Covid19-Sources

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.

Long COVID isn't novel: other viruses in history have had similar “long” arcs — with devastating repercussions

Brain changes including shrinkage, weakened connections and poorer performance on thinking and memory tests could explain ‘brain fog’ after COVID – even after ‘mild’ cases.

A team of scientists, led by researchers from East Carolina University’s Brody School of Medicine, have identified another problem stemming from COVID-19 infections — the potential for greater risk of Parkinson’s disease. The ECU contingent of researchers — Dr. Jeffrey Eells, Dr. Shaw Akula, Dr. Srinivas Sriramula and Dr. Dorcas O’Rourke — were joined by […]

The risk of developing dementia, psychosis or brain fog remains higher for two years for patients who have had Covid-19 than it does for those with other

Well, the data is pretty clear.The little ones (0-4) are hard hit.https://t.co/Kmvqs43Unt pic.twitter.com/BFOQNUqDGh— 😺 Annika 🕊 (@AnnikaTyckerAtt) May 21, 2023

This cross-sectional study assesses whether COVID-19 booster vaccination of pregnant people is associated with spontaneous abortion.

Nonetheless, our findings suggest that the risk of spontaneous abortion after mRNA Covid-19 vaccination either before conception or during pregnancy is consistent with the expected risk of spontaneous abortion; these findings add to the accumulating evidence about the safety of mRNA Covid-19 vaccination in pregnancy.

Nature Cell Biology - Monocytes, plasmacytoid and conventional dendritic cells are crucial for antiviral immune responses. A new study now compares severe and moderate cases of COVID-19 and links...

Cellular & Molecular Immunology - Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection

The recently emerged SARS-CoV-2 causing the ongoing COVID-19 pandemic is particularly virulent in the elderly while children are largely spared. Here, we explored the potential role of cross-reactive immunity acquired from pediatric vaccinations and exposure to common human pathogens in the protection and pathology of COVID-19. To that end, we sought for peptide matches to SARS-CoV-2 (identity ≥ 80%, in at least eight residues) in the proteomes of 25 human pathogens and in vaccine antigens, and subsequently predicted their T and B cell reactivity to identify potential cross-reactive epitopes. We found that viruses subject to pediatric vaccinations do not contain cross-reactive epitopes with SARS-CoV-2, precluding that they can provide any general protection against COVID-19. Likewise, common viruses including rhinovirus, respiratory syncytial virus, influenza virus, and several herpesviruses are also poor or null sources of cross-reactive immunity to SARS-CoV-2, discarding that immunological memory against these viruses can have any general protective or pathological role in COVID-19. In contrast, we found combination vaccines for treating diphtheria, tetanus, and pertussis infectious diseases (DTP vaccine) to be significant sources of potential cross-reactive immunity to SARS-CoV-2. DTP cross-reactive epitopes with SARS-CoV-2 include numerous CD8 and CD4 T cell epitopes with broad population protection coverage and potentially neutralizing B cell epitopes in SARS-CoV-2 Sp...

I’ve created new SARS-CoV-2 antibody escape calculator (https://t.co/UNwCwr8m6B) with latest data from @yunlong_caoTLDR: look at image below for likely future sites of antigenic evolution in XBB spike.For details, read full thread below. pic.twitter.com/yB43xtDIuL— Bloom Lab (@jbloom_lab) May 16, 2023

Occurrence of hyperglycemia upon infection is associated with worse clinical outcome in COVID-19 patients. However, it is still unknown whether SARS-CoV-2 directly triggers hyperglycemia. Herein, we interrogated whether and how SARS-CoV-2 causes hyperglycemia by infecting hepatocytes and increasing glucose production. We performed a retrospective cohort study including patients that were admitted at a hospital with suspicion of COVID-19. Clinical and laboratory data were collected from the chart records and daily blood glucose values were analyzed to test the hypothesis on whether COVID-19 was independently associated with hyperglycemia. Blood glucose was collected from a subgroup of nondiabetic patients to assess pancreatic hormones. Postmortem liver biopsies were collected to assess the presence of SARS-CoV-2 and its transporters in hepatocytes. In human hepatocytes, we studied the mechanistic bases of SARS-CoV-2 entrance and its gluconeogenic effect. SARS-CoV-2 infection was independently associated with hyperglycemia, regardless of diabetic history and beta cell function. We detected replicating viruses in human hepatocytes from postmortem liver biopsies and in primary hepatocytes. We found that SARS-CoV-2 variants infected human hepatocytes in vitro with different susceptibility. SARS-CoV-2 infection in hepatocytes yields the release of new infectious viral particles, though not causing cell damage. We showed that infected hepatocytes increase glucose production and this is associated with induction of PEPCK activity. Furthermore, our results demonstrate that SARS-CoV-2 entry in hepatocytes occurs partially through ACE2- and GRP78-dependent mechanisms. SARS-CoV-2 infects and replicates in hepatocytes and exerts a PEPCK-dependent gluconeogenic effect in these cells that potentially is a key cause of hyperglycemia in infected patients.

Nature Communications - Plasmacytoid DC (pDC) have been shown to secrete type I IFN and to be involved in controlling replication and spread of some viruses. Here the authors show that in severe...

BMJ Open's Infectious diseases topic collection brings together the latest and most up-to-date research and reviews in this subject.

To describe the prevalence of long COVID in children infected for the first time (n=332) or reinfected (n=243) with Omicron variant SARS-CoV-2, compared with test-negative children (n=311). 12-16% infected with Omicron met the research definition of long COVID at 3 and 6 months after infection, with no evidence of difference between cases of first-positive and reinfection (pchi-square=0.17).

Introduction: Post-COVID-19 syndrome (PCS) is characterized by a wide range of symptoms, predominantly fatigue and exertional intolerance. While disease courses during the first year post infection have been repeatedly described, little is known about long-term health consequences. Methods: We assessed symptom severity and various biomarkers at three time points post infection (3-8 months (mo), 9-16mo, 17-20mo) in 106 PCS patients with moderate to severe fatigue and exertional intolerance. A subset of patients fulfilled diagnostic criteria of myalgic encephalomyelitis/chronic fatigue syndrome (PCS-ME/CFS) based on the Canadian Consensus Criteria. Results: While PCS-ME/CFS patients showed persisting symptom severity and disability up to 20mo post infection, PCS patients reported an overall health improvement. Inflammatory biomarkers equally decreased in both groups. Lower hand grip force at onset correlated with symptom persistence especially in PCS-ME/CFS. Discussion: Debilitating PCS may persist beyond 20mo post infection, particularly in patients fulfilling diagnostic criteria for ME/CFS.

Dr Phoebe Kitscha explores some of the biology behind the effects of Covid-19 on the circulatory system, and the research into ways to prevent and treat these effects.

Background and Objectives SARS-CoV-2 infection has been associated with a syndrome of long-term neurologic sequelae that is poorly characterized. We aimed to describe and characterize in-depth features of neurologic postacute sequelae of SARS-CoV-2 infection (neuro-PASC). Methods Between October 2020 and April 2021, 12 participants were seen at the NIH Clinical Center under an observational study to characterize ongoing neurologic abnormalities after SARS-CoV-2 infection. Autonomic function and CSF immunophenotypic analysis were compared with healthy volunteers (HVs) without prior SARS-CoV-2 infection tested using the same methodology. Results Participants were mostly female (83%), with a mean age of 45 ± 11 years. The median time of evaluation was 9 months after COVID-19 (range 3–12 months), and most (11/12, 92%) had a history of only a mild infection. The most common neuro-PASC symptoms were cognitive difficulties and fatigue, and there was evidence for mild cognitive impairment in half of the patients (MoCA score

Long COVID is a public health emergency affecting millions of people worldwide,14 characterized by heterogenous symptoms across multiple organs systems. Here, we discuss the current evidence linking thrombo-inflammation to Post-acute sequelae of COVID-19 (PASC). Studies have found persistence of vascular damage with increased circulating markers of endothelial dysfunction, coagulation abnormalities with increased thrombin generation capacity, and abnormalities in platelet counts in PASC. Neutrophil phenotype resembles acute COVID-19 with an increase in activation and NETosis. These insights are potentially linked by elevated platelet-neutrophil aggregate formation. This hypercoagulable state in turn can lead to microvascular thrombosis, evidenced by microclots and elevated D-Dimer in the circulation, as well as perfusion abnormalities in the lung and brain of Long COVID patients. Also, COVID-19 survivors suffer from an increased rate of arterial and venous thrombotic events. We discuss three important, potentially intertwined hypotheses, that might contribute to thromboinflammation in Long COVID: Lasting structural changes, most prominently endothelial damage, caused during initial infection, a persistent viral reservoir, and immunopathology driven by a misguided immune system. Lastly, we outline the necessity for large, well-characterized clinical cohorts and mechanistic studies to clarify the contribution of thromboinflammation to Long COVID. Keywords: Long COVID, PASC, thrombosis, platelets, thromboinflammation

We aimed to identify trajectories of the evolution of post COVID-19 condition, up to two years after symptom onset. The ComPaRe long COVID e-cohort is a prospective cohort of patients with symptoms lasting at least two months after SARS-CoV2 infection. We used trajectory modelling to identify different trajectories in the evolution of post COVID-19 condition, based on symptoms collected every 60 days using the long COVID Symptom Tool. A total of 2,197 patients were enrolled in the cohort between December 2020 and July 2022 when the Omicron variant was not dominant. Three trajectories of the evolution of post COVID-19 condition were identified: “high persistent symptoms” (4%), “rapidly decreasing symptoms” (5%), and “slowly decreasing symptoms” (91%). Participants with high persistent symptoms were older and more likely to report a history of systemic diseases. They often reported tachycardia, bradycardia, palpitations, and arrhythmia. Participants with rapidly decreasing symptoms were younger and more likely to report a confirmed infection. They often reported diarrhoea and back pain. Participants with slowly decreasing symptoms were more likely to have functional diseases. Most of patients with post COVID-19 condition improve slowly over time, while 5% have rapid improvement in the two years after symptom onset and 4% have a persistent condition.

The first COVID-19 vaccine outside a clinical trial setting was administered on Dec 8, 2020. To ensure global vaccine equity, vaccine targets were set by the COVID-19 Vaccines Global Access (COVAX) Facility and WHO. However, due to vaccine shortfalls, these targets were not achieved by the end of 2021. We aimed to quantify the global impact of the first year of COVID-19 vaccination programmes. A mathematical model of COVID-19 transmission and vaccination was separately fit to reported COVID-19 mortality and all-cause excess mortality in 185 countries and territories. The impact of COVID-19 vaccination programmes was determined by estimating the additional lives lost if no vaccines had been distributed. We also estimated the additional deaths that would have been averted had the vaccination coverage targets of 20% set by COVAX and 40% set by WHO been achieved by the end of 2021. Based on official reported COVID-19 deaths, we estimated that vaccinations prevented 14·4 million (95% credible interval [Crl] 13·7–15·9) deaths from COVID-19 in 185 countries and territories between Dec 8, 2020, and Dec 8, 2021. This estimate rose to 19·8 million (95% Crl 19·1–20·4) deaths from COVID-19 averted when we used excess deaths as an estimate of the true extent of the pandemic, representing a global reduction of 63% in total deaths (19·8 million of 31·4 million) during the first year of COVID-19 vaccination. In COVAX Advance Market Commitment countries, we estimated that 41% of excess mortality (7·4 million [95% Crl 6·8–7·7] of 17·9 million deaths) was averted. In low-income countries, we estimated that an additional 45% (95% CrI 42–49) of deaths could have been averted had the 20% vaccination coverage target set by COVAX been met by each country, and that an additional 111% (105–118) of deaths could have been averted had the 40% target set by WHO been met by each country by the end of 2021. COVID-19 vaccination has substantially altered the course of the pandemic, saving tens of millions of lives globally. However, inadequate access to vaccines in low-income countries has limited the impact in these settings, reinforcing the need for global vaccine equity and coverage.

Just a reminder that if COVID-19 was 'just like the flu' and the people dying were 'gonna die anyway' there wouldn't be a WORLDWIDE, unprecedented in modern times, DROP in LIFE EXPECTANCY. pic.twitter.com/SkOHgAf2G2— Pedro Lérias (@RPLerias) May 11, 2023

We live in a world of microbes. They are not going away. Covid-19 and Covid-related sepsis have a lot to teach us, but only if we listen and learn.

Long COVID has a multifactorial nature with multiple pathophysiological factors at play. Viral factors, host factors (including systemic inflammation, and metabolic, endocrine, and endothelial dysfunction) and downstream impacts (tissue damage from the initial infection, hypoxia, dysbiosis, and autonomic nervous system dysfunction) are key elements underpinning the condition. Various factors culminate in the long-term persistence of the disorder (i.e., a thrombotic endothelialitis characterized by endothelial inflammation, hyperactivated platelets, and fibrinaloid microclots). We suggest a multipronged treatment agenda for Long COVID treatment trials, incorporating drugs targeting all potential mechanisms, including viral persistence, autoimmunity, immune dysregulation, and gut dysbiosis; with endothelialitis and coagulation abnormalities as two priorities.

Objective To assess the rates of vascular thrombotic adverse events in the first 35 days after one dose of the Ad26.COV2.S vaccine (Janssen/Johnson & Johnson) in healthcare workers in South Africa and to compare these rates with those observed in the general population. Design Open label, single arm, phase 3B study. Setting Sisonke study, South Africa, 17 February to 15 June 2021. Participants The Sisonke cohort of 477 234 healthcare workers, aged ≥18 years, who received one dose of the Ad26.COV2.S vaccine. Main outcome measures Observed rates of venous arterial thromboembolism and vaccine induced immune thrombocytopenia and thrombosis in individuals who were vaccinated, compared with expected rates, based on age and sex specific background rates from the Clinical Practice Research Datalink GOLD database (database of longitudinal routinely collected electronic health records from UK primary care practices using Vision general practice patient management software). Results Most of the study participants were women (74.9%) and median age was 42 years (interquartile range 33-51). Twenty nine (30.6 per 100 000 person years, 95% confidence interval 20.5 to 44.0) vascular thrombotic events occurred at a median of 14 days (7-29) after vaccination. Of these 29 participants, 93.1% were women, median age 46 (37-55) years, and 51.7% had comorbidities. The observed to expected ratios for cerebral venous sinus thrombosis with thrombocytopenia and pulmonary embolism with thrombocytopenia were 10.6 (95% confidence interval 0.3 to 58.8) and 1.2 (0.1 to 6.5), respectively. Because of the small number of adverse events and wide confidence intervals, no conclusions were drawn between these estimates and the expected incidence rates in the population. Conclusions Vaccine induced immune thrombocytopenia and thrombosis after one dose of the Ad26.COV2.S vaccine was found in only a few patients in this South African population of healthcare workers. These findings are reassuring if considered in terms of the beneficial effects of vaccination against covid-19 disease. These data support the continued use of this vaccine, but surveillance is recommended to identify other incidences of venous and arterial thromboembolism and to improve confidence in the data estimates. Trial registration ClinicalTrials.gov [NCT04838795][1]. All data relevant to the study are included in the article or uploaded as supplementary information. [1]: http://NCT04838795

Habt ihr schon von den kryptischen Corona-Varianten gehört? Ihre Spur führt in die Kanalisation. Erfahrt hier, was immunsupprimierte Dauerausscheider damit zu tun haben.

Severe acute respiratory syndrome coronavirus 2 intranasal infection causes testicular damage and associated hormonal changes despite a self-limiting pneumonia

This cohort study examines the clinical characteristics of men with coronavirus disease 2019 whose semen tested positive for severe acute respiratory syndrome coronavirus 2.

In December 2019, a novel coronavirus (SARS-CoV-2) was identified in COVID-19 patients in Wuhan, Hubei Province, China. SARS-CoV-2 shares both high sequence similarity and the use of the same cell entry receptor, angiotensin-converting enzyme 2 (ACE2), with severe acute respiratory syndrome coronavirus (SARS-CoV). Several studies have provided bioinformatic evidence of potential routes of SARS-CoV-2 infection in respiratory, cardiovascular, digestive and urinary systems. However, whether the reproductive system is a potential target of SARS-CoV-2 infection has not yet been determined. Here, we investigate the expression pattern of ACE2 in adult human testes at the level of single-cell transcriptomes. The results indicate that ACE2 is predominantly enriched in spermatogonia and Leydig and Sertoli cells. Gene Set Enrichment Analysis (GSEA) indicates that Gene Ontology (GO) categories associated with viral reproduction and transmission are highly enriched in ACE2-positive spermatogonia, while male gamete generation related terms are downregulated. Cell–cell junction and immunity-related GO terms are increased in ACE2-positive Leydig and Sertoli cells, but mitochondria and reproduction-related GO terms are decreased. These findings provide evidence that the human testis is a potential target of SARS-CoV-2 infection, which may have significant impact on our understanding of the pathophysiology of this rapidly spreading disease.