Antibody Testing Alone is Not the Key to Re-Opening Society
Immunity tests have too many unknowns right now to make them very useful in determining protective antibody status.
[Editor's Note: We asked experts from different specialties to weigh in on a timely Big Question: "How should immunity testing play a role in re-opening society?" Below, a virologist offers her perspective.]
With the advent of serology testing and increased emphasis on "re-opening" America, public health officials have begun considering whether or not people who have recovered from COVID-19 can safely re-enter the workplace.
"Immunity certificates cannot certify what is not known."
Conventional wisdom holds that people who have developed antibodies in response to infection with SARS-CoV-2, the coronavirus that causes COVID-19, are likely to be immune to reinfection.
For most acute viral infections, this is generally true. However, SARS-CoV-2 is a new pathogen, and there are currently many unanswered questions about immunity. Can recovered patients be reinfected or transmit the virus? Does symptom severity determine how protective responses will be after recovery? How long will protection last? Understanding these basic features is essential to phased re-opening of the government and economy for people who have recovered from COVID-19.
One mechanism that has been considered is issuing "immunity certificates" to individuals with antibodies against SARS-CoV-2. These certificates would verify that individuals have already recovered from COVID-19, and thus have antibodies in their blood that will protect them against reinfection, enabling them to safely return to work and participate in society. Although this sounds reasonable in theory, there are many practical reasons why this is not a wise policy decision to ease off restrictive stay-home orders and distancing practices.
Too Many Scientific Unknowns
Serology tests measure antibodies in the serum—the liquid component of blood, which is where the antibodies are located. In this case, serology tests measure antibodies that specifically bind to SARS-CoV-2 virus particles. Usually when a person is infected with a virus, they develop antibodies that can "recognize" that virus, so the presence of SARS-CoV-2 antibodies indicates that a person has been previously exposed to the virus. Broad serology testing is critical to knowing how many people have been infected with SARS-CoV-2, since testing capacity for the virus itself has been so low.
Tests for the virus measure amounts of SARS-CoV-2 RNA—the virus's genetic material—directly, and thus will not detect the virus once a person has recovered. Thus, the majority of people who were not severely ill and did not require hospitalization, or did not have direct contact with a confirmed case, will not test positive for the virus weeks after they have recovered and can only determine if they had COVID-19 by testing for antibodies.
In most cases, for most pathogens, antibodies are also neutralizing, meaning they bind to the virus and render it incapable of infecting cells, and this protects against future infections. Immunity certificates are based on the assumption that people with antibodies specific for SARS-CoV-2 will be protected against reinfection. The problem is that we've only known that SARS-CoV-2 existed for a little over four months. Although studies so far indicate that most (but not all) patients with confirmed COVID-19 cases develop antibodies, we don't know the extent to which antibodies are protective against reinfection, or how long that protection will last. Immunity certificates cannot certify what is not known.
The limited data so far is encouraging with regard to protective immunity. Most of the patient sera tested for antibodies show reasonable titers of IgG, the type of antibodies most likely to be neutralizing. Furthermore, studies have shown that these IgG antibodies are capable of neutralizing surrogate viruses as well as infectious SARS-CoV-2 in laboratory tests. In addition, rhesus monkeys that were experimentally infected with SARS-CoV-2 and allowed to recover were protected from reinfection after a subsequent experimental challenge. These data tentatively suggest that most people are likely to develop neutralizing IgG, and protective immunity, after being infected by SARS-CoV-2.
However, not all COVID-19 patients do produce high levels of antibodies specific for SARS-CoV-2. A small number of patients in one study had no detectable neutralizing IgG. There have also been reports of patients in South Korea testing PCR positive after a prior negative test, indicating reinfection or reactivation. These cases may be explained by the sensitivity of the PCR test, and no data have been produced to indicate that these cases are genuine reinfection or recurrence of viral infection.
Complicating matters further, not all serology tests measure antibody titers. Some rapid serology tests are designed to be binary—the test can either detect antibodies or not, but does not give information about the amount of antibodies circulating. Based on our current knowledge, we cannot be certain that merely having any level of detectable antibodies alone guarantees protection from reinfection, or from a subclinical reinfection that might not cause a second case of COVID-19, but could still result in transmission to others. These unknowns remain problematic even with tests that accurately detect the presence of antibodies—which is not a given today, as many of the newly available tests are reportedly unreliable.
A Logistical and Ethical Quagmire
While most people are eager to cast off the isolation of physical distancing and resume their normal lives, mere desire to return to normality is not an indicator of whether those antibodies actually work, and no certificate can confer immune protection. Furthermore, immunity certificates could lead to some complicated logistical and ethical issues. If antibodies do not guarantee protective immunity, certifying that they do could give antibody-positive people a false sense of security, causing them to relax infection control practices such as distancing and hand hygiene.
"We should not, however, place our faith in assumptions and make return to normality contingent on an arbitrary and uninformative piece of paper."
Certificates could be forged, putting susceptible people at higher exposure risk. It's not clear who would issue them, what they would entitle the bearer to do or not do, or how certification would be verified or enforced. There are many ways in which such certificates could be used as a pretext to discriminate against people based on health status, in addition to disability, race, and socioeconomic status. Tracking people based on immune status raises further concerns about privacy and civil rights.
Rather than issuing documents confirming immune status, we should instead "re-open" society cautiously, with widespread virus and serology testing to accurately identify and isolate infected cases rapidly, with immediate contact tracing to safely quarantine and monitor those at exposure risk. Broad serosurveillance must be coupled with functional assays for neutralization activity to begin assessing how protective antibodies might actually be against SARS-CoV-2 infection. To understand how long immunity lasts, we should study antibodies, as well as the functional capabilities of other components of the larger immune system, such as T cells, in recovered COVID-19 patients over time.
We should not, however, place our faith in assumptions and make return to normality contingent on an arbitrary and uninformative piece of paper. Re-opening society, the government, and the economy depends not only on accurately determining how many people have antibodies to SARS-CoV-2, but on a deeper understanding of how those antibodies work to provide protection.
Podcast: The future of brain health with Percy Griffin
Percy Griffin, director of scientific engagement for the Alzheimer’s Association, joins Leaps.org to discuss the present and future of the fight against dementia.
Today's guest is Percy Griffin, director of scientific engagement for the Alzheimer’s Association, a nonprofit that’s focused on speeding up research, finding better ways to detect Alzheimer’s earlier and other approaches for reducing risk. Percy has a doctorate in molecular cell biology from Washington University, he’s led important research on Alzheimer’s, and you can find the link to his full bio in the show notes, below.
Our topic for this conversation is the present and future of the fight against dementia. Billions of dollars have been spent by the National Institutes of Health and biotechs to research new treatments for Alzheimer's and other forms of dementia, but so far there's been little to show for it. Last year, Aduhelm became the first drug to be approved by the FDA for Alzheimer’s in 20 years, but it's received a raft of bad publicity, with red flags about its effectiveness, side effects and cost.
Meanwhile, 6.5 million Americans have Alzheimer's, and this number could increase to 13 million in 2050. Listen to this conversation if you’re concerned about your own brain health, that of family members getting older, or if you’re just concerned about the future of this country with experts predicting the number people over 65 will increase dramatically in the very near future.
Listen to the Episode
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4:40 - We talk about the parts of Percy’s life that led to him to concentrate on working in this important area.
6:20 - He defines Alzheimer's and dementia, and discusses the key elements of communicating science.
10:20 - Percy explains why the Alzheimer’s Association has been supportive of Aduhelm, even as others have been critical.
17:58 - We talk about therapeutics under development, which ones to be excited about, and how they could be tailored to a person's own biology.
24:25 - Percy discusses funding and tradeoffs between investing more money into Alzheimer’s research compared to other intractable diseases like cancer, and new opportunities to accelerate progress, such as ARPA-H, President Biden’s proposed agency to speed up health breakthroughs.
27:24 - We talk about the social determinants of brain health. What are the pros/cons of continuing to spend massive sums of money to develop new drugs like Aduhelm versus refocusing on expanding policies to address social determinants - like better education, nutritious food and safe drinking water - that have enabled some groups more than others to enjoy improved cognition late in life.
34:18 - Percy describes his top lifestyle recommendations for protecting your mind.
37:33 - Is napping bad for the brain?
39:39 - Circadian rhythm and Alzheimer's.
42:34 - What tests can people take to check their brain health today, and which biomarkers are we making progress on?
47:25 - Percy highlights important programs run by the Alzheimer’s Association to support advances.
Show links:
** After this episode was recorded, the Centers for Medicare and Medicaid Services affirmed its decision from last June to limit coverage of Aduhelm. More here.
- Percy Griffin's bio: https://www.alz.org/manh/events/alztalks/upcoming-...
- The Alzheimer's Association's Part the Cloud program: https://alz.org/partthecloud/about-us.asp
- The paradox of dementia rates decreasing: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455342/
- The argument for focusing more resources on improving institutions and social processes for brain health: https://www.statnews.com/2021/09/23/the-brain-heal...
- Recent research on napping: https://www.ocregister.com/2022/03/25/alzheimers-s...
- The Alzheimer's Association helpline: https://www.alz.org/help-support/resources/helpline
- ALZConnected, a free online community for people affected by dementia https://www.alzconnected.org/
- TrialMatch for people with dementia and healthy volunteers to find clinical trials for Alzheimer's and other dementia: https://www.alz.org/alzheimers-dementia/research_p...
Employers can create a culture of “Excellence From Anywhere” to reduce the risk of inequality among office-centric, hybrid, and fully remote employees.
COVID-19 prompted numerous companies to reconsider their approach to the future of work. Many leaders felt reluctant about maintaining hybrid and remote work options after vaccines became widely available. Yet the emergence of dangerous COVID variants such as Omicron has shown the folly of this mindset.
To mitigate the risks of new variants and other public health threats, as well as to satisfy the desires of a large majority of employees who express a strong desire in multiple surveys for a flexible hybrid or fully remote schedule, leaders are increasingly accepting that hybrid and remote options represent the future of work. No wonder that a February 2022 survey by the Federal Reserve Bank of Richmond showed that more and more firms are offering hybrid and fully-remote work options. The firms expect to have more remote workers next year and more geographically-distributed workers.
Although hybrid and remote work mitigates public health risks, it poses another set of health concerns relevant to employee wellbeing, due to the threat of proximity bias. This term refers to the negative impact on work culture from the prospect of inequality among office-centric, hybrid, and fully remote employees.
The difference in time spent in the office leads to concerns ranging from decreased career mobility for those who spend less facetime with their supervisor to resentment building up against the staff who have the most flexibility in where to work. In fact, a January 2022 survey by the company Slack of over 10,000 knowledge workers and their leaders shows that proximity bias is the top concern – expressed by 41% of executives - about hybrid and remote work.
To address this problem requires using best practices based on cognitive science for creating a culture of “Excellence From Anywhere.” This solution is based on guidance that I developed for leaders at 17 pioneering organizations for a company culture fit for the future of work.
Protect from proximity bias via the "Excellence From Anywhere" strategy
So why haven’t firms addressed the obvious problem of proximity bias? Any reasonable external observer could predict the issues arising from differences of time spent in the office.
Unfortunately, leaders often fail to see the clear threat in front of their nose. You might have heard of black swans: low-probability, high-impact threats. Well, the opposite kind of threats are called gray rhinos: obvious dangers that we fail to see because of our mental blindspots. The scientific name for these blindspots is cognitive biases, which cause leaders to resist best practices in transitioning to a hybrid-first model.
The core idea is to get all of your workforce to pull together to achieve business outcomes: the location doesn’t matter.
Leaders can address this by focusing on a shared culture of “Excellence From Anywhere.” This term refers to a flexible organizational culture that takes into account the nature of an employee's work and promotes evaluating employees based on task completion, allowing remote work whenever possible.
Addressing Resentments Due to Proximity Bias
The “Excellence From Anywhere” strategy addresses concerns about treatment of remote workers by focusing on deliverables, regardless of where you work. Doing so also involves adopting best practices for hybrid and remote collaboration and innovation.
By valuing deliverables, collaboration, and innovation through a focus on a shared work culture of “Excellence From Anywhere,” you can instill in your employees a focus on deliverables. The core idea is to get all of your workforce to pull together to achieve business outcomes: the location doesn’t matter.
This work culture addresses concerns about fairness by reframing the conversation to focus on accomplishing shared goals, rather than the method of doing so. After all, no one wants their colleagues to have to commute out of spite.
This technique appeals to the tribal aspect of our brains. We are evolutionarily adapted to living in small tribal groups of 50-150 people. Spending different amounts of time in the office splits apart the work tribe into different tribes. However, cultivating a shared focus on business outcomes helps mitigate such divisions and create a greater sense of unity, alleviating frustrations and resentments. Doing so helps improve employee emotional wellbeing and facilitates good collaboration.
Solving the facetime concerns of proximity bias
But what about facetime with the boss? To address this problem necessitates shifting from the traditional, high-stakes, large-scale quarterly or even annual performance evaluations to much more frequent weekly or biweekly, low-stakes, brief performance evaluation through one-on-one in-person or videoconference check-ins.
Supervisees agree with their supervisor on three to five weekly or biweekly performance goals. Then, 72 hours before their check-in meeting, they send a brief report, under a page, to their boss of how they did on these goals, what challenges they faced and how they overcame them, a quantitative self-evaluation, and proposed goals for next week. Twenty-four hours before the meeting, the supervisor responds in a paragraph-long response with their initial impressions of the report.
It’s hard to tell how much any employee should worry about not being able to chat by the watercooler with their boss: knowing exactly where they stand is the key concern for employees, and they can take proactive action if they see their standing suffer.
At the one-on-one, the supervisor reinforces positive aspects of performance and coaches the supervisee on how to solve challenges better, agrees or revises the goals for next time, and affirms or revises the performance evaluation. That performance evaluation gets fed into a constant performance and promotion review system, which can replace or complement a more thorough annual evaluation.
This type of brief and frequent performance evaluation meeting ensures that the employee’s work is integrated with efforts by the supervisor’s other employees, thereby ensuring more unity in achieving business outcomes. It also mitigates concerns about facetime, since all get at least some personalized attention from their team leader. But more importantly, it addresses the underlying concerns about career mobility by giving all staff a clear indication of where they stand at all times. After all, it’s hard to tell how much any employee should worry about not being able to chat by the watercooler with their boss: knowing exactly where they stand is the key concern for employees, and they can take proactive action if they see their standing suffer.
Such best practices help integrate employees into a work culture fit for the future of work while fostering good relationships with managers. Research shows supervisor-supervisee relationships are the most critical ones for employee wellbeing, engagement, and retention.
Conclusion
You don’t have to be the CEO to implement these techniques. Lower-level leaders of small rank-and-file teams can implement these shifts within their own teams, adapting their culture and performance evaluations. And if you are a staff member rather than a leader, send this article to your supervisor and other employees at your company: start a conversation about the benefits of addressing proximity bias using such research-based best practices.