Inoculum at the time of SARS-CoV-2 exposure and risk of disease severity
A relationship between the infecting dose and the risk of disease severity has not been demonstrated for SARS-CoV-2 infection. Here, we report three clusters of individuals that were potentially exposed to distinct inoculum in Madrid. Overall each group ...
Eurosurveillance | Outbreak caused by the SARS-CoV-2 Omicron variant in Norway, November to December 2021
In late November 2021, an outbreak of Omicron SARS-CoV-2 following a Christmas party with 117 attendees was detected in Oslo, Norway. We observed an attack rate of 74% and most cases developed symptoms. As at 13 December, none have been hospitalised. Most participants were 30–50 years old. Ninety-six percent of them were fully vaccinated. These findings corroborate reports that the Omicron variant may be more transmissible, and that vaccination may be less effective in preventing infection compared with Delta.
Virology, transmission, and pathogenesis of SARS-CoV-2
### What you need to know
Since the emergence of SARS-CoV-2 in December 2019, there has been an unparalleled global effort to characterise the virus and the clinical course of disease. Coronavirus disease 2019 (covid-19), caused by SARS-CoV-2, follows a biphasic pattern of illness that likely results from the combination of an early viral response phase and an inflammatory second phase. Most clinical presentations are mild, and the typical pattern of covid-19 more resembles an influenza-like illness—which includes fever, cough, malaise, myalgia, headache, and taste and smell disturbance—rather than severe pneumonia (although emerging evidence about long term consequences is yet to be understood in detail).1 In this review, we provide a broad update on the emerging understanding of SARS-CoV-2 pathophysiology, including virology, transmission dynamics, and the immune response to the virus. Any of the …
The recently emerged SARS-CoV-2 Omicron variant harbors 37 amino acid substitutions in the spike (S) protein, 15 of which are in the receptor-binding domain (RBD), thereby raising concerns about the effectiveness of available vaccines and antibody therapeutics. Here, we show that the Omicron RBD binds to human ACE2 with enhanced affinity relative to the Wuhan-Hu-1 RBD and acquires binding to mouse ACE2. Severe reductions of plasma neutralizing activity were observed against Omicron compared to the ancestral pseudovirus for vaccinated and convalescent individuals. Most (26 out of 29) receptor-binding motif (RBM)-directed monoclonal antibodies (mAbs) lost in vitro neutralizing activity against Omicron, with only three mAbs, including the ACE2-mimicking S2K146 mAb[1][1], retaining unaltered potency. Furthermore, a fraction of broadly neutralizing sarbecovirus mAbs recognizing antigenic sites outside the RBM, including sotrovimab[2][2], S2X259[3][3] and S2H97[4][4], neutralized Omicron. The magnitude of Omicron-mediated immune evasion and the acquisition of binding to mouse ACE2 mark a major SARS-CoV-2 mutational shift. Broadly neutralizing sarbecovirus mAbs recognizing epitopes conserved among SARS-CoV-2 variants and other sarbecoviruses may prove key to controlling the ongoing pandemic and future zoonotic spillovers.
### Competing Interest Statement
E.C., K.C., C.S., D.P., F.Z., A.D.M., A.L., L.P., M.S.P., D.C., H.K., J.N., N.F., J.diI., L.E.R., N.C., C.H.D., K.R.S., J.R.D., A.E.P., A.C., C.M., L.Y., D.S., L.S., L.A.P., C.H., A.T., H.W.V. and G.S. are employees of Vir Biotechnology Inc. and may hold shares in Vir Biotechnology Inc. L.A.P. is a former employee and shareholder in Regeneron Pharmaceuticals. Regeneron provided no funding for this work. The Veesler laboratory has received a sponsored research agreement from Vir Biotechnology Inc. HYC reported consulting with Ellume, Pfizer, The Bill and Melinda Gates Foundation, Glaxo Smith Kline, and Merck. She has received research funding from Emergent Ventures, Gates Ventures, Sanofi Pasteur, The Bill and Melinda Gates Foundation, and support and reagents from Ellume and Cepheid outside of the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
[1]: #ref-1
[2]: #ref-2
[3]: #ref-3
[4]: #ref-4
'Like drinking from a fire hose': Health care workers traumatized by pandemic
Hospitals are struggling to hold on to nurses and other professionals, staff are traumatized and the influx of patients feels like it's coming out of a fire hose, doctors say.
Doch, es gibt Daten zum Impfstatus von Covid-19-Intensivpatienten
Boris Reitschuster behauptet, es sei „Betrug“, wenn die Bundesregierung sage, ein Großteil der Covid-19-Patienten auf Intensivstationen sei ungeimpft. Das ist irreführend.
Ergebnisse aus dem wiederholten querschnittlichen Monitoring von Wissen, Risikowahrnehmung, Schutzverhalten und Vertrauen während des aktuellen COVID-19 Ausbruchsgeschehens
Ein Gemeinschaftsprojekt von Universität Erfurt, Robert Koch Institut, Bundeszentrale für gesundheitliche Aufklärung, Leibniz-Institut für Psychologie, Science Media Center, Bernhard Nocht Institut für Tropenmedizin und Yale Institute for Global Health
Eric Feigl-Ding auf Twitter: "💡New VACCINE RANKING of ability to neutralize #Omicron—Moderna appears to be the strongest against Omicron in this study, but still big drop. Pfizer next best (but we know infection efficacy is 30-34%), AstraZeneca & Sinopharm poor. J&J & Sputnik = zero.🧵https://t.co/5xmnXH2XaJ https://t.co/eZq8jbMEsQ" / Twitter
💡New VACCINE RANKING of ability to neutralize #Omicron—Moderna appears to be the strongest against Omicron in this study, but still big drop. Pfizer next best (but we know infection efficacy is 30-34%), AstraZeneca & Sinopharm poor. J&J & Sputnik = zero.🧵https://t.co/5xmnXH2XaJ https://t.co/eZq8jbMEsQ
In the last few days, the question of why more drug companies haven't been enlisted for vaccine production has come up. It's mostly due to this tweet:The problem is, as far as I can see, this is simply wrong. There are not
Bereits in den Anfängen der Corona-Epidemie in China deuteten erste Studien darauf hin, dass
bei Kindern eine COVID-19-Erkrankung (Corona)1 im Allgemeinen weniger schwerwiegend ver-
läuft als bei Erwachsenen. Diese Erkenntnis hat sich auch ein Jahr später nicht geändert. Kinder
(älter als ein Jahr) erkranken im Durchschnitt weniger schwer, Krankheitsverläufe sind häufig
asymptomatisch2. Hieraus kann jedoch nicht gefolgert werden, dass Kinder nur eine geringe oder
gar keine Rolle im Infektionsgeschehen spielen. Ferner ist nicht geklärt, in welchem Ausmaß sie
von Spätfolgenerkrankungen betroffen sind („Long Covid“). Um ihre Bedeutung für das Pande-
miegeschehen beurteilen zu können, muss zum einen geklärt werden, in welchem Ausmaß sie
sich selbst infizieren und zum anderen, wie effizient sie die Infektion weitergeben können. Ge-
rade in Hinblick auf die Schließung von Kindergärten und Schulen ist es wichtig, diese Fragen
zu beantworten. Hierzu sind in den vergangenen Monaten zwar zahlreiche Forschungsarbeiten
erschienen, aber eine Reihe von Argumenten für und wider die Schließung/Öffnung von Schulen
und Kindergärten wird nach wie vor kontrovers diskutiert. Dies liegt daran, dass verschiedene
Erhebungen unter ganz spezifischen Voraussetzungen entstanden sind. Dadurch ist die Interpre-
tation des Infektionsgeschehens nur unter spezifischen Einschränkungen möglich und die Aussa-
gen können nur in begrenztem Umfang die Frage zur Rolle von Kindern im Corona-Pandemiege-
schehen beantworten.
A Public Health Antibody Screening Indicates a 6-Fold Higher SARS-CoV-2 Exposure Rate than Reported Cases in Children - ScienceDirect
Antibody responses to virus reflect exposure and potential protection.We developed a highly specific and sensitive approach to measuring antibodies ag…
Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study
The majority of the Spanish population is seronegative to SARS-CoV-2 infection, even
in hotspot areas. Most PCR-confirmed cases have detectable antibodies, but a substantial
proportion of people with symptoms compatible with COVID-19 did not have a PCR test
and at least a third of infections determined by serology were asymptomatic. These
results emphasise the need for maintaining public health measures to avoid a new epidemic
wave.
Effectiveness of CoronaVac among healthcare workers in the setting of high SARS-CoV-2 Gamma variant transmission in Manaus, Brazil: A test-negative case-control study
Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, Gamma, emerged in the city of Manaus in late 2020 during a large resurgence of coronavirus disease (COVID-19), and has spread throughout Brazil. The effectiveness of vaccines in settings with widespread Gamma variant transmission has not been reported.
Methods We performed a matched test-negative case-control study to estimate the effectiveness of an inactivated vaccine, CoronaVac, in healthcare workers (HCWs) in Manaus, where the Gamma variant accounted for 86% of genotyped SARS-CoV-2 samples at the peak of its epidemic. We performed an early analysis of effectiveness following administration of at least one vaccine dose and an analysis of effectiveness of the two-dose schedule. The primary outcome was symptomatic SARS-CoV-2 infection.
Findings For the early at-least-one-dose and two-dose analyses the study population was, respectively, 53,176 and 53,153 HCWs residing in Manaus and aged 18 years or older, with complete information on age, residence, and vaccination status. Among 53,153 HCWs eligible for the two-dose analysis, 47,170 (89%) received at least one dose of CoronaVac and 2,656 individuals (5%) underwent RT-PCR testing from 19 January, 2021 to 13 April, 2021. Of 3,195 RT-PCR tests, 885 (28%) were positive. 393 and 418 case- control pairs were selected for the early and two-dose analyses, respectively, matched on calendar time, age, and neighbourhood. Among those who had received both vaccine doses before the RT-PCR sample collection date, the average time from second dose to sample collection date was 14 days (IQR 7-24). In the early analysis, vaccination with at least one dose was associated with a 0.50-fold reduction (adjusted vaccine effectiveness (VE), 49.6%, 95% CI 11.3 to 71.4) in the odds of symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the first dose. However, we estimated low effectiveness (adjusted VE 36.8%, 95% CI -54.9 to 74.2) of the two-dose schedule against symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the second dose. A finding that vaccinated individuals were much more likely to be infected than unvaccinated individuals in the period 0-13 days after first dose (aOR 2.11, 95% CI 1.36-3.27) suggests that unmeasured confounding led to downward bias in the vaccine effectiveness estimate.
Interpretation Evidence from this test-negative study of the effectiveness of CoronaVac was mixed, and likely affected by bias in this setting. Administration of at least one vaccine dose showed effectiveness against symptomatic SARS-CoV-2 infection in the setting of epidemic Gamma variant transmission. However, the low estimated effectiveness of the two-dose schedule underscores the need to maintain non-pharmaceutical interventions while vaccination campaigns with CoronaVac are being implemented.
Funding Fundação Oswaldo Cruz (Fiocruz); Municipal Health Secretary of Manaus
Evidence before this study We searched PubMed for articles published from inception of the pandemic until April 3, 2021, with no language restrictions, using the search terms “P.1” AND “vaccine” AND “SARS-CoV-2”. Additionally, we searched for “CoronaVac” AND “SARS-CoV-2”. Early studies have found plasma from convalescent COVID-19 patients and sera from vaccinated individuals have reduced neutralisation of the SARS-CoV-2 variant, Gamma or P.1, compared with strains isolated earlier in the pandemic. Pfizer BNT162b2 mRNA, Oxford-AstraZeneca ChAdOx1, and CoronaVac are the only vaccines for which such data has been published to date.
No studies reported effectiveness of any vaccine on reducing the risk of infection or disease among individuals exposed to P.1 or in settings of high P.1 transmission.
Added value of this study This study finds that vaccination with CoronaVac was 49.4% (95% CI 13.2 to 71.9) effective at preventing COVID-19 in a setting with likely high prevalence of the Gamma Variant of Concern. However, an analysis of effectiveness by dose was underpowered and failed to find significant effectiveness of the two-dose schedule of CoronaVac (estimated VE 37.1%, 95% CI -53.3 to 74.2).
Implications of all the available evidence These findings are suggestive for the effectiveness of CoronaVac in healthcare workers in the setting of widespread P.1 transmission but must be strengthened by observational studies in other settings and populations. Based on this evidence, there is a need to implement sustained non-pharmaceutical interventions even as vaccination campaigns continue.
### Competing Interest Statement
The authors have declared no competing interest.
### Funding Statement
We are grateful for Pan American Health Organization's support to the Fundação de Vigilância em Saúde from Amazonas State and the Municipal Health Secretary of Manaus in making the databases available for analysis. JC and AS are supported by the Oswaldo Cruz Foundation (Edital Covid-19 - resposta rápida: 48111668950485). OTR is funded by a Sara Borrell fellowship (CD19/00110) from the Instituto de Salud Carlos III. OTR acknowledges support from the Spanish Ministry of Science and Innovation through the Centro de Excelencia Severo Ochoa 2019-2023 Program and from the Generalitat de Catalunya through the CERCA Program.
### 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:
The study was approved by the Ethical Committee for Research of Federal University of Mato Grosso do Sul (CAAE: 43289221.5.0000.0021).
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
Deidentified databases as well as the R codes will be deposited in the repository https://github.com/juliocroda/VebraCOVID-19
https://github.com/juliocroda/VebraCOVID-19
Cognitive deficits in people who have recovered from COVID-19
There is growing concern about possible cognitive consequences of COVID-19, with reports of
‘Long COVID’ symptoms persisting into the chronic phase and case studies revealing neurological problems
in severely affected patients. However, there is little information regarding the nature and broader preva-
lence of cognitive problems post-infection or across the full spread of disease severity.
Methods: We sought to confirm whether there was an association between cross-sectional cognitive perfor-
mance data from 81,337 participants who between January and December 2020 undertook a clinically vali-
dated web-optimized assessment as part of the Great British Intelligence Test, and questionnaire items
capturing self-report of suspected and confirmed COVID-19 infection and respiratory symptoms.
Findings: People who had recovered from COVID-19, including those no longer reporting symptoms, exhib-
ited significant cognitive deficits versus controls when controlling for age, gender, education level, income,
racial-ethnic group, pre-existing medical disorders, tiredness, depression and anxiety. The deficits were of
substantial effect size for people who had been hospitalised (N = 192), but also for non-hospitalised cases
who had biological confirmation of COVID-19 infection (N = 326). Analysing markers of premorbid intelli-
gence did not support these differences being present prior to infection. Finer grained analysis of perfor-
mance across sub-tests supported the hypothesis that COVID-19 has a multi-domain impact on human
cognition.
Interpretation: Interpretation. These results accord with reports of ‘Long Covid’ cognitive symptoms that per-
sist into the early-chronic phase. They should act as a clarion call for further research with longitudinal and
neuroimaging cohorts to plot recovery trajectories and identify the biological basis of cognitive deficits in
SARS-COV-2 survivors.
Prevalence and 6‐month recovery of olfactory dysfunction: a multicentre study of 1363 COVID‐19 patients - Lechien - 2021 - Journal of Internal Medicine - Wiley Online Library
Objective
To investigate prevalence and recovery of olfactory dysfunction (OD) in COVID-19 patients according to the disease severity.
Methods
From 22 March to 3 June 2020, 2581 COVID-19 patients ...
Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasma
Nature - Cross-neutralization assays of early variants and the 501Y.V2 variant of SARS-CoV-2 show that plasma from individuals infected with 501Y.V2 effectively neutralizes all variants, indicating...
Screening and vaccination against COVID-19 to minimize school closure
Schools were closed extensively in 2020-2021 to counter COVID-19 spread, impacting students’ education and
well-being. With highly contagious variants expanding in Europe, safe options to maintain schools open are
urgently needed. We developed an agent-based model of SARS-CoV-2 transmission in school. We used empirical
contact data in a primary and a secondary school, and data from pilot screenings in 683 schools during the 2021
spring Alpha wave in France. We fitted the model to observed school prevalence to estimate the school-specific
reproductive number and performed a cost-benefit analysis examining different intervention protocols. We
estimated RAlpha=1.40 (95%CI 1.35-1.45) in the primary and RAlpha=1.46 (1.41-1.51) in the secondary school during
the wave, higher than Rt estimated from community surveillance. Considering the Delta variant and vaccination
coverage in Europe, we estimated RDelta=1.66 (1.60-1.71) and RDelta=1.10 (1.06-1.14) in the two settings,
respectively. Under these conditions, weekly screening with 75% adherence would reduce cases by 34% (95%CI 32-
36%) in the primary and 36% (35-39%) in the secondary school compared to symptom-based testing. Insufficient
adherence was recorded in pilot screening (median ≤53%). Regular screening would also reduce student-days lost
up to 80% compared to reactive closure. Moderate vaccination coverage in students would still benefit from
regular screening for additional control (23% case reduction with 50% vaccinated children). COVID-19 pandemic
will likely continue to pose a risk for school opening. Extending vaccination coverage in students, complemented
by regular testing largely incentivizing adherence, are essential steps to keep schools open, especially under the
threat of more contagious variants.
Gruell_and_Vanshylla_et_al_compiled.pdf - Google Drive
The Omicron variant of SARS-CoV-2 is causing a rapid increase in infections in various
countries. This new variant of concern carries an unusually high number of mutations in key
epitopes of neutralizing antibodies on the spike glycoprotein, suggesting potential immune
evasion. Here we assessed serum neutralizing capacity in longitudinal cohorts of vaccinated
and convalescent individuals, as well as monoclonal antibody activity against Omicron using
pseudovirus neutralization assays. We report a near-complete lack of neutralizing activity
against Omicron in polyclonal sera after two doses of the BNT162b2 vaccine, in convalescent
individuals, as well as resistance to different monoclonal antibodies in clinical use. However,
mRNA booster immunizations in vaccinated and convalescent individuals resulted in a
significant increase of serum neutralizing activity against Omicron. Our study demonstrates
that booster immunizations will be critical to substantially improve the humoral immune
response against the Omicron variant.
Nasal vaccine may aid fight against new viral variants
A new Yale study finds that intranasal vaccination is better than injection at providing broad-based protection against a variety of flu strains in mice.
The perils of flawed research and the ivermectin debacle
In this op-ed, epidemiologist Gideon Meyerowitz-Katz discusses problems with medical research that have become increasingly apparent during the pandemic.