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Correspondence from The New England Journal of Medicine — Neutralization of the SARS-CoV-2 Mu Variant by Convalescent and Vaccine Serum

This Medical News article discusses the stress and grief reactions that children and teens face after losing a parent or close caregiver to COVID-19.

Original Article from The New England Journal of Medicine — Waning Immune Humoral Response to BNT162b2 Covid-19 Vaccine over 6 Months

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The durability of immune memory after SARS-CoV-2 mRNA vaccination remains unclear. Here, we longitudinally profiled vaccine responses in SARS-CoV-2 naïve and recovered individuals for 6 months afte...

24049 samples from 8858 individuals (5549 who received a second dose of ChAdOx1 and 3205 BNT162b2) who remained anti-N negative were included in the analysis of anti-S waning over time. Three weeks after the second dose of vaccine BNT162b2 mean anti-S levels were 9039 (95%CI: 7946-10905) U/ml and ChadOx1 were 1025 (95%CI: 917-1146) U/ml. For both vaccines, waning anti-S levels followed a log linear decline from three weeks after the second dose of vaccination. At 20 weeks after the second dose of vaccine, the mean anti-S levels were 1521 (95%CI: 1432-1616) U/ml for BNT162b2 and 342 (95%CI: 322-365) U/ml for ChadOx1. We identified 197 breakthrough infections and found a reduced risk of infection post second dose of vaccine for individuals with anti-S levels greater than or equal to 500 U/ml compared to those with levels under 500 U/ml (HR 0.62; 95%CIs:0.44-0.87; p=0.007). Time to reach an anti-S threshold of 500 U/ml was estimated at 96 days for ChAdOx1 and 257 days for BNT162b2. We found an increased risk of a breakthrough infection for those who received the ChAdOx1 compared to those who received BNT162b2 (OR: 1.43, 95% CIs:1.18-1.73, p0.001).

Covid-19 and its effect on the brain can be serious, researchers are learning. Studies continue to discover more on long-term Covid and how it impacts patients.

Individuals with potential exposure to SARS-CoV-2 do not necessarily develop PCR or antibody positivity, suggesting some may clear sub-clinical infection before seroconversion. T-cells can contribute to the rapid clearance of SARS-CoV-2 and other coronavirus infections1–3. We hypothesised that pre-existing memory T-cell responses, with cross-protective potential against SARS-CoV-24–11, would expand in vivo to support rapid viral control, aborting infection. We measured SARS-CoV- 2-reactive T-cells, including those against the early transcribed replication transcription complex (RTC)12,13, in intensively monitored healthcare workers (HCW) remaining repeatedly negative by PCR, antibody binding, and neutralisation (seronegative HCW, SN-HCW). SN-HCW had stronger, more multispecific memory T-cells than an unexposed pre-pandemic cohort, and more frequently directed against the RTC than the structural protein-dominated responses seen post-detectable infection (matched concurrent cohort). SN-HCW with the strongest RTC-specific T-cells had an increase in IFI27, a robust early innate signature of SARS-CoV-214, suggesting abortive infection. RNA-polymerase within RTC was the largest region of high sequence conservation across human seasonal coronaviruses (HCoV) and SARS-CoV-2 clades. RNA-polymerase was preferentially targeted (amongst regions tested) by T-cells from pre-pandemic cohorts and SN-HCW. RTC epitope-specific T-cells cross-recognising HCoV variants were identified in SN-HCW. Enriched pre-existing RNA-polymerase-specific T-cells expanded in vivo to preferentially accumulate in the memory response after putative abortive compared to overt SARS-CoV-2 infection. Our data highlight RTC-specific T-cells as targets for vaccines against endemic and emerging Coronaviridae.

Some patients who have had COVID-19 develop symptoms resembling early Alzheimer's. Researchers are trying to figure out whether these people are more likely to develop the disease itself.

Während in Deutschland mit Booster-Impfungen auf die rasante Ausbreitung der aggressiven Delta-Variante reagiert wird, ist in Kolumbien eine andere Variante vorherrschend. Diese könnte im Pandemiegeschehen eine neue Herausforderung darstellen.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 231 million people globally, with more than 4.7 million deaths recorded by the World Health Organization as of 26 September 2021. In response to the pandemic, some countries (New Zealand, Vietnam, Taiwan, South Korea and others) have pursued suppression strategies, so-called Zero COVID policies, to drive and maintain infection rates as close to zero as possible and respond aggressively to new cases. In comparison, European countries and North America have adopted mitigation strategies (of varying intensity and effectiveness) that aim primarily to prevent health systems from being overwhelmed. With recent advances in our understanding of SARS-CoV-2 and its biology, and the increasing recognition there is more to COVID-19 beyond the acute infection, we offer a perspective on some of the long-term risks of mutational escape, viral persistence, reinfection, immune dysregulation and neurological and multi-system complications (Long COVID).

#CoronaInfo – eine Ansteckung mit dem Coronavirus SARS-CoV-2 kann viele Organe im Körper schädigen. Wie fast überall außerhalb der Atemwege ist auch beim Gehirn die Frage: verursacht das Virus den Schaden direkt, oder ist es wegen des fehlgeleiteten Immunsystems? … (1/9)

Tübingen – Wegen der verminderten Schutzwirkung der Coronaimpfstoffe gegen die Delta-Variante müssten sich mehr Menschen impfen lassen, um eine Herdenimmunität... #Studie #COVID19 #Impfen

Background The duration and magnitude of SARS-CoV-2 immunity after infection, especially with regard to the emergence of new variants of concern (VoC), remains unclear. Here, immune memory to primary infection and immunity to VoC was assessed in mild-COVID-19 convalescents one year after infection and in the absence of viral re-exposure or COVID-19 vaccination. Methods Serum and PBMC were collected from mild-COVID-19 convalescents at ~6 and 12 months after a COVID-19 positive PCR (n=43) and from healthy SARS-CoV-2-seronegative controls (n=15-40). Serum titers of RBD and Spike-specific Ig were quantified by ELISA. Virus neutralisation was assessed against homologous, pseudotyped virus and homologous and VoC live viruses. Frequencies of Spike and RBD-specific memory B cells were quantified by flow cytometry. Magnitude of memory T cell responses was quantified and phenotyped by activation-induced marker assay, while T cell functionality was assessed by intracellular cytokine staining using peptides specific to homologous Spike virus antigen and four VoC Spike antigens. Findings At 12 months after mild-COVID-19, 90% of convalescents remained seropositive for RBD-IgG and 88.9% had circulating RBD-specific memory B cells. Despite this, only 51.2% convalescents had serum neutralising activity against homologous live-SARS-CoV-2 virus, which decreased to 44.2% when tested against live B.1.1.7, 4.6% against B.1.351, 11.6% against P.1 and 16.2%, against B.1.617.2 VoC. Spike and non-Spike-specific T cells were detected in 50% of convalescents with frequency values higher for Spike antigen (95% CI, 0.29-0.68% in CD4+ and 0.11-0.35% in CD8+ T cells), compared to non-Spike antigens. Despite the high prevalence and maintenance of Spike-specific T cells in Spike 'high-responder' convalescents at 12 months, T cell functionality, measured by cytokine expression after stimulation with Spike epitopes corresponding to VoC was severely affected. Interpretations SARS-CoV-2 immunity is retained in a significant proportion of mild COVID-19 convalescents 12 months post-infection in the absence of re-exposure to the virus. Despite this, changes in the amino acid sequence of the Spike antigen that are present in current VoC result in virus evasion of neutralising antibodies, as well as evasion of functional T cell responses. ### Competing Interest Statement AS is currently a consultant for Gritstone, Flow Pharma, Arcturus, Epitogenesis, Oxfordimmunotech, Caprion and Avalia. La Jolla Institute for Immunology (AS and DW) has filed for patent protection for various aspects of T cell epitope and vaccine design work. Authors PGV, CMH, MGM, AELY, HB, ZAM, ZAD, AA, DA, AOS, AA, JG, CF, SO, EMM, DJL, GM, EJG, BAJR, DS, CKL, SGT, MRB, DW, RAB, SCB and BGB declare no conflict of interest. ### Funding Statement This work was funded by project grants from The Hospital Research Foundation and Women's and Children's Hospital Foundation, Adelaide, Australia. MGM is THRF Early Career Fellow. BGB is THRF Mid-Career Fellow. This project has been supported partly with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. 75N93021C00016 to A.S. and Contract No. 75N9301900065 to A.S, D.W. ### 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: Study protocols were approved by the Central Adelaide Clinical Human Research Ethics Committee (#13050) and the Women's and Children's Health Network Human research ethics (protocol HREC/19/WCHN/65), Adelaide, Australia. All participants provided written informed consent in accordance with the Declaration of Helsinki and procedures were carried out following the approved guidelines. 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

(1) Was sagen die Antikörperspiegel über meinen Schutz aus? Aktuell noch nicht viel, daher sollte man eine Booster Impfung auch nicht von einem Antikörpertest abhängig machen. ABER: Die Höher der Antikörper korreliert mit dem Schutz. Nur wie hoch ist gut?

Die Wissenschaft hat ihren Job gemacht, sagt der Virologe Christian Drosten im Gespräch mit der ZEIT. Der Impfstoff ist da. Was jetzt kommt, sei Sache der Politik.

Was macht das Immunsystem von geimpften Genesenen so besonders wirkungsvoll?

Twenty-five studies were included in the systematic review. The pooled seroconversion rates after two doses of mRNA vaccination were higher (83.1, 95%CI: 74.9–89.0, I2 =90%) as compared to a single dose (69.3, 52.4–82.3, I2 = 95%). The odds of seroconversion were lower in IMIDs as compared to healthy controls (0.05, 0.02–0.13, I2 = 21%). The seroconversion rates in patients with inflammatory bowel disease (95.2, 95%CI: 92.6–96.9, I2 = 0%), spondyloarthropathy (95.6, 95% CI: 83.4–98.9, I2 = 35%), and systemic lupus erythe- matosus (90.7, 95%CI: 85.4–94.2, I2 = 0%) were higher as compared to rheumatoid arthritis (79.5, 95% CI: 65.1–88.9, I2 = 85%), and vasculitis (70.5, 95% CI: 52.9–83.5, I2 = 51%). The seroconversion rates following double dose of mRNA were excellent (90%) in those on anti-tumour necrosis factor (TNF), anti-integrin (vedolizumab), anti-IL 17 (secukinumab), anti-IL6 (Tocilizumab) and anti-IL12/23 (Ustekinumab) therapies but attenuated (70%) in patients on anti-CD20 (Rituximab) or anti-cytotoxic T lymphocyte associated antigen (CTLA-4) therapies (Abatacept). The seroconversion rates were good (70–90%) with steroids, hydroxy- chloroquine, JAK inhibitors, mycophenolate mofetil and leflunomide. Combination of anti-TNF with immuno- modulators (azathioprine, 6-meracptopurine, methotrexate) resulted in an attenuated vaccine response as compared to anti-TNF monotherapy. Conclusion: Seroconversion rates after SARS-CoV-2 vaccination are lower in patients with IMIDs. Certain ther- apies (anti-TNF, anti-integrin, anti-IL 17, anti-IL6, anti-12/23) do not impact seroconversion rates while others (anti-CD20, anti-CTLA-4) result in poorer responses.

The findings of this study suggest that the use of heterologous ChAdOx1 nCoV-19 and mRNA prime-boost vaccination is an effective alternative to increase population immunity against Covid-19, including against the Delta variant which dominated the confirmed cases during the study period. These findings could have important implications for vaccination strategies and logistics, and consequently in the battle against the Covid-19 pandemic.

Dr. Maura Boldrini is studying the brains of people who died of COVID-19 to better understand how it causes neurological symptoms.

At the country-level, there appears to be no discernable relationship between percentage of population fully vaccinated and new COVID-19 cases in the last 7 days (Fig. 1). In fact, the trend line suggests a marginally positive association such that countries with higher percentage of population fully vaccinated have higher COVID-19 cases per 1 million people. Notably, Israel with over 60% of their population fully vaccinated had the highest COVID-19 cases per 1 million people in the last 7 days. The lack of a meaningful association between percentage population fully vaccinated and new COVID-19 cases is further exemplified, for instance, by comparison of Iceland and Portugal. Both countries have over 75% of their population fully vaccinated and have more COVID-19 cases per 1 million people than countries such as Vietnam and South Africa that have around 10% of their population fully vaccinated.

This study provided in-vivo evidence that inadvertent intravenous injection of COVID-19 mRNA-vaccines may induce myopericarditis. Brief withdrawal of syringe plunger to exclude blood aspiration may be one possible way to reduce such risk.

In the context of a hospital and ICU surge, a multidisciplinary daily plan supported by a dedicated critical care outreach team was associated with a low rate of cardiac arrest calls, no emergency intubations in the ward, and appropriate palliative care support for subjects with a ceiling of care de …

(1/x) Vor einem Jahr haben wir bereits mitgeteilt, dass man ohne weitere Präventionsmaßnahmen die Anzahl von #SARSCoV2 in der Raumluft nur mit sehr viel virenfreier Luftzufuhr und damit Abfuhr von virenhaltiger Luft benötigt, um einen Ausbruch über Aerosol zu verhindern.— Martin Kriegel (@KriegelMartin) November 6, 2021

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Nature Communications - Most people who are infected with SARS-CoV-2 seroconvert within a few weeks, but the determinants and duration of the antibody response are not known. Here, the authors...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing a worldwide epidemic. It spreads very fast and hits people of all ages, especially patients with underlying diseases such as diabetes. In this review, we focus on the influences of diabetes on the outcome of SARS-CoV-2 infection and the involved mechanisms including lung dysfunction, immune disorder, abnormal expression of angiotensin-converting enzyme 2 (ACE2), overactivation of mechanistic target of rapamycin (mTOR) signaling pathway, and increased furin level. On the other hand, SARS-CoV-2 may trigger the development of diabetes. It causes the damage of pancreatic β cells, which is probably mediated by ACE2 protein in the islets. Furthermore, SARS-CoV-2 may aggravate insulin resistance through attacking other metabolic organs. Of note, certain anti-diabetic drugs (OADs), such as peroxisome proliferator-activated receptor γ (PPARγ) activator and glucagon-like peptide 1 receptor (GLP-1R) agonist, have been shown to upregulate ACE2 in animal models, which may increase the risk of SARS-CoV-2 infection. However, Metformin, as a first-line medicine for the treatment of type 2 diabetes mellitus (T2DM), may be a potential drug benefiting diabetic patients with SARS-CoV-2 infection, probably via a suppression of mTOR signaling together with its anti-inflammatory and anti-fibrosis function in lung. Remarkably, another kind of OADs, dipeptidyl Peptidase 4 (DPP4) inhibitor, may also exert beneficial effects in ...