Covid19-Sources

Negativer Effekt: Eine zu salzreiche Kost kann die Energieversorgung wichtiger Kontrollzellen unseres Immunsystems schwächen – und dadurch

Scientific Reports - Cerebral hypoperfusion in post-COVID-19 cognitively impaired subjects revealed by arterial spin labeling MRI

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Aim To evaluate the effect of vaccination/booster administration dynamics on the reduction of excess mortality during COVID-19 infection waves in European countries. Methods We selected twenty-nine countries from the OurWorldInData project database according to their population size of more than one million and the availability of information on dominant SARS-CoV-2 variants during COVID-19 infection waves. After selection, we categorized countries according to their “faster” or “slower” vaccination rates. The first category included countries that reached 60% of vaccinated residents by October 2021 and 70% by January 2022. The second or “slower” category included all other countries. In the first or “faster” category, two groups, “boosters faster’’ and “boosters slower” were created. Pearson correlation analysis, linear regression, and chi-square test for categorical data were used to identify the association between vaccination rate and excess mortality. We chose time intervals corresponding to the dominance of viral variants: Wuhan, Alpha, Delta, and Omicron BA.1/2. Results The “faster” countries, as opposed to the “slower” ones, did better in protecting their residents from mortality during all periods of the SARS-CoV-2 pandemic and even before vaccination. Perhaps higher GDP per capita contributed to their better performance throughout the pandemic. During mass vaccination, when the Delta variant prevailed, the contrast in mortality rates between the “faster” and “slower” categories was strongest. The average excess mortality in the “slower” countries was nearly 5 times higher than in the “faster” countries, and the odds ratio (OR) was 4.9 (95% CI 4.4 to 5.4). Slower booster rates were associated with significantly higher mortality during periods dominated by Omicron BA.1 and BA.2, with an OR of 2.6 (CI 95%. 2.1 to 3.3). Among the European countries we analyzed, Denmark, Norway, and Ireland did best, with a pandemic mortality rate of 0.1% of the population or less. By comparison, Bulgaria, Serbia, and Russia had a much higher mortality rate of up to 1% of the population. Thus, slow vaccination and booster administration was a major factor contributing to an order of magnitude higher excess mortality in “slower” European countries compared to more rapidly immunized countries. ![Figure][1] ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Intramural Research Program of the National Library of Medicine, National Institutes of Health (SAS). ### 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: OurWorldinData public data depository. https://ourworldindata.org/coronavirus World bank open data https://data.worldbank.org/ 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, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data used in the study are from public resources and open-access databases. https://ourworldindata.org/coronavirus https://data.worldbank.org/ [1]: pending:yes

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) possess mutations that confer resistance to neutralizing antibodies within the Spike protein and are associated with breakthrough infection and reinfection. By contrast, less is known about the escape from CD8+ T cell-mediated immunity by VOC. Here, we demonstrated that all SARS-CoV-2 VOCs possess the ability to suppress major histocompatibility complex class I (MHC-I) expression. We identified several viral genes that contribute to the suppression of MHC I expression. Notably, MHC-I upregulation was strongly inhibited after SARS-CoV-2 but not influenza virus infection in vivo. While earlier VOCs possess similar capacity as the ancestral strain to suppress MHC-I, the Omicron subvariants exhibited a greater ability to suppress surface MHC-I expression. We identified a common mutation in the E protein of Omicron that further suppressed MHC-I expression. Collectively, our data suggest that in addition to escaping from neutralizing antibodies, the success of Omicron subvariants to cause breakthrough infection and reinfection may in part be due to its optimized evasion from T cell recognition.

Mortality Data Many Countries

Bis November 2022 gab es in Deutschland rund 36 Millionen offiziell registrierte SARS-CoV-2-Infektionen (1). Der Anteil unerkannter Infektionen wird auf das 1,5- bis 4-fache der erfassten Fälle geschätzt (2, 3). Der Anteil der nicht erfassten Fälle...

This study uses data from the US Department of Veterans Affairs to assess whether SARS-CoV-2 remains associated with higher risk of death compared with seasonal influenza in fall-winter 2022-2023.

Background: Different SARS-CoV-2 variants can differentially affect the prevalence of Post Covid-19 Condition (PCC). This prospective study assesses prevalence and severity of symptoms three months after an Omicron infection, compared to Delta, test-negative and population controls. This study also assesses symptomology after reinfection and breakthrough infections . Methods: After a positive SARS-CoV-2 test, cases were classified as Omicron or Delta based on ≥ 85% surveillance prevalence. Population controls were representatively invited and symptomatic test-negative controls enrolled after a negative SARS-CoV-2 test. Three months after enrolment, participants indicated point prevalence for 41 symptoms and severity of four symptoms. Permutation tests identified significantly elevated symptoms in cases compared to controls. PCC prevalence was estimated as the difference in prevalence of at least one elevated symptom in cases compared to population controls. Findings: At three months follow-up, five symptoms and severe dyspnea were significantly elevated in Omicron cases (n = 4138) compared to test-negative (n= 1672) and population controls (n= 2762). PCC prevalence was 10.4% for Omicron cases and 17.7% for Delta cases (n = 6855). Prevalence of severe fatigue and dyspnea were higher in reinfected compared to primary infected Omicron cases, while severity of symptoms did not significantly differ between Omicron cases with a booster or primary vaccination course. Interpretation: Three months after Omicron, prevalence of PCC is 41% lower than after Delta. Reinfection seems associated with more prevalent severe long-term symptoms compared to a first infection. A booster prior to infection does not seem to improve the outcome of long-term symptoms. Funding: The study is executed by the National Institute for Public Health and the Environment by order of the Ministry of Health, Welfare and Sport. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement The study is executed by the National Institute for Public Health by order of the Ministry of Health. The study is not the result of a competitive grant. The Dutch Ministry of Health, Welfare and Sport does not have a role in the design of this study, its execution, analyses and interpretation of results. ### 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: Utrecht Medical Ethics Committee of NedMec gave ethical approval for this work (protocol number 21-124/C) 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, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Supporting clinical documents including the study protocol and statistical analysis plan will be available immediately following publication of this Article for at least 1 year. Researchers who provide a methodologically sound proposal will within the applicable privacy legislation be allowed to access to the de-identified individual participant data that underlie the results reported in this article. Proposals should be sent to the corresponding author. These proposals will be reviewed and approved by the investigators on the basis of scientific merit. To gain access, data requestors will need to sign a data access agreement.

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has been associated mainly with a range of neurological symptoms, including brain fog and brain tissue loss, raising concerns about the virus's acute and potential chronic impact on the central nervous system. In this study, we utilized mouse models and human post-mortem tissues to investigate the presence and distribution of the SARS-CoV-2 spike protein in the skull-meninges-brain axis. Our results revealed the accumulation of the spike protein in the skull marrow, brain meninges, and brain parenchyma. The injection of the spike protein alone caused cell death in the brain, highlighting a direct effect on brain tissue. Furthermore, we observed the presence of spike protein in the skull of deceased long after their COVID-19 infection, suggesting that the spike's persistence may contribute to long-term neurological symptoms. The spike protein was associated with neutrophil-related pathways and dysregulation of the proteins involved in the PI3K-AKT as well as complement and coagulation pathway. Overall, our findings suggest that SARS-CoV-2 spike protein trafficking from CNS borders into the brain parenchyma and identified differentially regulated pathways may present insights into mechanisms underlying immediate and long-term consequences of SARS-CoV-2 and present diagnostic and therapeutic opportunities. ### Competing Interest Statement The authors have declared no competing interest.

Long covid follows 10-20% of first-time SARS-CoV-2 infections, but the societal burden of long covid and risk factors for the condition are not well-understood. Here, we report findings about self-reported sick leave and risk factors thereof from a hybrid survey and register study, which included 37,482 RT- PCR confirmed SARS-CoV-2 cases and 51,336 test-negative controls who were tested during the index and alpha waves. An additional 33 individuals per 1000 took substantial sick leave following acute infection compared to persons with no known history of infection, where substantial sick leave was defined as 1 month of sick leave within the period 1-9 months after the RT-PCR test date. Being female, ≥50 years, and having certain pre-existing conditions such as fibromyalgia increased risks for taking substantial sick leave. Further research exploring this heterogeneity is urgently needed and may provide important evidence for more targeted preventative strategies. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement No specific funding was received for this work. The study was conducted as part of the advisory tasks of the governmental institution Statens Serum Institut for the Danish Ministry of Health. ### 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: Ethics approval This study was performed as a surveillance study as part of the advisory tasks conducted by the governmental institution Statens Serum Institut (SSI) for the Danish Ministry of Health. The purpose of Statens Serum institut is to monitor and fight the spread of disease in accordance with section 222 of the Danish Health Act. According to Danish law, national surveillance activities carried out by SSI do not require approval from an ethics committee. Participation in the study was voluntary. The invitation letter to participants contained information about their rights under the Danish General Data Protection Regulation (rights to access data, rectification, deletion, restriction of processing and objection). After reading this information, it was considered informed consent if participants agreed and clicked on the link to fill in the questionnaires. 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, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The datasets used in this study comprise sensitive, individual-level information from completed questionnaires and national register data. According to the Danish data protection legislation, the authors are not permitted to share these sensitive data directly upon request. However, the data are available for research purposes upon request to the Danish Health Authority (register data, email: kontakt@sundhedsdata.dk) and Statens Serum Institut (questionnaire data, email: aii@ssi.dk), as well as within the framework of the Danish data protection legislation and any required permission from authorities. Data request processing can take an expected three to six months.

Nature Microbiology - Comparison of mucosal and systemic immunity after vaccination with the live-attenuated vaccine sCPD9, mRNA vaccine BNT162b2 or an adenovirus-vectored vaccine following...

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Successful COVID-19 prevention requires additional measures beyond vaccination, social distancing, and masking. A nasal spray solution containing human IgG1 antibodies against SARS-CoV-2 (COVITRAP™) was developed to strengthen other COVID-19 preventive arsenals. Here, we evaluated its pseudovirus neutralization potencies, preclinical and clinical safety profiles, and intranasal SARS-CoV-2 inhibitory effects in healthy volunteers ([NCT05358873][1]). COVITRAP™ exhibited broadly potent neutralizing activities against SARS-CoV-2 with PVNT50 values ranging from 0.0035 to 3.1997 μg/ml for the following variants of concern (ranked from lowest to highest): Alpha, Beta, Gamma, Ancestral, Delta, Omicron BA.1, Omicron BA.2, Omicron BA.4/5, and Omicron BA.2.75. It demonstrated satisfactory preclinical safety profiles based on evaluations of in vitro cytotoxicity, skin sensitization, intracutaneous reactivity, and systemic toxicity. Its intranasal administration in rats did not yield any detected circulatory levels of the human IgG1 anti-SARS-CoV-2 antibodies at any time point during the 120 hours of follow-up. A double-blind, randomized, placebo-controlled trial (RCT) was conducted on 36 healthy volunteers who received either COVITRAP™ or a normal saline nasal spray at a 3:1 ratio. Safety of the thrice-daily intranasal administration for 7 days was assessed using nasal sinuscopy, adverse event recording, and self-reporting questionnaires. COVITRAP™ was well tolerated, with no significant adverse effects in healthy volunteers for the entire 14 days of the study. The intranasal SARS-CoV-2 inhibitory effects of COVITRAP™ were evaluated in nasal fluids taken from volunteers pre- and post-administration using a SARS-CoV-2 surrogate virus neutralization test. SARS-CoV-2 inhibitory effects in nasal fluids collected immediately or six hours after COVITRAP™ application were significantly increased from baseline for all three variants tested, including Ancestral, Delta, and Omicron BA.2. In conclusion, COVITRAP™ was safe for intranasal use in humans to provide SARS-CoV-2 inhibitory effects in nasal fluids that lasted at least six hours. Therefore, COVITRAP™ can be considered an integral instrument for COVID-19 prevention. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT05358873 ### Funding Statement This study was sponsored by HIBIOCY Co., Ltd., and funded by the Program Management Unit Competitiveness (PMU-C) [Grant No. C10F650051], Ministry of Higher Education, Science, Research and Innovation, Thailand. ### 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: Ethics committee/IRB of the Department of Medical Services, Ministry of Public Health, Thailand gave ethical approval for this work. 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 work are contained in the manuscript. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT05358873&atom=%2Fmedrxiv%2Fearly%2F2022%2F10%2F05%2F2022.10.04.22280574.atom

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Due to the health crisis caused by SARS-CoV-2, the creation of a new vaccine platform based on mRNA was implemented. Globally, around 13.32 billion COVID-19 vaccine doses of diverse platforms have been given, and up to this date, 69.7% of the total population received at least one injection of a COVID-19 vaccine. Although these vaccines prevent hospitalization and severe forms of the disease, increasing evidence has shown they do not produce sterilizing immunity, allowing people to suffer frequent re-infections. Recent research has also raised concerns that mRNA vaccines could induce immune tolerance, which, added to that caused by the virus itself, could complicate the clinical course of a COVID-19 infection. Furthermore, recent investigations have found high IgG4 levels in people who were administered two or more injections of mRNA vaccines. 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. Altogether, evidence suggests that the reported increase in the IgG4 levels detected after repeated vaccination with the mRNA vaccines is not a protective mechanism; rather, it may be a part of the immune tolerance mechanism to the spike protein that could promote unopposed SARS-CoV2 infection and replication by suppressing natural antiviral responses. IgG4-induced suppression of the immune system due to repeated vaccination can also cause autoimmune diseases, promotes cancer growth, and autoimmune myocarditis in susceptible individuals.

On Feb 16, 2023, WHO issued a new clinical case definition for post-COVID-19 condition, also known as long COVID, in children and adolescents. It stated that the condition occurs in “individuals with a history of confirmed or probable SARS-CoV-2 infection, when experiencing symptoms lasting at least 2 months which initially occurred within 3 months of acute COVID-19”. Fatigue, altered smell or anosmia, and anxiety were picked out as being the symptoms most strongly associated with post-COVID-19 condition in children and adolescents.

Nature Genetics - The canonical BRG1/BRM-associated factor (cBAF) complex is recruited by HNF1A/B to angiotensin-converting enzyme 2 (ACE2) enhancers, promoting severe acute respiratory syndrome...

Diagnose-Hilfe: Wegen ihrer oft unspezifischen und vielfältigen Symptome sind Spätfolgen einer Corona-Infektion oft schwer eindeutig zu diagnostizieren.

COVID-19 kann zahlreiche Organe betreffen – aber begünstigt die Erkrankung auch kardiovaskuläre Ereignisse? Die bisher größte Analyse zum Thema, die

This work can help explain why some people continue to test positive for COVID-19 months after their infection seems to have resolved. | Coronavirus

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID patients have overlapping neurological, autonomic, pain, and post-exertional symptoms. We compared volumes of brainstem regions for 10 ME/CFS (CCC or ICC criteria), 8 long COVID (WHO Delphi consensus), and 10 healthy control (HC) subjects on 3D, T1-weighted MRI images acquired using sub-millimeter isotropic resolution using an ultra-high field strength of 7 Tesla. Group comparisons with HC detected significantly larger volumes in ME/CFS for pons (p = 0.004) and whole brainstem (p = 0.01), and in long COVID for pons (p = 0.003), superior cerebellar peduncle (p = 0.009), and whole brainstem (p = 0.005). No significant differences were found between ME/CFS and long COVID volumes. In ME/CFS, we detected positive correlations between the pons and whole brainstem volumes with “pain” and negative correlations between the midbrain and whole brainstem volumes with “breathing difficulty.” In long COVID patients a strong negative relationship was detected between midbrain volume and “breathing difficulty.” Our study demonstrated an abnormal brainstem volume in both ME/CFS and long COVID consistent with the overlapping symptoms.

Profound immune dysregulation and inflammation points a finger at a viral reservoir, viral reactivation or autoimmunity in long COVID.

As an important part of adaptive immunity, T cells are indispensable in the defense against pathogens including viruses. SARS-CoV-2 is a new human coronavirus that occurred at the end of 2019 and has caused the COVID-19 pandemic. Nevertheless, most of the infected patients recovered without any antiviral therapies, suggesting an effective immunity developed in the bodies. T cell immunity responds upon SARS-CoV-2 infection or vaccination and plays crucial roles in eliminating the viruses and generating T cell memory. Specifically, a subpopulation of CD4+ T cells could support the production of anti-SARS-CoV-2 antibodies, and cytotoxic CD8+ T cells are also protective against the infection. SARS-CoV-2–recognizing T cells could be detected in SARS-CoV-2–unexposed donors, but the role of these cross-reactive T cells is still in debate. T cell responses could be diverse across individuals, mainly due to the polymorphism of HLAs. Thus, compared to antibodies, T cell responses are generally less affected by the mutations of SARS-CoV-2 variants. Up to now, a huge number of studies on SARS-CoV-2–responsive T cells have been published. In this review, we introduced some major findings addressing the questions in the main aspects about T cell responses elicited by SARS-CoV-2, to summarize the current understanding of COVID-19.

Nature Medicine - With the lifting of the zero-COVID policy and requirements governing reporting case numbers in China, it has become imperative to estimate the dynamics and cumulative infection...

TOKYO -- Nerve disorder symptoms experienced by some COVID-19 patients may be caused by the infection of immune system cells that clean up the brain, ･･･

COVID-19 causes neurological damage, systemic inflammation, and immune cell abnormalities. COVID-19-induced neurological impairment may be caused by s…

Journal of Molecular Medicine - Studies showed that SARS-CoV-2 can directly target the kidney and induce renal damage. As the cell surface receptor for SARS-CoV-2 infection, the...

Background Vaccines against SARS-CoV-2 have been shown to reduce risk of infection as well as severe disease among those with breakthrough infection in adults. The latter effect is particularly important as immune evasion by Omicron variants appears to have made vaccines less effective at preventing infection. Therefore, we aimed to quantify the protection conferred by mRNA vaccination against hospitalization due to SARS-CoV-2 in adolescent and pediatric populations. Methods We retrospectively created a cohort of reported SARS-CoV-2 case records from Ontario’s Public Health Case and Contact Management Solution among those aged 4 to 17 linked to vaccination records from the COVaxON database on January 19, 2022. We used multivariable logistic regression to estimate the association between vaccination and hospitalization among SARS-CoV-2 cases prior to and during the emergence of Omicron. Results We included 62 hospitalized and 27,674 non-hospitalized SARS-CoV-2 cases, with disease onset from May 28, 2021 to December 4, 2021 (Pre-Omicron) and from December 23, 2021 to January 9, 2022 (Omicron). Among adolescents, two mRNA vaccine doses were associated with an 85% (aOR = 0.15; 95% CI: [0.04, 0.53]; p

The objective of the current investigation was to examine associations between symptomatic COVID-19 history, neurocognitive function, and psychiatric …