Identification of SARS-CoV-2 P.1-related lineages in Brazil provides new insights about the mechanisms of emergence of Variants of Concern
Identification of SARS-CoV-2 P.1-related lineages in Brazil provides new insights about the mechanisms of emergence of Variants of Concern Tiago Gräf 1A, Gonzalo Bello 2A, Taina Moreira Martins Venas 3, Elisa Cavalcante Pereira 3, Anna Carolina Dias Paixão 3; Luciana Reis Appolinario 3; Renata Serrano Lopes 3; Ana Carolina da Fonseca Mendonça 3; Alice Sampaio Barreto da Rocha 3; Fernando Couto Motta 3, Tatiana Schäffer Gregianini 4, Richard Salvato 4, Sandra Bianchini Fernandes 5, Darcita Buerg...
Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil
Despite an extensive network of primary care availability, Brazil has suffered profoundly during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Using daily data from state health offices, Castro et al. analyzed the pattern of spread of COVID-19 cases and deaths in the country from February to October 2020. Clusters of deaths before cases became apparent indicated unmitigated spread. SARS-CoV-2 circulated undetected in Brazil for more than a month as it spread north from Sã o Paulo. In Manaus, transmission reached unprecedented levels after a momentary respite in mid-2020. Faria et al. tracked the evolution of a new, more aggressive lineage called P.1, which has 17 mutations, including three (K417T, E484K, and N501Y) in the spike protein. After a period of accelerated evolution, this variant emerged in Brazil during November 2020. Coupled with the emergence of P.1, disease spread was accelerated by stark local inequalities and political upheaval, which compromised a prompt federal response.
Science , abh1558 and abh2644, this issue p. [821][1] and p. [815][2]
Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.
[1]: /lookup/doi/10.1126/science.abh1558
[2]: /lookup/doi/10.1126/science.abh2644
Booster Shots For mRNA Vaccines Likely Required Within Six Months To Protect Against Covid-19 Variants
The Moderna booster shots appear to be effective at neutralizing at least two of the new variants. But their new study also revealed the current vaccines don't protect against variants for as long as we initially hoped.
Vaccines highly effective against B.1.617.2 variant after 2 doses - GOV.UK
New study by PHE shows for the first time that 2 doses of the COVID-19 vaccines are highly effective against the B.1.617.2 variant first identified in India.
Wido pra pm krankschreibungen wegen covid 19 211220
Berufe in der Betreuung und Erziehung von Kindern waren von März bis Oktober 2020 am stärksten von Krankschreibungen im Zusammenhang mit Covid-19 betroffen. Eine Analyse der Arbeitsunfähigkeitsdaten der AOK-Mitglieder durch das Wissenschaftliche Institut der AOK (WIdO) zeigt, dass in diesem Zeitraum 2.672 je 100.000 Beschäftigte in dieser Berufs-gruppe krankheitsbedingt im Zusammenhang mit Covid-19 an ihrem Arbeitsplatz gefehlt ha-ben. Damit liegt deren Betroffenheit mehr als das 2,2-fache über dem Durchschnittswert von 1.183 Betroffenen je 100.000 AOK-versicherte Beschäftigte. Auch Gesundheitsberufe waren überdurchschnittlich oft im Zusammenhang mit Covid-19 arbeitsunfähig, stehen aber nicht mehr an der Spitze des Rankings. In einer früheren WIdO-Auswertung für die erste Phase der Pandemie von März bis Mai 2020 belegten Berufe in der Alten- und Krankenpflege die Spitzen-plätze, jetzt finden sie sich im Ranking auf Platz 7 und 8. Medizinische Fachangestellte sind nach der aktuellen Auswertung bezogen auf den Zeitraum von März bis Oktober 2020 noch stärker betroffen und stehen mit 2.469 Erkrankten je 100.000 Beschäftigten auf Platz 2 der Liste. „Beschäftigtengruppen, die in der Pandemie weiter am Arbeitsplatz präsent sein muss-ten und nicht ins Homeoffice gehen konnten, sind im bisherigen Verlauf der Pandemie stärker von Covid-19 betroffen. Dies sind insbesondere Berufe mit direktem Kontakt zu anderen Men-schen“, sagt Helmut Schröder, stellvertretender Geschäftsführer des WIdO.
Identification of a novel lineage bat SARS-related coronaviruses that use bat ACE2 receptor
Severe respiratory disease coronavirus-2 (SARS-CoV-2) causes the most devastating disease, COVID-19, of the recent century. One of the unsolved scientific questions around SARS-CoV-2 is the animal origin of this virus. Bats and pangolins are recognized as the most probable reservoir hosts that harbor the highly similar SARS-CoV-2 related viruses (SARSr-CoV-2). Here, we report the identification of a novel lineage of SARSr-CoVs, including RaTG15 and seven other viruses, from bats at the same location where we found RaTG13 in 2015. Although RaTG15 and the related viruses share 97.2% amino acid sequence identities to SARS-CoV-2 in the conserved ORF1b region, but only show less than 77.6% to all known SARSr-CoVs in genome level, thus forms a distinct lineage in the Sarbecovirus phylogenetic tree. We then found that RaTG15 receptor binding domain (RBD) can bind to and use Rhinolophus affinis bat ACE2 (RaACE2) but not human ACE2 as entry receptor, although which contains a short deletion and has different key residues responsible for ACE2 binding. In addition, we show that none of the known viruses in bat SARSr-CoV-2 lineage or the novel lineage discovered so far use human ACE2 efficiently compared to SARSr-CoV-2 from pangolin or some of the SARSr-CoV-1 lineage viruses. Collectively, we suggest more systematic and longitudinal work in bats to prevent future spillover events caused by SARSr-CoVs or to better understand the origin of SARS-CoV-2.
### Competing Interest Statement
The authors have declared no competing interest.
Comparison of the characteristics, morbidity, and mortality of COVID-19 and seasonal influenza: a nationwide, population-based retrospective cohort study
The presentation of patients with COVID-19 and seasonal influenza requiring hospitalisation
differs considerably. Severe acute respiratory syndrome coronavirus 2 is likely to
have a higher potential for respiratory pathogenicity, leading to more respiratory
complications and to higher mortality. In children, although the rate of hospitalisation
for COVID-19 appears to be lower than for influenza, in-hospital mortality is higher;
however, low patient numbers limit this finding. These findings highlight the importance
of appropriate preventive measures for COVID-19, as well as the need for a specific
vaccine and treatment.
Ist COVID-19 eine Gefäßerkrankung? Anfangs als reine Lungenkrankheit betrachtet, deuten immer mehr Studien darauf hin, dass eine COVID-19-Erkrankung die Blutgefäße schädigt und Gefäßerkrankungen wie Thrombosen, Lungenembolien oder Schlaganfälle begünstigt.
Relaxing restrictions at the pace of vaccinationincreases freedom and guards against furtherCOVID-19 waves in Europe
Mass vaccination offers a promising exit strategy for the COVID-19 pandemic. However, asvaccination progresses, demands to lift restrictions increase, despite most of the populationstill being susceptible. Using our age-stratified model and curated epidemiological andvaccination data, we quantified at which pace European countries can lift restrictions withoutoverwhelming their health-care systems. The analysed scenarios range from immediatelylifting restriction (accepting high mortality and morbidity) to reducing case numbers untiltest-trace-and-isolate programs facilitate control. In general, the age-dependent vaccinationroll-out implies a transient decrease in the average age of ICU patients and deaths by aboutseven years. The pace of vaccination determines the speed of lifting restrictions; all scenariosallow to steadily increase contacts starting in May 2021 and relax most restrictions byautumn 2021. Throughout summer, only moderate contact restrictions remain necessary.However, with the assumed vaccination protection, further waves among the unvaccinatedpopulation can only be avoided with high vaccine uptake (>90%).Strategies that maintainlow case numbers instead of high ones reduce infections and deaths by a factor eight andfour. Policies with low case numbers significantly benefit from vaccination, as the overallreduction in susceptibility will further diminish viral spread. Keeping case numbers low isthe safest long-term strategy because it i) considerably reduces mortality and morbidity,ii) offers better preparedness against escape virus variants, and iii) allows higher contactnumbers ("freedom") over the summer.
Novavax verschiebt Zulassungsantrag für seinen Coronaimpfstoff
Washington – Das US-Biotech-Unternehmen Novavax hat den Zulassungsantrag für seinen Coronaimpfstoff verschoben. Geplant sei nun ein Antrag auf Zulassung bei... #COVID-19 #Coronaimpfstoff #Novavax
Post-COVID syndrome in non-hospitalised patients with COVID-19: a longitudinal prospective cohort study
The on-going presence of either shortness of breath, anosmia, ageusia or fatigue as
long-lasting symptoms even in non-hospitalised patients was observed at four and seven
months post-infection and summarised as post-COVID syndrome (PCS). The continued assessment
of patients with PCS will become a major task to define and mitigate the socioeconomic
and medical long-term effects of COVID-19.
Chronisches Erschöpfungssyndrom / Myalgische Enzephalomyelitis: Wenn die Grippe einfach nicht weggeht
Man hat für nichts mehr Kraft. Kann kaum mehr aufstehen oder arbeiten gehen. Dazu: Muskelschmerzen, Nervenstörungen und Grippesymptome über Jahre und Jahrzehnte hinweg. All das können Hinweise auf ME/CFS sein.
Covid-19: Poor links between NHS and social care weakened England’s response, says NAO
Pre-pandemic issues such as severe budget cuts to local government and poor integration between the NHS and social care weakened England’s ability to respond to covid-19, the public spending watchdog has said.1
The National Audit Office (NAO) assessed the government’s response to the pandemic and also found many issues with transparency around personal protective equipment (PPE) contracts, provision of PPE for the social care sector when compared with the health sector, and inconsistencies between what providers and frontline staff were reporting in terms of having protective equipment.
Responding to the findings, the NHS Confederation’s chief executive, Danny Mortimer, said, “This report re-emphasises the long term issues that severely weakened the foundations of health and care, which meant the country was not better prepared to deal with the pandemic and its fallout . . .
“Importantly, this report also highlights the ever more pressing need to make sure reform of the social care sector is swift and far reaching. The two are sister services, and when one is hit hard, so is the …
Diverse Functional Autoantibodies in Patients with COVID-19 | Nature
COVID-19 manifests with a wide spectrum of clinical phenotypes that are characterized by exaggerated and misdirected host immune responses1–6. While pathological innate immune activation is well documented in severe disease1, the impact of autoantibodies on disease progression is less defined. Here, we used a high-throughput autoantibody (AAb) discovery technique called Rapid Extracellular Antigen Profiling (REAP)7 to screen a cohort of 194 SARS-CoV-2 infected COVID-19 patients and healthcare workers for autoantibodies against 2,770 extracellular and secreted proteins (the “exoproteome”). We found that COVID-19 patients exhibit dramatic increases in autoantibody reactivities compared to uninfected controls, with a high prevalence of autoantibodies against immunomodulatory proteins including cytokines, chemokines, complement components, and cell surface proteins. We established that these autoantibodies perturb immune function and impair virological control by inhibiting immunoreceptor signaling and by altering peripheral immune cell composition, and found that murine surrogates of these autoantibodies exacerbate disease severity in a mouse model of SARS-CoV-2 infection. Analysis of autoantibodies against tissue-associated antigens revealed associations with specific clinical characteristics and disease severity. In summary, these findings implicate a pathological role for exoproteome-directed autoantibodies in COVID-19 with diverse impacts on immune functionality and associations with clinical outcomes.
Die Covid-19-Pandemie und die damit einhergehenden Ausgangsbeschränkungen wirken sich deutlich auf die psychische Gesundheit aus. Das zeigt eine Studie der Donau-Universität Krems. Depressive Symptome und Schlafstörungen sind häufiger geworden.
In December 2020, two COVID-19 vaccines were granted Emergency Use Authorization(EUA)by FDA. Produced by Pfizer/BioNTech and Moderna, both vaccines use the same technology (mRNA) and are highly effective at preventing COVID-19infection. In February 2021, a COVID-19 vaccine developed by Janssen Biotech, Inc.was grantedanEUA by FDA.A comparison of key details for each vaccinecan be found below.This list is not exhaustive. For further details,see the FDA EUA document for Pfizer/BioNTech,Moderna,and Janssen. Note:head-to-head COVID-19 vaccine studieshave notbeenconducted. Therefore,directvaccine efficacycomparisonsarenot possibleat this time.
The origin of COVID: Did people or nature open Pandora’s box at Wuhan? - Bulletin of the Atomic Scientists
If the case that SARS2 originated in a lab is so substantial, why isn’t this more widely known? As is now obvious, there are many people who have reason not to talk about it.
Kids' COVID vaccine offers new hope to wipe out pandemic and relieve 'long hauler' issues
RELATED | Pfizer approves vaccine for 12-15 year old children. Early in the a. m. , most 12-year-olds like to hide under the covers. But for Wednesday, it's just different. “It’s very hard to wake her up in the morning and it’s hard to keep her awake,” said Melissa Lynch. She stated that her daughter, Wednesday, has struggled with COVID-19 for eight months, dealing with debilitating waves of symptoms that start like a cold, and then “...
Severe Acute Respiratory Syndrome Coronavirus 2... : Obstetrics & Gynecology
Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been approved for emergency use, but, despite elevated risk of severe disease, pregnant women were excluded from the clinical trials that led to their authorization.1 Placental findings can indicate potential clinical risk and could be an early signal for rare injury seen only after widespread use in the pregnant population.2–6
Maternal SARS-CoV-2 infection has been associated with decidual arteriopathy, fetal vascular malperfusion, and chronic histiocytic intervillositis.7–9 mRNA vaccines induce an immune response through activation of TLR3, which has been linked to decidual arteriopathy, growth restriction, preterm delivery, and fetal loss in mouse models.10–14
Our objective was to evaluate the frequency of these key placental lesions in patients who received SARS-CoV-2 vaccination in pregnancy.
Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women | Breastfeeding | JAMA | JAMA Network
This study assesses the immunogenicity of the current COVID-19 mRNA vaccines in pregnant and lactating women against both the original SARS-CoV-2 USA-WA1/2020 strain as well as against the B.1.1.7 and B.1.351 variants of concern.
Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes - ScienceDirect
In recent years, in vitro transcribed messenger RNA (mRNA) has emerged as a potential therapeutic platform. To fulfill its promise, effective delivery…
Prevalence of ongoing symptoms following coronavirus (COVID-19) infection in the UK - Office for National Statistics
Estimates of the prevalence of self-reported “long COVID” and the duration of ongoing symptoms following confirmed coronavirus infection, using UK Coronavirus (COVID-19) Infection Survey data.
(6) Dr Nisreen Alwan 🌻 auf Twitter: "#LongCovid risk is 12% in 17-24 year olds and 8% in 12-16 yo yet the govt is removing the one layer of protection these unvaccinated age groups have against #SARSCoV2 infection: masks in secondary schools and colleges. I don’t understand how this is acceptable. I really don’t. https://t.co/KkrnyrUS2e" / Twitter
#LongCovid risk is 12% in 17-24 year olds and 8% in 12-16 yo yet the govt is removing the one layer of protection these unvaccinated age groups have against #SARSCoV2 infection: masks in secondary schools and colleges. I don’t understand how this is acceptable. I really don’t. https://t.co/KkrnyrUS2e
Characteristics of Long Covid: findings from a social media survey
Many people are not recovering for months after being infected with SARS-CoV-2. Long Covid has emerged as a major public health concern that needs defining, quantifying, and describing. We aimed to explore the initial and ongoing symptoms of Long Covid following SARS-CoV-2 infection and describe its impact on daily life in people who were not admitted to hospital during the first two weeks of the illness. We co-produced a survey with people living with Long Covid. We collected the data through an online survey using convenience non-probability sampling, with the survey posted both specifically on Long Covid support groups and generally on social media. The criteria for inclusion were adults with lab-confirmed (PCR or antibody) or suspected COVID-19 managed in the community (non-hospitalised) in the first two weeks of illness. We used agglomerative hierarchical clustering to identify specific symptom clusters, and their demographic and functional correlates.
We analysed data from 2550 participants with a median duration of illness of 7.7 months (interquartile range (IQR) 7.4-8.0). The mean age was 46.5 years (standard deviation 11 years) with 82.8% females and 79.9% of participants based in the UK. 89.5% described their health as good, very good or excellent before COVID-19. The most common initial symptoms that persisted were exhaustion, chest pressure/tightness, shortness of breath and headache. Cough, fever, and chills were common initial symptoms that became less prevalent later in the illness, whereas cognitive dysfunction and palpitations became more prevalent later in the illness. 26.5% reported lab-confirmation of infection. The biggest difference in ongoing symptoms between those who reported testing positive and those who did not was loss of smell/taste. Ongoing symptoms affected at least 3 organ systems in 83.5% of participants.
Most participants described fluctuating (57.7%) or relapsing symptoms (17.6%). Physical activity, stress and sleep disturbance commonly triggered symptoms. A third (32%) reported they were unable to live alone without any assistance at six weeks from start of illness. 16.9% reported being unable to work solely due to COVID-19 illness. 66.4% reported taking time off sick (median of 60 days, IQR 20, 129). 37.0% reported loss of income due to illness, and 64.4% said they were unable to perform usual activities/duties.
Acute systems clustered broadly into two groups: a majority cluster (n=2235, 88%) with cardiopulmonary predominant symptoms, and a minority cluster (n=305, 12%) with multisystem symptoms. Similarly, ongoing symptoms broadly clustered in two groups; a majority cluster (n=2243, 88.8%) exhibiting mainly cardiopulmonary, cognitive symptoms and exhaustion, and a minority cluster (n=283, 11.2%) exhibited more multisystem symptoms. Belonging to the more severe multisystem cluster was associated with more severe functional impact, lower income, younger age, being female, worse baseline health, and inadequate rest in the first two weeks of the illness, with no major differences in the cluster patterns when restricting analysis to the lab-confirmed subgroup.
This is an exploratory survey of Long Covid characteristics. Whilst it is important to acknowledge that it is a non-representative population sample, it highlights the heterogeneity of persistent symptoms, and the significant functional impact of prolonged illness following confirmed or suspected SARS-CoV-2 infection. To study prevalence, predictors and prognosis, research is needed in a representative population sample using standardised case definitions (to include those not lab-confirmed in the first pandemic wave).
### Competing Interest Statement
NAA, MEO and CH experience(d) Long Covid symptoms.
### Funding Statement
The study received no specific funding.
### 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:
University of Southampton, Faculty of Medicine Ethics Committee (Reference 61434)
All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.
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 survey data is available on request provided ethics committee approval for sharing the anonymised data is granted.