Antibody-mediated protection against symptomatic COVID-19 can be achieved at low serum neutralizing titers
Multiple studies of vaccinated and convalescent cohorts have demonstrated that serum neutralizing antibody (nAb) titers correlate with protection against coronavirus disease 2019 (COVID-19). However, the induction of multiple layers of immunity after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure has complicated the establishment of nAbs as a mechanistic correlate of protection (CoP) and hindered the definition of a protective nAb threshold. Here, we show that a half-life–extended monoclonal antibody (adintrevimab) provides about 50% protection against symptomatic COVID-19 in SARS-CoV-2–naïve adults at serum nAb titers on the order of 1:30. Vaccine modeling results support a similar 50% protective nAb threshold, suggesting that low titers of serum nAbs protect in both passive antibody prophylaxis and vaccination settings. Extrapolation of adintrevimab pharmacokinetic data suggests that protection against susceptible variants could be maintained for about 3 years. The results provide a benchmark for the selection of next-generation vaccine candidates and support the use of broad, long-acting monoclonal antibodies as alternatives or supplements to vaccination in high-risk populations.
Drei Jahre nach Ausbruch der Corona-Pandemie sind in Deutschland praktisch alle Schutzmaßnahmen gefallen, auch der Sinn der Impfkampagnen wird angesichts neuer Berichte von schwerwiegenden Impfschäden vielfach in Zweifel gezogen.
SARS-CoV-2 is associated with changes in brain structure in UK Biobank - s41586-022-04569-5_reference.pdf
There is strong evidence for brain-related abnormalities in COVID-191–13
. It remains
unknown however whether the impact of SARS-CoV-2 infection can be detected in
milder cases, and whether this can reveal possible mechanisms contributing to brain
pathology. Here, we investigated brain changes in 785 UK Biobank participants (aged
51–81) imaged twice, including 401 cases who tested positive for infection with
SARS-CoV-2 between their two scans, with 141 days on average separating their
diagnosis and second scan, and 384 controls. The availability of pre-infection imaging
data reduces the likelihood of pre-existing risk factors being misinterpreted as
disease effects. We identified significant longitudinal effects when comparing the two
groups, including: (i) greater reduction in grey matter thickness and tissue-contrast in
the orbitofrontal cortex and parahippocampal gyrus, (ii) greater changes in markers
of tissue damage in regions functionally-connected to the primary olfactory cortex,
and (iii) greater reduction in global brain size. The infected participants also showed
on average larger cognitive decline between the two timepoints. Importantly, these
imaging and cognitive longitudinal effects were still seen after excluding the 15 cases
who had been hospitalised. These mainly limbic brain imaging results may be the
in vivo hallmarks of a degenerative spread of the disease via olfactory pathways, of
neuroinflammatory events, or of the loss of sensory input due to anosmia. Whether
this deleterious impact can be partially reversed, or whether these effects will persist
in the long term, remains to be investigated with additional follow up.
Robust T cell responses to Pfizer/BioNTech vaccine compared to infection and evidence of attenuated peripheral CD8+ T cell responses due to COVID-19
Our understanding of T cell responses in COVID-19 and vaccination is incomplete. Gao et al. examine SARS-CoV-2-specific T cell responses to infection and vaccination, revealing disparate kinetics between CD4+ and CD8+ T cells. Furthermore, compared to vaccination alone, circulating CD8+ T cells are attenuated during infection and in subsequent vaccination.
Comparison of Symptoms Associated With SARS-CoV-2 Variants Among Children in Canada
This cohort study quantifies and compares symptoms, emergency department chest radiography, treatments, and disposition across dominant SARS-CoV-2 variants among children presenting to emergency departments in Canada.
Children infected with Omicron more likely to have repeat ER visits: Canadian study
A new study of more than 1,400 Canadian children who contracted COVID-19 has found that fever and cough were associated more heavily with Omicron and Delta variants, but that serious outcomes like hospitalization and being moved to the intensive care unit remained even across all variants.
SARS-CoV-2 Infection Weakens Immune-Cell Response to Vaccination
The magnitude and quality of a key immune cell’s response to vaccination with two doses of the Pfizer-BioNTech COVID-19 vaccine were considerably lower in people with prior SARS-CoV-2 infection compared to people without prior infection, a study has found. In addition, the level of this key immune cell that targets the SARS-CoV-2 spike protein was substantially lower in unvaccinated people with COVID-19 than in vaccinated people who had never been infected. Importantly, people who recover from SARS-CoV-2 infection and then get vaccinated are more protected than people who are unvaccinated.
Unternehmen in Deutschland haben im vergangenen Jahr einen zusätzlichen zweistelligen Milliardenbetrag für Lohnfortzahlungen an erkrankte Mitarbeiter ausgegeben. Das geht aus einer Analyse des Instituts der deutschen Wirtschaft (IW) hervor.
Very excited that our PaxLC clinical trial on #longCOVID patients is now open, led by @hmkyale! This is a phase 2, 1:1 randomized, double-blind, placebo-controlled research study in 100 non-hospitalized highly symptomatic long COVID. (1/)https://t.co/hga9nt8EWv— Prof. Akiko Iwasaki (@VirusesImmunity) March 21, 2023
Dunkle Wolken am Horizont: Nach XBB.1.5 kommt XBB.1.16
Genomsequenzierung vom Team Ulrich Ellings für Österreich, 11. Kalenderwoche. XBB.1.5 ist weiterhin dominiert mit über 70% Probenanteil. Die BA.5-Variante, auf die der letzte angepasste Impfstoff z…
Patienten mit COVID-19 haben ein erhöhtes Risiko für die Bildung von Blutgerinnseln. Eine Behandlung mit Acetylsalicylsäure (ASS) könnte deswegen von Vorteil sein. In der britischen RECOVERY-Studie hat sich diese Erwartung jedoch nicht erfüllt. ASS konnte das Überleben von hospitalisierten COVID-19-Patienten nicht verbessern.
Acetylsalicylic Acid and Salicylic Acid Inhibit SARS-CoV-2 Replication in Precision-Cut Lung Slices
Aspirin, with its active compound acetylsalicylic acid (ASA), shows antiviral activity against rhino- and influenza viruses at high concentrations. We sought to investigate whether ASA and its metabolite salicylic acid (SA) inhibit SARS-CoV-2 since it might use similar pathways to influenza viruses. The compound-treated cells were infected with SARS-CoV-2. Viral replication was analysed by RTqPCR. The compounds suppressed SARS-CoV-2 replication in cell culture cells and a patient-near replication system using human precision-cut lung slices by two orders of magnitude. While the compounds did not interfere with viral entry, it led to lower viral RNA expression after 24 h, indicating that post-entry pathways were inhibited by the compounds.
Acetylsalicylsäure und Salicylsäure hemmen die SARS-CoV-2-Replikation in menschlichen Präzisionslungenschnitten - Fraunhofer ITEM
Aspirin mit seinem Wirkstoff Acetylsalicylsäure zeigt in hohen Konzentrationen eine antivirale Wirkung gegen Rhino- und Influenzaviren. Katherina Sewald und ihr Team haben zusammen mit Forschenden der Julius-Maximilians-Universität Würzburg untersucht, ob Acetylsalicylsäure und sein Metabolit Salicylsäure SARS-CoV-2 hemmen, da sie möglicherweise ähnliche Wege wie Influenzaviren nutzen.
Prior SARS-CoV-2 infection enhances and reshapes spike protein–specific memory induced by vaccination
The diversity of vaccination modalities and infection history are both variables that have an impact on the immune memory of individuals vaccinated against SARS-CoV-2. To gain more accurate knowledge of how these parameters imprint on immune memory, we conducted a long-term follow-up of SARS-CoV-2 spike protein–specific immune memory in unvaccinated and vaccinated COVID-19 convalescent individuals as well as in infection-naïve vaccinated individuals. Here, we report that individuals from the convalescent vaccinated (hybrid immunity) group have the highest concentrations of spike protein–specific antibodies at 6 months after vaccination. As compared with infection-naïve vaccinated individuals, they also display increased frequencies of an atypical mucosa-targeted memory B cell subset. These individuals also exhibited enhanced TH1 polarization of their SARS-CoV-2 spike protein–specific follicular T helper cell pool. Together, our data suggest that prior SARS-CoV-2 infection increases the titers of SARS-CoV-2 spike protein–specific antibody responses elicited by subsequent vaccination and induces modifications in the composition of the spike protein–specific memory B cell pool that are compatible with enhanced functional protection at mucosal sites.
New study solidifies the fact that Covid reverse trabscibes into human DNA similar to HIV causing persistent infection: pic.twitter.com/FY83mXnxg3— Chris Turnbull (@EnemyInAState) March 5, 2023
THREAD: some new Long Covid researchFirstly ONS infection survey reports there is strong evidence that previous infection protects adults from new Long Covid on reinfection, but NO evidence that it protects children. 1/2 pic.twitter.com/iIKYGJvQ1I— Prof. Christina Pagel 🇺🇦 (@chrischirp) March 3, 2023
COVID-19 vaccination linked to fewer cardiac events
Analyzing the most extensive datasets in the U.S., researchers from the Icahn School of Medicine at Mount Sinai have revealed that vaccination against COVID-19 is associated with fewer heart attacks, strokes, and other cardiovascular issues among people who were infected with SARS-CoV-2, the virus that causes COVID-19. The research letter, “Impact of Vaccination on Major Adverse Cardiovascular Events in Patients with COVID-19 Infection,” was published in the Journal of the American College of Cardiology on February 20. The research will also be presented in a poster session on March 5, 2023 in New Orleans, LA, at the American College of Cardiology’s 72nd Annual Scientific Session Together With World Heart Federation’s World Congress of Cardiology:
SARS-CoV-2 infection of thymus induces loss of function that correlates with disease severity
Lymphopenia, particularly when restricted to the T-cell compartment, has been described as one of the major clinical hallmarks in patients with corona…
SARS-CoV-2 M Protein Facilitates Malignant Transformation of Breast Cancer Cells
Coronavirus disease 2019 (COVID-19) has spread faster due to the emergence of SARS-CoV-2 variants, which carry an increased risk of infecting patients with comorbidities, such as breast cancer. However, there are still few reports on the effects of SARS-CoV-2 infection on the progression of breast cancer, as well as the factors and mechanisms involved. In the present study, we investigated the impact of SARS-CoV-2 proteins on breast cancer cells (BCC). The results suggested that SARS-CoV-2 M protein induced the mobility, proliferation, stemness and in vivo metastasis of a triple-negative breast cancer (TNBC) cell line, MDA-MB-231, which are involved in the upregulation of NFκB and STAT3 pathways. In addition, compared to MDA-MB-231 cells, the hormone-dependent breast cancer cell line MCF-7 showed a less response to M protein, with the protein showing no effects of promoting proliferation, stemness, and in vivo metastasis. Of note, coculture with M protein-treated MDA-MB-231 cells significantly induced the migration, proliferation, and stemness of MCF-7 cells, which are involved in the upregulation of genes related to EMT and inflammatory cytokines. Therefore, SARS-CoV-2 infection might promote the ability of aggressive BCC to induce the malignant phenotypes of the other non-aggressive BCC. Taken together, these findings suggested an increased risk of poor outcomes in TNBC patients with a history of SARS-CoV-2 infection, which required a long-term follow-up. In addition, th...
ROCKVILLE, MD – COVID-19 infections can cause potentially life-threatening heart issues. Studies suggest that people with COVID-19 are 55% more likely to suffer a major adverse cardiovascular event, including heart attack, stroke and death, than those without COVID-19. They’re also more likely to have other heart issues, like arrhythmias (abnormal heart rhythms) and myocarditis (inflammation of the heart muscle). Andrew Marks, a cardiologist and biophysics professor at Columbia University, Steven Reiken, a research scientist in Marks’ lab, and colleagues, have studied some of the changes that occur in the heart that could lead to these problems. Reiken will present their work on Monday February 20 at the 67th Annual Biophysical Society Meeting in San Diego, California.
Post-COVID syndrome is associated with capillary alterations, macrophage infiltration and distinct transcriptomic signatures in skeletal muscles
The SARS-CoV-2 pandemic not only resulted in millions of acute infections worldwide, but also caused innumerable cases of post-infectious syndromes, colloquially referred to as long COVID. Due to the heterogeneous nature of symptoms and scarcity of available tissue samples, little is known about the underlying mechanisms. We present an in-depth analysis of skeletal muscle biopsies obtained from eleven patients suffering from enduring fatigue and post-exertional malaise after an infection with SARS-CoV-2. Compared to two independent historical control cohorts, patients with post-COVID exertion intolerance had fewer capillaries, thicker capillary basement membranes and increased numbers of CD169+ macrophages. SARS-CoV-2 RNA could not be detected in the muscle tissues, but transcriptomic analysis revealed distinct gene signatures compared to the two control cohorts, indicating immune dysregulations and altered metabolic pathways. We hypothesize that the initial viral infection may have caused immune-mediated structural changes of the microvasculature, potentially explaining the exercise-dependent fatigue and muscle pain. ### Competing Interest Statement ND accepted speaker honoraria of Integra LifeSciences and serves as advisor for Alexion Pharmaceuticals. ### Funding Statement Helmholtz Association Initiative and Networking Fund grant KA1-Co-02 COVIPA (EW, LGTA, ML) European Commission grant Go Safe Horizon 2020, 870144 (ND) ### 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 Ethics Committee of the Charite - Universitaetsmedizin Berlin (EA2/066/20 and EA2/163/17) in accordance with the 1964 Declaration of Helsinki and its later amendments. 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 produced in the present study are available upon reasonable request to the authors.
Incident autoimmune diseases in association with a SARS-CoV-2 infection: A matched cohort study
Objectives To investigate whether the risk of developing an incident autoimmune disease is increased in patients with previous COVID-19 disease compared to people without COVID-19. Method A cohort was selected from German routine health care data covering 38.9 million individuals. Based on documented diagnoses, we identified individuals with polymerase chain reaction (PCR)-confirmed COVID-19 through December 31, 2020. Patients were matched 1:3 to control patients without COVID-19. Both groups were followed up until June 30, 2021. We used the four quarters preceding the index date until the end of follow-up to analyze the onset of autoimmune diseases during the post-acute period. Incidence rates (IR) per 1000 person-years were calculated for each outcome and patient group. Poisson models were deployed to estimate the incidence rate ratios (IRRs) of developing an autoimmune disease conditional on a preceding diagnosis of COVID-19. Results In total, 641,704 patients with COVID-19 were included. Comparing the incidence rates in the COVID-19 (IR=15.05, 95% CI: 14.69-15.42) and matched control groups (IR=10.55, 95% CI: 10.25-10.86), we found a 42.63% higher likelihood of acquiring autoimmunity for patients who had suffered from COVID-19. This estimate was similar for common autoimmune diseases, such as Hashimoto thyroiditis, rheumatoid arthritis, or Sjögren syndrome. The highest IRR was observed for autoimmune disease of the vasculitis group. Patients with a more severe course of COVID-19 were at a greater risk for incident autoimmune diseases. Conclusions SARS-CoV-2 infection is associated with an increased risk of developing new-onset autoimmune diseases after the acute phase of infection. ### Competing Interest Statement FT, FE, AV, MS, JJ, BK, LR, CS, and JS and report institutional funding for this project from the German Federal Ministry of Health. Unrelated to this study, JS reports grants for investigator-initiated research from the German GBA, the BMG, BMBF, EU, Federal State of Saxony, Novartis, Sanofi, ALK, and Pfizer. He also participated in advisory board meetings for Sanofi, Lilly, and ALK. MB reports payment for data analysis which is presented in this paper from DAK‐Gesundheit. Unrelated to this study, MB reports grants from German GBA, Pfizer and Sanofi Pasteur and consulting fees from Janssen‐Cilag. He participated in an advisory board for GSK. The other authors declare that they have no competing interest. ### Clinical Protocols ### Funding Statement This study is supported by a grant from the German Federal Ministry of Health (Bundesgesundheitsministerium) under Grant Number ZMI1-2521NIK705. ### 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 ethics committee of the TU Dresden gave ethical approval for this work (approval number: BO-EK (COVID)-482102021). 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 The raw data used in this study cannot be made available in the manuscript, the supplemental files, or in a public repository due to German data protection laws (Bundesdatenschutzgesetz). The aggregated data is stored on a secure drive at ZEGV.
Multiviral Quartet Nanocages Elicit Broad Anti-Coronavirus Responses for Proactive Vaccinology
Defending against future pandemics may require vaccine platforms that protect across a range of related pathogens. The presentation of multiple receptor-binding domains (RBDs) from evolutionarily-related viruses on a nanoparticle scaffold elicits a strong antibody response to conserved regions. Here we produce quartets of tandemly-linked RBDs from SARS-like betacoronaviruses coupled to the mi3 nanocage through a SpyTag/SpyCatcher spontaneous reaction. These Quartet Nanocages induce a high level of neutralizing antibodies against several different coronaviruses, including against viruses not represented on the vaccine. In animals primed with SARS-CoV-2 Spike, boost immunizations with Quartet Nanocages increased the strength and breadth of an otherwise narrow immune response. Quartet Nanocages are a strategy with potential to confer heterotypic protection against emergent zoonotic coronavirus pathogens and facilitate proactive pandemic protection. One Sentence Summary A vaccine candidate with polyprotein antigens displayed on nanocages induces neutralizing antibodies to multiple SARS-like coronaviruses. ### Competing Interest Statement M.H. is an inventor on a patent on spontaneous amide bond formation (EP2534484) and a SpyBiotech co-founder and shareholder. M.H. and A.H.K. are inventors on a patent on SpyTag003:SpyCatcher003 (UK Intellectual Property Office 1706430.4). P.J.B. and A.A.C. are inventors on a US patent application filed by the California Institute of Technology that covers the methodology to generate cross-reactive antibodies using mosaic nanoparticles. P.J.B., and A.A.C. are inventors on a US patent application filed by the California Institute of Technology that covers the monoclonal antibodies elicited by vaccination with Mosaic nanoparticles described in this work. P.J.B., A.A.C. and J.R.K. are inventors on a US patent application filed by the California Institute of Technology that covers the methods of isolating cross-reactive antibodies by vaccination with mosaic nanoparticles. All other authors have no competing interests to declare.
One-Fourth of COVID-19 Patients Have an Impaired Pulmonary Function after 12 Months of Illness Onset
Background: This longitudinal study evaluates the extent of impaired pulmonary function over time after SARS-CoV-2 infection across the full spectrum of COVID-1
COVID-19: Kann Metformin in der Frühphase eine Hospitalisierung...
Minneapolis/Minnesota – Die Wirkstoffe Ivermectin, Fluvoxamin und Metformin, die seit Beginn der Pandemie als mögliche Wirkstoffe gegen COVID-19 in der... #Metformin #Studie #COVID19 #NEJM
Epidemiological and clinical characteristics of children with confirmed COVID-19 infection in a tertiary referral hospital in Manila, Philippines - Tropical Medicine and Health
Background COVID-19 has challenged the under-resourced health systems of low- and middle-income countries, significantly affecting child health. Available published data on Filipino children with COVID-19 infection are limited. This study aims to describe the epidemiological and clinical characteristics of pediatric patients with confirmed COVID-19 in an infectious disease hospital in Manila, Philippines. Main text This cross-sectional study reviewed data on patients ages 0 to 18 years with confirmed COVID-19 infection, admitted to San Lazaro Hospital from January 25, 2020 to January 25, 2022. Demographic data and clinical characteristics obtained from COVID-19 case investigation forms were summarized and compared between severe and non-severe cases. Risk factors for disease severity and mortality were analyzed. Of 115 patients, 64% were males. There were 87 patients (75.7%) with asymptomatic, mild, or moderate disease, and 28 cases (24.3%) with severe or critical illness. The median age of all patients was 10 years (interquartile range: 4–15 years). The majority of patients (40.9%) were adolescents ages 13 to 18 years. Predominant symptoms were fever (73.9%) and cough (55.7%). Patients with severe or critical illness were more likely to experience difficulty of breathing (55.2% vs 44.8%, p
Incidence of Epilepsy and Seizures Over the First 6 Months After a COVID-19 Diagnosis
Background and Objectives The relationship between COVID-19 and epilepsy is uncertain. We studied the potential association between COVID-19 and seizures or epilepsy in the 6 months after infection.
Methods We applied validated methods to an electronic health records network (TriNetX Analytics) of 81 million people. We closely matched people with COVID-19 infections to those with influenza. In each cohort, we measured the incidence and hazard ratios (HRs) of seizures and epilepsy. We stratified data by age and by whether the person was hospitalized during the acute infection. We then explored time-varying HRs to assess temporal patterns of seizure or epilepsy diagnoses.
Results We analyzed 860,934 electronic health records. After matching, this yielded 2 cohorts each of 152,754 patients. COVID-19 was associated with an increased risk of seizures and epilepsy compared with influenza. The incidence of seizures within 6 months of COVID-19 was 0.81% (95% CI 0.75–0.88; HR compared with influenza 1.55 [1.39–1.74]). The incidence of epilepsy was 0.30% (0.26–0.34; HR compared with influenza 1.87 [1.54–2.28]). The HR of epilepsy after COVID-19 compared with influenza was greater in people who had not been hospitalized and in individuals younger than 16 years. The time of peak HR after infection differed by age and hospitalization status.
Discussion The incidence of new seizures or epilepsy diagnoses in the 6 months after COVID-19 was low overall, but higher than in matched patients with influenza. This difference was more marked in people who were not hospitalized, highlighting the risk of epilepsy and seizures even in those with less severe infection. Children appear at particular risk of seizures and epilepsy after COVID-19 providing another motivation to prevent COVID-19 infection in pediatric populations. That the varying time of peak risk related to hospitalization and age may provide clues as to the underlying mechanisms of COVID-associated seizures and epilepsy.
CPT=
: Current Procedural Terminology;
HRs=
: hazard ratios;
HCOs=
: healthcare organizations;
ICD=
: International Classification of Diseases ;
PNES=
: psychological nonepileptic attacks