Covid19-Sources

4433 bookmarks
Newest
Respiratory sequelae of COVID-19: pulmonary and extrapulmonary origins, and approaches to clinical care and rehabilitation
Respiratory sequelae of COVID-19: pulmonary and extrapulmonary origins, and approaches to clinical care and rehabilitation
Although the exact prevalence of post-COVID-19 condition (also known as long COVID) is unknown, more than a third of patients with COVID-19 develop symptoms that persist for more than 3 months after SARS-CoV-2 infection. These sequelae are highly heterogeneous in nature and adversely affect multiple biological systems, although breathlessness is a frequently cited symptom. Specific pulmonary sequelae, including pulmonary fibrosis and thromboembolic disease, need careful assessment and might require particular investigations and treatments. COVID-19 outcomes in people with pre-existing respiratory conditions vary according to the nature and severity of the respiratory disease and how well it is controlled. Extrapulmonary complications such as reduced exercise tolerance and frailty might contribute to breathlessness in post-COVID-19 condition. Non-pharmacological therapeutic options, including adapted pulmonary rehabilitation programmes and physiotherapy techniques for breathing management, might help to attenuate breathlessness in people with post-COVID-19 condition. Further research is needed to understand the origins and course of respiratory symptoms and to develop effective therapeutic and rehabilitative strategies.
·thelancet.com·
Respiratory sequelae of COVID-19: pulmonary and extrapulmonary origins, and approaches to clinical care and rehabilitation
Jean Fisch on Twitter
Jean Fisch on Twitter
This paper making the rounds at the moment claims that "excess deaths started in Mar 2021 in GER and is unlikely to come from covid but matches vaccines"It is rigged with issues which basically invalidate its claimLet me go through the major ones⤵️https://t.co/3LwsM9RbeL— Jean Fisch (@Jean__Fisch) June 1, 2023
·twitter.com·
Jean Fisch on Twitter
Recovery and symptom trajectories up to two years after SARS-CoV-2 infection: population based, longitudinal cohort study
Recovery and symptom trajectories up to two years after SARS-CoV-2 infection: population based, longitudinal cohort study
Objective To evaluate longer term symptoms and health outcomes associated with post-covid-19 condition within a cohort of individuals with a SARS-CoV-2 infection. Design Population based, longitudinal cohort. Setting General population of canton of Zurich, Switzerland. Participants 1106 adults with a confirmed SARS-CoV-2 infection who were not vaccinated before infection and 628 adults who did not have an infection. Main outcome measures Trajectories of self-reported health status and covid-19 related symptoms between months six, 12, 18, and 24 after infection and excess risk of symptoms at six months after infection compared with individuals who had no infection. Results 22.9% (95% confidence interval 20.4% to 25.6%) of individuals infected with SARS-CoV-2 did not fully recover by six months. The proportion of individuals who had an infection who reported not having recovered decreased to 18.5% (16.2% to 21.1%) at 12 months and 17.2% (14.0% to 20.8%) at 24 months after infection. When assessing changes in self-reported health status, most participants had continued recovery (68.4% (63.8% to 72.6%)) or had an overall improvement (13.5% (10.6% to 17.2%)) over time. Yet, 5.2% (3.5% to 7.7%) had a worsening in health status and 4.4% (2.9% to 6.7%) had alternating periods of recovery and health impairment. The point prevalence and severity of covid-19 related symptoms also decreased over time, with 18.1% (14.8% to 21.9%) reporting symptoms at 24 months. 8.9% (6.5% to 11.2%) of participants reported symptoms at all four follow-up time points, while in 12.5% (9.8% to 15.9%) symptoms were alternatingly absent and present. Symptom prevalence was higher among individuals who were infected compared with those who were not at six months (adjusted risk difference 17.0% (11.5% to 22.4%)). Excess risk (adjusted risk difference) for individual symptoms among those infected ranged from 2% to 10%, with the highest excess risks observed for altered taste or smell (9.8% (7.7% to 11.8%)), post-exertional malaise (9.4% (6.1% to 12.7%)), fatigue (5.4% (1.2% to 9.5%)), dyspnoea (7.8% (5.2% to 10.4%)), and reduced concentration (8.3% (6.0% to 10.7%)) and memory (5.7% (3.5% to 7.9%)). Conclusions Up to 18% of individuals who were not vaccinated before infection had post-covid-19 condition up to two years after infection, with evidence of excess symptom risk compared with controls. Effective interventions are needed to reduce the burden of post-covid-19 condition. Use of multiple outcome measures and consideration of the expected rates of recovery and heterogeneity in symptom trajectories are important in the design and interpretation of clinical trials. Registrations [ISRCTN18181860][1], . We are open to sharing de-identified individual participant data that underlie the results reported in this article. Requests can be made to the corresponding author at miloalan.puhan@uzh.ch. Data requestors will need to sign a data access agreement. [1]: /external-ref?link_type=ISRCTN&access_num=ISRCTN18181860
·bmj.com·
Recovery and symptom trajectories up to two years after SARS-CoV-2 infection: population based, longitudinal cohort study
Biological mechanisms underpinning the development of long COVID
Biological mechanisms underpinning the development of long COVID
As COVID-19 evolves from a pandemic to an endemic disease, the already staggering number of people that have been or will be infected with SARS-CoV-2 is only destined to increase, and the majority of humanity will be infected. It is well understood that COVID-19, like many other viral infections, leaves a significant fraction of the infected with prolonged consequences. Continued high number of SARS-CoV-2 infections, viral evolution with escape from post-infection and vaccinal immunity, and reinfections heighten the potential impact of Long COVID. Hence, the impact of COVID-19 on human health will be seen for years to come until more effective vaccines and pharmaceutical treatments become available. To that effect, it is imperative that the mechanisms underlying the clinical manifestations of Long COVID be elucidated. In this article, we provide an in-depth analysis of the evidence on several potential mechanisms of Long COVID and discuss their relevance to its pathogenesis.
·cell.com·
Biological mechanisms underpinning the development of long COVID
Sequencing of bivalent Moderna and Pfizer mRNA vaccines reveals nanogram to microgram quantities of expression vector dsDNA per dose
Sequencing of bivalent Moderna and Pfizer mRNA vaccines reveals nanogram to microgram quantities of expression vector dsDNA per dose
Several methods were deployed to assess the nucleic acid composition of four expired vials of the Moderna and Pfizer bivalent mRNA vaccines. Two vials from each vendor were evaluated with Illumina sequencing, qPCR, RT-qPCR, Qubit™ 3 fluorometry and Agilent Tape Station™ electrophoresis. Multiple assays support DNA contamination that exceeds the European Medicines Agency (EMA) 330ng/mg requirement and the FDAs 10ng/dose requirements. These data may impact the surveillance of vaccine mRNA in breast milk or plasma as RT-qPCR assays targeting the vaccine mRNA cannot discern DNA from RNA without RNase or DNase nuclease treatments. Likewise, studies evaluating the reverse transcriptase activity of LINE-1 and vaccine mRNA will need to account for the high levels of DNA contamination in the vaccines. The exact ratio of linear fragmented DNA versus intact circular plasmid DNA is still being investigated. Quantitative PCR assays used to track the DNA contamination are described.
·osf.io·
Sequencing of bivalent Moderna and Pfizer mRNA vaccines reveals nanogram to microgram quantities of expression vector dsDNA per dose
Two Cases of Neurological Complications After mRNA Vaccination for COVID-19 (P1-1.Virtual)
Two Cases of Neurological Complications After mRNA Vaccination for COVID-19 (P1-1.Virtual)
Objective: We present two patients with neurological complications following COVID-19 mRNA vaccination. Background: Post-vaccinal myelitis and demyelination is well described. We investigated two patients presenting inflammatory demyelination following mRNA based vaccination against COVID-19. Design/Methods: Patients were referred to the treating neurologist for a second opinion as possible cases of multiple sclerosis. Clinical neurological evaluation, MRI imaging of brain and spine as well as serum and cerebrospinal fluid (CSF) analysis was performed. Results: In case 1, the patient developed left-side numbness and difficulty walking six weeks post-second dose of the Moderna mRNA COVID-19 vaccine. She was found to have an enhancing thoracic cord lesion on MRIs, and CSF ELISA studies showed highly elevated IgG levels against the spike protein receptor-binding domain (S1-RBD) of COVID 19. In case 2, the patient began to hiccup and vomit, developed diplopia, and right-side weakness and numbness around two days post-second dose of the Moderna vaccine. MRIs showed two lesions on her brain and a C4 enhancing lesion on her spinal cord. CSF showed oligoclonal bands. However, further analysis of her spinal fluid showed highly elevated IgG antibodies to the S1-RBD. Conclusions: Initially, case 1 was diagnosed with transverse myelitis and possible multiple sclerosis, and case 2 with multiple sclerosis. Both patients likely would have received long-term immunosuppressive therapy had vaccine complications not been suspected. The presence of CSF antibodies to the S1-RBD protein suggests an immune response to the mRNA COVID-19 vaccinations crossing over to the CNS as the likely cause of these neurological complications. In patients developing acute neurological complaints in the period following vaccination, even with the presence of oligoclonal bands, CSF should be analyzed for reactivity against the S1-RBD. Further investigation is required to explain the mechanism of this response and subsequent complications. Both patients are clinically improving and will continue to be managed by a neurologist. Disclosure: Miss Malin has nothing to disclose. Mr. Lin has nothing to disclose. Ms. Roche has nothing to disclose. Ms. Griffin has nothing to disclose.
·n.neurology.org·
Two Cases of Neurological Complications After mRNA Vaccination for COVID-19 (P1-1.Virtual)
Onkologen empfehlen Impfung - «Turbokrebs» ist kein medizinischer Begriff
Onkologen empfehlen Impfung - «Turbokrebs» ist kein medizinischer Begriff
Die Covid-Impfung soll Menschen vor einer schweren Erkrankung bewahren. Doch in sozialen Medien wird verbreitet, dass zurückgegangene Krebstumore angeblich «seit der Impfung leider wieder aufflammen, aufgrund der Schädigung ihres Immunsystems durch die COVID-Impfung». Tumore seien so groß wie nie, daher würden sie als «Turbokrebs» bezeichnet. Ist an diesem angeblichen Phänomen etwas dran?
·dpa-factchecking.com·
Onkologen empfehlen Impfung - «Turbokrebs» ist kein medizinischer Begriff
Dichotomy of neutralizing antibody, B cell and T cell responses to SARS-CoV-2 vaccination and protection in healthy adults
Dichotomy of neutralizing antibody, B cell and T cell responses to SARS-CoV-2 vaccination and protection in healthy adults
Heterogeneity in SARS-CoV-2 vaccine responses is not understood. Here, we identify four patterns of live-virus neutralizing antibody responses: individuals with hybrid immunity (with confirmed prior infection); rare individuals with low responses (paucity of S1-binding antibodies); and surprisingly, two further groups with distinct serological repertoires. One group – broad responders – neutralize a range of SARS-CoV-2 variants, whereas the other – narrow responders – neutralize fewer, less divergent variants. This heterogeneity does not correlate with Ancestral S1-binding antibody, rather the quality of the serological response. Furthermore, IgDlowCD27-CD137+ B cells and CCR6+ CD4+ T cells are enriched in broad responders before dose 3. Notably, broad responders have significantly longer infection-free time after their third dose. Understanding the control and persistence of these serological profiles could allow personalized approaches to enhance serological breadth after vaccination. ### Competing Interest Statement CSw reports interests unrelated to this Correspondence: grants from BMS, Ono-Pharmaceuticals, Boehringer-Ingelheim, Roche-Ventana, Pfizer and Archer Dx, unrelated to this work; personal fees from Genentech, Sarah Canon Research Institute, Medicxi, Bicycle Therapeutics, GRAIL, Amgen, AstraZeneca, BMS, Illumina, GlaxoSmithKline, MSD, and Roche-Ventana, unrelated to this work; and stock options from Apogen Biotech, Epic Biosciences, GRAIL, and Achilles Therapeutics, unrelated to this Correspondence. SGam reports funding from AstraZeneca to evaluate monoclonal antibodies subsequent to this work. DLVB reports grants from AstraZeneca unrelated to this work. The authors have no additional financial interests.
·biorxiv.org·
Dichotomy of neutralizing antibody, B cell and T cell responses to SARS-CoV-2 vaccination and protection in healthy adults
Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation
Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation
Background Post-COVID-19 syndrome (PCS) is a lingering disease with ongoing symptoms such as fatigue and cognitive impairment resulting in a high impact on the daily life of patients. Understanding the pathophysiology of PCS is a public health priority, as it still pose...
·researchsquare.com·
Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation
IgG4 Antibodies Induced by Repeated Vaccination May Generate Immune Tolerance to the SARS-CoV-2 Spike Protein
IgG4 Antibodies Induced by Repeated Vaccination May Generate Immune Tolerance to the SARS-CoV-2 Spike Protein
Less than a year after the global emergence of the coronavirus SARS-CoV-2, a novel vaccine platform based on mRNA technology was introduced to the market. Globally, around 13.38 billion COVID-19 vaccine doses of diverse platforms have been administered. To date, 72.3% of the total population has been injected at least once with a COVID-19 vaccine. As the immunity provided by these vaccines rapidly wanes, their ability to prevent hospitalization and severe disease in individuals with comorbidities has recently been questioned, and increasing evidence has shown that, as with many other vaccines, they do not produce sterilizing immunity, allowing people to suffer frequent re-infections. Additionally, recent investigations have found abnormally high levels of IgG4 in people who were administered two or more injections of the mRNA vaccines. HIV, Malaria, and Pertussis vaccines have also been reported to induce higher-than-normal IgG4 synthesis. Overall, there are three critical factors determining the class switch to IgG4 antibodies: excessive antigen concentration, repeated vaccination, and the type of vaccine used. It has been suggested that an increase in IgG4 levels could have a protecting role by preventing immune over-activation, similar to that occurring during successful allergen-specific immunotherapy by inhibiting IgE-induced effects. However, emerging evidence suggests that the reported increase in IgG4 levels detected after repeated vaccination with the mRNA vaccines may not be a protective mechanism; rather, it constitutes an immune tolerance mechanism to the spike protein that could promote unopposed SARS-CoV2 infection and replication by suppressing natural antiviral responses. Increased IgG4 synthesis due to repeated mRNA vaccination with high antigen concentrations may also cause autoimmune diseases, and promote cancer growth and autoimmune myocarditis in susceptible individuals.
·mdpi.com·
IgG4 Antibodies Induced by Repeated Vaccination May Generate Immune Tolerance to the SARS-CoV-2 Spike Protein
SARS-CoV-2 clearance after breakthrough infection correlates with fit and happy T cells
SARS-CoV-2 clearance after breakthrough infection correlates with fit and happy T cells
We will regularly encounter severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but there is uncertainty about the contribution that T cells make to clear the virus. Koutsakos et al.1 shed light on the response of memory T cells acquired from vaccination to a breakthrough infection. They demonstrate a direct correlation between the T cell response, their functionality and viral clearance. Furthermore, they show that T cell responses are robust after multiple activations over 2 years. SARS-CoV-2, the cause of the coronavirus disease 2019 (COVID-19) pandemic, has inflicted great suffering worldwide. Respiratory viruses have short incubation times and rapidly produce infectious progeny, as seen with the four human coronaviruses (HCoV) that cause cold-like symptoms, as well as severe disease in immunocompromised individuals. Disease protection depends on the generation of a coordinated innate and adaptive immune response. COVID-19 vaccines have provided relief from severe disease without the risks associated with infection.
·onlinelibrary.wiley.com·
SARS-CoV-2 clearance after breakthrough infection correlates with fit and happy T cells
Neurological and psychiatric risk trajectories after SARS-CoV-2 infection: an analysis of 2-year retrospective cohort studies including 1 284 437 patients
Neurological and psychiatric risk trajectories after SARS-CoV-2 infection: an analysis of 2-year retrospective cohort studies including 1 284 437 patients
COVID-19 is associated with increased risks of neurological and psychiatric sequelae in the weeks and months thereafter. How long these risks remain, whether they affect children and adults similarly, and whether SARS-CoV-2 variants differ in their risk profiles remains unclear.
·thelancet.com·
Neurological and psychiatric risk trajectories after SARS-CoV-2 infection: an analysis of 2-year retrospective cohort studies including 1 284 437 patients
Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection
Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection
This study aims to develop a definition of postacute sequelae of SARS-CoV-2 infection (PASC) based on self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections using a cohort of adults with and without SARS-CoV-2 infection.
·jamanetwork.com·
Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection
SARS-CoV-2, long COVID, prion disease and neurodegeneration
SARS-CoV-2, long COVID, prion disease and neurodegeneration
On the last day of the year 2019 a novel Betacoronavirus (2019-nCov), now known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and causing the highly transmissible and lethal pneumonia COVID-19 was first reported in Wuhan, Hubei Province in Central China (Huang et al., 2020; Fu et al., 2022; Lu and Sun, 2022). Since then ongoing research and long-term studies of the sequelae of SARS-CoV-2 infection have indicated that post-infection, recovery from COVID-19 and/or COVID-19 aftermath is associated with long-term physiological and neurological deficits known generically as “long COVID” (Roy et al., 2021; Ahmad et al., 2022; Baazaoui and Iqbal, 2022). Multiple independent epidemiological and clinical studies further indicate that SARS-CoV-2 infection and “long COVID” strongly correlate with the onset of progressive neurological disturbances that include Alzheimer's disease (AD), prion disease (PrD) and other neurodegenerative disorders. These are apparent: (i) especially in aged and/or senile COVID-19 patients; (ii) in patients experiencing overlapping or inter-current illnesses that include heart disease, diabetes, hypertension, neuropsychiatric and other age-related neurological disorders; and (iii) in those COVID-19 patients who have experienced a particularly virulent and/or a near fatal episode of SARS-CoV-2 infection (Farheen et al., 2021; Flud et al., 2022; Fu et al., 2022). Conversely, increasing numbers of epidemiological studies suggest that elderly people with neurological deficits commonly observed in AD are highly vulnerable to SARS-CoV-2 infection, and especially the development of more severe forms of COVID-19 disease (Chiricosta et al., 2021; Hsu et al., 2021; Fu et al., 2022). The recent finding that the SARS-CoV-2 “S1” spike protein essential for viral infectivity contains prion-like domains associated with immune-evasion and the promotion of protein aggregation and aggregate “seeding” is particularly intriguing (Baazaoui and Iqbal, 2022; Bernardini et al., 2022; Tetz and Tetz, 2022). Based on these and other very recent findings this “Opinion” paper will: (i) address our current understanding of the emerging role of SARS-CoV-2 infection with “long COVID” with special reference to AD and PrD; (ii) will review the latest findings of the SARS-CoV-2 “S1” spike protein and its preferred interaction with the ubiquitous angiotensin converting enzyme-2 (ACE2) receptor (ACE2R); and (iii) will highlight the interplay of the molecular biology and neuropathology of SARS-CoV-2 with the unusual and immune-evasive character of prion neurobiology, AD and PrD.
·ncbi.nlm.nih.gov·
SARS-CoV-2, long COVID, prion disease and neurodegeneration