For almost three years, scientists have raced to understand the immune responses in patients who develop severe COVID-19, with an enormous effort aimed at defining where healthy immunity ends and destructive immunity begins.

In the early days of the COVID-19 pandemic, much attention focused on reports of harmful inflammation and so-called cytokine storms – dangerous immune overreactions that can lead to tissue damage and death – in patients with severe COVID-19. It wasn’t long before researchers began to identify antibodies that target the patient’s own body rather than attacking SARS-CoV-2, the virus the causes COVID-19.

Those studies revealed that patients with severe COVID-19 share some of the key traits of chronic autoimmune diseases – diseases in which the patient’s immune systems chronically attack their own tissues. Scientists have long suspected and sometimes even documented links between viral infection and chronic autoimmune diseases, but the research remains murky. However, the COVID-19 pandemic has offered an opportunity to better understand potential connections between these conditions.

As an immunologist and member of an interdisciplinary team of physicians and scientists investigating the intersection between COVID-19 and autoimmunity, I have been working to understand the origins of these untamed antibody responses and their long-term effects. Led by Ignacio Sanz, a specialist in investigating the immune dysfunctions that underlie autoimmune diseases like lupus, our group has long suspected that these misdirected immune responses may follow patients well after recovery and could even contribute to the debilitating set of symptoms commonly referred to as “long COVID-19.”

Our new study, published in the journal Nature, helps shed light on these questions. We now know that in patients with severe COVID-19, many of the developing antibodies responsible for neutralizing the viral threat are simultaneously targeting their own organs and tissues. We also show that self-directed antibodies can persist for months or even years in those suffering from long COVID-19.

As researchers like us continue to study COVID-19, our understanding of the link between antiviral immunity and chronic autoimmune disease is rapidly evolving.

The immune system makes mistakes when under duress

It’s easy to assume that your immune system is laser-focused on identifying and destroying foreign invaders, but that isn’t the case – at least under some circumstances. Your immune system, even in its healthy state, contains a contingent of cells that are fully capable of targeting and destroying your own cells and tissues.

To prevent self-destruction, the immune system relies on an intricate series of fail-safes that are collectively termed self-tolerance to identify and eliminate potentially traitorous immune cells. One of the most important steps in this process occurs as the immune system builds up its arsenal against a potential threat.

When your immune system first encounters a pathogen or even a perceived threat – such as a vaccine that resembles a virus – it rapidly recruits “B” cells that have the potential to become antibody-producers. Then, any of these “naive” B cell recruits – naive being a technical term used in immunology – that demonstrate an ability to competently attack the invader are put into a boot camp of sorts.

Here, the cells are trained to better recognize and combat the threat. The training period is intense and mistakes are not tolerated; B cells with any discernible potential for misdirected attacks against their host are killed. However, like any training process, this buildup and mobilization takes time – typically a week or two.

So, what happens when the threat is more immediate – when someone is quite literally fighting for their life in an intensive care unit?

Researchers now know that under the stress of severe viral infection with SARS-CoV-2, that training process collapses. Instead, it is replaced by an emergency response in which new recruits with little training are rushed into battle.

Friendly fire is the unfortunate result.

High-risk immune responses are mostly transient

Our team’s new work reveals that in the heat of battle with severe COVID-19, the same antibodies responsible for fighting the virus are uncomfortably prone to targeting a patient’s own tissue. Importantly, this effect seems mostly restricted to severe disease. We identified the cells that produce these rogue antibodies much less frequently in patients with mild forms of the illness whose immune responses were more measured.

So, does that mean that everyone who gets severe COVID-19 develops an autoimmune disorder?

Fortunately, no. By following patients after their infection has resolved, we have found that months later, most of the concerning indications of autoimmunity have subsided. And this makes sense. Though we are identifying this phenomenon in human COVID-19, researchers studying these emergency immune responses for more than a decade in mice have determined that they are mostly short-lived.

“Mostly” being the operative word.

Implications for recovery from long COVID-19

Although most people fully recover from their run-in with the virus, up to 30% have not returned to normal even three months after recovery. This has created a group of patients who are experiencing what is known as post-acute sequelae of COVID-19, or PASC – the technical terminology for long COVID-19.

With debilitating symptoms that can include the long-term loss of taste, smell or both, general fatigue, brain fog and a variety of other conditions, these patients have continued to suffer and are rightfully looking for answers.

An obvious question for researchers who are studying these patients is whether the same self-targeted antibodies that are emerging in severe COVID-19 are lingering in those who suffer from long COVID-19. They are. Our new study makes clear that newly developed self-antibodies can persist for months. What’s more, in work currently under development and not yet peer-reviewed, we find that these responses are not restricted to those recovering from severe illness, and are readily identifiable in a large subset of long COVID-19 patients who had recovered from more mild illness as well.

Just as it was in the race to better understand the causes of acute disease earlier in the pandemic, we researchers are now working to get a more complete understanding of the cells and antibodies directing this self-attack for months and years following the resolution of infection.

Are they directly contributing to the symptoms long COVID-19 sufferers are experiencing? If so, are there therapeutic interventions that could blunt or eliminate the threats they pose? Are long COVID-19 patients at increased risk for the development of true, chronic autoimmune diseases in the future? Or, is all of this just a red herring – a temporary quirk of the immune system that will resolve on its own?

Only time and continued work in this critical area will tell.

Matthew Woodruff, Instructor of Human Immunology, Emory University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Labor Day 2022 comes smack bang in the middle of what is increasingly looking like a pivotal year in the history of American unions.

The summer has seen a steady stream of workforce mobilizations. Employees at Trader Joe’s locations in Massachusetts and Minneapolis both voted to unionize. Meanwhile, restaurant chain Chipotle saw the first of its stores unionize, following a vote by workers at an outlet in Lansing, Michigan.

It comes on the back of a wave of successful efforts to mobilize at Starbucks and Amazon. The growth of unionized stores at Starbucks in particular has been stunning. Since baristas in Buffalo, New York, became the first at the chain to unionize in December 2021, colleagues at a further 234 outlets have followed suit in recent months.

Likewise, the success of an independent Amazon Labor Union – formed in 2020 by Chris Smalls, an Amazon worker fired for protesting what he saw as inadequate COVID-19 safety precautions – in forming the first plant of the retail giant to have a unionized workforce has inspired others to do likewise.

It comes as polling shows that public support of unions is at its highest since 1965, with the backing of 71% of Americans. Something is definitely happening in the labor movement in 2022.

A different kind of organizing

As a scholar of the labor movement who has observed union drives for two decades, what I find almost as striking as the victories is the unconventional nature of the organizing campaigns.

Workers at Amazon and Trader Joe’s are setting up independent unions, whereas at Starbucks and Chipotle, employees are teaming up with established unions. But that difference apart, the dynamics at play are remarkably similar: The campaigns are being led by determined young workers. For the most part, it is bottom-up unionizing, rather than being driven by official, seasoned union representatives.

Inspired by pro-union sentiment in political movements, such as Bernie Sanders’ presidential bids, Black Lives Matter and the Democratic Socialists of America, individuals are spearheading the efforts for workplace reform rather than professional union organizers. Indeed, one would be hard-pressed to find many experienced organizers among the recent successful campaigns.

Instead, the campaigns have involved a significant degree of “self-organization” – that is, workers “talking union” to each other in the warehouse and coffee shops and reaching out to colleagues in other shops in the same city and across the nation. This marks a sea change from the way the labor movement has traditionally operated, which has tended to be more centralized and led by seasoned union officials.

A labor revival

Perhaps more important than the victories at Starbucks, Amazon, Trader Joe’s and Chipotle themselves is their potential for creating a sense of optimism and enthusiasm around union organizing, especially among younger workers.

The elections follow years of union decline in the U.S., both in terms of membership and influence.

Prior to the COVID-19 pandemic, these recent labor wins would probably have seemed unimaginable. Powerful, wealthy corporations like Amazon and Starbucks appeared invincible then, at least in the context of National Labor Relations Board rules, which are stacked heavily against pro-union workers. Under NLRB rules, employers can – and do – force workers, on the threat of dismissal, to attend anti-union sessions, often led by highly paid external consultants.

Starbucks has said it has been “consistent in denying any claims of anti-union activity. They are categorically false.” But the NLRB has alleged that the coffee chain has fired and coerced workers, placed union supporters under surveillance and retaliated against them.

The NLRB has also filed a complaint against Starbucks for unlawfully withholding wage and benefit increases from pro-union workers, and currently has almost 300 open unfair labor practices charges lodged against Starbucks management. Amazon, which in the past has advertised for analysts to monitor “labor organizing threats,” has said it respects workers’ rights to join or not join unions.

The significance of the recent victories is not primarily about the 8,000 new union members at Amazon or a gradual flow of new union members at Starbucks. It is about instilling in workers the belief that if pro-union workers can win at Amazon and Starbucks, they can win anywhere.

Historic precedents show that labor mobilization can be infectious.

In 1936 and 1937, workers at the Flint plant of General Motors brought the powerful automaker to its knees in a sit-down strike that quickly inspired similar action elsewhere. In the reported words of a Chicago doctor, when explaining a subsequent sit-down strike by wet nurses in the city: “It’s just one of those funny things. They want to strike because everyone else is doing it.”

Seizing the moment

The pandemic has created an opportunity for unions.

After working on the front lines for over two years, many essential workers such as those at Amazon and Trader Joe’s believe they have not been adequately rewarded for their service during the pandemic and have not been treated with respect by their employers.

This appears to have helped spur the popularity of smaller, workplace-specific unions.

The homegrown nature of these campaigns deprives chains of employing a decades-old trope at the heart of corporate anti-union campaigns: that a union is an external “third party” that doesn’t understand or care about the concerns of employees and is more interested in collecting dues.

But those arguments mostly ring hollow when the people doing the unionizing are colleagues they work alongside day in and day out.

It has the effect of nullifying that central argument of anti-union campaigns despite the many millions of dollars that companies often pumped into them.

An unfavorable legal landscape

This “self-organization” is consistent with what was envisioned by the authors of the 1935 Wagner Act, the statute that provides the foundation of today’s union representation procedures.

The National Labor Relations Board’s first chair, J. Warren Madden, understood that self-organization could be fatally undermined if corporations were allowed to engage in anti-union pressure tactics:

“Upon this fundamental principle – that an employer shall keep his hands off the self-organization of employees – the entire structure of the act rests,” he wrote.“ Any compromise or weakening of that principle strikes at the root of the law.”

Over the past half century, anti-union corporations and their consultants and law firms – assisted by Republican-controlled NLRBs and right-wing judges – have undermined that process of worker self-organization by enabling union elections to become employer-dominated.

But for the long-term decline in union membership to be reversed, I believe pro-union workers will need stronger protections. Labor law reform is essential if the almost 50% of nonunion American workers who say they want union representation are to have any chance of getting it.

Dispelling fear, futility and apathy

Lack of popular interest has long been an obstacle to labor law reform.

Meaningful labor law reform is unlikely to happen unless people are engaged with the issues, understand them and believe they have a stake in the outcome.

But media interest in the campaigns at Starbucks and Amazon suggests the American public may finally be paying attention.

It isn’t known where this latest labor movement – or moment – will lead. It could evaporate or it may just spark a wave of organizing across the low-wage service sector, stimulating a national debate over workers’ rights in the process.

The biggest weapons that anti-union corporations have in suppressing labor momentum are the fear of retaliation and a sense that unionization is futile. The recent successes show unionizing no longer seems so frightening or so futile.

This is an updated version of an article originally published on April 4, 2022.

John Logan, Professor and Director of Labor and Employment Studies, San Francisco State University

This article is republished from The Conversation under a Creative Commons license. Read the original article.

On Sept. 1, 2022, the Centers for Disease Control and Prevention endorsed the use of updated COVID-19 booster shots that are specifically tailored to combat the two most prevalent omicron subvariants, BA.4 and BA.5. The decision comes just a day after the Food and Drug Administration’s emergency use authorization of the shots. The CDC’s backing will enable a full roll-out of the reformulated vaccines to begin within days.

The new booster shots – one by Moderna and another from Pfizer-BioNTech – come as more than 450 people are still dying of COVID-19 every day in the U.S.

As of Aug. 31, 2022, only 48.5% of booster-eligible people in the U.S. have received their first booster shot, and just under 34% of those eligible have received their second. These low numbers may in part be influenced by people waiting for the newer versions of the vaccines to provide better protection. But booster shots have proven to be an essential layer of protection against COVID-19.

Prakash Nagarkatti and Mitzi Nagarkatti are immunologists who study infectious disorders and how vaccines trigger different aspects of the immune system to fight infection. They weigh in on how the updated booster shots train the immune system and how protective they might be against COVID-19.

1. What is different about the updated booster shots?

The newly authorized shots are the first updates to the original COVID-19 vaccines that were introduced in late 2020. They use the same mRNA technology as the original vaccines. The key difference between the original COVID-19 shots and the new “bivalent” version is that the latter consists of a mixture of mRNA that encodes the spike proteins of both the original SARS-CoV-2 virus and the more recent omicron subvariants, BA.4 and BA.5.

As of late August 2022, the BA.4 and BA.5 omicron subvariants are dominant worldwide. In the U.S., currently 89% of COVID-19 infections are caused by BA.5 and 11% are caused by BA.4.

The inability of the original vaccine strains to prevent reinfection and to trigger long-term protective immunity prompted the need for the reformulated vaccines.

2. How does a bivalent vaccine trigger an immune response?

In an actual COVID-19 infection, the SARS-CoV-2 virus uses its protruding spike protein to latch onto human cells and gain entry into cells. The spike protein triggers the production of so-called neutralizing antibodies, which bind to the spike protein and prevent the virus from invading other cells.

But when the virus mutates, as we know that it does, the antibodies that were previously produced in response to the virus can no longer effectively bind to the newly mutated spike protein. In this respect, the SARS-CoV-2 virus acts like a chameleon – a master of disguise – by changing its body configuration and escaping recognition by the immune system.

The ongoing viral mutations are why antibodies produced in response to the original vaccine strains have over time become less effective at fending off infections by new variants.

The concept of bivalent vaccines aimed at protecting against two different strains of a virus is not new. For instance, Cervarix is an FDA-approved bivalent vaccine that provides protection against two different types of human papillomaviruses that cause cancer.

3. How protective will the new shots be against infection?

There are as of yet no human studies on the efficacy of the new bivalent vaccine at preventing reinfections and providing long-term immune protection.

However, in human clinical trials and laboratory studies, both Pfizer-BioNTech and Moderna found that their initial version of the bivalent vaccine, which was directed against the original SARS-CoV-2 virus and an earlier omicron strain, BA.1, induced a strong immune response and longer protection against both the original strain and the BA.1 variant. In addition, the companies reported that the same early combination generated a significant antibody response against the newest omicron subvariants, BA.4 and BA.5, though this antibody response was lower than that seen against subvariant BA.1.

Based on those results, in spring 2022 the FDA rejected the BA.1 bivalent boosters because the agency felt the boosters may fall short of providing sufficient protection against the newest strains, BA.4 and BA.5, which were by then spreading quickly throughout the U.S. and the world. So the FDA asked Pfizer-BioNTech and Moderna to develop bivalent vaccines specifically targeting BA.4 and BA.5, instead of BA.1.

Because clinical trials are time-consuming, the FDA was willing to consider animal studies and other laboratory findings, such as the ability of antibodies to neutralize the virus, to decide whether to authorize the bivalent boosters.

This decision has stirred up controversy over whether it is appropriate for the FDA to approve a booster without direct human data to support it. However, the FDA has stated that millions of people have safely received the mRNA vaccines – which were originally tested in humans – and that the changes in the mRNA sequences in the vaccines do not affect vaccine safety. Thus, it concluded that the bivalent vaccines are safe and that there is no need to wait for human clinical trials.

It is also noteworthy that influenza vaccines are introduced each year based on prediction of the strain that is likely to be dominant, and such formulations do not undergo new clinical trials.

Based on available evidence from the previous COVID-19 vaccines, we believe it is very likely that the new boosters will continue to offer strong protection from severe COVID-19 leading to hospitalization and death. But whether they will protect against reinfection and breakthrough infections remains to be seen.

4. Will it only be a booster shot?

The bivalent vaccines can only be used as a booster shot at least two months after the completion of the primary series – or initial required shots – or following a previous booster shot. The Moderna bivalent vaccine is authorized for use in people 18 years of age, while the Pfizer bivalent vaccine is authorized for those 12 years of age and older.

Because of the superiority of the bivalent vaccines, the FDA has also removed the use authorization for the original monovalent Moderna and Pfizer COVID-19 vaccines for booster purposes in individuals 18 years of age and older and 12 years of age and older, respectively.

The new bivalent vaccines contain a lower dose of mRNA, and as such are meant to be used only as boosters and not in people who have never received a COVID-19 vaccination.

5. Will the new shots protect against future variants?

How well the bivalent vaccines will perform in the face of new variants that might arise will depend on the nature of future spike protein mutations.

If it is a minor mutation or set of mutations when compared to the original strain or to omicron variants BA.4 and BA.5, the new shots will provide good protection. However, if a hypothetical new strain were to possess highly unique mutations in its spike protein, then it’s likely that it could once again dodge immune protection.

On the flip side, the successful development of the updated vaccines demonstrates that the mRNA vaccine technology is nimble and innovative enough that – within a couple of months of the emergence of a new variant – it is now likely possible to develop and distribute new vaccines that are tailor-made to fight an emerging variant.

This article has been updated to reflect the CDC’s endorsement of the reformulated shots.

Prakash Nagarkatti, Professor of Pathology, Microbiology and Immunology, University of South Carolina and Mitzi Nagarkatti, Professor of Pathology, Microbiology and Immunology, University of South Carolina

This article is republished from The Conversation under a Creative Commons license. Read the original article.