Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 11 de 11
Filtrar
Más filtros










Intervalo de año de publicación
1.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-22281076

RESUMEN

BackgroundSeroprevalence and the proportion of people with neutralizing activity against SARS-CoV-2 variants was high in early 2022. Since it is unclear how immunity in the general population evolves, the aim of this study was to assess the development of functional and hybrid immunity in the general population during a period of high incidence of infections with Omicron variants. MethodsThis prospective population based multi-region cohort study is part of the Corona Immunitas research programme in Switzerland. In March 2022, we randomly selected individuals from the general population in southern (canton of Ticino) and north-eastern (canton of Zurich) Switzerland, who were assessed again in June/July 2022. We supplemented the June/July 2022 sample with a random sample from western Switzerland (canton of Vaud). We assessed SARS-CoV-2 specific IgG antibodies against spike and nucleocapsid proteins and the presence of SARS-CoV-2 neutralising antibodies against three variants (wildtype, Delta, Omicron). FindingsIn June/July 2022, seroprevalence was >98% in 2553 individuals from the general Swiss population. The proportion of individuals with neutralising antibodies against wildtype, Delta, and Omicron was 94.2%, 90.8%, and 84.9%, and at least 51% of the participants developed hybrid immunity. Individuals with hybrid immunity had, compared to those with only vaccine- or infection-induced immunity, highest levels of both, anti-spike IgG antibodies titres (4518 vs. 4304 vs. 269 WHO U/ml) and neutralisation capacity against wildtype (99.8% vs. 98% vs. 47.5%), Delta (99% vs. 92.2% vs. 38.7%), and Omicron (96.4% vs. 79.5% vs. 47.5%). InterpretationThis first study on functional and hybrid immunity in the general population after Omicron waves showed that SARS-CoV-2 has become endemic. The high levels of antibodies and neutralization in the general populations support the emerging recommendations of some countries where booster vaccinations are still strongly recommended for vulnerable persons but less strongly recommended for individuals in the general population. FundingThe Corona Immunitas research network is coordinated by the Swiss School of Public Health (SSPH+) and funded by fundraising of SSPH+ including funds of the Swiss Federal Office of Public Health and private funders (ethical guidelines for funding stated by SSPH+ were respected), by funds of the cantons of Switzerland (Vaud, Zurich, and Basel), and by institutional funds of the Universities. Study registrationISRCTN18181860 Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched Pubmed, Medline, Scopus and Web of Knowledge, for primary population-based studies prospectively assessing infection-, vaccine-induced, and hybrid immunity and the respective neutralising activity of antibodies against SARS-CoV-2 and its variants of concern. We included articles published between 1 January and 28 September 2022, without language restrictions, and retrieved 540 publications after deduplication. None of the screened studies measured the prevalence of immune response and neutralisation capacity prospectively in population-based, representative samples accounting for type of acquired immunity. Evidence from five studies, all conducted in non-representative, convenience and relatively small samples (N<254), and/or in sub-populations (e.g., healthcare workers and children), shows that hybrid immunity confers higher immune protection and exhibits better neutralising capacity compared to vaccine- and infection-induced immunity. Furthermore, one of the screened studies highlights that antibodies developed by individuals with hybrid immunity show the slowest decline over a period of 10 months. Added value of this studyWe took advantage of an ongoing cohort study on anti-SARS-CoV-2 seroprevalence conducted in a representative sample of the general Swiss population (N=2553) using standard, previously validated methods, to measure changes over time in seroprevalence, neutralisation capacity against wildtype and variants of concerns of the virus (i.e., ACE2r-block), waning of antibodies, and new infections. This is the first study, conducted in the general population and during the pandemic phase characterized by very high incidence of Omicron infections, to assess the extent of hybrid immunity (51%) and neutralising antibodies against the wildtype (94.2%), Delta (90.8%), and Omicron variants (84.9%). Our findings show that individuals with hybrid immunity, compared to those with only vaccine- or infection-induced immunity, had the highest levels of both anti-spike IgG antibodies titres and neutralisation capacity against wildtype, Delta, and Omicron variants. We also found that, from March to June/July 2022, anti-spike IgG antibodies remained stable in the general population (>96%), while anti-nucleocapsid IgG antibodies fluctuated due to their fast waning (7.3% of participants anti-nucleocapsid IgG antibodies became undetectable) and the parallel spread of Omicron infections (18.6% of participants acquired anti-nucleocapsid IgG antibodies). Implications of all the available evidenceBy mid-2022, SARS-CoV-2 has become endemic, and a majority of individuals developed hybrid immunity with high levels of neutralisation against the wildtype, Delta, and Omicron variants of SARS-CoV-2. Combined with existing evidence, our results indicate that hybrid immunity confers higher levels of neutralising activity compared to both vaccine-induced and infection-induced immunity. This study extends findings on the immunological protection conferred by hybrid immunity from sub-populations to the general population. The high levels of antibodies and neutralization in the general populations support the emerging recommendations of some countries where booster vaccinations are still strongly recommended for vulnerable persons but less strongly recommended for individuals in the general population. Monitoring the prevalence, waning, and neutralising activity of antibodies against potential new variants of concern in populations remains crucial.

2.
Preprint en Inglés | bioRxiv | ID: ppbiorxiv-501852

RESUMEN

The rapid evolution of SARS-CoV-2 has led to a severe attrition of the pool of monoclonal antibodies still available for COVID-19 prophylaxis or treatment. Omicron subvariants notably escape most antibodies developed so far, with Bebtelovimab last amongst clinically approved therapeutic antibodies to display still good activity against all of them including the currently dominant BA.4/BA.5. We recently described P2G3, a broadly active SARS-CoV-2 monoclonal antibody, which targets a region of Spike partly overlapping with the site recognized by Bebtelovimab. Here, we reveal that P2G3 efficiently neutralizes SARS-CoV-2 omicron subvariants including BA.4/BA.5. We further demonstrate that P2G3 neutralizes Omicron BA.2 and BA.4 mutants escaping Bebtelovimab blockade, whereas the converse is not true. FundingEU COVICIS program; private foundation advised by CARIGEST SA.

3.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-22274436

RESUMEN

BackgroundThe rapid worldwide spread of the mildly pathogenic SARS-CoV-2 Omicron variant has led to the suggestion that it will induce levels of collective immunity that will help putting an end to the COVID19 pandemics. MethodsConvalescent serums from non-hospitalized individuals previously infected with Alpha, Delta or Omicron BA.1 SARS-CoV-2 or subjected to a full mRNA vaccine regimen were evaluated for their ability to neutralize a broad panel of SARS-CoV-2 variants. FindingsPrior vaccination or infection with the Alpha or to a lesser extent Delta strains conferred robust neutralizing titers against most variants, albeit more weakly against Beta and even more Omicron. In contrast, Omicron convalescent serums only displayed low level of neutralization activity against the cognate virus and were unable to neutralize other SARS-CoV-2 variants. InterpretationModerately symptomatic Omicron infection is only poorly immunogenic and does not represent a substitute for vaccination. FundingEPFL COVID Fund; private foundation advised by CARIGEST SA; Private Foundation of the Geneva University Hospitals; General Directorate of Health of the canton of Geneva, the Swiss Federal Office of Public Health.

4.
Preprint en Inglés | bioRxiv | ID: ppbiorxiv-484873

RESUMEN

The SARS-CoV-2 Omicron variant exhibits very high levels of transmission, pronounced resistance to authorized therapeutic human monoclonal antibodies and reduced sensitivity to vaccine-induced immunity. Here we describe P2G3, a human monoclonal antibody (mAb) isolated from a previously infected and vaccinated donor, which displays picomolar-range neutralizing activity against Omicron BA.1, BA.1.1, BA.2 and all other current variants, and is thus markedly more potent than all authorized or clinically advanced anti-SARS-CoV-2 mAbs. Structural characterization of P2G3 Fab in complex with the Omicron Spike demonstrates unique binding properties to both down and up spike trimer conformations at an epitope that partially overlaps with the receptor-binding domain (RBD), yet is distinct from those bound by all other characterized mAbs. This distinct epitope and angle of attack allows P2G3 to overcome all the Omicron mutations abolishing or impairing neutralization by other anti-SARS-COV-2 mAbs, and P2G3 accordingly confers complete prophylactic protection in the SARS-CoV-2 Omicron monkey challenge model. Finally, although we could isolate in vitro SARS-CoV2 mutants escaping neutralization by P2G3 or by P5C3, a previously described broadly active Class 1 mAb, we found these viruses to be lowly infectious and their key mutations extremely rare in the wild, and we could demonstrate that P2G3/P5C3 efficiently cross-neutralized one anothers escapees. We conclude that this combination of mAbs has great prospects in both the prophylactic and therapeutic settings to protect from Omicron and other VOCs.

5.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21267776

RESUMEN

To better understand the development of immunity against SARS-CoV-2 over time, we evaluated humoral and cellular responses a population-based cohort of SARS-CoV-2-infected individuals covering the full spectrum of COVID-19 up to 217 days after diagnosis. We characterized anti-Spike (S)-IgA and -IgG antibody responses in 431 individuals and found that about 85% develop and maintain anti-S-IgG responses over time. In a subsample of 64 participants selected for a detailed characterization of immune responses, we additionally evaluated anti-Nucleocapsid (N)-IgG antibodies and T cell responses specific to viral Membrane (M), N, and S proteins. Most participants had detectable T cell responses to at least one of the four peptide pools analyzed, which were more frequent than antibody seropositivity. We found a moderate correlation between antibody and T cell responses, which declined over time and suggests important variability in response patterns between individuals. The heterogeneity of immune trajectories was further analyzed using cluster analyses taking into account joint antibody and T cell responses over time. We identified five distinct immune trajectory patterns, which were characterized by specific antibody, T cell and T cell subset patterns along with disease severity and demographic factors. Higher age, male sex, higher disease severity and being a non-smoker was significantly associated with stronger immune responses. Overall, the results highlight that there is a consistent and maintained antibody response among most SARS-CoV-2-infected individuals, while T cell responses appear to be more heterogenous but potentially compensatory among those with low antibody responses. One Sentence SummaryPresence of heterogenous immune response trajectories after SARS-CoV-2 infection with potential compensatory role of T cells among individuals with low antibody responses.

6.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21255150

RESUMEN

The detection of SARS-CoV-2-specific antibodies in the serum of an individual indicates prior infection or vaccination. However, it provides limited insight into the protective nature of this immune response. Neutralizing antibodies recognizing the viral Spike are far more revealing, yet their measurement traditionally requires virus- and cell-based systems that are costly, time-consuming, poorly flexible and potentially biohazardous. Here we present a cell-free quantitative neutralization assay based on the competitive inhibition of trimeric SARS-CoV-2 Spike protein binding to the angiotensin converting enzyme 2 (ACE2) viral receptor. This high-throughput method matches the performance of the gold standard live virus infectious assay, as verified with a panel of 206 seropositive donors with varying degrees of infection severity and virus-specific IgG titers, achieving 96.7% sensitivity and 100% specificity. Furthermore, it allows for the parallel assessment of neutralizing activities against multiple SARS-CoV-2 Spike variants of concern (VOC), which is otherwise unpredictable even in individuals displaying robust neutralizing antibody responses. Profiling serum samples from 59 hospitalized COVID-19 patients, we found that although most had high activity against the 2019-nCoV Spike and to a lesser extent the B.1.1.7 variant, only 58% could efficiently neutralize a Spike derivative containing mutations present in the B.1.351 variant. In conclusion, we have developed an assay that has proven its clinical relevance in the large-scale evaluation of effective neutralizing antibody responses to VOC after natural infection and that can be applied to the characterization of vaccine-induced antibody responses and of the potency of human monoclonal antibodies. Once sentence summaryMultiplexed cell-free neutralization assay for quantitative assessment of serum antibody responses against Spike mutations in SARS-COV-2 variants

7.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-21250915

RESUMEN

BackgroundWhile facing a second wave in SARS-CoV-2 pandemic, in November 2020 the Swiss Federal Office of Public Health (FOPH) authorized the use of rapid antigen tests (RATs) in addition to the gold-standard reverse transcription-polymerase chain reaction (RT-PCR). MethodsWe implemented the use of RAT in the emergency ward of our university hospital for rapid patients triaging and compared performances of four different antigen tests. All results were compared to SARS-CoV-2 specific RT-PCR (reference standard). ResultsTriaging patients using RAT in association with RT-PCR allowed us to isolate promptly positive patients and to save resources, in a context of rapid RT-PCR reagents shortage. Among 532 patients with valid results, overall sensitivities were 48.3% for One Step Exdia and 41.2% for Standard Q(R), Panbio-and BD Veritor. All four antigen tests exhibited specificity above 99%. Sensitivity increased up to 74.6%, 66.2%, 66.2% and 64.8% for One Step Exdia, Standard Q, Panbio, and BD Veritor respectively, when considering viral loads above 105copies/ml, up to 100%, 97.8%, 96.6% and 95.6% for viral loads above 106 copies/ml and 100% (for all tests) when considering viral loads above 107 copies/ml. Sensitivity was significantly higher for patients presenting with symptoms onset within 4 days (74.3%, 69.2%, 69.2% and 64%, respectively) versus patients with evolution of symptoms for more than 4 days (36.8%, 21.1%, 21.1% and 23.7%, respectively). Sensitivities of all RAT assays were of only 33% among hospitalized patients without COVID-19 symptoms. ConclusionRAT might represent a useful epidemiological resource in selected clinical settings as a complementary tool to the molecular tests for rapid patients triaging, but the lower sensitivity compared to RT-PCR, especially in late presenters and subjects without COVID-19 symptoms, must be taken into account in order to correctly use RAT for triaging.

8.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20246934

RESUMEN

COVID-19 SARS-CoV-2 infection exhibits wide inter-individual clinical variability, from silent infection to severe disease and death. The identification of high-risk patients is a continuing challenge in routine care. We aimed to identify factors that influence clinical worsening. We analyzed 52 cell populations, 71 analytes, and RNA-seq gene expression in the blood of severe patients from the French COVID cohort upon hospitalization (n = 61). COVID-19 patients showed severe abnormalities of 27 cell populations relative to healthy donors (HDs). Forty-two cytokines, neutrophil chemo-attractants, and inflammatory components were elevated in COVID-19 patients. Supervised gene expression analyses showed differential expression of genes for neutrophil activation, interferon signaling, T- and B-cell receptors, EIF2 signaling, and ICOS-ICOSL pathways in COVID-19 patients. Unsupervised analysis confirmed the prominent role of neutrophil activation, with a high abundance of CD177, a specific neutrophil activation marker. CD177 was the most highly differentially-expressed gene contributing to the clustering of severe patients and its abundance correlated with CD177 protein serum levels. CD177 levels were higher in COVID-19 patients from both the French and "confirmatory" Swiss cohort (n = 203) than in HDs (P< 0.01) and in ICU than non-ICU patients (P< 0.001), correlating with the time to symptoms onset (P = 0.002). Longitudinal measurements showed sustained levels of serum CD177 to discriminate between patients with the worst prognosis, leading to death, and those who recovered (P = 0.01). These results highlight neutrophil activation as a hallmark of severe disease and CD177 assessment as a reliable prognostic marker for routine care.

9.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20239244

RESUMEN

BackgroundUnderstanding community-based SARS-CoV-2 transmission is crucial to inform public health decisions. Research on SARS-CoV-2 transmission within households and other close settings using serological testing is scarce. MethodsWe invited COVID-19 cases diagnosed between February 27 and April 1, 2020 in canton of Vaud, Switzerland, to participate, along with household members and other close contacts. Anti-SARS-CoV-2 IgG antibodies were measured using a Luminex immunoassay. We estimated factors associated with serological status using generalized estimating equations. FindingsOverall, 219 COVID-19 index cases, 302 household members, and 69 other close contacts participated between May 4 and June 27, 2020. More than half of household members (57{middle dot}2%, 95%CI 49{middle dot}7-64{middle dot}3) had developed a serologic response to SARS-CoV-2, while 19{middle dot}0% (95%CI 10{middle dot}0-33{middle dot}2) of other close contacts were seropositive. After adjusting for individual and household characteristics, infection risk was higher in household members aged 65 or more than in younger adults (aOR 3{middle dot}63, 95%CI 1{middle dot}05-12{middle dot}60), and in those not strictly adhering to simple hygiene rules like hand washing (aOR 1{middle dot}80, 95%CI 1{middle dot}02-3{middle dot}17). The risk was lower when more than 5 people outside home were met during the semi-confinement, compared to none (aOR 0{middle dot}35, 95%CI 0{middle dot}16-0{middle dot}74). The individual risk of household members to be seropositive was lower in large households (22% less per each additional person). InterpretationWe find that, during semi-confinement, household members of a COVID-19 case were at very high risk of getting infected, 3 times more than close contacts outside home. This highlights the need to provide clear messages on specific protective measures applicable at home. For elderly couples, who were especially at risk, providing them external support for daily basic activities is essential. FundingCenter for Primary Care and Public Health (Unisante), Canton of Vaud, Leenaards Foundation, Fondation pour lUniversite de Lausanne. SerocoViD is part of Corona Immunitas coordinated by SSPH+.

10.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20217497

RESUMEN

ObjectiveCoronavirus disease (COVID-19) has been associated with a large variety of neurological disorders. However the mechanisms underlying these neurological complications remain elusive. In this study we aimed at determining whether neurological symptoms were caused by SARS-CoV-2 direct infection or by either systemic or local pro-inflammatory mediators. MethodsWe checked for SARS-CoV-2 RNA by RT-qPCR, SARS-CoV-2-specific antibodies and for 49 cytokines/chemokines/growth factors (by Luminex) in the cerebrospinal fluids (CSF) +/-sera of a cohort of 22 COVID-19 patients with neurological presentation and 55 neurological control patients (inflammatory [IND], non-inflammatory [NIND], multiple sclerosis [MS]). ResultsWe detected SARS-CoV-2 RNA and virus-specific antibodies in the CSF of 0/22 and 10/21 COVID-19 patients, respectively. Of the four categories of tested patients, the CSF of IND exhibited the highest level of cytokines, chemokines and growth factors. In contrast, COVID-19 patients did not present overall upregulation of inflammatory mediators in the CSF. However, the CSF of patients with severe COVID-19 (ICU patients) exhibited higher concentrations of CCL2, CXCL8, and VEGF-A in the CSF than patients with a milder form of COVID-19. In addition, we could show that intrathecal CXCL8 synthesis was linked to an elevated barrier index and correlated to the increase of peripheral inflammation (serum HGF and CXCL10). ConclusionOur results point at an absence of massive SARS-CoV-2 infection or inflammation of the central nervous system, but highlight a specific impairment of the neurovascular unit linked to intrathecal production of CXCL8.

11.
Preprint en Inglés | medRxiv | ID: ppmedrxiv-20153536

RESUMEN

We have determined SARS-CoV-2-specific antibody responses in a cohort of 96 individuals with acute infection and in 578 individuals enrolled in a seroprevalence population study in Switzerland including three groups, i.e. subjects with previous RT-PCR confirmed SARS-CoV-2 infections (n=90), positive patient contacts (n=177) and random selected subjects (n=311). SARS-CoV-2 antibody responses specific to the Spike (S), in the monomeric and native trimeric forms, and/or the nucleocapsid (N) proteins were equally sensitive in the acute infection phase. Interestingly, as compared to anti-S antibody responses, those against the N protein appear to wane in the post-infection and substantially underestimated the proportion of SARS-CoV-2 infections in the groups of patient positive contacts, i.e. 10.9 to 32.2% reduction and in the random selected general population, i.e. up to 45% reduction. The overall reduction in seroprevalence targeting only anti-N IgG antibodies for the total cohort ranged from 9.4 to 31%. Of note, the use of the S protein in its native trimer form was more sensitive as compared to monomeric S proteins. These results indicate that the assessment of anti-S IgG antibody responses against the native trimeric S protein should be implemented to estimate SARS-CoV-2 infections in population-based seroprevalence studies.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...