Category: Covid-19

Our study provides first results on how the COVID-19 pandemics reshaping of the U.S. population is expected to repercuss into the future. Despite the general perception that the COVID-19 pandemic mainly affected old populations, our projections show that population pyramids will exhibit consequences of the pandemic until at least 2060. These rippling effects are expected when modeling the consequences of COVID-19 pandemic-induced changes in all three processes: mortality, fertility, and migration. We highlight three of the most important results from our study.

First, among the three demographic processes, the loss of net migration during the COVID-19 pandemic years is expected to have the biggest long-term impact on the size of the U.S. population. In light of concerns about below-replacement fertility and baby boomer cohorts reaching retirement age, migration represents one important mechanism for slowing down population aging. The number of resettled people in the U.S. has been declining since 1980 but declined even more dramatically after the Trump administrations 2017 Executive Order titled Protecting the Nation from Foreign Terrorist Entry into the United States6,28. Then, after the enactment of Title 42 in March 2020, immigration and resettlement to the U.S. reached the lowest level of the past forty years. Title 42 was harmful for hundreds of thousands of people and ultimately resulted in the expulsion of over 1 million migrants and asylum seekers at the U.S. border, a decision that had no clear statistical relationship with reducing COVID-19 cases19,29. Our results show that the decline in migration resulted in the loss of U.S. population at all ages, but especially at working and reproductive ages. This result highlights that the COVID-19 pandemics effect on migration is more consequential for population size than its effect on mortality, a finding that is consistent with a similar study on Spain8. Government policy responses during crises can have profound effects on the population, through entirely different channels than their desired effect.

Second, in the next four decades there is projected to be fewer reproductive-aged (1549 years old) people in the U.S. This is a result of fewer migrants in childbearing ages, as well as, to a lesser extent, COVID-19 pandemic deaths and second-order implications of migration and mortality for never-born children. Our estimates are likely conservative, as the effects of long COVID, or the prevalence of COVID-19 symptoms long after infection, remain to be seen. Long COVID is similar to other post-acute infections in its ability to cause health complications and disabilities30,31. While less is known about its mortality consequences, it stands to reason that long COVID will be a future contributor to premature deaths.

Third, the high mortality rates of the older age population during the COVID-19 pandemic have led to a small reduction in the U.S. dependency ratio. The magnitude of this reduction is attenuated by missing migration, which by itself would likely increase the dependency ratio. In 2025, almost one half of the reduction in the dependency ratio due to mortality is projected to be balanced out due to missing migration. The balance between population health and national economic stability remains a point of discussion in the U.S.32,33,34. The economic stimulus for COVID-19 pandemic relief and public health policies were important for alleviating the individual economic burden brought on by the COVID-19 pandemic and for aiding in the reduction of COVID-19 cases and mortality, but also placed extraordinary fiscal burden on the U.S. Our dependency ratio projections provide indicators for how demographic changes brought about by the COVID-19 pandemic might continue to affect public finances in the long-term. It should also be noted that, while the dependency ratio is projected to remain slightly smaller as an effect of the COVID-19 pandemic, dependence on working-age individuals may increase due to higher healthcare needs among the older population following the COVID-19 pandemic. Additionally, we note that our calculations of dependency ratio are relatively simplistic. More nuanced calculations of dependency ratios (e.g., the non-working-aged dependency ratio) necessitate estimations of the number of working vs. non-working people at each age35,36,37, and this data are not available in projected form from the UNWPP.

Although the UNWPP data represent a gold standard in terms of population projections, our counterfactual analysis is subject to three limitations. First, our findings are based on UNWPPs medium scenario, i.e., not the most aggressive or the most conservative estimate. As the baseline mortality, fertility, and migration rates and counts represent forecasts themselves, they are subject to uncertainty, which is carried over to our counterfactual estimates. We attempt to mitigate this by focusing on the difference between baseline and counterfactual scenarios. Thus, because mortality, fertility, and migration conditions are set to equal after 2024, there is little room for forecasting errors to compound over time, as these will mostly cancel out. Moreover, the published UNWPP forecasts for the year 2022 correspond well with preliminary estimates of mortality, fertility, and migration4,6,18, generating further trust in our baseline and counterfactual estimates for the COVID-19 pandemic period. Additionally, due to the nature of counterfactual analyses, it is not possible to truly know what observed rates and counts would have been in the absence of the COVID-19 pandemic. While we estimate these to the best of our ability, all analyses must be considered with this limitation in mind.

Second, our finding that changes in migration during the COVID-19 pandemic are projected to exert the biggest long-term effects on population size may partially be driven by the lack of adequate age- and sex-specific migration counts for the U.S. and the application of model migration schedules38 for both the baseline and the counterfactual scenario. We assume a family migration schedule, with migrants concentrated in young and working ages. This also means that the second-order effects of migration through never-born children are particularly large in our study. Immigration to the U.S. has traditionally been concentrated in working ages39 and it is plausible that the largest declines in migration during the COVID-19 pandemic occurred in these age groups. Although it is entirely possible that migration decreased more in other age-groups, including ages older than reproductive ages, existing data on foreign-born immigration to the U.S. indicate that different types of migration (i.e., refugees/asylum seekers, students, work visas, immigrant visas) were similarly affected during the COVID-19 pandemic6. Moreover, the enactment of Title 42 during the COVID-19 pandemic contributed to declines in migration to the U.S. and targeted a broad range of countries19,20,21,22. Thus, our decision to use similar migration schedules for our baseline and counterfactual scenario appears justified. While we are limited by the lack of migration data at smaller temporal windows (e.g., month or week), future work with better data availability might consider analyzing this to gain a more nuanced understanding of how these processes vary across other temporal dimensions.

Third, following UNWPP, we assume that mortality, fertility, and migration return to their pre-COVID-19 pandemic trajectories after a few years. There is inconclusive evidence about what signals the end of a pandemic or epidemic40, so it is possible that the assumptions from UNWPP are incorrect. Should that be the case, and mortality continue to remain higher than expected, and fertility and/or migration continue to remain lower than expected, then our estimates represent an underestimation. The indirect consequences of the COVID-19 pandemic may continue to negatively affect the U.S. mortality, fertility, and migration environments well into the future, and we are not able to measure these indirect consequences here. First, long COVID and unmet healthcare needs during the COVID-19 pandemic may increase the risk of mortality in the long run. Other consequences of the COVID-19 pandemic, such as the loss of next of kin41, learning loss42, or racist and xenophobic behavior against Asians and Asian-Americans43,44 may also exert negative effects on population health and mortality for generations to come. Second, the experience of economic uncertainty and stress related to the balancing of work and childcare obligations during the COVID-19 pandemic may have raised doubts among some couples about having (additional) children in the future45,46. Finally, migration to the U.S. may remain below expected levels in the future, as some individuals who would have migrated to the U.S. may have died during the COVID-19 pandemic, or established families in their country of origin or other countries with less restrictive migration policies. Based on these reflections about the potential long arm of the COVID-19 pandemic, the findings presented in this manuscript, which assume a short pandemic shock, most likely represent a lower bound.

Despite these limitations, our approach is valuable because it considers the interacting effects of changes to population processes. The U.S. will face a variety of public health challenges in the coming years that may have long-lasting effects on the population size and structure, and the COVID-19 pandemic is just one of these challenges. The maternal health and midlife mortality crises are likely to affect the U.S. population through multiple avenues. Demographic predictions warn that a total abortion ban could lead to excess pregnancy-related deaths of nearly 25%47,48, while other work suggests that it may have consequences for in-vitro fertilization rates, contributing to a decline in number of births49. Additionally, if the midlife mortality crisis in the U.S. persists50,51, and if rising mortality rates from the opioid epidemic are not curtailed, then deaths among reproductive-aged people will continue to rise, resulting in fewer people at young adult and midlife ages. Applying the cohort component projection method to these crises will be valuable for understanding the magnitude of their consequences for the U.S. population. It will also be valuable to apply this approach to other countries (beyond Spain and Australia8,9), as the COVID-19 pandemic unequally affected each nation.

The consequences of the COVID-19 pandemic are not over. They ripple beyond immediate, independent changes to mortality, fertility, and migration to affect the population structure of the United States for decades to come. It is thus important to move from process-specific models to a broader and more informative approach that accounts for co-occurring disruptions in mortality, fertility, and migration. As this paper shows, such a design is a powerful tool for quantifying the relative size of different effects of the COVID-19 pandemic and for projecting their effects over time. Because the United States is known for having exceptionally high COVID-19 mortality52, it is important to note that COVID-19 pandemic-induced migration changes are projected to have a comparatively large and longer-lasting effect on population size.

Read the original here:

Projecting the long-term effects of the COVID-19 pandemic on U.S. population structure - Nature.com

Request blocked. We can't connect to the server for this app or website at this time. There might be too much traffic or a configuration error. Try again later, or contact the app or website owner. If you provide content to customers through CloudFront, you can find steps to troubleshoot and help prevent this error by reviewing the CloudFront documentation. Generated by cloudfront (CloudFront)Request ID: FbA-F7Xbsod61GldyBuQ8KJIbh93eAjV1euax87fuBJdc-j9aO_lmw==

Read the original here:

Fom COVID-19 report to COVID action plan - NJ Spotlight News

Eddie Dominguez, professor in the School of Art, Art History and Design, recently completed a two-segment public art project for Bryan Health Systems to commemorate the communitys experiences during the COVID-19pandemic.

A 12-foot-by-22-foot mosaic mural located at Bryan East includes a cluster of clouds with words submitted by hospital staff, who were asked to reflect on their experiences during the pandemic. The second work, located at Bryan West, includes three nine-foot pillars with mosaics. The first has geometric patterns featuring colors and shapes. The second is a sky with eagles, swans and flowers cascading into a lower landscape. The third includes more of the collected words onclouds.

They had put a call out that they were interested in looking for an artist that would do a COVID memorial to honor the first responders at the hospital, Dominguez said. I dont generally respond to calls like that, but when I saw this, there was a calling a feeling that I had about the way I function in public art work projects, and I thought this was a venue for that philosophy, so I went ahead andapplied.

Bob Ravenscroft, system vice president and chief marketing and development officer at Bryan Health, said shortly after the availability of a COVID-19 vaccine and between surges of hospital utilization, they were approached by a handful of people with an affinity for art who were interested in funding a permanent thank you for what they called the heroic effort of our team. Bryan Health wanted something that would be meaningful to their team since they saw thousands of patients at both Bryan East and Bryan Westcampuses.

Eddie responded to the RFP, and his proposal easily emerged as the best concept, Ravenscroft said. Eddie suggested commissioning sculptures that would very directly incorporate the voice of our team, engaging with doctors, nurses and support staff that cared for critically ill and dying patients and what they felt during this challengingtime.

The sculptures turned out beautifully. We often see staff and visitors reflecting on the words embedded in the beautiful tile work. While it was created to memorialize efforts here in Nebraska during a worldwide pandemic, it seems to work for just about any feeling people have when they or a loved one is hospitalized and for those who work every day to care forthem.

The project offered a different way for Dominguez to engage with thecommunity.

The hospital gave me all of the vocabulary that I used in the image, so in that way, it was community engaged without people being physically connected to the work, and I was satisfied with that, Dominguezsaid.

He also worked with six University of NebraskaLincoln students throughout the two-year project, including two who were not artmajors.

I had a nice range of people, and we had a real nice time learning all about how to make it work together, Dominguez said. I think they really loved it and got invested in it. We all bonded in a really beautifulway.

Clouds are featured in both pieces, which was an inspiration forDominguez.

I think that when we look up into the sky, theres always this kind of optimism and hope, he said. And when we look up at the clouds, theyre fleeting and drifting. Ive always had a thing for clouds. I put the words in the clouds, and I think it kind of feels like sending up prayers. Theres a native philosophy like that when people look up into the sky. And maybe it wasnt completely my intention, but you allow the creativity to express itself, and this is how it came out. I have a garden at the bottom, and then the clouds falling out of that. I think theyre really pretty beautiful images, and they have a lot ofsentiment.

Dominguez had his own health issues during the making of the pieces and found himself in and out of hospitals at times throughout theprocess.

I felt like I was in it physically, he said. Its odd how that worked out, but I began to understand by being in these situations what the staff did, what the nurses did, what everybodys job was and how meaningful and important everybodys positions are in hospitals. I was grateful to witness that with a greater understanding because I think that it fed thisproject.

Being a part of this project meant a lot to Dominguez, especially since it was an opportunity to give back to thecommunity.

This provided an opportunity for me to do that to leave something for my community that Im a part of, he said. And the hospital is just a few blocks from my house, so it even felt like it was in my neighborhood. It was a rewarding feeling. And thats why I think public art is important because we can generate community interest in it, through it, withit.

Allison Achtenhagen (Bachelor of Fine Arts 2023) worked on the pieces with Dominguez from August 2022 to July 2023. She is now an artist-in-residence at the Kansas City ClayGuild.

Id briefly had one or two conversations with Eddie prior to him approaching me to work on this project, she said. Id seen the beginning of it through social media, and it looked absolutely amazing, so when I was given the opportunity to become a part of it, it was an easyyes.

I worked on this project with him throughout my senior year, which was a time of huge change, big decisions and questioning what comes next for me, so being able to talk with Eddie as we worked and get his perspective and opinions was life-changing. I also loved watching him navigate all of the issues that came up throughout this process and feeling like he trusted us to help in those trickiermoments.

Luke Keilig, a senior art major, has worked with Dominguez through UCARE for twoyears.

I was involved from the start of the making process, he said. I helped glaze tiles, fired them in the kiln and helped sort them into the design he envisioned. I also helped during the installation process. Working with Eddie was an experience I will never forget. He is a unique and caring individual who cares deeply about the community and his students. I learned a lot about ceramics, but he has also taught me things about life and evencooking.

While the words within the works are expressions from the pandemic, they are are universal, too, Dominguezsaid.

Like all poetry or language, it can have several meanings, he said. Maybe the umbrella was that it was a memorial to the COVID experience, but I think it was also speaking to what goes on in a hospital. I was really grateful to have the opportunity to do it. I got more out of it than I could haveimagined.

See original here:

Dominguez creates art commemorating COVID-19 pandemic | Nebraska Today | University of NebraskaLincoln - Nebraska Today

A rogue governor who seized power despite repeated attempts by the legislature to stop him. Reckless and politicized government scientists who ran a media smear campaign against peers and citizens who challenged their policies. Carnage to the mental health, well-being, and financial fortunes of millions of Americans, especially children.

Four years ago, former Democratic Gov. Tom Wolf ordered all non-life-sustaining businesses in Pennsylvania to close their doors to slow the spread of COVID-19. The week prior, he shut down all Pennsylvania schools. The governor was empowered to take these unilateral actions under the Proclamation of Disaster Emergency he signed on March 6, 2020.

Wolfs actions seemed sensible at first. A deadly virus was sweeping the world, killing even the young and healthy. The government scientists at the Centers for Disease Control and Prevention said it would just take 15 days to flatten the curve of COVID and save lives. Who wouldnt want to save lives? A two-week shutdown seemed right.

But Wolf would not stop at two weeks. After his initial 90-day emergency declaration was set to expire, he extended it for over a year. During that time, Wolf ignored his own legislatures votes to limit his power. He defied a federal judges ruling that his actions were unconstitutional. After 15 months, Pennsylvanians ended Wolfs authoritarian reign through a successful ballot initiative, limiting a governors ability to use emergency powers.

It was a rare instance where citizens were able to exert control over a chaotic, dangerous, and powerful government bureaucracy that politicized a pandemic and upended lives.

Pennsylvanians could rein in politicians but entrenched federal bureaucracies they could not. No bureaucracy eroded public trust during the pandemic quite like the CDC. The health agency made and directed policies that were based on faulty information and, as whistleblowers would report, refused to change course, even when presented with truthful information.

To be frank, we are responsible for some pretty dramatic, pretty public mistakes, from testing, to data, to communications, said CDC director Rochelle Walensky. None more so than the CDCs dogmatic insistence on the six-foot social distancing requirement that upended American society. Despite evidence presented by scientists that three feet would suffice for social distancing, then CDC head Anthony Fauci refused to change protocols.

Of course, the CDC was going to make missteps in a fast-moving pandemic. The problem is that when presented with evidence to counter their policies, the CDC became dogmatic and political.

That entrenched bureaucracy led by Fauci and aided and abetted by the Biden administration sought to undermine, silence, and discredit dissenters. Independent journalists were able to scour Twitters (now Xs) files after Elon Musk bought the company. What those journalists uncovered was more akin to 1950s Moscow KGB tactics than what we would expect in a free society.

Thanks to Musk, independent journalist Matt Taibbi was able to uncover the Biden administration pressuring with success Twitter executives to elevate or suppress information that, Taibbi said, was true but inconvenient.

But the worst act of Faucis attempts to discredit and undermine those opposing him was his response to the Great Barrington Declaration. In October 2020, three epidemiologists Martin Kulldorff of Harvard, Sunetra Gupta of Oxford, and Jay Bhattacharya of Stanford challenged the CDC and called for a more balanced and measured approach.

Time would prove the Barrington doctors right. But at the time, Fauci and Francis Collins, the head of the National Institutes of Health, had an email exchange in which they discussed a devastating takedown to undermine and discredit Bhattacharya and the others as fringe doctors. What followed was a slew of coverage in the Washington Post, the New York Times, ABC News, and other outlets undermining the Barrington doctors credibility.

The disinformation campaign against Kulldorff, Bhattacharya, and others led them to file a lawsuit against the federal government and public health leaders. In the lawsuit, the plaintiffs contend that Fauci coordinated directly with Facebook and/or other social-media firms to suppress disfavored speakers and content of speech on social media.

Our children were the most impacted. In 2021, 42% of high school students reported persistent sadness and hopelessness. Depression and despair were highest among female and LGBTQ students. During the same time, the Mayo Clinic reported higher rates of suicidal ideation, self-harm, eating disorders, and substance abuse among minors than in previous years.

For science to be trusted, it requires questions and doubts. So, too, for the government. Many Americans raised objections and questioned the CDCs data and its use of it to infringe on civil liberties. Those people were demonized and discredited. Fauci said those who challenged the CDC were ignoring science. Ugly smear campaigns against the people who had the courage to speak truth to power should not be forgotten.

While COVID-19 may no longer be a global threat, an increasingly authoritarian government still is.

More here:

Four years later, COVID-19 shutdowns remind us the government is the ultimate tyrant - The Philadelphia Inquirer

The page you requested was not found. You may have followed an old link or typed the address incorrectly.

We've also been doing some house cleaning so the page may have been moved or removed.

Please try searching for what you are looking for or you could go to the home page and start from there. Or you may be interested in today's top stories.

Go here to see the original:

Up Close with Bill Ritter: COVID-19 lockdown 4th anniversary and the lessons learned - WABC-TV

Following early implementation and national responses to suppress the spread of COVID-19, Singapore reported one of the lowest mortality rates in the world25. Having experienced two pandemics previously, the severe acute respiratory syndrome (SARS) in 2003 and influenza A (H1N1) in 2008, the government developed the DORSCON risk assessment to facilitate containment measures across sectors26. The government responded swiftly by activating the risk assessment to the second highest level of DORSCON Orange just 15days after the first case was reported. Early efforts to contain the virus focused on reducing the risk of transmission.

At the start of the pandemic, the public was advised to exercise social responsibility if feeling unwell by seeking medical attention immediately. To ensure primary care remains accessible and affordable in times of national emergency, the government activated the Public Health Preparedness Clinics (PHPC) scheme involving more than 900 general practitioners on 18 February 202027. In addition to polyclinics, patients with respiratory symptoms were offered subsidised treatment and medications at PHPC, where the wait times are usually shorter. This reduces the load of patients with acute conditions on polyclinics as similar treatment options were available at PHPC. At the same time, pre-emptive measures were also put in place. Patients with respiratory symptoms were issued with mandatory five days of sick leave and they were legally required to stay home and only leave to seek additional medical attention28. However, for patients who were sick but had work attendance incentives tied to sick leave, this policy could have deterred them from seeking treatment, overall reducing the number of acute visits29.

Non-pharmaceutical interventions, such as mask-wearing, good hygiene practices and social distancing, were also encouraged to reduce the transmission of COVID-19. These measures were found to reduce the transmission of other viral respiratory infections with similar modes of transmission as COVID-1930,31. Additionally, travel restrictions also limited the spread of other respiratory infections across national borders32. In Singapore, the implementation of non-pharmaceutical interventions was associated with a reduction in the prevalence of respiratory viruses such as influenza, which consistently remained low until the end of 202033.

In the early stages of the pandemic, primary care was used to test for suspected cases before they were referred to hospitals for further treatment. Despite efforts to mitigate the risk of cross-infection between patients by setting up segregation zones and triaging patients by their COVID-19 risk profile, patients may be reluctant to visit the doctor lest they be exposed to infected cases34. A study conducted in Singapore revealed that 40% of patients with chronic conditions missed their healthcare appointments during the outbreak, with 72% doing so voluntarily due to a greater perceived risk of infections at a healthcare institution35. This sentiment was also prevalent in other countries36. Studies elsewhere have shown that patients with underlying chronic conditions did not seek medical care for fear of exposure to COVID-1937. These could have led to a drop in overall primary care visits.

As the number of cases started to spike, the government imposed Circuit Breaker to keep cases under control. The public was advised to avoid going out unless necessary as work-from-home arrangements became the default and schools shifted to home-based learning. Non-essential services were deferred while essential services were scaled down whenever possible. For patients who required medication refills, these were done through a medication delivery service if applicable38. All social gathering events were also banned, which reduced the spread of acute respiratory infections.

Our analysis revealed a contrasting pattern in the reduction of acute and chronic visits associated with Circuit Breaker in the unadjusted and adjusted models. In the unadjusted model, we observed a larger reduction in acute visits, while the adjusted model showed a greater reduction in chronic visits. Notably, patients were 0.85years older during Circuit Breaker compared to DORSCON Orange (average age: 60.9 vs. 60.1years, p<0.001), a demographic factor that likely contributed to the increased reduction in chronic visits in the adjusted model. This divergence in the reduction of acute and chronic visits, evident across both models, highlights the vulnerability of specific patient populations, particularly those older and with chronic conditions. This underscores the need for targeted interventions and strategic resource allocation during public health crises.

During this period, there was also a push for telehealth services39. This may have resulted in the conversion of some face-to-face primary care visits from polyclinics to telehealth visits, which could have freed up some of the appointments in polyclinics to be reallocated to patients with chronic conditions. Towards the end of Circuit Breaker, primary healthcare services in hospitals were allowed to resume in phases where patients with chronic medical conditions were attended to first to ensure continuity of chronic care22. This might also have encouraged patients with chronic medical conditions to seek care in polyclinics, as the fear of seeking primary care subsided. Thus, the proportion of daily chronic visits appears to increase faster than acute visits during Circuit Breaker.

Similar findings have been observed in other countries. Following the lockdown in the UK, there was a significant reduction in virtual and face-to-face primary care consultations related to specific health conditions, including acute respiratory and cardiovascular conditions40. Three months after the restriction was lifted, remote and in-person consultations were still lower than pre-lockdown levels. Other studies conducted in the UK also reported substantial reduction with slow recovery in primary care attendance associated with asthma exacerbation and chronic obstructive pulmonary disease41,42,43. The authors hypothesise that the reduction in primary care visits may have been due to the reprioritisation of primary health services in which general practitioners (GPs) were required to balance COVID-19 infection care with primary care services coupled with fears associated with COVID-19 infection. To protect the patients, GPs were advised to minimise the number of in-person consultations. Across the world, healthcare services for other conditions were scaled back as resources were redirected to care for COVID-19 cases. This has caused delays in healthcare delivery for other conditions. This delay or avoidance of seeking care can increase morbidity and mortality44.

There are limitations to this study. The data used in this study is limited to a cluster of public primary care clinics. Primary healthcare services in Singapore are delivered through a network of public primary care clinics and private general practitioner clinics. At the time of this study, 20 public primary care clinics were in operation, comprising only 20% of the sector45. Additionally, the distribution of chronic care needs addressed by public clinics is significantly imbalanced, with 80% of chronic care needs addressed by public care clinics45. Likewise, the proportion of acute care needs addressed by private clinics is much higher. Furthermore, telemedicine played a crucial role in providing primary care services during the pandemic while minimizing physical contact. The inherent variation in attendance patterns between public clinics, private clinics, and telemedicine may introduce complexities in generalizing the findings across the primary care landscape in Singapore.

While our study shed light on the impact of DORSCON Orange and Circuit Breaker on primary care utilisation, the impact may not be directly attributable to these policies as there were other nationwide measures concurrently rolled out such as public education and enforcement of non-pharmaceutical interventions. Additionally, the reprioritisation of primary care services also affected other primary care services that were not examined in this study. Moreover, as the relaxation of the Circuit Breaker measures occurred gradually in a phased approach, our model may only partially encapsulate the complete impact of these policies on primary care visits.

Lastly, primary care manages more than just acute and chronic medical conditions; it includes preventive health screening, immunisation, and dental services.

Despite these limitations, this study provides an understanding of primary care utilisation in the face of the COVID-19 national response. The unintended effect of restrictive measures may have been overlooked and understanding it can help inform future policy discussions on balancing infectious disease care and essential primary care services.

Our findings add to the growing body of literature on the impact of the COVID-19 national response on healthcare utilisation. Understanding the impact of national responses on primary care is especially crucial as primary care serves as the first point of contact with patients, not just in the face of COVID-19 but also in the growing burden of chronic conditions. It is important to recognise the challenges that other patients may face. Disruption in essential primary care services, particularly chronic care management, may lead to profound health consequences. Further studies with a longer observation period may be needed to understand the prolonged impact of COVID-19.

The study was approved by the ethics committee of the National University of Singapore Institutional Review Board (NUS-IRB-2021-611). All methods were carried out in accordance with relevant guidelines and regulations. Informed consent was obtained from all subjects and/or their legal guardian(s).

Go here to read the rest:

Impact of COVID-19 national response on primary care utilisation in Singapore: an interrupted time-series analysis ... - Nature.com

Niazkar, H. R., Zibaee, B., Nasimi, A. & Bahri, N. The neurological manifestations of COVID-19: A review article. Neurol. Sci. 41, 16671671 (2020).

Article PubMed PubMed Central Google Scholar

Stefanou, M. I. et al. Neurological manifestations of long-COVID syndrome: A narrative review. Ther. Adv. Chronic Dis. 13, 20406223221076890. https://doi.org/10.1177/20406223221076890 (2022).

Article PubMed PubMed Central Google Scholar

Kurushina, O. V. & Barulin, A. E. Central nervous system lesions in COVID-19. Neurosci. Behav. Physiol. 51, 12221227. https://doi.org/10.1007/s11055-021-01183-2 (2021).

Article CAS PubMed Google Scholar

Khalil, M. et al. Neurofilaments as biomarkers in neurological disorders. Nat. Rev. Neurol. 14, 577589. https://doi.org/10.1038/s41582-018-0058-z (2018).

Article CAS PubMed Google Scholar

Barro, C. et al. Serum GFAP and NfL levels differentiate subsequent progression and disease activity in patients with progressive multiple sclerosis. Neurol. Neuroimmunol. Neuroinflamm. 10, e200052. https://doi.org/10.1212/NXI.0000000000200052 (2022).

Article PubMed PubMed Central Google Scholar

Andreasson, U., Blennow, K. & Zetterberg, H. Update on ultrasensitive technologies to facilitate research on blood biomarkers for central nervous system disorders. Alzheimers Dement. 3, 98102. https://doi.org/10.1016/j.dadm.2016.05.005 (2016).

Article Google Scholar

Frontera, J. A. et al. Comparison of serum neurodegenerative biomarkers among hospitalized COVID-19 patients versus non-COVID subjects with normal cognition, mild cognitive impairment, or Alzheimers dementia. Alzheimers Dement. 18, 899910. https://doi.org/10.1002/alz.12556 (2022).

Article CAS PubMed Google Scholar

Plantone, D. et al. Brain neuronal and glial damage during acute COVID-19 infection in the absence of clinical neurological manifestations. J. Neurol. Neurosurg. Psychiatry 93, 13431348. https://doi.org/10.1136/jnnp-2022-329933 (2022).

Article PubMed Google Scholar

Verde, F. et al. Serum neurofilament light chain levels in COVID-19 patients without major neurological manifestations. J. Neurol. 269, 56915701 (2022).

Article CAS PubMed PubMed Central Google Scholar

Virhammar, J. et al. Biomarkers for central nervous system injury in cerebrospinal fluid are elevated in COVID-19 and associated with neurological symptoms and disease severity. Eur. J. Neurol. 28, 33243331. https://doi.org/10.1111/ene.14703 (2021).

Article PubMed PubMed Central Google Scholar

Ameres, M. et al. Association of neuronal injury blood marker neurofilament light chain with mild-to-moderate COVID-19. J. Neurol. 267, 34763478. https://doi.org/10.1007/s00415-020-10050-y (2020).

Article CAS PubMed PubMed Central Google Scholar

Woo, M.S., Malsy, J., Pttgen, J., Seddiq Zai, S., Ufer, F. et al. Frequent neurocognitive deficits after recovery from mild COVID-19. Brain Commun. 2(2), fcaa205 https://doi.org/10.1093/braincomms/fcaa205 (2020).

Taskiran-Sag, A. et al. Subacute neurological sequelae in mild COVID-19 outpatients. Tuberk Toraks 70(1), 2736. https://doi.org/10.5578/tt.20229904 (2022) (English).

Article PubMed Google Scholar

Apple, A. C. et al. Risk factors and abnormal cerebrospinal fluid associate with cognitive symptoms after mild COVID-19. Ann. Clin. Transl. Neurol. 9(2), 221226. https://doi.org/10.1002/acn3.51498 (2022).

Article CAS PubMed PubMed Central Google Scholar

Hellmuth, J. et al. Persistent COVID-19-associated neurocognitive symptoms in non-hospitalized patients. J. Neurovirol. 27(1), 191195. https://doi.org/10.1007/s13365-021-00954-4 (2021).

Article CAS PubMed PubMed Central Google Scholar

Owens, C. D. et al. Vascular mechanisms leading to progression of mild cognitive impairment to dementia after COVID-19: Protocol and methodology of a prospective longitudinal observational study. PLoS One. 18(8), e0289508. https://doi.org/10.1371/journal.pone.0289508 (2023).

Article CAS PubMed PubMed Central Google Scholar

Arnetz, J. E., Arble, E., Sudan, S. & Arnetz, B. B. Workplace cognitive failure among nurses during the COVID-19 pandemic. Int J Environ Res Public Health 18, 10394. https://doi.org/10.3390/ijerph181910394 (2021).

Article CAS PubMed PubMed Central Google Scholar

Mattioli, F. et al. Neurological and cognitive sequelae of Covid-19: A four-month follow-up. J Neurol 268, 44224428. https://doi.org/10.1007/s00415-021-10579-6 (2021).

Article CAS PubMed PubMed Central Google Scholar

Alicandro, G., Gerli, A. G., Remuzzi, G., Centanni, S. & La Vecchia, C. Updated estimates of excess total mortality in Italy during the circulation of the BA.2 and BA.45 Omicron variants: April-July 2022. Med Lav 113, e2022046. https://doi.org/10.23749/mdl.v113i5.13825 (2022).

Article PubMed PubMed Central Google Scholar

Stufano, A. et al. Oxidative damage and post-COVID syndrome: A cross-sectional study in a cohort of Italian workers. Int J Mol Sci. 24(8), 7445. https://doi.org/10.3390/ijms24087445 (2023).

Article PubMed PubMed Central Google Scholar

Global Burden of Disease Long COVID Collaborators. Estimated global proportions of individuals with persistent fatigue, cognitive, and respiratory symptom clusters following symptomatic COVID-19 in 2020 and 2021. JAMA 328(16), 16041615. https://doi.org/10.1001/jama.2022.18931 (2022).

Article PubMed Central Google Scholar

WHO Working Group on the Clinical Characterisation and Management of COVID-19 Infection. A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect. Dis. 20, e192e197 https://doi.org/10.1016/S1473-3099(20)30483-7 (2020).

CDC. Division of Population Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention https://www.cdc.gov/alcohol/checkyourdrinking/index (2023).

Corsi, G., Nava, S. & Barco, S. Un nuovo strumento per misurare lo stato funzionale globale a lungo termine dei pazienti con malattia da coronavirus 2019: la scala PCFS (Post-COVID-19 Functional Status) [A novel tool to monitor the individual functional status after COVID-19: the Post-COVID-19 Functional Status (PCFS) scale]. G Ital. Cardiol. (Rome) 21, 757. https://doi.org/10.1714/3431.34198 (2020).

Article PubMed Google Scholar

Mazzotti, E. et al. II Patient Health Questionnaire (PHQ) per lo screening dei disturbi psichiatrici: Uno studio di validazione nei confronti della Intervista Clinica Strutturata per il DSM-IV asse I (SCID-I). Ital. J. Psychopathol. 9, 122 (2003).

Google Scholar

Stratta, P., Rinaldi, O., Daneluzzo, E. & Rossi, A. Utilizzo della versione Italiana del Cognitive Failures Questionnaire (CFQ) in un campione di studenti: uno studio di validazione. Riv. Psichiatr. 41, 260265 (2006).

Google Scholar

Kroenke, K., Spitzer, R. L. & Williams, J. B. The PHQ-9: Validity of a brief depression severity measure. J. Gen. Intern. Med. 16, 606613. https://doi.org/10.1046/j.1525-1497.2001.016009606.x (2001).

Article CAS PubMed PubMed Central Google Scholar

Broadbent, D. E., Cooper, P. F., FitzGerald, P. & Parkes, K. R. The Cognitive Failures Questionnaire (CFQ) and its correlates. Br. J. Clin. Psychol. 21, 116. https://doi.org/10.1111/j.2044-8260.1982.tb01421.x (1982).

Article CAS PubMed Google Scholar

Benkert, P. et al. Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: A retrospective modelling and validation study. Lancet Neurol. 21, 246257. https://doi.org/10.1016/S1474-4422(22)00009-6 (2022).

Article PubMed Google Scholar

Bergman, J. et al. Neurofilament light in CSF and serum is a sensitive marker for axonal white matter injury in MS. Neurol. Neuroimmunol. Neuroinflamm. 3, e271. https://doi.org/10.1212/NXI.0000000000000271 (2016).

Article PubMed PubMed Central Google Scholar

Pezzini, A. & Padovani, A. Lifting the mask on neurological manifestations of COVID-19. Nat. Rev. Neurol. 16, 636644. https://doi.org/10.1038/s41582-020-0398-3 (2020).

Article CAS PubMed PubMed Central Google Scholar

Zetterberg, H. & Blennow, K. From cerebrospinal fluid to blood: The third wave of fluid biomarkers for Alzheimers disease. J. Alzheimers Dis. 64, S271S279. https://doi.org/10.3233/JAD-179926 (2018).

Article PubMed Google Scholar

Papa, L. et al. Time course and diagnostic accuracy of glial and neuronal blood biomarkers GFAP and UCH-L1 in a large cohort of trauma patients with and without mild traumatic brain injury. JAMA Neurol. 73, 551560. https://doi.org/10.1001/jamaneurol.2016.0039 (2016).

Article PubMed PubMed Central Google Scholar

Thelin, E. P. et al. Serial sampling of serum protein biomarkers for monitoring human traumatic brain injury dynamics: A systematic review. Front. Neurol. 8, 300. https://doi.org/10.3389/fneur.2017.00300 (2017).

Article PubMed PubMed Central Google Scholar

Welch, R. D. et al. Modeling the kinetics of serum glial fibrillary acidic protein, ubiquitin carboxyl-terminal hydrolase-L1, and S100B concentrations in patients with traumatic brain injury. J. Neurotrauma 34, 19571971. https://doi.org/10.1089/neu.2016.4772 (2017).

Article PubMed PubMed Central Google Scholar

Baig, A. M., Khaleeq, A., Ali, U. & Syeda, H. Evidence of the COVID-19 virus targeting the CNS: Tissue distribution, hostvirus interaction, and proposed neurotropic mechanisms. ACS Chem. Neurosci. 11, 995998. https://doi.org/10.1021/acschemneuro.0c00122 (2020).

Article CAS PubMed Google Scholar

Boroujeni, M. E. et al. Inflammatory response leads to neuronal death in human post-mortem cerebral cortex in patients with COVID-19. ACS Chem. Neurosci. 12, 21432150. https://doi.org/10.1021/acschemneuro.1c00111 (2021).

Article CAS PubMed Google Scholar

Gupta, A. et al. Extrapulmonary manifestations of COVID-19. Nat. Med. 26, 10171032. https://doi.org/10.1038/s41591-020-0968-3 (2020).

Article CAS PubMed Google Scholar

Peluso, M. J. et al. Plasma markers of neurologic injury and inflammation in people with self-reported neurologic postacute sequelae of SARS-CoV-2 infection. Neurol. Neuroimmunol. Neuroinflamm. 9(5), e200003. https://doi.org/10.1212/NXI.0000000000200003.PMID:35701186 (2022).

Article PubMed PubMed Central Google Scholar

Kanberg, N. et al. Neurochemical signs of astrocytic and neuronal injury in acute COVID-19 normalizes during long-term follow-up. EBioMedicine 70, 103512. https://doi.org/10.1016/j.ebiom.2021.103512 (2021).

Article CAS PubMed PubMed Central Google Scholar

Newcombe, V. F. J. et al. Post-acute blood biomarkers and disease progression in traumatic brain injury. Brain 145(6), 20642076. https://doi.org/10.1093/brain/awac126 (2022).

Article PubMed PubMed Central Google Scholar

Bark, L. et al. Central nervous system biomarkers GFAp and NfL associate with post-acute cognitive impairment and fatigue following critical COVID-19. Sci. Rep. 13(1), 13144. https://doi.org/10.1038/s41598-023-39698-y (2023).

Article ADS CAS PubMed PubMed Central Google Scholar

Liu, T. C. et al. Perceived cognitive deficits in patients with symptomatic SARS-CoV-2 and their association with post-COVID-19 condition. JAMA Netw. Open 6, e2311974. https://doi.org/10.1001/jamanetworkopen.2023.11974 (2023).

Article PubMed PubMed Central Google Scholar

Tavares-Jnior, J. W. L. et al. COVID-19 associated cognitive impairment: A systematic review. Cortex 152, 7797. https://doi.org/10.1016/j.cortex.2022.04.006 (2022).

Article PubMed PubMed Central Google Scholar

Ferrucci, R. et al. Brain positron emission tomography (PET) and cognitive abnormalities one year after COVID-19. J. Neurol. 270, 18231834. https://doi.org/10.1007/s00415-022-11543-8 (2023).

Article CAS PubMed PubMed Central Google Scholar

Hosp, J. A. et al. Cognitive impairment and altered cerebral glucose metabolism in the subacute stage of COVID-19. Brain 144, 12631276. https://doi.org/10.1093/brain/awab009 (2021).

Article PubMed Google Scholar

Henneghan, A. M., Lewis, K. A., Gill, E. & Kesler, S. R. Cognitive impairment in non-critical, mild-to-moderate COVID-19 survivors. Front. Psychol. 17(13), 770459. https://doi.org/10.3389/fpsyg.2022.770459.PMID:35250714;PMCID:PMC8891805 (2022).

Article Google Scholar

Tavares-Jnior, J. W. L. et al. COVID-19 associated cognitive impairment: A systematic review. Cortex 152, 7797. https://doi.org/10.1016/j.cortex.2022.04.006 (2022).

Article PubMed PubMed Central Google Scholar

Baseler, H. A., Aksoy, M., Salawu, A., Green, A. & Asghar, A. U. R. The negative impact of COVID-19 on working memory revealed using a rapid online quiz. PLoS One 17(11), e0269353. https://doi.org/10.1371/journal.pone.0269353 (2022).

Article CAS PubMed PubMed Central Google Scholar

Quan, M. et al. Post-COVID cognitive dysfunction: Current status and research recommendations for high risk population. Lancet Reg. Health West Pac. 5(38), 100836. https://doi.org/10.1016/j.lanwpc.2023.100836 (2023).

Article Google Scholar

Beck, J. W. & Flow, A. The effects of contracting COVID-19 on cognitive failures at work: Implications for task performance and turnover intentions. Sci. Rep. 12, 8826. https://doi.org/10.1038/s41598-022-13051-1 (2022).

Article ADS CAS PubMed PubMed Central Google Scholar

Lu, X., Yu, H. & Shan, B. Relationship between employee mental health and job performance: Mediation role of innovative behavior and work engagement. Int. J. Environ. Res. Public Health 19(11), 6599. https://doi.org/10.3390/ijerph19116599 (2022).

Visit link:

Neurofilament light chain and glial fibrillary acid protein levels are elevated in post-mild COVID-19 or asymptomatic ... - Nature.com

Bonham and her collaborators wanted to better understand why this scarring occurs, determine if it is similar to progressive pulmonary fibrosis and see if there is a way to identify patients at risk.

Researchers followed 16 UVA Health patients who survived severe COVID-19, including 14 who were hospitalized and placed on a ventilator during treatment. All had trouble breathing and suffered fatigue and abnormal lung function at their first outpatient checkup.

After six months, researchers found that the patients could be divided into two groups. One groups lung health improved, prompting the researchers to label them early resolvers. The other group, dubbed late resolvers, continued to suffer lung problems and pulmonary fibrosis.

Looking at blood samples taken before the recovery paths diverged, the team found that late resolvers had significantly fewer immune cells known as monocytes white blood cells that play a critical role fending off disease circulating in their blood. The cells were abnormally depleted in patients who continued to suffer lung problems compared both to those who recovered and healthy control subjects.

The decrease in monocytes also correlated with the severity of the patients ongoing symptoms. That suggests that doctors may be able to use a simple blood test to identify patients likely to suffer long-haul COVID and to improve their care.

About half of the patients we examined still had lingering, bothersome symptoms and abnormal tests after six months, Bonham said. We were able to detect differences in their blood from the first visit, with fewer blood monocytes mapping to lower lung function.

The researchers also wanted to determine if severe COVID-19 could cause progressive lung scarring like idiopathic pulmonary fibrosis. They found the two conditions had very different effects on immune cells, suggesting that even though symptoms were similar, the underlying causes were very different. This held true in patients with the most persistent long-haul COVID-19 symptoms.

Idiopathic pulmonary fibrosis is progressive and kills patients within three to five years, Bonham said. It was a relief to see that all our COVID patients, even those with long-haul symptoms, were not similar.

Because of the small numbers of participants in UVAs study, and because they were mostly male (for easier comparison with idiopathic pulmonary fibrosis, a disease that strikes mostly men), the researchers say larger studies with other medical centers are needed to bear out the findings.

Still, they are hopeful that their new discovery will provide doctors a useful tool to identify COVID-19 patients at risk for long-haul lung problems and help guide them to recovery.

We are only beginning to understand the biology of how the immune system impacts pulmonary fibrosis, Bonham said. My team and I were humbled and grateful to work with the outstanding patients who made this study possible.

The researchers havepublished their findings in the scientific journal Frontiers in Immunology. The research team consisted of Grace C. Bingham, Lyndsey M. Muehling, Chaofan Li, Yong Huang, Shwu-Fan Ma, Daniel Abebayehu, Imre Noth, Jie Sun, Judith A. Woodfolk, Thomas H. Barker and Bonham. Noth disclosed that he has received personal fees from Boehringer Ingelheim, Genentech and Confo unrelated to the research project. In addition, he has a patent pending related to idiopathic pulmonary fibrosis. Bonham and all other members of the research team had no financial conflicts to disclose.

To keep up with the latest medical research news from UVA, subscribe to UVA Healths Making of Medicineblog.

The UVA research was supported by the National Institutes of Health, grants R21 AI160334 and U01 AI125056; NIHs National Heart, Lung and Blood Institute, grants 5K23HL143135-04 and UG3HL145266; UVAs Engineering in Medicine Seed Fund; the UVA Global Infectious Diseases Institutes COVID-19 Rapid Response; a UVA Robert R. Wagner Fellowship; and a Sture G. Olsson Fellowship in Engineering.

Read the original:

Blood Test Could Predict Risk of Long-Term COVID-19 Lung Problems - UVA Today

Stanford researchers aim to get ahead of coronavirus evolution by designing antiviral drugs that continue to work on Paxlovid-resistant mutants. (Image credit: Getty Images)

Although COVID-19 has faded from the headlines, SARS-CoV-2 the coronavirus behind the pandemic is still rampantly infecting people around the world. Public health officials fear as the virus continues to evolve, it will eventually hit upon a diabolical mutation that renders current treatments ineffective, triggering a new wave of severe infection and social disruption.

In pursuit of new therapies to avoid this dark fate, researchers at Stanford have now unveiled a compound that measures up as a potentially powerful anti-coronavirus drug, detailed in a paper published March 13 in Science Translational Medicine. Dubbed ML2006a4, the compound works in the same way as Paxlovid the most effective oral drug available to date by binding to coronavirus particles and preventing the virus from making copies of itself. Compared to Paxlovid, though, ML2006a4 binds more tightly and durably, courtesy of the Stanford team custom-crafting the compound atom-by-atom.

In preclinical experiments, the compound prevented deadly infections in mice at a superior rate compared to Paxlovid. In addition, the new compound is potent enough that it could likely be formulated without an additional component present in Paxlovid that poses severe drug interaction concerns. Importantly, ML2006a4 also performed well against coronavirus variants that have already evolved degrees of resistance to Paxlovid, suggesting the compounds honed affinity makes it less vulnerable to mutant virus strains.

At this point entering the fifth year of the pandemic, Paxlovid is our only really good drug against SARS-CoV-2, but its proven fairly easy for the virus to evolve resistance to it, said Michael Lin, the senior author of the study, who is an associate professor of neurobiology and of bioengineering in the schools of Medicine and Engineering and a member of Stanford Bio-X. As new waves of coronavirus keep crashing down, we need to have alternative drugs that are more tolerant of mutations and not as easy for the virus to defeat.

For the study, Lin worked closely with lead author Michael Westberg, now an assistant professor at Aarhus University in Denmark. From 2018 until 2022, Westberg worked in Lins lab as a visiting scholar at Stanford Bio-X, funded by the Novo Nordisk Foundation, through a joint program designed to strengthen international collaborations and the exchange of scientific expertise between Stanford and Denmark.

Before the pandemic outbreak in 2020, Lins lab had already been investigating the broad class of drugs known as viral protease inhibitors. These drugs target protease enzymes that viruses need for disassembling bulky viral proteins as part of their replication cycle. Like a key fitting into a lock, protease inhibitors occupy the spaces, or active sites, where proteases normally link up with those bulky proteins, thus nipping replication in the bud.

Specifically, the Stanford researchers had gained familiarity with hepatitis C virus protease, which has similarities to coronavirus versions. Although Westberg had come to Stanford to work on other projects, the global emergency prompted a pivot. When the pandemic hit, we asked if we could put our expertise to good use, said Lin.

Their early research, posted online in September 2020, demonstrated that a hepatitis C drug, boceprevir, slotted reasonably well into the coronavirus protease site. Other scientists built off those findings, including at the pharmaceutical company Pfizer, which ultimately created Paxlovid and received regulatory approval for its use in December 2021. We knew then that we were on the right track, said Lin, and we were motivated to keep going and make an even more effective drug.

The Lin lab pooled its collective chemical knowledge to design improvements to their iterative boceprevir-based compounds. Much of the work involved modifying the compound on the atomic scale in intricately detailed computer models to fit more snugly in the coronavirus protease active site.

Basically, you put your drug in the active site and you look for gaps where it doesnt tightly fit. Then you fill those gaps, said Lin.

The Stanford researchers approached this challenge in a rational way by adding different configurations of atoms of carbon, nitrogen, and oxygen to the compounds as permitted by the laws of biochemistry.

Theres a lot of creativity and intuition involved because everyone is working with the same three atoms, but there are essentially infinite ways to arrange them, said Lin. Making these modifications, its like playing atomic Tetris.

The resulting compounds were then tested against actual coronavirus particles at the Stanford In Vitro Biosafety Level 3 Service Center. After multiple rounds of honing, Lins team arrived at the compound designated ML2006a4.

In studies with SARS-CoV-2-infected mice, ML2006a4 worked as well as Paxlovid in promoting survival, while offering better protection of the rodents lungs and lowering overall virus load in the body.

The researchers attribute this success to ML2006a4s extremely refined fit inside coronavirus protease, where the compound boasted a 20-fold higher binding affinity than Paxlovid. That better fit equates to stronger chemical bonds, meaning the drug can stay bound to the protease for a longer time. In this temporal regard, ML2006a4 indeed proved quite sticky: The inhibitor remained attached for approximately330minutes, or greater thanfivehours, whereas the corresponding Paxlovid inhibitor typically fell off its target in just abouttwo minutes.

From a medication perspective, such staying power translates to spaced-out, smaller doses that can still prevent disease from worsening while giving the immune system a chance to kill off the invaders. The long-lived drug-enzyme complex helps ensure that the virus doesnt escape and replicate before your next medication dose, said Lin.

In this way, ML2006a4 offers other advantages compared to Paxlovid. Technically, Paxlovid is two drugs packaged together: nirmatrelvir, the actual protease inhibitor, and ritonavir, a drug that prevents the liver from quickly breaking down nirmatrelvir, boosting nirmatrelvirs performance. Yet the slowing of the livers metabolism by ritonavir means that other drugs can toxically build up, forcing patients to take the risk of temporarily stopping their normal medications.

According to Lin, an oral pill based on ML2006a4 might not require ritonavir to prop up drug levels enough between typical 12-hour administrations to effectively keep coronavirus in check, but this would need to be tested to make sure, said Lin. We also continue to make improved versions of ML2006a4 with better potency and duration of activity, he added.

For the promising compounds to move forward, Lin and colleagues are seeking additional investment. So far, their funding has mostly consisted of small grants geared toward early-stage drug discovery. The group now feels their compounds are ready for expanded preclinical testing with an eye toward clinical trials in human patients.

Were very excited how far weve come and how successful our drug discovery has been on a shoestring budget, said Lin. We hope to see this promising compound developed further to stay ready for what SARS-CoV-2 throws at us next.

Additional Stanford co-authors on the paper include Shirit Einav, professor of medicine infectious diseases and of microbiology and immunology; Catherine Blish, the George E. and Lucy Becker Professor in Medicine and professor of medicine infectious diseases; Jaishree Garhyan, director of Biosafety Level 3 (BSL3) Service; Daniel Fernandez, director of crystallography; Puja Bhavesh Patel, research professional; Chenzhou Hao, research scientist; doctoral student Yan Wu; postdoctoral scholars Xinzhi Zou, Chieh-Wen Lo, and Marwah Karim; instructor in medicine Arjun Rustagi; former postdoctoral scholars Yichi Su and Lin Ning; and former researcher Aimee Beck. Lin is also an associate professor, by courtesy, of chemical and systems biology, and a member of the Cardiovascular Institute, the Maternal & Child Health Research Institute, Sarafan ChEM-H, the Stanford Cancer Institute, and the Wu Tsai Neurosciences Institute.

Funding for the research was provided by Stanfords Sarafan ChEM-H and the Innovative Medicines Accelerator, a Harrington Scholar-Innovator Award, Emergent Ventures at the Mercatus Center at George Mason University, a Stanford-Coulter Translational Research Grant, the National Institutes of Health, the Denver Foundation, the Novo Nordisk Foundation and the Stanford Bio-X Program, a Bio-X Stanford Interdisciplinary Graduate Student Fellowship, the Houston EM Foundation, and the PhRMA Foundation.

To read all stories about Stanford science, subscribe to the biweekly Stanford Science Digest.

Original post:

Drug design at the atomic level to thwart COVID-19 | Stanford News - Stanford University News

U.S.marriages have reboundedto pre-pandemic levels with nearly 2.1 million in 2022.

Thats a 4% increase from the year before. The Centers for Disease Control and Prevention released the data Friday but has not released marriage data for last year.

In 2020, the first year of the Covid-19 pandemic, there were 1.7 million U.S. weddings the lowest number recorded since 1963. The pandemic threw many marriage plans into disarray, with communities ordering people to stay at home and banning large gatherings to limit the spread of Covid-19.

Marriages then rose in 2021, but not to pre-pandemic levels. They ticked up again in 2022 and surpassed 2019 marriage statistics by a small margin.

New York, the District of Columbia and Hawaii saw the largest increases in marriages from 2021 to 2022. Nevada home to Las Vegas famous wedding chapels continued to have the highest marriage rate in the nation, though it slightly decreased from 2021.

The number and rate of U.S. divorces in 2022 fell slightly, continuing a downward trend, the CDC said.

Overall,marriagesremain far less common than they once were in the U.S.

According to data that goes back to 1900, weddings hit their height in 1946, when the marriage rate was 16.4 per 1,000 people. The rate was above 10 in the early 1980s before beginning a decades-long decline. In 2022, the marriage rate was 6.2 per 1,000 population.

The Associated Press

The Associated Press

Go here to see the original:

Marriages in the U.S. are back to pre-pandemic levels, CDC says - NBC News