Paxlovid: Die rettende Pille, die kaum jemand kennt
In Freiburg produziert der US-Konzern Pfizer sein Medikament Paxlovid für den Weltmarkt. Warum aber wird es in Deutschland bisher kaum genutzt, obwohl es das Risiko schwerer Verläufe einer Covid-Infektion massiv senken soll? Von Tim Diekmann.
Was?? Es sind nicht die Long Lockdown Adeno-Dogs? *Shocked* https://t.co/X9bkkXr1b7SARS-CoV-2 ORF1abA1061S Mutation resultiert in einem PARP14 identen Peptid, das über HLA-A präsentiert wird und autoreaktive zytotoxische T-Zellen begünstigt.— molecular.sylvia (@SylviaGruber88) June 30, 2022
The Omicron BA.4/5 subvariants are leading to a new wave in Europe and the United States, with an impact of some increase in hospitalizationshttps://t.co/y0LvkzoCRb @SarahNev @JamieSmythF @jburnmurdoch @TWenseleers pic.twitter.com/pBuS7Xc5Li— Eric Topol (@EricTopol) June 17, 2022
Closing schools and workplaces linked to reduced early COVID deaths
Closing schools and workplaces appear to have been the most effective strategies to mitigate deaths from COVID-19 in the early days of the pandemic's first wave, according to a study of 130 countries.
Dies ist eine äußerst wichtige Studie, die darauf hindeutet, dass eine Infektion durch frühere Varianten die schützende Immunität gegen nachfolgende Varianten verändern und sogar beeinträchtigen kann – ein Prozess, der von den Autoren als „Hybrid-Immundämpfung“…#COVID19 pic.twitter.com/uBqYpwQiVI— Ralf Wittenbrink (@RWittenbrink) June 15, 2022
Practical Indicators for Risk of Airborne Transmission in Shared Indoor Environments and Their Application to COVID-19 Outbreaks - acs.est.1c06531
Some infectious diseases, including COVID-19, can undergo airborne
transmission. This may happen at close proximity, but as time indoors increases, infections
can occur in shared room air despite distancing. We propose two indicators of infection
risk for this situation, that is, relative risk parameter (Hr) and risk parameter (H). They
combine the key factors that control airborne disease transmission indoors: virus-
containing aerosol generation rate, breathing flow rate, masking and its quality, ventilation
and aerosol-removal rates, number of occupants, and duration of exposure. COVID-19
outbreaks show a clear trend that is consistent with airborne infection and enable
recommendations to minimize transmission risk. Transmission in typical prepandemic
indoor spaces is highly sensitive to mitigation efforts. Previous outbreaks of measles, influenza, and tuberculosis were also assessed.
Measles outbreaks occur at much lower risk parameter values than COVID-19, while tuberculosis outbreaks are observed at higher
risk parameter values. Because both diseases are accepted as airborne, the fact that COVID-19 is less contagious than measles does
not rule out airborne transmission. It is important that future outbreak reports include information on masking, ventilation and
aerosol-removal rates, number of occupants, and duration of exposure, to investigate airborne transmission.
Immune boosting by B.1.1.529 (Omicron) depends on previous SARS-CoV-2 exposure
The Omicron, or Pango lineage B.1.1.529, variant of SARS-CoV-2 carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection from severe disease, often attributed to primed cellular immunity. We investigated T and B cell immunity against B.1.1.529 in triple mRNA vaccinated healthcare workers (HCW) with different SARS-CoV-2 infection histories. B and T cell immunity against previous variants of concern was enhanced in triple vaccinated individuals, but magnitude of T and B cell responses against B.1.1.529 spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less durable binding antibody against B.1.1.529. Previously infection-naïve HCW who became infected during the B.1.1.529 wave showed enhanced immunity against earlier variants, but reduced nAb potency and T cell responses against B.1.1.529 itself. Previous Wuhan Hu-1 infection abrogated T cell recognition and any enhanced cross-reactive neutralizing immunity on infection with B.1.1.529.
An update on excess mortality in the second year of the COVID-19 pandemic in Germany
AStA Wirtschafts- und Sozialstatistisches Archiv - In this short note, we apply the method of De Nicola et al. (2022) to the most recent available data, thereby providing up-to-date estimates of...
Think you know flu? Read this fascinating study from @nicd_sa et al - with detailed sampling, estimated over 40% of population got infected per season on average, and 17% had repeat infection within same season. Also evidence of asymptomatic transmission: https://t.co/pXIITwGYT8 pic.twitter.com/JOZyvzFqG7— Adam Kucharski (@adamjkucharski) May 19, 2021
In Australien wird mittlerweile über einen "plötzlichen Erwachsenentod" (SADS Sudden Adult Death Syndrome, analog zum plötzlichen Kindstod) berichtet. https://t.co/BOaQ3UTssK1/N— Martin Sauter (@Martin__Sauter) June 14, 2022
Case numbers of acute hepatitis of unknown aetiology among children in 24 countries up to 18 April 2022 compared to the previous 5 years
An increase of acute hepatitis of unknown aetiology has been reported among children in multiple countries worldwide. With a rapid online survey among hospitals in and outside of Europe, we describe case numbers recorded from 1 January to 18 April 2022 vs the previous 5 years. Of 24 countries that responded, we identified 5/17 European and 1/7 non-European countries with an elevation in probable cases of unexplained acute hepatitis, and severe cases were elevated in five European countries.
Corona: Informationen, Schulschließungen und Tests wirken gegen Infektion
Unter den sogenannten nicht-pharmazeutischen Maßnahmen zur Eindämmung der Corona-Pandemie waren öffentliche Informationskampagnen und Schulschließungen am effektivsten. Sie senkten die Reproduktionszahl, also die Anzahl an Menschen, die eine infizierte Person im Durchschnitt ansteckt, um 0,35 bzw. 0,24. Dies ist das Ergebnis einer Studie unter Beteiligung des IfW Kiel, die auch systematisch Daten außerhalb der USA und Chinas, unter anderem aus Deutschland, auswertete.
Humoral and cellular immune memory to four COVID-19 vaccines
Multiple COVID-19 vaccines, representing diverse vaccine platforms, successfully protect against symptomatic COVID-19 cases and deaths. Head-to-head comparisons of T cell, B cell, and antibody responses to diverse vaccines in humans are likely to be informative for understanding protective immunity against COVID-19, with particular interest in immune memory. Here, SARS-CoV-2-spike-specific immune responses to Moderna mRNA-1273, Pfizer/BioNTech BNT162b2, Janssen Ad26.COV2.S and Novavax NVX-CoV2373 were examined longitudinally for 6 months. 100% of individuals made memory CD4+ T cells, with cTfh and CD4-CTL highly represented after mRNA or NVX-CoV2373 vaccination. mRNA vaccines and Ad26.COV2.S induced comparable CD8+ T cell frequencies, though only detectable in 60-67% of subjects at 6 months. A differentiating feature of Ad26.COV2.S immunization was a high frequency of CXCR3+ memory B cells. mRNA vaccinees had substantial declines in antibodies, while memory T and B cells were comparatively stable. These results may also be relevant for insights against other pathogens.
Unusual Involvement of Basal Ganglia and Dentate Nucleus in Children with Acute Encephalopathy with COVID-19
Indian Journal of Pediatrics - Children account for 1% to 5% of diagnosed COVID-19 infection with relatively mild presentation compared to adults. The frequency of neurological involvement in acute...
Neurodevelopmental Outcomes at 1 Year in Infants Following SARS-CoV-2 Exposure in Utero
This cohort study investigates whether in utero exposure to SARS-CoV-2 is associated with risk for neurodevelopmental disorders in the first 12 months after birth.
In wenigen Fällen können Long COVID oder ein Multisystemisches Entzündungssyndrom auch nach einer COVID-19-Impfung auftreten. Fallberichte deuten zurzeit auf ein deutlich geringeres Risiko als nach einer Infektion hin. Die Datengrundlage ist jedoch...
Exclusive: Zahawi orders long Covid shake-up as teacher cases rise
Education secretary to issue new guidance on long Covid, as unions say teachers should get up to 12 months of full-paid leave if diagnosed with the condition
COVID and the Heart: It Spares No One | Johns Hopkins Bloomberg School of Public Health
New evidence suggests anyone infected with COVID is at higher risk for heart issues—a risk that persists even in relatively healthy people long after the illness has passed.
Correlates of protection, thresholds of protection, and immunobridging in SARS-CoV-2 infection
Several studies show neutralizing antibody levels are an important correlate of immune protection from COVID-19 and have estimated the relationship between neutralizing antibodies and protection. However, a number of these studies appear to yield quite different estimates of the level of neutralizing antibodies required for protection. Here we show that after normalization of antibody titers current studies converge on a consistent relationship between antibody levels and protection from COVID-19. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work is supported by an Australian government Medical Research Future Fund awards GNT2002073 (to MPD, SJK, AKW), MRF2005544 (to SJK, AKW, JAJ and MPD), MRF2005760 (to MPD), MRF2007221 (to JAT and MS), an NHMRC program grant GNT1149990 (SJK and MPD), and the Victorian Government (SJK, AKW, JAJ). JAJ, DSK and SJK are supported by NHMRC fellowships. AKW, DC and MPD are supported by NHMRC Investigator grants. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health. The funding source had no role in the writing of the manuscript or the decision to submit it for publication, nor in data collection, analysis, or interpretation; or any aspect pertinent to the study. Authors were not precluded from accessing data in the study, and they accept responsibility to submit for publication. ### 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: All data were publicly available and the raw data use was either extracted from publications (Feng et al. Nature Medicine 2021, Gilbert et al. Science 2021) or provided by the authors on request (Bergwerk et al. New England Journal of Medicine 2021). Analysis of this publicly available data was approved under the UNSW Sydney Human Research Ethics Committee (approval HC200242). 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 and code will be made available on GitHub upon publication.
The Department of Immunization, Vaccines and Biologicals thanks the donors whose unspecified financial support has made the production of this document possible.
1WHO/IVB/13.01
The ability to assess the protective efficacy of a vaccine by measuring the proportion
of vaccinees who generate a particular immune response, without having to measure
clinical outcomes, has significant advantages. The availability and quality of such
substitute endpoints1 are important for vaccine development, licensure and effectiveness
monitoring. A better understanding of the interrelationships between vaccination,
the immune response, protection, and clinical outcomes is thus of interest not only
to regulatory authorities but also to microbiologists, immunologists, epidemiologists
and statisticians.
This is a complex and controversial topic, and many aspects need clarification.
Although regulatory bodies have drawn up definitions for “correlates” and “surrogates”
of protection for the purpose of licensure, these terms are not used consistently among
regulators, nor in the broader literature. Different study designs, each with their strengths
and weaknesses, have been used to evaluate immunological substitute endpoints of
vaccine-induced protection. Various statistical tools have been developed to evaluate
these endpoints, but few epidemiologists are familiar with the details of these methods.
Immunological substitute endpoints can be relative or absolute quantities, and further
information is needed on how they are affected by factors such as the challenge dose,
the mechanism of action of the vaccine, the environment, or host characteristics.
This document presents an overview of definitions and methods relating to studies
of substitute endpoints. It aims to facilitate communication and to encourage the
development of a broad research agenda on the issue. Although the greatest interest
in this topic currently relates to vaccines, immunological correlates of protection have
far-reaching implications for passive protection (maternal immunity and immunoglobulin
prophylaxis), risk screening (e.g. tuberculin or rubella antibody testing in pregnant
women) as well as for a basic understanding of pathogenesis and immunity.
Complex Correlates of Protection After Vaccination
Although the immune correlate of protection by vaccines is often antibody to prevent acquisition and cellular functions to clear infection, the situation may be
This paper attempts to summarize current knowledge about immune responses to vaccines that correlate with protection. Although the immune system is redundant, almost all current vaccines work through antibodies in serum or on mucosa that block infection or bacteremia/viremia and thus provide a correlate of protection. The functional characteristics of antibodies, as well as quantity, are important. Antibody may be highly correlated with protection or synergistic with other functions. Immune memory is a critical correlate: effector memory for short-incubation diseases and central memory for long-incubation diseases. Cellular immunity acts to kill or suppress intracellular pathogens and may also synergize with antibody. For some vaccines, we have no true correlates, but only useful surrogates, for an unknown protective response.