Antiretroviral therapy has had an enormous impact on treating HIV infections around the world. The millions of people currently taking these treatments under medical supervision can reasonably expect to reduce their viral loads to undetectable levels, eliminate the risk of transmission and live a normal life span. However, antiretroviral therapy is not without shortcomings. People need to take these medications regularly for life, and low compliance can lead to drug resistance.
HIV presents challenges to antibodies
Antibodies are proteins that serve as major players in the immune system’s response to pathogens, which cause disease, and allergens, which cause allergic reactions. Antibodies recognize specific markers, or antigens, on a potentially harmful substance and help the body eliminate it.
Over the past few decades, researchers have been able to isolate individual antibodies specific to the individual pathogen or allergen they are meant to attack. With this advance, monoclonal antibodies made in the lab have become a major segment of the pharmaceutical industry. You can see numerous ads on TV or in magazines promoting monoclonal antibodies to treat osteoporosis, autoimmune disorders and various types of cancers.
Antibodies can also be used to treat viral infections, including COVID-19. But using antibodies gets more complicated with HIV, the virus that causes AIDS in people.
One reason is that HIV has an enormous number of variants circulating across the world and even within a single infected individual. In fact, the genetic variation of HIV within a single patient exceeds the genetic variation of all circulating influenza strains worldwide during an entire flu season.
The immune system of an individual infected with HIV creates antibodies to neutralize the virus. However, because these antibodies can usually recognize only one particular strain, they are unable to neutralize other HIV strains circulating in the population. Furthermore, HIV can mutate within an infected individual and escape antibodies specific to the variant causing the original infection.
This ability to mutate and escape ongoing immune responses is a critical factor in the virus’s ability to continuously replicate, a hallmark of AIDS. It also makes it difficult to design an antibody treatment that can account for HIV’s enormous genetic variability.
Broadly neutralizing antibodies show promise
The discovery of rare individuals who make anti-HIV antibodies that can be effective against up to 80% of circulating strains, however, has boosted prospects for antibody treatments for HIV.
These broadly neutralizing antibodies, or bnAbs, have seen impressive results. Monkey studies have found that a single administration of bnAbs can prevent infection from SHIV, the nonhuman primate version of HIV. One study found that two broadly neutralizing antibodies were able to reduce viral loads to undetectable levels in infected monkeys.
In people, one study administering two bnAbs also saw suppression of HIV replication and nearly undetectable viral loads. One early-phase clinical trial in 2021 showed that one bnAb could potentially offer protection against HIV infection.
Long-term production of antibodies
All the monkey and human studies mentioned above required re-administering the broadly neutralizing antibodies every three weeks or so to maintain effective concentrations. This runs into the same problem antiretroviral therapies face in terms of requiring the individual to retake the drug frequently for life. But researchers have found a potential solution.
Using a small virus that doesn’t cause disease, called an adeno-associated virus, to deliver broadly neutralizing antibodies into the body can stimulate muscle cells to continually produce these antibodies. Because muscle cells have a prolonged life span and can last on average 10 to 16 years, they can be turned into factories that produce the antibodies essentially for life.
One study my colleagues and I conducted using adeno-associated virus found that one monkey was able to produce these antibodies for over six years after a single injection.
Another monkey that researchers dubbed the “The Miami Monkey” is considered functionally cured, meaning its viral loads have been at undetectable levels for prolonged periods even without continuous antiviral drug therapy. Two other monkeys have also been cured of their AIDS virus infections with this approach.
Adeno-associated virus vectors for HIV antibody therapies still face one more hurdle: anti-drug antibodies, or antibodies the body produces in response to the antibodies in the treatment. Anti-drug antibodies can result when the body registers an antibody treatment as foreign and mounts an immune response against it, negating the treatment. They have also have caused problems for antibody treatments in cancer and autoimmune disorders. That may especially be the case for broadly neutralizing antibodies, which have unusual structures that deviate from what the body normally expects an antibody to look like.
Researchers are working hard to develop simple and accessible approaches to help patients build tolerance to broadly neutralizing antibodies. Some of these approaches include delivering treatments to other areas that have greater immune tolerance than the muscle, such as to the liver and through the mouth.
Ronald C. Desrosiers receives funding from the National Instituyes of Health. He receives no corporate/commercial/company support.treatment genetic antibodies therapy monoclonal antibodies covid-19 transmission suppression
We can turn to popular culture for lessons about how to live with COVID-19 as endemic
As COVID-19 transitions from a pandemic to an endemic, apocalyptic science-fiction and zombie movies contain examples of how to adjust to the new norm…
In 2021, conversations began on whether the COVID-19 pandemic will, or even can, end. As a literary and cultural theorist, I started looking for shifts in stories about pandemics and contagion. It turns out that several stories also question how and when a pandemic becomes endemic.
The 2020 film Peninsula, a sequel to the Korean zombie film, Train to Busan, ends with a group of survivors rescued and transported to a zombie-free Hong Kong. In it, Jooni (played by Re Lee) spent her formative years living through the zombie epidemic. When she is rescued, she responds to being informed that she’s “going to a better place” by admitting that “this place wasn’t bad either.”
Jooni’s response points toward the shift in contagion narratives that has emerged since the spread of COVID-19. This shift marks a rejection of the push-for-survival narratives in favour of something more indicative of an endemic.
Contagion follows a general cycle: outbreak, epidemic, pandemic and endemic. The determinants of each stage rely upon the rate of spread within a specified geographic region.
Etymologically, the word “endemic” has its origins with the Greek words én and dēmos, meaning “in the people.” Thus, it refers to something that is regularly found within a population.
Infectious disease physician Stephen Parodi asserts that an endemic just means that a disease, while still prevalent within a population, no longer disrupts our daily lives.
Similarly, genomics and viral evolution researcher Aris Katzourakis argues that endemics occur when infection rates are static — neither rising nor falling. Because this stasis occurs differently with each situation, there is no set threshold at which a pandemic becomes endemic.
Not all diseases reach endemic status. And, if endemic status is reached, it does not mean the virus is gone, but rather that things have become “normal.”
We’re most likely familiar with contagion narratives. After all, Steven Soderbergh’s 2011 film Contagion, was the most watched film on Canadian Netflix in March 2020. Conveniently, this was when most Canadian provinces went into lockdown during the early stages of the COVID-19 pandemic.
In survival-based contagion narratives, characters often discuss methods for survival and generally refer to themselves as survivors. Contagion chronicles the transmission of a deadly virus that is brought from Hong Kong to the United States. In response, the U.S. Centers for Disease Control is tasked with tracing its origins and finding a cure. The film follows Mitch Emhoff (Matt Damon), who is immune, as he tries to keep his daughter safe in a crumbling Minneapolis.
Ultimately, a vaccine is successfully synthesized, but only after millions have succumbed to the virus.
Like many science fiction and horror films that envision some sort of apocalyptic end, Contagion focuses on the basic requirements for survival: shelter, food, water and medicine.
However, it also deals with the breakdown of government systems and the violence that accompanies it.
A “new” normal
In contrast, contagion narratives that have turned endemic take place many years after the initial outbreak. In these stories, the infected population is regularly present, but the remaining uninfected population isn’t regularly infected.
A spin-off to the zombie series The Walking Dead takes place a decade after the initial outbreak. In the two seasons of The Walking Dead: World Beyond (2020-2021) four young protagonists — Hope (Alexa Mansour), Iris (Aliyah Royale), Silas (Hal Cumpston) and Elton (Nicolas Cantu) — represent the first generation to come of age within the zombie-infested world.
The four youth spent their formative years in an infected world — similar to Jooni in Peninsula. For these characters, zombies are part of their daily lives, and their constant presence is normalized.
The setting in World Beyond has electricity, helicopters and modern medicine. Characters in endemic narratives have regular access to shelter, food, water and medicine, so they don’t need to resort to violence over limited resources. And notably, they also don’t often refer to themselves as survivors.
Endemic narratives acknowledge that existing within an infected space alongside a virus is not necessarily a bad thing, and that not all inhabitants within infected spaces desire to leave. It is rare in endemic narratives for a character to become infected.
Instead of going out on zombie-killing expeditions in the manner that occurs frequently in the other Walking Dead stories, the characters in World Beyond generally leave the zombies alone. They mark the zombies with different colours of spray-paint to chronicle what they call “migration patterns.”
The zombies have therefore just become another species for the characters to live alongside — something more endemic.
The Walking Dead, Fear the Walking Dead (2015-), Z Nation (2014-18), and many other survival-based stories seem to return to the past. In contrast, endemic narratives maintain a present and sometimes even future-looking approach.
Learning from stories
According to film producer and media professor Mick Broderick, survival stories maintain a status quo. They seek a “nostalgically yearned-for less-complex existence.” It provides solace to imagine an earlier, simpler time when living through a pandemic.
However, the shift from survival to endemic in contagion narratives provides us with many important possibilities. The one I think is quite relevant right now is that it presents us with a way of living with contagion. After all, watching these characters survive a pandemic helps us imagine that we can too.
Krista Collier-Jarvis does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.disease control pandemic covid-19 vaccine spread lockdown transmission hong kong
Has the pandemic changed our personalities? New research suggests we’re less open, agreeable and conscientious
COVID-related changes in our personalities could go some way to explaining the widespread decrease in wellbeing.
For many of us, some personality traits stay the same throughout our lives while others change only gradually. However, evidence shows that significant events in our personal lives which induce severe stress or trauma can be associated with more rapid changes in our personalities.
A new study, published in PLOS ONE, suggests the COVID pandemic has triggered much greater shifts in personality than we would expect to have seen naturally over this period. In particular, the researchers found that people were less extroverted, less open, less agreeable and less conscientious in 2021 and 2022 compared with before the pandemic.
This study included more than 7,000 participants from the US, aged between 18 and 109, who were assessed before the pandemic (from 2014 onwards), early in the pandemic in 2020, and then later in the pandemic in 2021 or 2022.
At each time point, participants completed the “Big Five Inventory”. This assessment tool measures personality on a scale across five dimensions: extroversion versus introversion, agreeableness versus antagonism, conscientiousness versus lack of direction, neuroticism versus emotional stability, and openness versus closedness to experience.
There weren’t many changes between pre-pandemic and 2020 personality traits. However, the researchers found significant declines in extroversion, openness, agreeableness and conscientiousness in 2021/2022 compared with before the pandemic. These changes were akin to a decade of normal variation, suggesting the trauma of the COVID pandemic had accelerated the natural process of personality change.
Interestingly, younger adults’ personalities changed the most in the study. They showed marked declines in agreeableness and conscientiousness, and a significant increase in neuroticism in 2021/2022 compared with pre-pandemic. This may be due in part to social anxiety when emerging back into society, having missed out on two years of normality.
Personality and wellbeing
Many of us became more health-conscious during the pandemic, for example by eating better and doing more exercise. A lot of us sought whatever social connections we could find virtually, and tried to refocus our attention on psychological, emotional and intellectual growth – for example, by practising mindfulness or picking up new hobbies.
Nonetheless, mental health and wellbeing decreased significantly. This makes sense given the drastic changes we went through.
Notably, personality significantly impacts our wellbeing. For example, people who report high levels of conscientiousness, agreeableness or extroversion are more likely to experience the highest level of wellbeing.
So the personality changes detected in this study may go some way to explaining the decrease in wellbeing we’ve seen during the pandemic.
If we look more closely, the pandemic appears to have negatively affected the following areas:
our ability to express sympathy and kindness towards others (agreeableness);
our capacity to be open to new concepts and willing to engage in novel situations (openness);
our tendency to seek out and enjoy other people’s company (extraversion);
our desire to strive towards our goals, do tasks well or take responsibilities towards others seriously (conscientiousness).
All of these traits influence our interaction with the environment around us, and as such, may have played a role in our wellbeing decline. For example, working from home may have left us feeling demotivated and as though our career was going nowhere (lower conscientiousness). This in turn may have affected our wellbeing by making us feel more irritable, depressed or anxious.
Over time, our personalities usually change in a way that helps us adapt to ageing and cope more effectively with life events. In other words, we learn from our life experiences and this subsequently impacts our personality. As we age, we generally see increases in self-confidence, self-control and emotional stability.
However, participants in this study recorded changes in the opposite direction to the usual trajectory of personality change. This is understandable given that we faced an extended period of difficulties, including constraints on our freedoms, lost income and illness. All these experiences have evidently changed us – and our personalities.
This study provides us with some very useful insights into the impacts of the pandemic on our psyche. These impacts may subsequently influence many aspects of our lives, such as wellbeing.
Knowledge allows us to make choices. So you might like to take the time to reflect on your experiences over the past few years, and how these personality changes may have affected you.
Any changes may well have protected you during the height of the pandemic. However, it’s worth asking yourself how useful these changes are now that the acute phase of the pandemic is behind us. Do they still serve you well, or could you try to rethink your perspective?
Jolanta Burke does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.social distancing pandemic covid-19
Coalesce lands fresh capital to transform data at ‘enterprise scale’
Coalesce is a startup that offers data transformation tools geared mainly toward enterprise customers. Today the company closed a $26 million Series A…
Coalesce is a startup that offers data transformation tools geared mainly toward enterprise customers. Today the company closed a $26 million Series A funding round led by Emergence Capital with participation from 11.2 Capital and GreatPoint Ventures, bringing the company’s total raised to $31.92 million. Co-founder and CEO Armon Petrossian tells TechCrunch that the cash will be put toward building out Coalesce’s product and ecosystem.
Petrossian met Coalesce’s other co-founder, Satish Jayanthi, at WhereScape, where the two were responsible for solving data warehouse problems for large organizations. (In computing, a “data warehouse” refers to systems used for reporting and data analysis — analysis usually germane to business intelligence.) Their clients often encountered challenges in transforming data, Petrossian says, as well as documenting these transformations in a way that made intuitive sense.
To Petrossian’s point, a survey commissioned by data integration platform Matillion found that as much as 57% of the time involved in analytics projects is spent tackling data transformation hurdles. Moreover, 75% percent of data teams feel that outdated migration and maintenance processes are costing them productivity and capital.
“Companies have been struggling with data transformation and optimization since the early days of data warehousing, and with the enormous growth of the cloud, that challenge has only increased,” he told TechCrunch via email. “We are on a mission to radically improve the analytics landscape by making enterprise-scale data transformations as efficient and flexible as possible.”
Coalesce offers tools designed to simplify modeling, cleansing and governance of data primarily in the Snowflake cloud, powered by what Petrossian describes as a “column-aware” architecture that leverages metadata to manage data transformations with an understanding of how the data is related or connected. Users can take advantage of data transformation automation templates that can be edited, packaged and shared, either with code or a visual design tool.
Often, companies approach Coalesce with specific problems, Petrossian said, like needing to transform data from different databases, apps and systems to follow a certain spec or standard. Other customers seek to speed up business intelligence queries by removing the need to search across multiple data sources and formats.
“Our product solves the largest bottleneck in analytics today by combining the speed of an intuitive graphical user interface with the flexibility of code, plus a healthy dose of automation, to enable rapid data transformations,” Petrossian continued. “With Coalesce, the data can be organized in an easy to access and read fashion while using automation to streamline the process and limit the amount of time needed by highly skilled engineers to code manually.”
Petrossian sees Coalesce competing with “extract, transform, and load” data integration vendors, including Informatica and Talend. The aforementioned Matillion also occupies that space, as does Incorta and Etleap.
Fortunately for Coalesce, the ETL market is massive, with one estimate putting it at $10.75 million as of early 2021. While demurring when asked about revenue, Petrossian claimed that Coalesce’s business is quite strong, with “multiple” Fortune 500 customers paying for the startup’s services.
“Our company was born during the pandemic and has given us an opportunity to serve enterprise Fortune 500 companies that are resilient to the potential looming recession,” Petrossian added. “The Coalesce platform is easing the burden of companies struggling to find talented data engineers or architects by providing them with a tool that empowers their existing teams to be much more efficient without compromising flexibility at scale.”
Coalesce currently has 40 salaried employees, spread across locations in four different countries. Petrossian wouldn’t commit to hiring a certain number this year but said the plan is to invest generally in Coalesce’s marketing, sales and engineering operations.
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