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1.
Nat Med ; 28(3): 496-503, 2022 03.
Article in English | MEDLINE | ID: covidwho-1655606

ABSTRACT

Infection-neutralizing antibody responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or coronavirus disease 2019 vaccination are an essential component of antiviral immunity. Antibody-mediated protection is challenged by the emergence of SARS-CoV-2 variants of concern (VoCs) with immune escape properties, such as omicron (B.1.1.529), which is rapidly spreading worldwide. Here we report neutralizing antibody dynamics in a longitudinal cohort of coronavirus disease 2019 convalescent and infection-naive individuals vaccinated with mRNA BNT162b2 by quantifying SARS-CoV-2 spike protein antibodies and determining their avidity and neutralization capacity in serum. Using live-virus neutralization assays, we show that a superior infection-neutralizing capacity against all VoCs, including omicron, developed after either two vaccinations in convalescents or a third vaccination or breakthrough infection of twice-vaccinated, naive individuals. These three consecutive spike antigen exposures resulted in an increasing neutralization capacity per anti-spike antibody unit and were paralleled by stepwise increases in antibody avidity. We conclude that an infection-plus-vaccination-induced hybrid immunity or a triple immunization can induce high-quality antibodies with superior neutralization capacity against VoCs, including omicron.


Subject(s)
COVID-19 , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , COVID-19/prevention & control , Humans , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Vaccination
2.
Med Microbiol Immunol ; 211(1): 71-77, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1640849

ABSTRACT

On November 26, 2021, the World Health Organization classified B.1.1.529 as a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VoC), named omicron. Spike-gene dropouts in conventional SARS-CoV-2 PCR systems have been reported over the last weeks as indirect diagnostic evidence for the identification of omicron. Here, we report the combination of PCRs specific for heavily mutated sites in the spike gene and nanopore-based full-length genome sequencing for the rapid and sensitive identification of the first four COVID-19 patients diagnosed in Germany to be infected with omicron on November 28, 2021. This study will assist the unambiguous laboratory-based diagnosis and global surveillance for this highly contagious VoC with an unprecedented degree of humoral immune escape. Moreover, we propose that specialized diagnostic laboratories should continuously update their assays for variant-specific PCRs in the spike gene of SARS-CoV-2 to readily detect and diagnose emerging variants of interest and VoCs. The combination with established nanopore sequencing procedures allows both the rapid confirmation by whole genome sequencing as well as the sensitive identification of newly emerging variants of this pandemic ß-coronavirus in years to come.


Subject(s)
COVID-19 , Nanopore Sequencing , Humans , Mutation , Polymerase Chain Reaction , SARS-CoV-2
3.
Euro Surveill ; 26(43)2021 10.
Article in English | MEDLINE | ID: covidwho-1547185

ABSTRACT

BackgroundIn the SARS-CoV-2 pandemic, viral genomes are available at unprecedented speed, but spatio-temporal bias in genome sequence sampling precludes phylogeographical inference without additional contextual data.AimWe applied genomic epidemiology to trace SARS-CoV-2 spread on an international, national and local level, to illustrate how transmission chains can be resolved to the level of a single event and single person using integrated sequence data and spatio-temporal metadata.MethodsWe investigated 289 COVID-19 cases at a university hospital in Munich, Germany, between 29 February and 27 May 2020. Using the ARTIC protocol, we obtained near full-length viral genomes from 174 SARS-CoV-2-positive respiratory samples. Phylogenetic analyses using the Auspice software were employed in combination with anamnestic reporting of travel history, interpersonal interactions and perceived high-risk exposures among patients and healthcare workers to characterise cluster outbreaks and establish likely scenarios and timelines of transmission.ResultsWe identified multiple independent introductions in the Munich Metropolitan Region during the first weeks of the first pandemic wave, mainly by travellers returning from popular skiing areas in the Alps. In these early weeks, the rate of presumable hospital-acquired infections among patients and in particular healthcare workers was high (9.6% and 54%, respectively) and we illustrated how transmission chains can be dissected at high resolution combining virus sequences and spatio-temporal networks of human interactions.ConclusionsEarly spread of SARS-CoV-2 in Europe was catalysed by superspreading events and regional hotspots during the winter holiday season. Genomic epidemiology can be employed to trace viral spread and inform effective containment strategies.


Subject(s)
COVID-19 , Cross Infection , Cross Infection/epidemiology , Genome, Viral , Genomics , Germany/epidemiology , Hospitals , Humans , Phylogeny , SARS-CoV-2
4.
Euro Surveill ; 25(24)2020 06.
Article in English | MEDLINE | ID: covidwho-605372

ABSTRACT

Containment strategies and clinical management of coronavirus disease (COVID-19) patients during the current pandemic depend on reliable diagnostic PCR assays for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we compare 11 different RT-PCR test systems used in seven diagnostic laboratories in Germany in March 2020. While most assays performed well, we identified detection problems in a commonly used assay that may have resulted in false-negative test results during the first weeks of the pandemic.


Subject(s)
Betacoronavirus/genetics , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Diagnostic Equipment , Pneumonia, Viral/diagnosis , COVID-19 , COVID-19 Testing , COVID-19 Vaccines , Clinical Laboratory Techniques/instrumentation , Feces/virology , Germany , Humans , Laboratories , Multiplex Polymerase Chain Reaction/instrumentation , Multiplex Polymerase Chain Reaction/methods , Pandemics , Real-Time Polymerase Chain Reaction/instrumentation , Real-Time Polymerase Chain Reaction/methods , Reverse Transcriptase Polymerase Chain Reaction/instrumentation , Reverse Transcriptase Polymerase Chain Reaction/methods , SARS-CoV-2 , Sensitivity and Specificity
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