognitive dysfunction among young adults and middled-aged adults in the general population. Method The Canadian COVID-19 Experiences Project (CCEP) survey involves 1,958 adults with equal representation of vaccinated and vaccine hesitant adults between the ages of 18 and 54 years. The sample comprised 1,958 adults with a mean age of 37 years ( SD =10.4); 60.8% were female. The primary outcome was symptoms of cognitive dysfunction assessed via an abbreviated form of the Barkley Deficits in Executive Functioning Scale (BDEFS) and performance on a validated decision-making task. Results Young and middle-aged adults with a positive SARS-CoV-2 infection history reported a significantly higher number of symptoms of executive dysfunction ( M adj =1.89, SE =0.08, CI : 1.74, 2.04; n =175) than their non-infected counterparts ( M adj =1.63, SE =0.08, CI : 1.47,1.80; n =1,599; β=0.26, p =.001). Among those infected, there was a dose-response relationship between COVID-19 symptom severity and level of executive dysfunction, with moderate (β=0.23, CI : 0.003-0.46) and very/extremely severe (β= 0.69, CI : 0.22-1.16) COVID-19 symptoms being associated with significantly greater dysfunction, compared to asymptomatic. These effects remained reliable and of similar magnitude after controlling for age, sex, vaccination status, income, and geographic region, and after removal of those who had been intubated during hospitalization. Similar effects were found for the decision-making task. Conclusions Positive SARS-CoV-2 infection history and COVID-19 symptom severity are associated with executive dysfunction among young and middle-aged adults with no history of medically induced coma. These findings are evident on self-reported and task-related indicators of cognitive function. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was supported by an operating grant to P. Hall (PI), G. Fong (co-PI) and S. Hitchman (co-I) by the Canadian Institutes for Health Research (CIHR), Institute for Population and Public Health (GA3-177733). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study protocol was reviewed by and received approval from the University of Waterloo Office of Research Ethics. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors
·medrxiv.org·
Executive dysfunction following SARS-CoV-2 infection: A cross-sectional examination in a population-representative sample
Reduced Neutralization of SARS-CoV-2 Omicron Variant by Vaccine Sera and Monoclonal Antibodies
Reduced Neutralization of SARS-CoV-2 Omicron Variant by Vaccine Sera and Monoclonal Antibodies
Due to numerous mutations in the spike protein, the SARS-CoV-2 variant of concern Omicron (B.1.1.529) raises serious concerns since it may significantly limit the antibody-mediated neutralization and increase the risk of reinfections. While a rapid increase in the number of cases is being reported worldwide, until now there has been uncertainty about the efficacy of vaccinations and monoclonal antibodies. Our in vitro findings using authentic SARS-CoV-2 variants indicate that in contrast to the currently circulating Delta variant, the neutralization efficacy of vaccine-elicited sera against Omicron was severely reduced highlighting T-cell mediated immunity as essential barrier to prevent severe COVID-19. Since SARS-CoV-2 Omicron was resistant to casirivimab and imdevimab, genotyping of SARS-CoV-2 may be needed before initiating mAb treatment. Variant-specific vaccines and mAb agents may be required to treat COVID-19 due to Omicron and other emerging variants of concern. ### Competing Interest Statement S.C. was a member of a clinical advisory board for Biontech. T.W. received speaker and consultancy fees from Gilead Sciences, Merck Sharp Dome, and Janssen Pharmaceuticals. All other authors declare no conflict of interest. ### Funding Statement This study has been performed with the support of the Goethe-Corona-Fund of the Goethe University Frankfurt (MW) and the Federal Ministry of Education and Research (COVIDready; grant 02WRS1621C (MW). We are thankful for the numerous donations to the Goethe-Corona-Fund and the support of our SARS-CoV-2 research. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board of the Ethics Committee of the Faculty of Medicine at Goethe University Frankfurt (2021-201, 20-864 and 250719). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Sequences are available on GISAID (www.gisaid.org, access date 12/2021), under the following accession numbers. Omicron strains used in this study are as follows: B.1.1.529 (EPI\_ISL\_6959868; GenBank ID: [OL800703][1]), B.1.1.529 (EPI\_ISL\_6959871; GenBank ID: [OL800702][2]) . GenBank accession number for the SARS-CoV-2 B.1.617.2 (Delta) isolate IND8424/2021 ( GenBank ID: [MZ315141][3]). [1]: /lookup/external-ref?link_type=GEN&access_num=OL800703&atom=%2Fmedrxiv%2Fearly%2F2021%2F12%2F13%2F2021.12.07.21267432.atom [2]: /lookup/external-ref?link_type=GEN&access_num=OL800702&atom=%2Fmedrxiv%2Fearly%2F2021%2F12%2F13%2F2021.12.07.21267432.atom [3]: /lookup/external-ref?link_type=GEN&access_num=MZ315141&atom=%2Fmedrxiv%2Fearly%2F2021%2F12%2F13%2F2021.12.07.21267432.atom
·medrxiv.org·
Reduced Neutralization of SARS-CoV-2 Omicron Variant by Vaccine Sera and Monoclonal Antibodies
2021-12-16-COVID19-Report-49.pdf
2021-12-16-COVID19-Report-49.pdf
To estimate the growth of the Omicron variant of concern (1) and its immune escape (2–9) characteristics, we analysed data from all PCR-confirmed SARS-CoV-2 cases in England excluding those with a history of recent international travel. We undertook separate analyses according to two case definitions. For the first definition, we included all cases with a definitive negative S-gene Target Failure (SGTF) result and specimen dates between 29/11/2021 and 11/12/2021 inclusive. For the second definition, we included cases with a positive genotype result and specimen date between 23/11/2021 and 11/12/2021 inclusive. We chose a later start date for the SGTF definition to ensure greater specificity of SGTF for Omicron. We used logistic and Poisson regression to identify factors associated with testing positive for Omicron compared to non-Omicron (mostly Delta) cases. We explored the following predictors: day, region, symptomatic status, sex, ethnicity, age band and vaccination status. Our results suggest rapid growth of the frequency of the Omicron variant relative to Delta, with the exponential growth rate of its frequency estimated to be 0.34/day (95% CI: 0.33-0.35) [2.0 day doubling time] over the study period from both SGTF and genotype data. The distribution of Omicron by age, region and ethnicity currently differs markedly from Delta, with 18–29-year-olds, residents in the London region, and those of African ethnicity having significantly higher rates of infection with Omicron relative to Delta. Hospitalisation and asymptomatic infection indicators were not significantly associated with Omicron infection, suggesting at most limited changes in severity compared with Delta. To estimate the impact of Omicron on vaccine effectiveness (VE) for symptomatic infection we used conditional Poisson regression to estimate the hazard ratio of being an Omicron case (using SGTF definition) compared with Delta, restricting our analysis to symptomatic cases and matching by day, region, 10-year age band, sex and ethnicity. We found a significant increased risk of an Omicron case compared to Delta for those with vaccine status AZ 2+weeks post-dose 2 (PD2) , Pfizer 2+w PD2, AZ 2+w post-dose 3 (PD3) and PF 2+w PD3 vaccine states with hazard ratios of 1.86 (95%CI: 1.67-2.08), 2.68 (95%CI: 2.54-2.83), 4.32 (95%CI: 3.84-4.85) and 4.07 (95%CI: 3.66-4.51), respectively, where PD3 states are categorised by the dose 1/2 vaccine used. Depending on the Delta VE estimates used (10), these estimates translate into Omicron VE estimates of between 0% and 20% PD2 and between 55% and 80% PD3 against Omicron, consistent with other estimates (11). Similar estimates were obtained using genotype data, albeit with greater uncertainty. To assess the impact of Omicron on reinfection rates we relied on genotype data, since SGTF is associated with a higher observed rate of reinfection, likely due to reinfections typically having higher Ct values than primary infections and therefore being subject to a higher rate of random PCR target failure. Controlling for vaccine status, age, sex, ethnicity, asymptomatic status, region and specimen date and using conditional Poisson regression to predict reinfection status, Omicron was associated with a 5.41 (95% CI: 4.87-6.00) fold higher risk of reinfection compared with Delta. This suggests relatively low remaining levels of immunity from prior infection.
·imperial.ac.uk·
2021-12-16-COVID19-Report-49.pdf
Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants - 2022.01.25.22269794v1.full.pdf
Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants - 2022.01.25.22269794v1.full.pdf
Virus-like particle (VLP) and live virus assays were used to investigate neutralizing immunity to Delta32 and Omicron SARS-CoV-2 variants in 239 samples from 125 fully vaccinated individuals. In uninfected, non-boosted individuals, VLP neutralization titers to Delta and Omicron were reduced 2.7-fold and 15.4-fold, respectively, compared to wild-type (WT), while boosted individuals (n=23) had 18-fold increased titers. Delta breakthrough infections (n=39) had 57-fold and 3.1-fold titers whereas Omicron breakthrough infections (n=14) had 5.8-fold and 0.32-fold titers compared to uninfected non-boosted and boosted individuals, respectively. The difference in titers (p=0.049) was related to a higher proportion of moderate to severe infections in the Delta cohort (p=0.014). Correlation of neutralizing and spike quantitative antibody titers was decreased with Delta or Omicron compared to WT. Neutralizing antibodies in Delta and Omicron breakthrough infections increase overall, but the relative magnitude of increase is greater in more clinically severe infection and against the specific infecting variant.
·medrxiv.org·
Neutralizing immunity in vaccine breakthrough infections from the SARS-CoV-2 Omicron and Delta variants - 2022.01.25.22269794v1.full.pdf