Category: Covid-19

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Longitudinal soluble marker profiles reveal strong association between cytokine storms resulting from macrophage … – Nature.com

June 5, 2024

Cohort study

The BEAT-COVID cohort was collected at the LUMC, Leiden, The Netherlands. Individuals diagnosed with PCR-positive COVID-19, who required hospital admission between April 2020 and March 2021 were invited to participate17,18,19,20. The majority of infections was with Wuhan-like viruses; the Netherlands experienced<1% circulating alpha variant until January 2021 nationally (in Dutch: https://www.rivm.nl/corona/actueel/virusvarianten).

Clinical care was provided according to local and national guidelines and not influenced by study participation. Initially (April-Aug 2020), care was supportive only (wave-1, March 2020August 2020), however, from August 2020 onwards patients received dexamethasone (wave-2, August 2020March 2021). Since our study was initiated shortly after the onset of the pandemic in The Netherlands, criteria for hospital admission were also different between the waves. In wave-1 hospital admission was limited to the more severe cases, and generally admission occurred later after onset of symptoms compared to wave-2 as a result of capacity and national guidelines. In addition, SARS-CoV2 PCR testing was only available for hospital admitted patients whereas it was mandatory for all individuals with symptoms in the 2nd wave; hence, people were aware of the infection earlier and may thus have behaved differently.

Patients were included both on the regular ward as well as on the ICU. Inclusion criteria were: admission at LUMC, SARS-CoV-2 PCR positive, and minimum 18 years old. Exclusion criteria were: no informed consent from the patient or a representative. All participants were unvaccinated against SARS-CoV-2. Upon signing informed consent, blood samples were collected 3 times (MondayWednesdayFriday) a week during hospitalization and at an outpatient visit 612 weeks post discharge. Statistical sample size calculation was not performed, the sample size was determined based on availability. Anti-IL6R antibodies were only used in a few patients during our study.

In addition to the patients with COVID-19 disease, a control group of healthy individuals was collected in July 2020 for comparative analyses. None of these healthy volunteers had experienced the infection yet, as was confirmed by serological analyses Semi-quantitative detection of SARS-CoV-2 anti-nucleocapsid (N) protein IgG antibodies was performed on the Abbott Architect platform21,22. In this antibody chemiluminescent microparticle immunoassay (CMIA) test, the SARS-CoV-2 antigen coated paramagnetic microparticles bind to the IgG, respectively, IgM antibodies that attach to the viral nucleocapsid protein in human serum samples. The Sample/Calibrator index values of chemiluminescence in relative light units (RLU) of 1.40 (IgG assay) respectively 1.00 (IgM assay) and above were considered as positive per the manufacturers instructions. Samples were collected from 8 males and 4 females (as the ratio of hospital admissions at that time was 2:1), with a median age of 64 (range 6072). Healthy volunteers were sampled 5 times, also at 2 day intervals and samples were processed identically to those from the individuals included in the BEAT-COVID cohort.

Ethical approval for the study protocol was provided by LUMC Medical Ethics committee (protocol NL73740.058.20). The study was registered at the International Clinical Trials Registry Platform no. NL8589 (https://trialsearch.who.int/Trial2.aspx?TrialID=NL8589). The study complied with the latest version of the Declaration of Helsinki. The principal investigator had access to information to identify individual patients.

The Severity of COronavirus Disease Assessment (SCODA) disease severity-score was developed to track day-to-day disease severity in hospital admitted COVID-19 patients23. The score was based on the 4C mortality score, but constant parameters were substituted with parameters associated with breathing and oxygenation to better reflect the daily condition and its changes23. The SCODA score was developed such that there was continuous scoring during admission on the ward and ICU to permit longitudinal assessment of severity during both types of admission. The SCODA score consisted of the following parameters: respiratory rate, peripheral oxygen saturation on room air (ward only), P/F Ratio (ICU only), oxygen flow (ward only), FiO2 (ICU only), Glasgow Coma Scale (GCS), blood urea level and C-reactive protein (CRP)23. The most severely ill patients admitted to the ICU could reach a maximum severity-score of 17.

We defined the recovery time point, per definition after the highest severity-score for that individual patient, as a SCODA score of a daily severity-score of7, with no subsequent increases. SCODA scores were included in the analysis when matched serum samples and measurements on the soluble analytes were available.

Blood samples were collected by venipuncture including a 8.5ml SST Vacutainer tube (Becton Dickinson, VWR, Amsterdam, The Netherlands). Upon clotting samples were centrifuged (10 min, 3000 rpm) within one hour by the central clinical chemistry laboratory and aliquoted for research purposes. Samples were stored at 80C to guarantee optimal sample quality.

The following cytokine and chemokine reagent kits were selected to analyse the sera of the study cohort; the Bio-Plex Pro human Chemokine panel (40-plex, #171AK99MR2), Bio-Plex Pro human Cytokine Screening panel (48-plex, #12,007,283), Bio-Plex Pro Human Inflammation panel (37-plex, #171AL001M) and a custom made panel of IL-17F, IL-21, IL-23, IL-25, IL-31, IL-33 of the Bio-Plex Pro human Th17 cytokine panel (all Bio-Rad, Veenendaal, the Netherlands). Assays were performed according to manufacturers instructions with manufacturers specific standards and QC control samples. All samples were thawed and diluted 1:4 in sample Diluent HB and run as single measurement with the streptavidin PE (1:200, Becton Dickinson, Erembodegem, Belgium) detection label. Samples were acquired on a Bio-Plex 200 system and analysed with Bio-Plex manager software v6.2. In total 131 analytes were measured, in case measurements were out of range or zero for more than 75% of the samples, analytes were removed from the analysis. When analytes were present in more than one assay panel, the analyte with the largest dynamic working range was selected for downstream analysis to ensure maximum detection window, this resulted in data analysis on 74 unique markers.

Samples were coded, stored directly at 80C upon collection and not thawed before the first measurement, to minimize the loss of detection due to low level or instable analytes. Measurements were performed continuously when 76 samples were available from the study. Thus, longitudinal samples from an individual were not necessarily measured at the same time but throughout the study period. To ensure technical or inter-assay variation would not impact the analysis, a reference control sample, generated by pooling sera of 4 severely ill COVID-19 patients was included in all assays. The reference control was aliquoted to avoid repeated freezing and thawing cycles, maintaining the quality of the reference sample. After each acquisition all standard curves were checked for performance, outliers were deleted and curve fitting optimized (Regression Type: Logistic5PL with standard recovery between 70 and 130%). Datapoints out of range below the LLOQ were set to 0 pg/ml and above the ULOQ were set to maximum (200.000 pg/ml).

Evaluation of the reference control sample showed limited variation in the calculated concentrations for most analytes measured between assays (analytes: n=74), assays: 11 plates; median %CV=56.7% (Supplementary Fig.6A). Analytes with large %CV were mostly produced in high levels with standard curve characteristics of a steep slope and less sensitivity in the lower ranges, impacting the calculated concentration even with minimal fluorescence differences.

Normalized soluble marker levels were+1 (to avoid zero as possible outcome), log2-transformed. Data was visualised and modelled using R (R Core Team, 2023), RStudio (Posit Team, 2023) and packages (R Core Team, 2023), ggplot2 (Wickham H, 2016), ggdendro (De Vries A, Ripley BD, 2022), mixOmics (Rohart F, Gautier B, Singh A, Le Cao K-A, 2017), caret (Kuhn M, 2008), glmnet (Friedman J, Tibshirani R, Hastie T, 2010), psych (Revelle W, 2023), pROC (Robin X, Turck N et al., 2011), ggpubr (Kassambara A, 2023) and GLMMadaptive (Rizopoulos D, 2023). Statistical testing comparing medians of two groups was performed using MannWhitney U. In addition, for analysis of differential soluble analyte levels between disease outcome groups and healthy controls or between waves MannWhitney U was performed and p values were adjusted for multiple testing by BenjaminiHochberg correction. The heatmap is clustered row-wise based on complete-linkage hierarchical clustering. Supervised dimensionality reduction was carried out using partial least squares-discriminant analysis (PLS-DA), separating disease outcome groups and correlation analyses were performed using Spearmans Rank and BenjaminiHochberg correction was performed on p-values.

For identification of the best-classifying soluble analyte signatures-profiles to model outcome (fatal outcome yes or no), ICU admission, high maximum disease severity and time to disease recovery at the earliest available time point (closest to hospital admission), logistic regression with lasso regularisation was performed. Leave-one-out cross-validation and train-test split (training set=70%, test set=30% of dataset) were used to assess the performance of the trained regression models. The classifying performance was further assessed by evaluating sensitivity, specificity, receiver operating characteristic (ROC) curve and area under the ROC curve (AUC).

The progression over time of each soluble analyte was modelled using linear mixed effects models for the total cohort. Linear mixed models are an extension of the simple linear regression models when multiple measurements on the same subject are collected and use random effects to capture the serial correlation. Wave of sample collection was included as confounder into the model. To enhance comparability of the patients and stages of the disease process the number of days since disease onset was used for the timing of the samples within each patient. The non-linear progression over time was captured using natural cubic splines. To compare the progression between the different outcome groups the main effect and the interaction term between the days since disease onset and the outcome groups was added in the model. Similarly to explore association of each soluble analyte with the disease severity the main effect and the interaction term between the days since disease onset and disease severity was added in the model. For soluble analytes with values outside the limits of detection, the truncated normal distribution was used. Finally to capture the serial correlation random intercept and random slope terms were used.

Pathway analyses for exploratory purpose were performed in Ingenuity Pathway Analysis (Qiagen, Germany) with input of 40 significantly different analytes in a core analysis with the Ingenuity Knowledge database as reference set. The 40 significant analytes were selected based on the association between circulating levels and daily SCODA severity-score tested over time to identify different mean progressions during follow up.

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Longitudinal soluble marker profiles reveal strong association between cytokine storms resulting from macrophage ... - Nature.com

Washington Wednesday: Origins of COVID-19 | WORLD – WORLD News Group

June 5, 2024

MARY REICHARD, HOST: Its Wednesday the 5th of June, 2024. Glad to have you along for todays edition of The World and Everything in It. Good morning, Im Mary Reichard.

MYRNA BROWN, HOST: And Im Myrna Brown.

First up: Washington Wednesday.

On Monday, members of the U.S. House Committee on Oversight and Accountability questioned Dr. Anthony Fauci. Hes the former head of the National Institute of Allergy and Infectious Diseases.

Lawmakers asked him about restrictions introduced during the pandemic, such as social distancing. They asked about his communication with intelligence agencies and the role of the United States in funding research.

So did the U.S. fund research to create viruses not found in natureand could the pandemic have been caused by a man-made lab leak?

WORLDs Washington Bureau Reporter Leo Briceno has the story.

LEO BRICENO: On a cultural level, COVID-19s origin has been a source of intrigue for several years. Heres comedian Jon Stewart on The Late Show with Stephen Colbert in 2021 discussing the possibility of a lab leak.

JON STEWART: Theres a novel respiratory coronavirus overtaking Wuhan, China. What do we do? Oh, you know who we could ask? The Wuhan novel respiratory coronavirus lab. The disease is the same name as the lab.

But while many skeptics look at that possibility as a conspiracy theory, Dr. Anthony Fauci told lawmakers on Monday that hes open to the idea that it could have come from a lab.

ANTHONY FAUCI: I feel, based on the data that I have seen, that the more likely explanation, not definitive, but the more likely explanation, is a natural spillover from an animal reservoir. But since there has not been definitive proof one way or the other, we have to keep an open mind that it could be either the concept of it is not a conspiracy theory.

Fauci has said similar things in the past. Whats really troubling Republicans, however, is the question: is it possible that American-funded experimentation with genetically-modified pathogens could be responsible? Fauci doesnt think so.

FAUCI: You cant get away from the fact that the viruses that were studied. That the NIH gave them a grant to study. Dont pull back on the fact that no matter what you did with those viruses, they were phylogenetically so different they could not possibly be the precursor to SARS COV-2.

The questions of COVID-19s origin overlap with Republican concern over funding the NIH awarded to Eco Health Global, a company working out of Wuhans virology labs. Arizona congresswoman Debbie Lesko.

DEBBIE LESKO: Did the National Institute of Health fund the potentially dangerous enhanced potential pandemic pathogens gain of function research at the Wuhan Institute of Virology?

FAUCI: I would not characterize it the way you did

Gain of function research, is a nebulous term. In its most general form, it means any attempt to genetically modify a pathogen to enhance its properties in some way. On its face it sounds scary. But experts say experimentation like it keeps medicine one step ahead of newly emerging diseases.

Faucis arrival to the House on Monday isnt the first time hes testified before congress on the practice. Back in 2021, he was called before the Senate. Heres Sen. Rand Paul confronting Fauci on his statements about research conducted in Wuhan.

RAND PAUL: Dr. Fauci, I dont expect you today to admit that you approved of NIH funding for gain of function research in Wuhan, but your repeated denials have worn thin and a majority of Americans, frankly, dont believe you. Even the NIH now admits that that eco-health alliance did perform experiments in Wuhan that created viruses not found in nature that actually did gain in lethality. You can deny it all you want, but even the Chinese authors of the paper, in their paper, admit that viruses not found in nature were created and, yes, they gained in infectivity.

Fauci maintains that work done in Wuhan wasnt gain of function research because it doesnt live up to the definition laid out by the National Institutes of Health.

FAUCI: I go back to what I said. That the gain of function research by the operative and regulatory definition of P3CO does not include at all the viruses that were studied under

By the P3CO standard, gain of function is experimentation with a highly transmissible pathogen thats capable of uncontrollable spread in humans and likely to cause significant morbidity.

Fauci says that while EcoHealth was experimenting with the genetic enhancement of viruses, the research would have fallen below that P3CO standard.

FAUCI: The broad definition of gain of function in my mind is not applicable here and does nothing but confuse the situation. And that is the reason why after three years of deliberation by the bodies including the NSABB as well as the national academies, it was decided to make an operative and regulatory definitionThe definition that I use is not my personal definition, its a codified, regulatory and operative definition made by a body that has nothing to do with me.

But he also cant definitively say he knows everything that went on at that lab. Heres Fauci sparring with congresswoman Lesko.

FAUCI: We know what viruses they were studying

LESKO: How? How do you know? You never went there.

FAUCI: Im telling you that the NIH funded research on these viruses if someone else somewhere in China was doing something else

LESKO: Thats the problem. Because NIH didnt go there, you didnt get the reports that were needed, how in the world would you know? Im going to go on with my next question.

FAUCI: Then youre not hearing what Im saying

While controversial, gain of function itself isnt illegal. In fact, it encompasses some of regularly accepted practices. Insulin, for instance, comes from E. Coli bacteria genetically manipulated to produce the diabetes drug.

Democrats like California representative Raul Ruiz came to Faucis defense on Monday. He stressed that definitions are important to understanding what really went on in Wuhan.

RUIZ: This has been a source of great conspiratorial accusations that are false regardless of the people making those accusation, knowing the true definition of gain of function. Now, under the 3PCO, it is not allowed to enhance the transmissibility or the pathogenicity of a potential pandemic pathogen. Thats already been settled. Dr. Fauci and NIAID did not fund P3CO-defined gain of function research.

Still, some lawmakers want stricter limits on the research. Heres Congressman Brad Wenstrup of Ohio, the chairman of the select subcommittee on the Coronavirus Pandemic. Some of the background noise youll hear is Republicans coming out of their weekly conference in the Capitol basement.

BRAD WENSTRUP: So youre just working with viruses that arent infectious to humans. But when you start taking parts from one virus, adding it to another and working different combinations. If youre doing that, it doesnt matter what you start with. Its what you end up with.

In November, House Republicans tried to pass a bill that would have prevented government dollars from going to gain of function research, but the bill didnt go anywhere in the Senate.

I asked Wenstrup if he thought Democrats would get behind a congressional plan to set limits on gain of function practices.

WENSTRUP: Probably not right now, as long as Dr. Fauci is in favor of it still. I dont think that they will.

Fauci stepped down from leading the National Institute of Allergy and Infectious Diseases in 2022, but as Mondays hearing illustrates, his influence on public health policy continues.

Reporting for WORLD, Im Leo Briceno.

WORLD Radio transcripts are created on a rush deadline. This text may not be in its final form and may be updated or revised in the future. Accuracy and availability may vary. The authoritative record of WORLD Radio programming is the audio record.

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Washington Wednesday: Origins of COVID-19 | WORLD - WORLD News Group

Fauci pushes back partisan attacks in fiery House hearing over COVID origins and controversies – The Associated Press

June 5, 2024

WASHINGTON (AP) Dr. Anthony Fauci, the top U.S. infectious disease expert until leaving the government in 2022, was back before Congress on Monday, calling simply preposterous Republican allegations that hed tried to cover up origins of the COVID-19 pandemic.

A GOP-led subcommittee has spent over a year probing the nations response to the pandemic and whether U.S.-funded research in China may have played any role in how it started yet found no evidence linking Fauci to wrongdoing.

Hed already been grilled behind closed doors, for 14 hours over two days in January. But Monday, Fauci testified voluntarily in public and on camera at a hearing that quickly deteriorated into partisan attacks.

Republicans repeated unproven accusations against the longtime National Institutes of Health scientist while Democrats apologized for Congress besmirching his name and bemoaned a missed opportunity to prepare for the next scary outbreak.

He is not a comic book super villain, said Rep. Jamie Raskin, D-Md., saying the Select Subcommittee on the Coronavirus Pandemic had failed to prove a list of damaging allegations.

Fauci was the public face of the governments early COVID-19 response under then-President Donald Trump and later as an adviser to President Joe Biden. A trusted voice to millions, he also was the target of partisan anger and choked up Monday as he recalled death threats and other harassment of himself and his family, threats he said still continue. Police later escorted hecklers out of the hearing room.

The main issue: Many scientists believe the virus most likely emerged in nature and jumped from animals to people, probably at a wildlife market in Wuhan, the city in China where the outbreak began. Theres no new scientific information supporting that the virus might instead have leaked from a laboratory. A U.S. intelligence analysis says theres insufficient evidence to prove either way -- and a recent Associated Press investigation found the Chinese government froze critical efforts to trace the source of the virus in the first weeks of the outbreak.

Fauci has long said publicly that he was open to both theories but that theres more evidence supporting COVID-19s natural origins, the way other deadly viruses including coronavirus cousins SARS and MERS jumped into people. It was a position he repeated Monday as Republican lawmakers questioned if he worked behind-the-scenes to squelch the lab-leak theory or even tried to influence intelligence agencies.

I have repeatedly stated that I have a completely open mind to either possibility and that if definitive evidence becomes available to validate or refute either theory, I will ready accept it, Fauci said. He later invoked a fictional secret agent, decrying a conspiracy theory that I was parachuting into the CIA like Jason Bourne and told the CIA that they should really not be talking about a lab leak.

Republicans also have accused Fauci of lying to Congress in denying that his agency funded gain of function research the practicing of enhancing a virus in a lab to study its potential real-world impact at a lab in Wuhan.

NIH for years gave grants to a New York nonprofit called EcoHealth Alliance that used some of the funds to work with a Chinese lab studying coronaviruses commonly carried by bats. Last month, the government suspended EcoHealths federal funding, citing its failure to properly monitor some of those experiments.

The definition of gain of function covers both general research and especially risky experiments to enhance the ability of potentially pandemic pathogens to spread or cause severe disease in humans. Fauci stressed he was using the risky experiment definition, saying it would be molecularly impossible for the bat viruses studied with EcoHealths funds to be turned into the virus that caused the pandemic.

In an exchange with Rep. H. Morgan Griffith, R-Va., Fauci acknowledged that the lab leak is still an open question since its impossible to know if some other lab, not funded by NIH money, was doing risky research with coronaviruses.

Fauci did face a new set of questions about the credibility of NIHs National Institute of Allergy and Infectious Diseases, which he led for 38 years. Last month, the House panel revealed emails from an NIAID colleague about ways to evade public records laws, including by not discussing controversial pandemic issues in government email.

Fauci denounced the actions of that colleague and insisted that to the best of my knowledge I have never conducted official business via my personal email.

The pandemics origins werent the only hot topic. The House panel also blasted some public health measures taken to slow spread of the virus before COVID-19 vaccines, spurred by NIAID research, helped allow a return to normalcy. Ordering people to stay 6 feet apart meant many businesses, schools and churches couldnt stay open, and subcommittee chairman Rep. Brad Wenstrup, R-Ohio, called it a burdensome and arbitrary rule, noting that in his prior closed-door testimony Fauci had acknowledged it wasnt scientifically backed.

Fauci responded Monday that the 6-feet distancing wasnt his guideline but one created by the Centers for Disease Control and Prevention before scientists had learned that the new virus was airborne, not spread simply by droplets emitted a certain distance.

The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institutes Science and Educational Media Group. The AP is solely responsible for all content.

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Fauci pushes back partisan attacks in fiery House hearing over COVID origins and controversies - The Associated Press

Class of COVID-19: This year’s graduating class started high school in lockdown. Here are their stories – The Spokesman Review

June 5, 2024

Hallye Matherly woke up early the morning of her first day of freshman year at Ferris High School.

She rolled out of bed, brushed her teeth and got dressed . Then the first-day-of-school jitters kicked in.

I remember I called my best friend at that point, and I was just like, Im so scared, like, are you in class? she recalled.

Nervous, she made her way to school. Or rather, to her school-issued laptop, on which she signed into a Zoom meeting of her class, greeted by dozens of little black boxes on her computer screen.

Matherlys first-day-of-high-school memory juxtaposes the traditional tale of crossing the threshold to a daunting new building, but its not unique among her class. Members of the Class of 2024 were in eighth grade when an unknown pneumonia-like illness began spreading in Wuhan, China. At the end of February that school year, the first person in the United States died by the virus. By March, schools announced they were closing for two weeks to mitigate the spread.

They went on the intercom and said that there was going to be a two-week shutdown, and I could hear the cheers emanating from every single room in the entire school, Ferris senior Dylan Kolts said.

The two-week closure became six, then the rest of the school year and that became the beginning of their freshman year, when students collectively but separately logged onto their school-issued laptops to mark their first day of high school.

How long are we going to be stuck here? Ferris High School senior Isaac Woods recalls thinking. I missed leaving my house and seeing my friends and ended up just not really interacting with anybody that often.

The awkwardness was difficult for students. Already, they braced for entering a new era of life, navigating more rigorous classes in a strange school filled with hundreds of new faces. The pandemic obscured these new faces for a whole class of students, relegating them to a screen full of black boxes in a virtual classroom.

No one was wanting to interact or be social in any sort of way, and there was just a struggle for everyone to stay in it because it was just so different from what we had traditionally been doing; especially as a freshman, it just did not feel right. I was like, Is this what high school is going to be like for the rest of my four years? said Kau Roberton, senior at Lewis and Clark High School.

It wasnt. Most schools shifted midyear to a hybrid virtual/in-person model in which students did some schooling online and came to classrooms for a shorter schedule with fewer peers.

Regardless, the semester spent in their rooms, behind their computer screens shaped this class entry to high school, forcing them to miss milestones like their homecoming dance or first football game. Many seniors said distance learning caused a lag in their academic and social development, but they feel theyve caught up as they cross the graduation stage next week.

I feel like it took me till my junior year to actually have a high school year, Kolts said.

He didnt see a person outside of his family for a full calendar year during the height of the pandemic, when his parents followed quarantine and social -distancing protocols. He recalls sneaking away from his parents at a park to spend a moment with his then girlfriend.

It kind of felt like I was really isolated, he said. I just sat at my house and played video games.

Without having sports as an avenue to meet peers, Woods said he didnt make any friends his freshman year, just kept in loose contact with his circle from eighth grade. As soon as football, track and wrestling started up again and school returned to the physical realm, he found his people.

It affected all of us kind of in the same way where we lost a lot of connections, but when we came back, we made different connections with people, he said.

Watching current-day freshmen live out their high school milestones COVID-free, Matherly cant help but be jealous. Shell never experience matriculation from eighth grade, her freshman homecoming dance and football games as a freshman.

It was a pretty big milestone, going into high school that we kind of missed completely and didnt get to take it in, like, Oh, were about to be high schoolers, can you believe it? Matherly said. It was no school for a couple weeks and then boom, were freshmen.

The effects werent just social. Matherly almost failed her freshman year. The adjustment to a high school course load, acclimating to new technology and being in an unsuitable learning environment made online school a difficult task.

Just being able to be at home and be in my own room, I can just lay in bed and sleep if I wanted and just kind of do what I want, Matherly said. I just felt like I was at home. I didnt feel like I was in the learning mindset that I would usually be in at school.

Grading standards changed during online school. It was unmotivating for Ferris Nolan Matheney, and the lack of drive transferred to his in-person experience, he said.

Matheney said if his freshman year was in person, he would have been better at algebra. He is now taking calculus, but he feels like he lacks a basic skill he needs after his freshman year online.

Ferris senior Aidan Ackerman is in the same boat as Matheney. Ackerman said if he had gone to in-person school freshman year, he would have been better at math and English.

He remembered not paying attention to video calls, even when teachers urged involvement.

They made a big point that you have to stay and participate, but a lot of people didnt, he said.

Turning her camera on to a class full of strangers terrified Matherly, she said.

They wanted us to turn on our cameras, and I refused because I dont know any of these people, I dont want them to see me, she said.

Ferris senior Brendan Washington said COVID kept him from bonding with his teachers compared to an in-person experience.

They arent as strong as they are now, Washington said. Its definitely hard to build relationships with teachers from a distance.

A 4.0 student prepandemic, Kolts grades fell during distance learning. Diagnosed with ADHD, it was hard for him to focus on his studies while at home.

With the help of extra attentive teachers when students returned to in-person learning, Kolts doesnt feel he lost too much learning in online school.

Band during freshman year was the worst year event ever, and I think every senior can agree on that, said Roberton, a saxophone player.

During online learning, he recorded himself playing on his school-issued laptop and sent the poor-quality audio to his band teacher. He missed playing with other musicians, lacking the camaraderie in presenting a piece of music together.

It was really frustrating because we couldnt play with other people or see how we sounded in a group setting, he said.

Despite the atypical start to his high school career, Roberton isnt graduating by mourning the freshman year he didnt have. He doesnt feel stunted, socially or academically, and when he begins his freshman year at the University of Washington studying music, hell recall the tenacity required to keep playing his saxophone alone in his room into a low-quality recording on his laptop in lieu of band class.

Its really important to stick to those things that you are interested in and that you think youll excel in, because I dont see a future in which I wouldnt be playing music now, Roberton said. During freshman year, band and music was really unmotivating and discouraging, and Im glad that even though that was the case, I was able to continue. I just say, stick with your passions, even if they seem like theyre going through a rough spot at the time.

Intern reporter Alexandria Osborne contributed to this article.

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Class of COVID-19: This year's graduating class started high school in lockdown. Here are their stories - The Spokesman Review

Virus Behind COVID-19 Could Linger In Sperm For 110 Days After Infection Starts – IFLScience

June 5, 2024

SARS-CoV-2, the virus whose name we all wish we didnt know, can hang around in sperm for 110 days after infection according to a new study. Theres long been a suggestion that COVID-19 could have a negative impact on sperm, but the authors believe their study is the first to show just how long the virus can linger in semen samples.

We mostly think about respiratory symptoms when we think of COVID-19 cough, breathlessness, loss of sense of smell but weve learned during the course of this pandemic that the virus is not super picky when it comes to which tissues it invades. Traces of SARS-CoV-2 have previously been identified in the testicles and in penile tissue, but limited research has focused on whether it can be detected in semen.

A team of researchers from Brazil set out to address this knowledge gap. Semen samples were collected from 13 COVID-19 patients aged 21-50 who had a range of symptoms from mild to severe. All were inpatients at the Hospital das Clnicas, run by the Faculty of Medicine of the University of So Paulo.

The samples were analyzed up to 90 days after the patients were discharged, and 110 days after their diagnoses. PCR tests for SARS-CoV-2 in semen were negative in all cases, but when the researchers looked at the sperm cells themselves, they did find evidence of virus in 72.7 percent of samples from those with moderate and severe COVID-19.

One of the patients who had only had a mild infection also showed evidence of virus in sperm, and in two of the other samples the team observed structural abnormalities in the sperm similar to what has previously been seen in COVID-19 patients.

Based on this, the team concluded that 11 of the 13 patients in their sample were showing signs of lingering SARS-CoV-2 in their sperm up to 110 days after first being diagnosed with the infection.

Moreover, explained the studys senior author Jorge Hallak in a statement, we found that the sperm produced extracellular traps based on nuclear DNA. In other words, genetic material in the nucleus decondensed, the sperms cell membranes ruptured, and the DNA was expelled into the extracellular medium, forming networks similar to those described previously in the systemic inflammatory response to SARS-CoV-2."

These kinds of traps are an important part of the immune response, capturing harmful microbes, but if they become overactive they can cause damage to tissues. The authors suggest that during a COVID-19 infection, sperm may sacrifice" themselves by producing these traps to help the bodys defenses. It was not previously known that sperm were involved in immunity in this way, so Hallak says this finding could represent a scientific paradigm shift.

Hallak and colleagues have been advocating for caution when it comes to understanding how COVID-19 may affect reproductive health since the early months of the pandemic. These results add to the growing body of evidence in this area, as well as highlighting a potential new function of sperm.

Although this is a small study and despite the fact that virus was only detected within the sperm cells and that tests on the semen as a whole were negative Hallak suggests that anyone seeking to conceive, or to have their sperm used for assisted reproduction, might consider a break of at least six months after having COVID-19.

The study is published in the journal Andrology.

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Virus Behind COVID-19 Could Linger In Sperm For 110 Days After Infection Starts - IFLScience

VDH: A second juvenile has died of COVID-19 – Vermont Biz

June 5, 2024

by Timothy McQuiston, Vermont Business Magazine The Vermont Department of Health reported on May 22 that a second juvenile in the "Under 10" category has died of COVID-19 since the pandemic began here in March 2020. It has been a year and a half since a Vermonter under the age of 30 has died from COVID. The VDH changed its reporting methods in 2022.

The VDH sent this report on the most recent under 30 deaths:

For the week ending May 29, the Vermont Department of Health is reporting that COVID-19 cases were 53, down from 57 the previous week. Cases had been falling in Aprile and May and were as low as 31 at the beginning of May. There was one fatality last week and five the previous week, including the juvenile.

The pandemic death total stands at 1,154 as of May 25, 2024 (the most recent data available). Total reported deaths in January were 29, which is the highest monthly total since November 2022. There were 16 fatalities in February, 12 in March, 3 in April and 5 so far in May. April deaths were the fewest from COVID since July 2021.

Of the total deaths to date, 930 have been of Vermonters 70 or older. There have been 4 deaths of Vermonters under 30 since the beginning of the pandemic.

CDC states that already an estimated 97% of Americans have some level of immunity, from either vaccination or infection or both, which they said will help keep down new transmission and lessen serious outcomes.

More recently, on March 7, 2024, a study by a nationwide collaborative group including University of Vermont Larner scientists, published in Nature Communications, explored how the human body responded to mRNA COVID-19 vaccinessuch as PfizerBioNTech Moderna. Both vaccines work by helping the body produce antibodies against the COVID-19 viruss spike protein, but the study team found that the efficacy of the vaccines varied among subjects.

Researchers found that individuals over the age of 65, men, those with higher weight, smokers, diabetics, and those with a history of emphysema tended to have lower antibody levels. To contrast, subjects who had been diagnosed with COVID-19 previouslyparticularly those with COVID-19 severe enough to lead to hospitalizationhad significantly higher levels of anti-S1 than other groups in the study. Surprisingly, those who had taken the Moderna vaccine also reported a significantly higher level of anti-S1 than the PfizerBioNTech recipients.

Report Timeframe: May 5 to May 11, 2024

(see data tables below)

The hospitalizations dataset contains day-level data reported from all Vermont hospitals each Tuesday. Reported numbers are subject to correction.

The number of reportable COVID-19 cases is still available in this report, below. Laboratory-confirmed and diagnosed COVID-19 cases and COVID-19 outbreaks must still be reported to the Vermont Department of Health.

There were 3 outbreaks last week, all at Long-Term Care Facilities.

Vermont has the second lowest state fatality rate in the US (133.3 per 100K; Hawaii 104.9/100K). Mississippi (449.4/100K) and Oklahoma (446.4/100K) have the highest rates. The US average is 298.4/100K (CDC data).

There has been a total of 1,191,702 COVID-related deaths to date in the US (CDC) and 7,049,617 globally (WHO).

Following an analysis of COVID-19 data, the VDH reported in January 2023 a cumulative 86 additional COVID-associated deaths that occurred over the course of the pandemic but had not been previously reported. Most of those deaths occurred in 2022.

As of April 30, 2024, hospitals are no longer required to report COVID-19 Hospital data. CDC strongly encourages hospitals to continue reporting these data, but following the May 1st COVID-19 Surveillance Report, the Vermont Department of Health will no longer be providing updated Hospitalization Levels with their weekly report.

The average hospitalization has fallen under one per day, while the Seven-Day Rolling Average of people coming to emergency departments of the state's hospitals with a COVID diagnosis is under 5.

Starting May 8th, the COVID-19 Surveillance Report includes additional information on the impact of COVID-19 in Vermont.

Vermont Department of Health recommendations: Preventing COVID-19 (healthvermont.gov)

COVID-19 Update for the United States

Early Indicators

Test Positivity

% Test Positivity

4.2%

(May 19 to May 25, 2024)

Trend in % Test Positivity

+0.8% in most recent week

Emergency Department Visits

% Diagnosed as COVID-19

0.4%

(May 19 to May 25, 2024)

Trend in % Emergency Department Visits

+5.1% in most recent week

These early indicators represent a portion of national COVID-19 tests and emergency department visits. Wastewater information also provides early indicators of spread.

Severity Indicators

Hospitalizations

Hospitalization Rate per 100,000 population

1

(May 5 to May 11, 2024)

Trend in Hospitalization Rate

No change in most recent week

Deaths

% of All Deaths in U.S. Due to COVID-19

0.6%

(May 19 to May 25, 2024)

Trend in % COVID-19 Deaths

No change in most recent week

CDC | Test Positivity data through: May 25, 2024; Emergency Department Visit data through: May 25, 2024; Hospitalization data through: May 11, 2024; Death data through: May 25, 2024. Posted: June 3, 2024 2:50 PM ET

The Delta variant took off in August 2021, which resulted in the heaviest number of deaths before vaccines and their boosters helped alleviate serious COVID cases. Multiple Omicron variants are now circulating and appear more virulent than previous variants, but perhaps not more dangerous, according to the CDC.

New COVID-19 variant JN.1: Experts explain symptoms, how to spot and treat the new strain

AP April 5, 2023: WHO downgrades COVID pandemic, says it's no longer a global health emergency

Walk-in vaccination clinics run by the state closed on January 31, 2023. Learn more

Vermonters are reminded that all state COVID testing sites were closed as of June 25, 2022. PCR and take-home tests are available through doctors' offices, pharmacies and via mail from the federal government. The federal government officially ended its pandemic response as of May 11, 2023. See more information BELOW or here: https://www.healthvermont.gov/covid-19/testing.

Starting May 11, 2023, the CDC and Vermont Department of Health will no longer use the COVID-19 Community Level to measure COVID-19 activity in the U.S. and Vermont. Instead, Vermont's statewide COVID-19 level will be measured by the rate of COVID-19 in people being admitted to the hospital, per 100,000 residents.

Focusing on hospitalization data is a better estimate of how COVID-19 is impacting the community now that reported COVID-19 cases represent a smaller proportion of actual infections. This also allows us to compare Vermonts hospitalization levels with other parts of the country.

The Delta variant caused a surge in COVID-related fatalities last fall and into the winter.

The highest concentration of deaths was from September 2021 through February 2022. Overall, December 2020 and January 2022 were the worst months with 72 fatalities each.

The US confirmed its first case of COVID-19 on January 20, 2020.

Vermonters ages 6 months and older are eligible for COVID-19 vaccines. Getting vaccinated against COVID-19 is the safer way to build protection from serious illnesseven for those who have already had COVID-19. Learn more about COVID-19 vaccines (CDC)

COVID-19 vaccines are free and widely available. Anyone can get vaccinated in Vermont, including those who live in another state, are non-U.S. citizens, or who have no insurance. See Vermont's current vaccine rates

Know your rights when getting free vaccines.

You are considered up-to-date if you are over the age of 6 years old and have received a bivalent (updated) COVID-19 vaccine.Learn more about kid vaccines

If you are unable or choose not to get a recommended bivalent mRNA vaccine, you will be up to date if you received the Novavax COVID-19 vaccine doses approved for your age group.

Find more on recommended doses from CDC

COVID Vaccine Information for Health Care Professionals

More on COVID-19 Vaccines (CDC)

Recommended COVID Vaccine Doses (CDC)

Find a COVID-19 vaccine near you.

Image

Use Vaccines.gov to find a location near you, then call or visit the location's website to make an appointment.

Vaccines.gov

Everyone 6 months of age and older is eligible to get a COVID-19 vaccination.Most children are also now eligible for a bivalent dose that offers increased protection against the original strain and omicron variants.

See more on recommended vaccine doses by age group (CDC)

Resources for parents and caregivers

https://www.vermontfamilynetwork.org/ccfk/

Tips for Helping Kids Feel Ready for Any Vaccine (Vermont Family Network)

#factsheet

What Families with Children Should Know About COVID-19 Vaccines (translated)

https://www.youtube.com/watch?v=lWcqHOgQIVg&t=5s

Conversations About COVID-19 Vaccines for Children with Vermont Pediatricians (American Academy of Pediatrics)

If you cannot get vaccines through any of the options above, our local health offices

offer immunization clinics by appointment.

Need a ride? If you do not have transportation to get a free COVID-19 vaccine or booster, please contact your local public transportation provider or callVermont Public Transportation Association (VPTA)

at 833-387-7200.

English language learners, or immigrant or refugee community members, who would like to learn about more about vaccine clinics can contact theAssociation of Africans Living in Vermont

(AALV) at 802-985-3106.

If you lost your vaccine card or your information is wrong:

Recommendations for keeping your vaccination card and record up to date

Find more COVID-19 translations

See the rest here:

VDH: A second juvenile has died of COVID-19 - Vermont Biz

Claim that Portuguese court found COVID-19 PCR tests to be 97% inaccurate based on misinterpreted findings – Health Feedback

June 5, 2024

CLAIM

MSM Silent As Court Holds PCR Covid Tests 97% Inaccurate - Unfit for Purpose

DETAILS

Factually inaccurate: A Portuguese courts conclusion that PCR tests are 97% inaccurate is based on misinterpreted findings. The findings were related to how well PCR tests could measure contagiousness, but were misconstrued to mean that most positive PCR tests are inaccurate.

KEY TAKE AWAY

PCR tests work by detecting a virus genetic material in biological samples like blood or saliva. These tests are highly sensitive and specific. Trace amounts of viral genetic material, left behind after an initial infection is over, can still be detected by PCR tests even when the infected person is no longer contagious. While PCR tests are excellent at detecting current and recent infections, there can be uncertainty when it comes to using them to determine if a person is still contagious.

The articles appearance in May 2024 belies the fact that this claim dates back to November 2020. In fact, much of the article was lifted from a November 2020 op-ed published by RT (formerly Russia Today), a media outlet controlled by the Russian government and known to spread disinformation. Science Feedback debunked similar claims in 2020 and 2021 (see reviews here, here, and here).

The claim is based on a ruling by Lisbons Court of Appeals regarding a case for habeas corpus, brought by a group of four German holidaymakers. The Regional Health Authority for the Azores required the group to isolate and quarantine after one of them received a positive COVID-19 PCR test result. This took place in August 2020 and was in line with Portugals COVID-19 policies at that time.

The court ultimately ruled that the groups confinement was illegal and ordered the four to be released. This decision was based in part on the courts assessment of the reliability of PCR tests. According to a report by The Portugal News, the judges concluded that the probability of a person receiving a false positive [from a PCR test] is 97% or higher, citing the following statement from Jaafar at al. in a letter to the editor of the journal Clinical Infectious Diseases[1]:

at a cycle threshold (ct) of 25, about 70% of samples remained positive in cell culture (i.e. were infectious); at a ct of 30, 20% of samples remained positive; at a ct of 35, 3% of samples remained positive; and at a ct above 35, no sample remained positive (infectious) in cell culture

The judges spelled out their interpretation of this statement in their decision. The decision was primarily published in Portuguese, but it provided an English translation for the judges understanding of the letter by Jaafar and colleagues:

This means that if a person gets a positive PCR test result at a cycle threshold of 35 or higher (as applied in most US labs and many European labs), the chance that the person is infectious is less than 3%. The chance that the person received a false positive result is 97% or higher.

However, this is a misinterpretation of the scientists findings, as well explain below.

In brief, the letter by Jaafar and colleagues dealt with the question of how well positive PCR tests correlate with a persons contagiousness.

PCR tests are considered the gold standard for COVID-19 testing[2,3]. As such, they form the basis of public health responses like isolation and quarantine. On a broader scale, they can inform school and business closures, as well as travel restrictions.

However, one potential issueas this New York Times report highlightedis that while contagiousness is a reason for isolation, a positive PCR result in itself may not necessarily mean a person is contagious. PCR tests are highly sensitive, which means they can detect even trace amounts of viral genetic material. This material can remain in the body for some time after the initial infection has passed and a person is no longer contagious.

In short, this means that infected people who are no longer contagious may isolate themselves unnecessarily if they still test positive (see Figure 1 below for an illustration).

Figure 1 How viral load evolves as disease progresses, and the implications for the accuracy of diagnostic tests like PCR and antigen tests. Source: Puhach et al.[3]

PCR tests detect the presence of the virus by makingor in scientific parlance, amplifyingcopies of a small part of the virus genetic material. The number of times the genetic material needs to be amplified (amplification cycles) to reach the threshold for a positive result is called the cycle threshold (Ct) value. The Ct value depends on how much virus is present in a sample. The more virus, the fewer the amplification cycles needed to reach the threshold for a positive result (low Ct value).

For that reason, some scientists suggest that Ct values should also be considered when determining the need for isolation, rather than rely solely on a positive or negative result. A high viral load (low Ct value) indicates that a person is likely infectious and needs to isolate.

But this approach also comes with caveats: interpreting a low viral load (high Ct value) is more difficult. It might indicate that a person is recovering and is no longer infectious. But it could also mean a person is still in the early stages of infection and will shortly become infectious (see Figure 1 above for an illustration).

To address the question of how well Ct values from PCR tests indicate contagiousness, Jaafar and colleagues collected the Ct values of approximately 3,000 PCR tests and checked whether the same samples contained live virus by using viral cultures. Viral cultures involve growing the virus, hence they can detect live, replicating virus and therefore provide a proxy measure for contagiousness.

The researchers reported that positive PCR results with a Ct of 25 were associated with up to 70% of positive viral culture results. But when they looked at positive PCR results with a Ct value of 30, the proportion of positive viral culture results fell to 20%. At a Ct of 35, fewer than 3% of cultures were positive.

This finding, which was cited as part of the basis for the Lisbon court ruling and for Turners claim, doesnt mean that PCR tests are 97% inaccurate. What it means is that the smaller the amount of viral genetic material in a sample (and the higher the Ct), the smaller the chance that live virusa marker of contagiousnessis present.

It also doesnt mean that PCR tests have a 97% chance of producing false positives. A false-positive result occurs when the test is positive in the absence of viral genetic material. The letter, on the other hand, explored the issue of trace amounts of viral material that are detectable by PCR tests and is unrelated to the problem of false positives.

In this blog post, virologist Ian Mackay explained that A positive RT-PCR result doesnt prove that replicating (also called infectious or viable) virus is present. It proves that its genetic material the RNA is present. But since RNA breaks down easily, the presence of viral RNA in biological samples indicates that the source of that RNAthe virusis likely present in the body. Therefore, PCR tests can still serve as a surrogate indicator of the presence of the infectious virus.

While viral cultures are an alternative to PCR tests for detecting live virus, they are slower and more expensive, Mackay explained. Hence viral cultures arent as widely used as PCR tests for detecting COVID-19 cases.

Vasco Bareto, a principal investigator at the Chronic Diseases Research Center of the NOVA University Lisbon, told Portuguese daily Pblico that the judges interpreted the results from Jaafar et al. incorrectly. PCR tests have a specificity and sensitivity greater than 95%. That is, in the overwhelming majority of cases they detect the virus that causes Covid-19, he said.

In conclusion, a Portuguese courts conclusion that PCR tests are 97% inaccurate is based on misinterpreted findings. The letter by Jaafar and colleagues didnt report that PCR tests have a 97% chance of producing false-positive results. Instead, their findings suggest that positive PCR results at high Ct valuesindicating very little viral genetic materialmay be a sign that a person likely isnt contagious.

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Claim that Portuguese court found COVID-19 PCR tests to be 97% inaccurate based on misinterpreted findings - Health Feedback

June 5, 2024: This Week’s PCT Grand Rounds to Feature PCORnet-Based COVID-19 and Diabetes Assessment … – Rethinking Clinical Trials

June 5, 2024

Dr. Russell Rothman and Dr. Jason Block

In this Fridays PCT Grand Rounds, Russell Rothman of Vanderbilt University Medical Center and Jason Block of Harvard Medical School will present The NIH COvid-19 and Diabetes Assessment (CODA) Study: Leveraging PCORnet for a Novel Cohort Study.

The Grand Rounds session will be held on Friday, June 7, 2024, at 1:00 pm eastern.

Rothman is a professor of internal medicine, pediatrics, and health policy, the Ingram Professor of Integrative and Population Health, and the senior vice president for population and public health at Vanderbilt University Medical Center. He also serves as the director of Vanderbilts Institute for Medicine and Public Health. Block is an associate professor of population medicine at Harvard Medical School, a faculty member in the Harvard Center for Population and Development Studies, and a general internal medicine physician at Brigham and Womens Hospital.

Join the online meeting.

More here:

June 5, 2024: This Week's PCT Grand Rounds to Feature PCORnet-Based COVID-19 and Diabetes Assessment ... - Rethinking Clinical Trials

Researchers look at how funding supported COVID-19 research, treatments and more – CBS19 News

June 5, 2024

The COVID-19 pandemic presented an unprecedented public-health challenge. The scientific community needed to rapidly act to come up with solutions to not only combat the virus but understand how we can prevent something like this from happening again, said Taison D. Bell, MD, of UVA Healths Division of Pulmonary and Critical Care Medicine and Division of Infectious Diseases and International Health. The NIH is the largest public funder of biomedical research, so we believe it was vital to study how $4 billion of NIH funding was allocated and used during the pandemic.

See more here:

Researchers look at how funding supported COVID-19 research, treatments and more - CBS19 News

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