A wired baby in a neonatal intensive care unit.
I'll never forget the experience of having a child in the neonatal intensive care unit (NICU).
Now more than ever, we're working to remove the barriers between new parents and their infants.
It was another layer of uncertainty that filtered into my experience of being a first-time parent. There was so much I didn't know, and the wires attached to my son's small body for the first week of his life were a reminder of that.
I wanted to be the best mother possible. I deeply desired to bring my son home to start our lives. More than anything, I longed for a wireless baby whom I could hold and love freely without limitations.
The wires suggested my baby was fragile and it left me feeling severely unprepared, anxious, and depressed.
In recent years, research has documented the ways that NICU experiences take a toll on parents' mental health. But thankfully, medical technology is rapidly being developed to help reduce the emotional fallout of the NICU. Now more than ever, we're working to remove the barriers between new parents and their infants. The latest example is the first ever wireless monitoring system that was recently developed by a team at Northwestern University.
After listening to the needs of parents and medical staff, Debra Weese-Mayer, M.D., a professor of pediatric autonomic medicine at Feinberg School of Medicine, along with a team of materials scientists, engineers, dermatologists and pediatricians, set out to develop this potentially life-changing technology. Weese-Mayer believes wireless monitoring will have a significant impact for people on all sides of the NICU experience.
"With elimination of the cumbersome wires," she says, "the parents will find their infant more approachable/less intimidating and have improved access to their long-awaited but delivered-too-early infant, allowing them to begin skin-to-skin contact and holding with reduced concern for dislodging wires."
So how does the new system work?
Very thin "skin like" patches made of silicon rubber are placed on the surface of the skin to monitor vitals like heart rate, respiration rate, and body temperature. One patch is placed on the chest or back and the other is placed on the foot.
These patches are safer on the skin than previously used adhesives, reducing the cuts and infections associated with past methods. Finally, an antenna continuously delivers power, often from under the mattress.
The data collected from the patches stream from the body to a tablet or computer.
New wireless sensor technology is being studied to replace wired monitoring in NICUs in the coming years.
(Northwestern University)
Weese-Mayer hopes that wireless systems will be standard soon, but first they must undergo more thorough testing. "I would hope that in the next five years, wireless monitoring will be the standard in NICUs, but there are many essential validation steps before this technology will be embraced nationally," she says.
Until the new systems are ready, parents will be left struggling with the obstacles that wired monitoring presents.
Physical intimacy, for example, appears to have pain-reducing qualities -- something that is particularly important for babies who are battling serious illness. But wires make those cuddles more challenging.
There's also been minimal discussion about how wired monitoring can be particularly limiting for parents with disabilities and mobility aids, or even C-sections.
"When he was first born and I was recovering from my c-section, I couldn't deal with keeping the wires untangled while trying to sit down without hurting myself," says Rhiannon Giles, a writer from North Carolina, who delivered her son at just over 31 weeks after suffering from severe preeclampsia.
"The wires were awful," she remembers. "They fell off constantly when I shifted positions or he kicked a leg, which meant the monitors would alarm. It felt like an intrusion into the quiet little world I was trying to mentally create for us."
Over the last few years, researchers have begun to dive deeper into the literal and metaphorical challenges of wired monitoring.
For many parents, the wires prompt anxiety that worsens an already tense and vulnerable time.
I'll never forget the first time I got to hold my son without wires. It was the first time that motherhood felt manageable.
"Seeing my five-pound-babies covered in wires from head to toe rendered me completely overwhelmed," recalls Caila Smith, a mom of five from Indiana, whose NICU experience began when her twins were born pre-term. "The nurses seemed to handle them perfectly, but I was scared to touch them while they appeared so medically frail."
During the nine days it took for both twins to come home, the limited access she had to her babies started to impact her mental health. "If we would've had wireless sensors and monitors, it would've given us a much greater sense of freedom and confidence when snuggling our newborns," Smith says.
Besides enabling more natural interactions, wireless monitoring would make basic caregiving tasks much easier, like putting on a onesie.
"One thing I noticed is that many preemie outfits are made with zippers," points out Giles, "which just don't work well when your baby has wires coming off of them, head to toe."
Wired systems can pose issues for medical staff as well as parents.
"The main concern regarding wired systems is that they restrict access to the baby and often get tangled with other equipment, like IV lines," says Lamia Soghier, Medical Director of the Neonatal Intensive Care Unit at Children's National in Washington, D.C , who was also a NICU parent herself. "The nurses have to untangle the wires, which takes time, before handing the baby to the family."
I'll never forget the first time I got to hold my son without wires. It was the first time that motherhood felt manageable, and I couldn't stop myself from crying. Suddenly, anything felt possible and all the limitations from that first week of life seemed to fade away. The rise of wired-free monitoring will make some of the stressors that accompany NICU stays a thing of the past.
Kirstie Ennis, an Afghanistan veteran who survived a helicopter crash but lost a limb, pictured in May 2021 at Two Rivers Park in Colorado.
Laurencin, who is a University of Connecticut professor of chemical, materials and biomedical engineering, teamed up with experts in tissue bioengineering and regenerative medicine from Harvard, Columbia, UC Irvine and SASTRA University in India. Laurencin and his colleagues at the Connecticut Convergence Institute for Translation in Regenerative Engineering made a bold commitment to regenerate an entire limb within 15 years – by the year 2030.
Dr. Cato Laurencin pictured in his office at UConn.
Photo Credit: UConn
Regenerative Engineering -- A Whole New Field
Limb regeneration in humans has been a medical and scientific fascination for decades, with little to show for the effort. However, Laurencin believes that if we are to reach the next level of 21st century medical advances, this puzzle must be solved.
An estimated 185,000 people undergo upper or lower limb amputation every year. Despite the significant advances in electromechanical prosthetics, these individuals still lack the ability to perform complex functions such as sensation for tactile input, normal gait and movement feedback. As far as Laurencin is concerned, the only clinical answer that makes sense is to regenerate a whole functional limb.
Laurencin feels other regeneration efforts were hampered by their siloed research methods with chemists, surgeons, engineers all working separately. Success, he argues, requires a paradigm shift to a trans-disciplinary approach that brings together cutting-edge technologies from disparate fields such as biology, material sciences, physical, chemical and engineering sciences.
As the only surgeon ever inducted into the academies of Science, Medicine and Innovation, Laurencin is uniquely suited for the challenge. He is regarded as the founder of Regenerative Engineering, defined as the convergence of advanced materials sciences, stem cell sciences, physics, developmental biology and clinical translation for the regeneration of complex tissues and organ systems.
But none of this is achievable without early clinician participation across scientific fields to develop new technologies and a deeper understanding of how to harness the body's innate regenerative capabilities. "When I perform a surgical procedure or something is torn or needs to be repaired, I count on the body being involved in regenerating tissue," he says. "So, understanding how the body works to regenerate itself and harnessing that ability is an important factor for the regeneration process."
The Birth of the Vision
Laurencin's passion for regeneration began when he was a sports medicine fellow at Cornell University Medical Center in the early 1990s. There he saw a significant number of injuries to the anterior cruciate ligament (ACL), the major ligament that stabilizes the knee. He believed he could develop a better way to address those injuries using biomaterials to regenerate the ligament. He sketched out a preliminary drawing on a napkin one night over dinner. He has spent the next 30 years regenerating tissues, including the patented L-C ligament.
As chair of Orthopaedic Surgery at the University of Virginia during the peak of the wars in Iraq and Afghanistan, Laurencin treated military personnel who survived because of improved helmets, body armor and battlefield medicine but were left with more devastating injuries, including traumatic brain injuries and limb loss.
"I was so honored to care for them and I so admired their steadfast courage that I became determined to do something big for them," says Laurencin.
When he tells people about his plans to regrow a limb, he gets a lot of eye rolls, which he finds amusing but not discouraging. Growing bone cells was relatively new when he was first focused on regenerating bone in 1987 at MIT; in 2007 he was well on his way to regenerating ligaments at UVA when many still doubted that ligaments could even be reconstructed. He and his team have already regenerated torn rotator cuff tendons and ACL ligaments using a nano-textured fabric seeded with stem cells.
Even as a finalist for the $4 million NIH Pioneer Award for high-risk/high-reward research, he faced a skeptical scientific audience in 2014. "They said, 'Well what do you plan to do?' I said 'I plan to regenerate a whole limb in people.' There was a lot of incredulousness. They stared at me and asked a lot of questions. About three days later, I received probably the best score I've ever gotten on an NIH grant."
In the Thick of the Science
Humans are born with regenerative abilities--two-year-olds have regrown fingertips--but lose that ability with age. Salamanders are the only vertebrates that can regenerate lost body parts as adults; axolotl, the rare Mexican salamander, can grow extra limbs.
The axolotl is important as a model organism because it is a four-footed vertebrate with a similar body plan to humans. Mapping the axolotl genome in 2018 enhanced scientists' genetic understanding of their evolution, development, and regeneration. Being easy to breed in captivity allowed the HEAL team to closely study these amphibians and discover a new cell type they believe may shed light on how to mimic the process in humans.
"Whenever limb regeneration takes place in the salamander, there is a huge amount of something called heparan sulfate around that area," explains Laurencin. "We thought, 'What if this heparan sulfate is the key ingredient to allowing regeneration to take place?' We found these groups of cells that were interspersed in tissues during the time of regeneration that seemed to have connections to each other that expressed this heparan sulfate."
Called GRID (Groups that are Regenerative, Interspersed and Dendritic), these cells were also recently discovered in mice. While GRID cells don't regenerate as well in mice as in salamanders, finding them in mammals was significant.
"If they're found in mice. we might be able to find these in humans in some form," Laurencin says. "We think maybe it will help us figure out regeneration or we can create cells that mimic what grid cells do and create an artificial grid cell."
What Comes Next?
Laurencin and his team have individually engineered and made every single tissue in the lower limb, including bone, cartilage, ligament, skin, nerve, blood vessels. Regenerating joints and joint tissue is the next big mile marker, which Laurencin sees as essential to regenerating a limb that functions and performs in the way he envisions.
"Using stem cells and amnion tissue, we can regenerate joints that are damaged, and have severe arthritis," he says. "We're making progress on all fronts, and making discoveries we believe are going to be helping people along the way."
That focus and advancement is vital to Ennis. After laboring over the decision to have her leg amputated below the knee, she contracted MRSA two weeks post-surgery. In less than a month, she went from a below-the-knee-amputee to a through-the-knee amputee to an above-the-knee amputee.
"A below-the-knee amputation is night-and-day from above-the-knee," she said. "You have to relearn everything. You're basically a toddler."
Kirstie Ennis pictured in July 2020.
Photo Credit: Ennis' Instagram
The clock is ticking on the timeline Laurencin set for himself. Nine years might seem like forever if you're doing time but it might appear fleeting when you're trying to create something that's never been done before. But Laurencin isn't worried. He's convinced time is on his side.
"Every week, I receive an email or a call from someone, maybe a mother whose child has lost a finger or I'm in communication with a disabled American veteran who wants to know how the progress is going. That energizes me to continue to work hard to try to create these sorts of solutions because we're talking about people and their lives."
He devotes about 60 hours a week to the project and the roughly 100 students, faculty and staff who make up the HEAL team at the Convergence Institute seem acutely aware of what's at stake and appear equally dedicated.
"We're in the thick of the science in terms of making this happen," says Laurencin. "We've moved from making the impossible possible to making the possible a reality. That's what science is all about."
A top infectious disease physician explains why immunity derived from natural infection and the vaccines should be long-lasting.
There are two major arms of the immune system: B cells (which produce antibodies) and T cells (which are formed specifically to attack and kill pathogens). T cells are divided into two types, CD4 cells ("helper" T cells) and CD8 cells ("cytotoxic" T cells).
Each arm, once stimulated by infection or vaccine, should hopefully make "memory" banks. So if the body sees the pathogen in the future, these defenses should come roaring back to attack the virus and protect you from getting sick. Plenty of research in COVID-19 indicates a likely long-lasting response to the vaccine or infection. Here are seven of the most compelling reasons:
REASON 1: Memory B Cells Are Produced By Vaccines and Natural Infection
In one study, 12 volunteers who had never had Covid-19--and were fully vaccinated with two Pfizer/BioNTech shots-- underwent biopsies of their lymph nodes. This is where memory B cells are stored in places called "germinal centers". The biopsies were performed three, four, six, and seven weeks after the first mRNA vaccine shot, and were stained to reveal that germinal center memory B cells in the lymph nodes increased in concentration over time.
Natural infection also generates memory B cells. Even after antibody levels wane over time, strong memory B cells were detected in the blood of individuals six and eight months after infection in different studies. Indeed, the half-lives of the memory B cells seen in the study examining patients 8 months after COVID-19 led the authors to conclude that "B cell memory to SARS-CoV-2 was robust and is likely long-lasting." Reason #2 tells us that memory B cells can be active for a very long time indeed.
REASON #2: Memory B Cells Can Produce Neutralizing Antibodies If They See Infection Again Decades Later
Demonstrated production of memory B cells after vaccination or natural infection with COVID-19 is so important because memory B cells, once generated, can be activated to produce high levels of neutralizing antibodies against the pathogen even if encountered many years after the initial exposure. In one amazing study (published in 2008), researchers isolated memory B cells against the 1918 flu strain from the blood of 32 individuals aged 91-101 years. These people had been born on or before 1915 and had survived that pandemic.
Their memory B cells, when exposed to the 1918 flu strain in a test tube, generated high levels of neutralizing antibodies against the virus -- antibodies that then protected mice from lethal infection with this deadly strain. The ability of memory B cells to produce complex antibody responses against an infection nine decades after exposure speaks to their durability.
REASON #3: Vaccines or Natural Infection Trigger Strong Memory T Cell Immunity
All of the trials of the major COVID-19 vaccine candidates measured strong T cell immunity following vaccination, most often assessed by measuring SARS-CoV-2 specific T cells in the phase I/II safety and immunogenicity studies. There are a number of studies that demonstrate the production of strong T cell immunity to COVID-19 after natural infection as well, even when the infection was mild or asymptomatic.
The same study that showed us robust memory B cell production 8 months after natural infection also demonstrated strong and sustained memory T cell production. In fact, the half-lives of the memory T cells in this cohort were long (~125-225 days for CD8+ and ~94-153 days for CD4+ T cells), comparable to the 123-day half-life observed for memory CD8+ T cells after yellow fever immunization (a vaccine usually given once over a lifetime).
A recent study of individuals recovered from COVID-19 show that the initial T cells generated by natural infection mature and differentiate over time into memory T cells that will be "put in the bank" for sustained periods.
REASON #4: T Cell Immunity Following Vaccinations for Other Infections Is Long-Lasting
Last year, we were fortunate to be able to measure how T cell immunity is generated by COVID-19 vaccines, which was not possible in earlier eras when vaccine trials were done for other infections (such as measles, mumps, rubella, pertussis, diphtheria). Antibodies are just the "tip of the iceberg" when assessing the response to vaccination, but were the only arm of the immune response that could be measured following vaccination in the past.
Measuring pathogen-specific T cell responses takes sophisticated technology. However, T cell responses, when assessed years after vaccination for other pathogens, has been shown to be long-lasting. For example, in one study of 56 volunteers who had undergone measles vaccination when they were much younger, strong CD8 and CD4 cell responses to vaccination could be detected up to 34 years later.
REASON #5: T Cell Immunity to Related Coronaviruses That Caused Severe Disease is Long-Lasting
SARS-CoV-2 is a coronavirus that causes severe disease, unlike coronaviruses that cause the common cold. Two other coronaviruses in the recent past caused severe disease, specifically Severely Acute Respiratory Distress Syndrome (SARS) in late 2002-2003 and Middle East Respiratory Syndrome (MERS) in 2011.
A study performed in 2020 demonstrated that the blood of 23 recovered SARS patients possess long-lasting memory T cells that were still reactive to SARS 17 years after the outbreak in 2003. Many scientists expect that T cell immunity to SARS-CoV-2 will be equally durable to that of its cousin.
REASON #6: T Cell Responses from Vaccination and Natural Infection With the Ancestral Strain of COVID-19 Are Robust Against Variants
Even though antibody responses from vaccination may be slightly lower against various COVID-19 variants of concern that have emerged in recent months, T cell immunity after vaccination has been shown to be unperturbed by mutations in the spike protein (in the variants). For instance, T cell responses after mRNA vaccines maintained strong activity against different variants (including P.1 Brazil variant, B.1.1.7 UK variant, B.1.351 South Africa variant and the CA.20.C California variant) in a recent study.
Another study showed that the vaccines generated robust T cell immunity that was unfazed by different variants, including B.1.351 and B.1.1.7. The CD4 and CD8 responses generated after natural infection are equally robust, showing activity against multiple "epitopes" (little segments) of the spike protein of the virus. For instance, CD8 cells responds to 52 epitopes and CD4 cells respond to 57 epitopes across the spike protein, so that a few mutations in the variants cannot knock out such a robust and in-breadth T cell response. Indeed, a recent paper showed that mRNA vaccines were 97.4 percent effective against severe COVID-19 disease in Qatar, even when the majority of circulating virus there was from variants of concern (B.1.351 and B.1.1.7).
REASON #7: Coronaviruses Don't Mutate Quickly Like Influenza, Which Requires Annual Booster Shots
Coronaviruses are RNA viruses, like influenza and HIV (which is actually a retrovirus), but do not mutate as quickly as either one. The reason that coronaviruses don't mutate very rapidly is that their replicating mechanism (polymerase) has a strong proofreading mechanism: If the virus mutates, it usually goes back and self-corrects. Mutations can arise with high rates of replication when transmission is very frequent -- as has been seen in recent months with the emergence of SARS-CoV-2 variants during surges. However, the COVID-19 virus will not be mutating like this when we tamp down transmission with mass vaccination.
In conclusion, I and many of my infectious disease colleagues expect the immunity from natural infection or vaccination to COVID-19 to be durable. Let's put discussion of boosters aside and work hard on global vaccine equity and distribution since the pandemic is not over until it is over for us all.