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On 24th November 2021, the sequence of a new SARS-CoV-2 viral isolate Omicron-B.1.1.529 was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titers of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic Alpha, Beta, Gamma, or Delta are substantially reduced, or the sera failed to neutralize. Titers against Omicron are boosted by third vaccine doses and are high in both vaccinated individuals and those infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of the large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses and uses mutations that confer tight binding to ACE2 to unleash evolution driven by immune escape. This leads to a large number of mutations in the ACE2 binding site and rebalances receptor affinity to that of earlier pandemic viruses.
RESUMEN
OBJECTIVES: No studies have examined longitudinal patterns of naturally exhaled SARS-CoV-2 RNA viral load (VL) during acute infection. We report this using facemask sampling (FMS) and assessed the relationship between emitted RNA VL and household transmission. METHODS: Between December 2020 and February 2021, we recruited participants within 24 hours of a positive RT-qPCR on upper respiratory tract sampling (URTS) (day 0). Participants gave FMS (for 1 hour) and URTS (self-taken) on seven occasions up to day 21. Samples were analysed by RT-qPCR (from sampling matrix strips within the mask) and symptom diaries were recorded. Household transmission was assessed through reporting of positive URTS RT-qPCR in household contacts. RESULTS: Analysis of 203 FMS and 190 URTS from 34 participants showed that RNA VL peaked within the first 5 days following sampling. Concomitant URTS, FMS RNA VL, and symptom scores, however, were poorly correlated, but a higher severity of reported symptoms was associated with FMS positivity up to day 5. Of 28 participants who had household contacts, 12 (43%) reported transmission. Frequency of household transmission was associated with the highest (peak) FMS RNA VL obtained (negative genome copies/strip: 0% household transmission; 1 to 1000 copies/strip: 20%; 1001 to 10 000 copies/strip: 57%; >10 000 copies/strip: 75%; p = 0.048; age adjusted OR of household transmission per log increase in copies/strip: 4.97; 95% CI, 1.20-20.55; p = 0.02) but not observed with peak URTS RNA VL. DISCUSSION: Exhaled RNA VL measured by FMS is highest in early infection, can be positive in symptomatic patients with concomitantly negative URTS, and is strongly associated with household transmission.
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COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , ARN Viral , Carga Viral , MáscarasRESUMEN
BACKGROUND: Human to human transmission of SARS-CoV-2 is driven by the respiratory route but little is known about the pattern and quantity of virus output from exhaled breath. We have previously shown that face-mask sampling (FMS) can detect exhaled tubercle bacilli and have adapted its use to quantify exhaled SARS-CoV-2 RNA in patients admitted to hospital with Coronavirus Disease-2019 (COVID-19). METHODS: Between May and December 2020, we took two concomitant FMS and nasopharyngeal samples (NPS) over two days, starting within 24 h of a routine virus positive NPS in patients hospitalised with COVID-19, at University Hospitals of Leicester NHS Trust, UK. Participants were asked to wear a modified duckbilled facemask for 30 min, followed by a nasopharyngeal swab. Demographic, clinical, and radiological data, as well as International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) mortality and deterioration scores were obtained. Exposed masks were processed by removal, dissolution and analysis of sampling matrix strips fixed within the mask by RT-qPCR. Viral genome copy numbers were determined and results classified as Negative; Low: ≤999 copies; Medium: 1000-99,999 copies and High ≥ 100,000 copies per strip for FMS or per 100⯵l for NPS. RESULTS: 102 FMS and NPS were collected from 66 routinely positive patients; median age: 61 (IQR 49 - 77), of which FMS was positive in 38% of individuals and concomitant NPS was positive in 50%. Positive FMS viral loads varied over five orders of magnitude (<10-3.3 x 106 genome copies/strip); 21 (32%) patients were asymptomatic at the time of sampling. High FMS viral load was associated with respiratory symptoms at time of sampling and shorter interval between sampling and symptom onset (FMS High: median (IQR) 2 days (2-3) vs FMS Negative: 7 days (7-10), pâ¯=â¯0.002). On multivariable linear regression analysis, higher FMS viral loads were associated with higher ISARIC mortality (Medium FMS vs Negative FMS gave an adjusted coefficient of 15.7, 95% CI 3.7-27.7, pâ¯=â¯0.01) and deterioration scores (High FMS vs Negative FMS gave an adjusted coefficient of 37.6, 95% CI 14.0 to 61.3, pâ¯=â¯0.002), while NPS viral loads showed no significant association. CONCLUSION: We demonstrate a simple and effective method for detecting and quantifying exhaled SARS-CoV-2 in hospitalised patients with COVID-19. Higher FMS viral loads were more likely to be associated with developing severe disease compared to NPS viral loads. Similar to NPS, FMS viral load was highest in early disease and in those with active respiratory symptoms, highlighting the potential role of FMS in understanding infectivity.
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COVID-19 , SARS-CoV-2 , Humanos , Máscaras , Persona de Mediana Edad , ARN Viral , Carga ViralRESUMEN
On the 24 th November 2021 the sequence of a new SARS CoV-2 viral isolate spreading rapidly in Southern Africa was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titres of Omicron by sera from vaccinees and convalescent subjects infected with early pandemic as well as Alpha, Beta, Gamma, Delta are substantially reduced or fail to neutralize. Titres against Omicron are boosted by third vaccine doses and are high in cases both vaccinated and infected by Delta. Mutations in Omicron knock out or substantially reduce neutralization by most of a large panel of potent monoclonal antibodies and antibodies under commercial development. Omicron S has structural changes from earlier viruses, combining mutations conferring tight binding to ACE2 to unleash evolution driven by immune escape, leading to a large number of mutations in the ACE2 binding site which rebalance receptor affinity to that of early pandemic viruses.
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BACKGROUND AND OBJECTIVES: Cognitive models of psychosis implicate interpretation biases as one of the mechanisms involved in the formation and maintenance of symptoms. First we measured the strength of association between interpretation biases and psychosis-relevant traits. Next we manipulated these biases and quantified the effects of doing so on psychosis-relevant outcomes. METHODS: Experiment 1 used two measures of interpretation bias in a healthy sample (n = 70). Experiment 2 used a novel cognitive bias modification procedure (CMB-pa) in individuals with moderate trait paranoia (n = 60). RESULTS: Experiment 1 revealed that over a third of the variance in interpretation bias could be explained by the combined effect of trait measures of paranoia/psychosis. In Experiment 2, CBM-pa produced training-congruent changes in the interpretation of new ambiguous information and influenced the interpretation, attribution and distress associated with a real-life social event. LIMITATIONS: The potentially confounding effects of elevated anxiety and depression on interpretation bias and the restricted range of outcome measures to assess the wider effects of CBM-pa. CONCLUSIONS: These studies are consistent with interpretation biases contributing to the maintenance of paranoia. CBM-pa could next be adapted and evaluated to test its efficacy as a therapeutic intervention.
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Trastornos Paranoides/psicología , Trastornos Psicóticos/psicología , Adulto , Ansiedad/psicología , Terapia Cognitivo-Conductual , Depresión/psicología , Femenino , Humanos , MasculinoRESUMEN
A Variante de Preocupação Ômicron (B.1.1.529) trouxe uma grande expansão mundial dos contágios pelo SARS-CoV-2, mesmo em países onde a imunização contra o vírus já estava avançada. Para compreender como a coleção de mutações da Glicoproteína S da Ômicron leva ao escape da resposta imunológica, um esforço internacional de pesquisa que incluiu cientistas da Rede Genômica Fiocruz analisou as estruturas de proteínas, além da neutralização da capacidade de causar infecção ao expôr amostras da Ômicron a diferentes preparados contendo anticorpos como: 1) o soro de pacientes infectados com outras amostras do vírus, 2) os chamados "anticorpos monoclonais" selecionados em laboratório, e 3) o soro de pessoas vacinadas.O presente artigo, fruto desta colaboração para o estudo de múltiplos fatores envolvidos no escape da resposta imune apresentado pela Ômicron, demonstrou que a nova variante é quase 17 vezes mais resistente à neutralização pelos anticorpos gerados em resposta a uma linhagem da primeira onda da pandemia. O estudo mostra ainda que um esquema vacinal de três doses aumenta consideravelmente a resposta ao vírus, incluindo a neutralização da variante Ômicron, que não era suficiente apenas com duas doses do imunizante. O artigo mostra ainda que a estrutura de porções da Glicoproteína S da Ômicron estão envolvidas em "compensar" a ação de anticorpos através de uma ligação mais forte à ACE2, molécula que atua como receptor viral nas células humanas.