nikomer75 boosted
nikomer75 boosted

Here's a terrific new paper from one of my classmates about #ImmuneCheckpointInhibitor induced #myocarditis. This work finds that CD8+ T-cells are the critical mediator of heart inflammation, and identifies the alpha-myosin cardiac protein as a candidate autoantigen: nature.com/articles/s41586-022 #science #medicine #immunology #cardiology #oncology #Tcell #genomics #scRNAseq

Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin

cardiab.biomedcentral.com/arti

Persistent clotting protein pathology in Long COVID/Post-Acute Sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin - Cardiovascular Diabetology

Background Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection, the cause of coronavirus disease 2019 (COVID-19), is characterized by acute clinical pathologies, including various coagulopathies that may be accompanied by hypercoagulation and platelet hyperactivation. Recently, a new COVID-19 phenotype has been noted in patients after they have ostensibly recovered from acute COVID-19 symptoms. This new syndrome is commonly termed Long COVID/Post-Acute Sequelae of COVID-19 (PASC). Here we refer to it as Long COVID/PASC. Lingering symptoms persist for as much as 6 months (or longer) after acute infection, where COVID-19 survivors complain of recurring fatigue or muscle weakness, being out of breath, sleep difficulties, and anxiety or depression. Given that blood clots can block microcapillaries and thereby inhibit oxygen exchange, we here investigate if the lingering symptoms that individuals with Long COVID/PASC manifest might be due to the presence of persistent circulating plasma microclots that are resistant to fibrinolysis. Methods We use techniques including proteomics and fluorescence microscopy to study plasma samples from healthy individuals, individuals with Type 2 Diabetes Mellitus (T2DM), with acute COVID-19, and those with Long COVID/PASC symptoms. Results We show that plasma samples from Long COVID/PASC still contain large anomalous (amyloid) deposits (microclots). We also show that these microclots in both acute COVID-19 and Long COVID/PASC plasma samples are resistant to fibrinolysis (compared to plasma from controls and T2DM), even after trypsinisation. After a second trypsinization, the persistent pellet deposits (microclots) were solubilized. We detected various inflammatory molecules that are substantially increased in both the supernatant and trapped in the solubilized pellet deposits of acute COVID-19 and Long COVID/PASC, versus the equivalent volume of fully digested fluid of the control samples and T2DM. Of particular interest was a substantial increase in α(2)-antiplasmin (α2AP), various fibrinogen chains, as well as Serum Amyloid A (SAA) that were trapped in the solubilized fibrinolytic-resistant pellet deposits. Conclusions Clotting pathologies in both acute COVID-19 infection and in Long COVID/PASC might benefit from following a regime of continued anticlotting therapy to support the fibrinolytic system function.

cardiab.biomedcentral.com

Liver injury in hospitalized patients with COVID-19: An International observational cohort study

medrxiv.org/content/10.1101/20

Liver injury in hospitalized patients with COVID-19: An International observational cohort study

Background Using a large dataset, we evaluated prevalence and severity of alterations in liver enzymes in COVID-19 and association with patient-centred outcomes. Methods We included hospitalized patients with confirmed or suspected SARS-CoV-2 infection from the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) database. Key exposure was baseline liver enzymes (AST, ALT, bilirubin). Patients were assigned Liver Injury Classification score based on 3 components of enzymes at admission: Normal; Stage I) Liver injury: any component between 1-3x upper limit of normal (ULN); Stage II) Severe liver injury: any component >= 3x ULN. Outcomes were hospital mortality, utilization of selected resources, complications, and durations of hospital and ICU stay. Analyses used logistic regression with associations expressed as adjusted odds ratios (OR) with 95% confidence intervals (CI). Results Of 17,531 included patients, 46.2% (8099) and 8.2% (1430) of patients had stage 1 and 2 liver injury respectively. Compared to normal, stages 1 and 2 were associated with higher odds of mortality (OR 1.53 [1.37-1.71]; OR 2.50 [2.10-2.96]), ICU admission (OR 1.63 [1.48-1.79]; OR 1.90 [1.62-2.23]) and invasive mechanical ventilation (OR 1.43 [1.27-1.70]; OR 1.95 (1.55-2.45).Stages 1 and 2 were also associated with higher odds of developing sepsis (OR 1.38 [1.27-1.50]; OR 1.46 [1.25-1.70]), acute kidney injury (OR 1.13 [1.00-1.27]; OR 1.59 [1.32-1.91]), and acute respiratory distress syndrome (OR 1.38 [1.22-1.55]; OR 1.80 [1.49-2.17]). Conclusions Liver enzyme abnormalities are common among COVID-19 patients and associated with worse outcomes. What is known? What is new here? ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial na ### Funding Statement Recipient: Funding received by the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC). This work was made possible by the UK Foreign, Commonwealth and Development Office and Wellcome [215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z and 220757/Z/20/Z] the Bill & Melinda Gates Foundation [OPP1209135] URL: <https://wellcome.org/> <https://www.gov.uk/government/organisations/foreign-commonwealth-development-office> The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript ### 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: The ISARIC-WHO Clinical Characterisation Protocol was approved by the World Health Organization Ethics Review Committee (RPC571 and RPC572). Local ethics approval was obtained for each participating country and site according to local regulations. 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 Data availability Statement: The data that underpin this analysis are highly detailed clinical data on individuals hospitalised with COVID-19. Due to the sensitive nature of these data and the associated privacy concerns, they are available via a governed data access mechanism following review of a data access committee. Data can be requested via the IDDO COVID-19 Data Sharing Platform (<http://www.iddo.org/covid-19>). The Data Access Application, Terms of Access and details of the Data Access Committee are available on the website. Briefly, the requirements for access are a request from a qualified researcher working with a legal entity who have a health and/or research remit a scientifically valid reason for data access which adheres to appropriate ethical principles. The full terms are at <https://www.iddo.org/document/covid-19-data-access-guidelines>. A small subset of sites who contributed data to this analysis have not agreed to pooled data sharing as above. In the case of requiring access to these data, please contact the corresponding author in the first instance who will look to facilitate access.

www.medrxiv.org

Innate immune response to SARS-CoV-2 infection contributes to neuronal damage in human iPSC-derived peripheral neurons

biorxiv.org/content/10.1101/20

Innate immune response to SARS-CoV-2 infection contributes to neuronal damage in human iPSC-derived peripheral neurons

Severe acute respiratory coronavirus 2 (SARS-CoV-2) infection causes neurological disease in some patients suggesting that infection can affect both the peripheral and central nervous system (PNS and CNS, respectively). It is not clear whether the outcome of SARS-CoV-2 infection of PNS and CNS neurons is similar, and which are the key factors that cause neurological disease: SARS-CoV-2 infection or the subsequent immune response. Here, we addressed these questions by infecting human induced-pluripotent stem cell-derived CNS and PNS neurons with the beta strain of SARS-CoV-2. Our results show that SARS-CoV-2 infects PNS neurons more efficiently than CNS neurons, despite lower expression levels of angiotensin converting enzyme 2. Infected PNS neurons produced interferon lambda 1, several interferon stimulated genes and proinflammatory cytokines. They also displayed neurodegenerative-like alterations, as indicated by increased levels of sterile alpha and Toll/interleukin receptor motif-containing protein 1, amyloid precursor protein and alpha-synuclein and lower levels of nicotinamide mononucleotide adenylyltransferase 2 and beta-III-tubulin. Interestingly, blockade of the Janus kinase and signal transducer and activator of transcription pathway by Ruxolitinib did not increase SARS-CoV-2 infection, but reduced neurodegeneration, suggesting that an exacerbated neuronal innate immune response contributes to pathogenesis in the PNS. ### Competing Interest Statement The authors have declared no competing interest.

www.biorxiv.org

ASYMPTOMATIC OR LATENT PERSISTENT INFECTION IN CHILDREN.

SARS COV-2 WAS DETECTED IN BIOPSIES OF TONSILS OR ADENOIDS
IN 25% OF ASYMPTOMATIC CHILDREN
None had experienced signs or symptoms

Authors point out:
lymphoid tissue may be a Reservoir of SARS-CoV-2

sciencedirect.com/science/arti

nikomer75 boosted
nikomer75 boosted

Sat down to eat at a "Saizeriya" (Japanese Italian chain) restaurant in Tokyo and immediately noticed the CO2 meter on top of the UV-C disinfection box on top of the counter. Wow.

I've seen the CO2 meter at several restaurants including a ramen place and an okonomiyaki restaurant, and now I'm seeing UV-C. Japan is so far ahead in recognizing #COVIDisAirborne. #COVID19

nikomer75 boosted
nikomer75 boosted

Remember when leaders ended public health measures claiming that they could always reinstate them when hospitals were overwhelmed again? Well, that’s happening now. Where are the mask mandates? Where is the urgency?

washingtonpost.com/health/2022

#BringBackMasks #COVID #COVID19 #PublicHealth

Show older
Qoto Mastodon

QOTO: Question Others to Teach Ourselves
An inclusive, Academic Freedom, instance
All cultures welcome.
Hate speech and harassment strictly forbidden.