Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment
Nature Neuroscience - Long COVID is a major public health issue since 2020 and exhibits frequent neurological symptoms. Greene et al. propose that brain fog results from leaky brain blood vessels...
Audiovestibular adverse events following COVID-19 vaccinations
Evidence regarding audiovestibular adverse events post COVID-19 vaccination to date has been inconclusive regarding a potential association. This stud…
Clinical development of antivirals against SARS-CoV-2 and its variants
The unceasing global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) calls for the development of novel therapeutics. Although …
COVID-19 antiviral treatment should be taken for longer, says study
The currently recommended five-day course of molnupiravir, an antiviral treatment, may not be long enough to treat COVID-19, according to a new paper involving UCL researchers.
Long COVID linked to persistently high levels of inflammatory
A University of Cambridge-led study identifies the protein interferon gamma (IFN-γ) as a potential biomarker for Long COVID fatigue and highlights an immunological mechanism underlying the disease,
Möglicherweise Labortest zur Diagnose von Long Covid gefunden
DMZ – WISSENSCHAFT ¦ Sarah Koller ¦ Studie zeigt: Spontane, persistente, T-Zell-abhängige IFN-γ-Freisetzung bei Patienten mit Long Covid Nach einer akuten Infektion mit dem schweren akuten respiratorischen Syndrom-Coronavirus-2 (SARS-CoV-2) erleben einige Patienten persistente Symptome über 12 Wochen hinaus, was als Long Covid bezeichnet wird. Ein Verständnis der Mechanismen, die diese debilitierende Krankheit verursachen, und die Identifizierung von Biomarkern für diagnostische, therapeutische und Überwachungszwecke sind dringend erforderlich. Mithilfe hochsensitiver FluoroSpot-Tests wurden persistente hohe Spiegel von Interferon-γ (IFN-γ) aus peripheren Blutmononuklearzellen (PBMCs) von Patienten mit Long Covid nachgewiesen. Diese IFN-γ-Freisetzung wurde ohne ex vivo Peptidstimulation beobachtet und bleibt bei Patienten mit Long Covid persistierend erhöht im Vergleich zur Rückbildung bei Patienten, die sich von akuter SARS-CoV-2-Infektion erholen. Die IFN-γ-Freisetzung war CD8+ T-Zell-vermittelt und abhängig von der Antigenpräsentation durch CD14+ Zellen. Längsschnittliche Nachuntersuchungen unserer Studienkohorte zeigten, dass eine Verbesserung und Auflösung der Symptome mit einem Rückgang der IFN-γ-Produktion auf Baselinewerte korrelierte. Die Studie hebt einen potenziellen Mechanismus von Long Covid hervor und ermöglicht die Suche nach Biomarkern und Therapeutika bei Patienten mit Long Covid. Eine beträchtliche Anzahl von Menschen, die mit dem schweren akuten respiratorischen Syndrom-Coronavirus-2 (SARS-CoV-2) infiziert sind, zeigt anhaltende, belastende Symptome und/oder das Auftreten neuer Symptome nach COVID-19. Diese sind schwer in spezifische Endotypen zu unterteilen und werden im Allgemeinen als Post-COVID-Syndrom, postakute Folgen von SARS-CoV-2 (PASC) oder Long Covid gruppiert. Es besteht kein Konsens zur Diagnose von Long Covid, und die Ursachen von Long Covid bleiben unklar, was zu einem Mangel an zugelassenen pharmakologischen therapeutischen Interventionen für diesen beeinträchtigenden Zustand führt. Long Covid zeigt eine Vielzahl von rezidivierenden und remittierenden Symptomen und eine multisystemische Organeinbindung mit Prävalenzraten von 0,2 bis 33%. Es ist wahrscheinlich, dass einige Unterschiede zwischen Studien auf Unterschiede in den diagnostischen Kriterien und der Definition von Long Covid zurückzuführen sind. Die Pathogenese dieser heterogenen Krankheit ist unklar, ebenso wie das Fehlen diagnostischer Biomarker und Behandlungen. Zusätzlich zu dem diagnostischen Dilemma gibt es zunehmende Hinweise darauf, dass Long Covid nicht mit der Schwere der vorangegangenen akuten Erkrankung korreliert, da es auch Patienten betrifft, die asymptomatisch und/oder milde SARS-CoV-2-Infektionen hatten. Obwohl einige Patienten ohne therapeutische Interventionen besser werden, haben viele nicht verbesserte und/oder rezidivierende und sich verschlechternde Symptome. Berichte von einigen Patienten mit Long Covid legen nahe, dass eine Impfung ihre Symptome verbessert oder lindert; jedoch bleibt die pathophysiologische Grundlage für diese Befunde unbekannt. Angesichts des dringenden klinischen Bedarfs, die pathophysiologische Grundlage von Long Covid zu bestimmen und die relevanten Biomarker zur Diagnose zu ermitteln und zur objektiven Krankheitsüberwachung beizutragen, untersuchten die Wissenschaftlerinnen udn Wissenschaftler die Zytokinsekretion von peripheren Blutmononuklearzellen (PBMCs). Diese PBMCs stammten entweder aus einer Kohorte von undifferenzierten Patienten mit der Diagnose Long Covid (definiert durch klinische Symptome), Kontrollen von nie infizierten Individuen oder aus einer längsschnittlichen Nachuntersuchung von akut infizierten Personen, die kein Long Covid entwickelt hatten. Darüber hinaus wurden zur besseren Verständigung des Krankheitsverlaufs und der immunologischen Parameter eine Immunphänotypisierung in Kombination mit intrazellulärer Zytokinfärbung von Spender-PBMCs durchgeführt. Damit wird gezeigt, dass eine SARS-CoV-2-Infektion eine starke Zunahme der Interferon-γ-(IFN-γ)-Freisetzung durch Cluster von Differenzierung 8-positiven (CD8+) T-Zellen sowie kleinere Anstiege anderer proinflammatorischer Zytokine induziert, die keine ex vivo Peptidstimulation erfordern. Dieser Zustand hält mehrere Monate nach einer akuten SARS-CoV-2-Infektion an, kehrt dann jedoch bei gesunden Personen auf den Ausgangswert zurück. Im Gegensatz dazu bleibt die spontane Freisetzung von IFN-γ aus PBMCs von Patienten mit Long Covid hoch. Die Genesung von Long Covid-Symptomen ist mit einer Rückkehr der IFN-γ-Spiegel auf den Ausgangswert verbunden, was auf eine Korrelation zwischen IFN-γ-Spiegeln und Long Covid-Symptomen hinweist. Wir bestimmen auch, dass diese IFN-γ-Produktion durch CD8+ T-Zellen eine Antigenpräsentation durch CD14+ Monozyten und den Kontakt mit dem Haupthistokompatibilitätskomplex (MHC) der Klasse I erfordert. Zusammen wurden IFN-γ-Freisetzung als potenziellen Biomarker bei einigen Patienten mit Long Covid und heben einen immunologischen Mechanismus hervorgehoben, der dieser beeinträchtigenden Krankheit zugrunde liegt, was den Weg für die Entwicklung dringend benötigter Therapien ebnen könnte. Eine Infektion mit SARS-CoV-2 löst spontane und anhaltende IFN-γ-Produktion bei einer Untergruppe von Patienten mit Long Covid aus. Die Wissenschaftlerinnen und Wissenschaftler haben kürzlich einen hochsensitiven T-Zell-FluoroSpot-Test gemeldet, der SARS-CoV-2-spezifische Interleukin-2 (IL-2)- und IFN-γ-Antworten bei Patienten mit Long Covid misst. Die Freisetzung von Zytokinen nach Stimulation von PBMCs von Patienten mit Long Covid mit SARS-CoV-2-Antigenen ermöglichte es uns, die Häufigkeit von T-Zellen, die für sich überlappende Peptidpools von Spike (S)-, Nucleocapsid (N)- und Membran (M)-Proteinen spezifisch sind, zu bestimmen. Neben der Verwendung von in vitro Peptiden zur Stimulation der Zytokinfreisetzung von PBMCs haben wir auch spontane Zytokinfreisetzung ohne Stimulation mit SARS-CoV-2-Antigenen gemessen. Die Detektion von zytokinsezierenden Zellen aus nicht stimulierten PBMCs ist normalerweise sehr niedrig, aber ein signifikant höherer Anteil/Prozentsatz von Zellen, die IFN-γ produzieren, wurde in PBMCs von Patienten mit Long Covid im Vergleich zu ungeimpften vorpandemischen historischen Negativkontrollproben zwischen 2014 und 2019 eindeutig beobachtet. Zur Studie
Nature Medicine - Individuals with COVID-19 are at an increased risk for an array of neurologic disorders at 12 months, even in those who were not hospitalized during the acute phase of the infection.
Mounting research shows that COVID-19 leaves its mark on the brain, including with significant drops in IQ scores
Two new high-profile studies add to the increasingly worrisome picture of how even mild cases of COVID-19 can have detrimental effects on brain health.
COVID-19 vaccines and adverse events of special interest: A multinational Global Vaccine Data Network (GVDN) cohort study of 99 million vaccinated individuals - PubMed
This multi-country analysis confirmed pre-established safety signals for myocarditis, pericarditis, Guillain-Barré syndrome, and cerebral venous sinus thrombosis. Other potential safety signals that require further investigation were identified.
Long Covid: Gestörte Blutversorgung im Hirn wohl Grund für Bewusstseinstrübungen
Erinnerungs- und Konzentrationsprobleme sind häufige Beschwerden bei Long Covid. Laut einer Studie ist eine gestörte Blutversorgung im Gehirn hierfür mitursächlich.
Clinical characteristics of 4,520 paediatric patients infected with the SARS-CoV-2 omicron variant, in Xi'an, China
Background and objectiveSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has broad tissue tropism and high transmission, which are likely to perpetuate the pandemic. The study aim to analyze the clinicopathogenic characteristics in paediatric patients.MethodsIn this single-centre study, we retrospectively included all confirmed cases infected by SARS-CoV-2 infection at Xi’an Children's Hospital, China, from 1 December to 31 December 2022. The demographic, clinical, laboratory, and radiological features of the patients were analysed.ResultsA total of 4,520 paediatric patients with SARS-CoV-2 omicron variant infections were included. Of these, 3,861 (85.36%) were outpatients, 659 (14.64%) were hospitalised patients, and nine patients (0.20%) died. Of the nine patients who died, five were diagnosed with acute necrotising encephalopathy (ANE). The most common symptoms were fever in 4,275 (94.59%) patients, cough in 1,320 (29.20%) patients, convulsions in 610 (13.50%) patients, vomiting in 410 (9.07%) patients, runny nose/coryza in 277 (6.13%) patients, hoarseness of voice in 273 (6.04%) patients. A blood cell analysis showed a slight elevation of monocytes (mean: 11.14 ± 0.07%). The main diagnoses for both outpatients and inpatients were respiratory infection with multisystem manifestations.ConclusionsA high incidence of convulsions is a typical characteristic of children infected with SARS-CoV-2. Five of the nine COVID-19 fatalities were associated with ANE. This ...
The long-term neurodevelopmental outcomes of toddlers with SARS-CoV-2 infection in the neonatal period: a prospective observational study - Italian Journal of Pediatrics
Background The effect of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) virus in the neonatal period on developing brain is still unknown. This study aims to investigate the long-term neurodevelopmental outcomes of newborns exposed to SARS-CoV-2 & Delta variant. Methods At a tertiary referral center, a prospective observational cohort research was carried out. All babies who were equal to or more than 34 gestational weeks gestation and were admitted to the NICU between January 2021 and January 2022 due to SARS-CoV-2 infection (Delta - or Delta +) were included in the study. Infants who were hospitalized for non-SARS-CoV-2 reasons at similar dates and who had no history of invasive mechanical ventilation were incorporated as a control group using a 2:1 gender and gestational age match. Thirty infants were assigned to the study group and sixty newborns to the control group based on the sample size calculation. These toddlers’ neurodevelopment was evaluated between the ages of 18 and 24 months using the Bayley-II scale. Results We enrolled 90 infants. SARS-CoV-2-positive infants had poorer psychomotor development index (PDI) scores and significantly greater mildly delayed performances (MDPs) at 18–24 months (PDI p = 0.05, MDPs p = 0.03, respectively). Delta variant showed statistically significant lower MDI and PDI scores (MDI p=0.03, PDI p=0.03, respectively). A smaller head circumference of SARS-CoV-2-positive toddlers was detected in the first year (p
SARS-CoV-2-infection- and vaccine-induced antibody responses are long lasting with an initial waning phase followed by a stabilization phase
SARS-CoV-2 mRNA-based vaccine-induced immunity is thought to wane quickly based on short-term studies. Using longitudinal data, Srivastava et al. find that participants with hybrid immunity show faster, higher antibody responses after initial vaccination, but boosters evened out differences. Modeling of antibody kinetics revealed an initial rapid decay followed by a stabilization phase, challenging the idea that vaccine immunity fades quickly.
Yang and colleagues demonstrate that SARS-CoV-2 can infect hPSC-derived midbrain dopamine
(DA) neurons and induce cellular senescence. Several drug candidates were identified
to rescue SARS-CoV-2 infection and DA neuron senescence. Inflammation and cellular
senescence were also identified in substantia nigra tissue of COVID-19 patients.
Robust SARS-CoV-2 Neutralizing Antibodies Sustained through Three Months Post XBB.1.5 mRNA Vaccine Booster
SARS-CoV-2-neutralizing antibodies were substantially expanded one month after a shot of XBB.1.5 monovalent mRNA vaccine (XBB.1.5 MV) booster, but the durability of this response remained unknown. Here, we addressed this question by performing neutralization assays on four viral variants (D614G, BA.5, XBB.1.5, and JN.1) using sera from 39 adult participants obtained at ∼1 month and ∼3 months post an XBB.1.5 MV booster. Our findings indicate that the resultant neutralizing antibody titers were robust and generally maintained at stable levels for the study period, similar to those following XBB infection. Importantly, this durability of neutralizing antibody titers contrasts with the decline observed after a booster of the original monovalent or BA.5 bivalent mRNA vaccine. Our results are in line with the recent national data from the Centers for Disease Control and Prevention, showing the efficacy against symptomatic SARS-CoV-2 infection is sustained for up to 4 months after an XBB.1.5 MV booster. ### Competing Interest Statement D.D.H. is a co-founder of TaiMed Biologics and RenBio, consultant to WuXi Biologics and Brii Biosciences, and board director for Vicarious Surgical. Aubree Gordon served on a scientific advisory board for Janssen Pharmaceuticals. Other authors declare no competing interests.
Connecticut University researchers report that teachers are 13% more likely to die from lupus, multiple sclerosis, rheumatoid arthritis and other autoimmune diseases than other professionals. Secondary school teachers were at the greatest risk: those 35–44 years old were 143% more likely to die from autoimmune disease. The researchers speculate that teachers might have an increased risk as they are exposed to a large variety of viruses on a frequent basis. Some studies have linked Epstein–Barr virus to multiple sclerosis. Epstein–Barr virus is more common among secondary school age children than younger children, which could explain why secondary school teachers are more likely to die from autoimmune disease than are infant school teachers. However, a teacher's overall risk for dying from autoimmune disease is low. AV
Post-COVID cognitive deficits at one year are global and associated with elevated brain injury markers and grey matter volume reduction: national prospective study
The spectrum, pathophysiology, and recovery trajectory of persistent post-COVID-19 cognitive deficits are unknown, limiting our ability to develop prevention and treatment strategies. We report the one-year cognitive, serum biomarker, and neuroimaging findings from a prospective, national long...
Immune escape of Omicron lineages BA.1, BA.2, BA.5.1, BQ.1, XBB.1.5, EG.5.1 and JN.1.1 after vaccination, infection and hybrid immunity
Since their emergence in late 2021, SARS-CoV-2 Omicron replaced earlier variants of concern and marked a new phase in the SARS-CoV-2 pandemic. Until the end of 2023, Omicron lineages continue to circulate and continue to evolve, with new lineages causing infection waves throughout 2022 and 2023. In the population, this leads to a complex immunological exposure background, characterized by immunity derived through vaccination, in the 5th year of the pandemic in the majority of individuals followed by at least one or even multiple infections or only natural infection in individuals that did not receive a vaccine. In this study, we use eight authentic SARS-CoV-2 isolates (ancestral lineage B.1 and the seven Omicron lineages BA.1, BA.2, BA.5.1, BQ.1, XBB.1.5, EG.5.1 and JN.1.1) in a live virus neutralization assay to study immune escape in 97 human sera or plasma of different immunological backgrounds (vaccination, hybrid immunity due to one or two natural infections and natural infection without vaccination in children and adults). We showed a gradually increasing immune escape after vaccination and hybrid immunity in from B.1 to BA.1/BA.2 to BA.5.1 to BQ.1 to XBB.1.5 to EG.5.1, but remarkably, no more enhanced immune escape of JN.1.1 compared to EG.5.1, with the latter two showing almost identical neutralization titers in individuals with hybrid immunity due to one or more infections. In vaccinated but never infected individuals, neutralization was markedly reduced or completely lost for XBB.1.5., EG.5.1 and JN.1.1, while in those with hybrid immunity, titers were reduced but almost all sera still showed some degree of neutralization. After a single infection without vaccination, reduced or complete loss of neutralization occurred for BQ.1, XBB.1.5, EG.5.1 and JN.1.1 compared to BA.1/BA.2. Furthermore, we observed that, although absolute titers differed between groups, the pattern of immune escape between the variants remains comparable across groups, with strongest loss of neutralization for BQ.1, XBB.1.5, EG.5.1 and JN.1.1 was observed across the different immunological backgrounds. Our results show gradually increasing antibody escape of evolving Omicron lineages over the last two years of Omicron circulation until variant EG.5.1, but not anymore for the currently dominant lineages JN.1.1, suggesting other mechanisms than immune escape to be behind the rapid global emergence of JN.1. ### Competing Interest Statement IE has received research funding and speakers fees from Moderna for an unrelated research project (IIS). CSE received funding from Pfizer for an unrelated research project (IIS). All other authors: No conflict of interest.
Prevalence of persistent SARS-CoV-2 in a large community surveillance study
Nature - Using viral sequence data, individuals with persistent SARS-CoV-2 infections were identified, and had higher odds of self-reporting long COVID, in a large community surveillance study.
Dr.med.Hank Schiffers, MD, MBA, Lean Sensei on Twitter / X
#LongCovid #Leistungssport #COVIDistnichtMild - Kanutin Kriegerstein beendet KarriereStand: 17.08.2022 13:01 UhrDie Kanu-Olympia-Zweite von Rio de Janeiro, Steffi Kriegerstein, hat ihre Karriere wegen der Folgen einer Corona-Infektion beendet. Seehttps://t.co/EtxCSXdaov— Dr.med.Hank Schiffers, MD, MBA, Lean Sensei (@leanhealth) February 20, 2023
A clot too far: An embalmer dissects antivax misinformation about blood clots in Died Suddenly | Science-Based Medicine
"Died Suddenly" features embalmers claiming that COVID-19 vaccines cause massive deadly clots, SBM has recruited an experienced embalmer to dissect the claims.
No apparent association between mRNA COVID-19 vaccination and venous thromboembolism
By January 2022 over ten billion doses of COVID-19 vaccines had been administered worldwide. Concerns about COVID-19 vaccine-associated thrombosis aro…
Record long-term sickness bodes ill for UK economic growth
Years of austerity, followed by Covid, have left Britain with unhealthy workers and businesses struggling to recruit, but the road to recovery, of all kinds, will be long