I Study Coronavirus in a Highly Secured Biosafety Lab – Here’s Why I Feel Safer Here Than in the World Outside
By Troy Sutton
It's quiet in the laboratory, almost peaceful. But I'm holding live SARS-CoV-2 in my hands and this virus is not to be taken lightly.
As I dilute the coronavirus to infect cultured cells, I hear the reassuring sound of purified air being blown by my respirator into my breathing space. There are three layers of nitrile and protective materials between me and the virus, and every part of my body is wrapped in protective equipment.
Thanks to these precautions and other features of our high containment lab, I'm not nervous about being up close and personal with this dangerous pathogen.
As an expert on respiratory virus transmission and vaccine development, I've halted all other research in my lab so we can devote our expertise to studying SARS-CoV-2, the virus that causes COVID-19. The goal is to understand the virus and develop a vaccine, fast.
We do this research in what's called a high-containment biosafety level 3-enhanced lab, with stringent precautions in place to protect everyone from the potentially deadly pathogens we work with. In addition to SARS-CoV-2, researchers study the microbes that cause diseases including tuberculosis, anthrax and avian influenza in other facilities of this type across the U.S.
As a result of our precautions, many colleagues have told me they feel safer inside the containment lab than they do shopping for groceries during the pandemic. Here's why.
Biosafety levels are defined by how much risk is involved in working with particular pathogens. The Conversation, CC BY-ND
Suiting Up Like You’re on a Space Mission
When performing a SARS-CoV-2 experiment, my days start by coordinating with a least one of my lab members – we always work in pairs inside containment. We outline the experiment step-by-step, check we have all of the required supplies, confirm and review any procedures and communicate with the facility staff.
First thing on site, we check multiple gauges and monitors to ensure the facility is functioning properly. Then we enter the changeroom, where we remove all of our street clothes, including jewelry and underwear. We don't want to bring any potentially contaminated clothing or items out of containment at the end of the day. "You enter and leave containment as you were at birth" is our saying.
We don scrubs, close-toed laboratory shoes, a full-body disposable suit, shoe covers, multiple pairs of gloves and a surgical gown. Most importantly, we also put on our air-purifying respirators. This device includes a Batman-style utility belt that houses a motor attached to an air filter capable of filtering out any infectious agents in the air. Powered by a battery pack that will last at least six hours, the respirator blows purified air up a tube into a hood that covers my entire head and shoulders. The hood is under positive pressure so no air from the environment can enter my breathing space.
Through the clear plastic face shield I can see that we look like astronauts in space suits. Once fully equipped, we enter the containment facility and proceed to our designated virus culture and animal holding rooms. This whole process has taken between 30 and 45 minutes.
Inside the lab, experiments are done under a vented hood that sucks air away to be filtered. Penn State, CC BY-ND
The facility itself is a giant vacuum. All of the air flows from outside into the lab. It exhausts through air filters that remove any stray infectious agents. The facility is designed to accommodate failures. If one filter fails, there's a second one, and all work stops until both are working again.
Within this space our work is divided into rooms where we grow virus in cells in plastic dishes. There are separate spaces where we house animals that we use to evaluate how the virus is transmitted and if our vaccines are working.
When we're done for the day, the materials we used are treated with bleach or stored safely. All waste is sealed in plastic bags and treated in a pressurized, high-heat oven called an autoclave to ensure any remaining virus is dead.
To leave the lab, as we move through various anterooms toward the exit, at every stage we remove a layer of gloves and protective equipment. We also regularly spray our suits and respirators with powerful disinfectants. At the last step, we remove our respirator and scrubs and "shower out" of the facility. Even the wastewater from the shower is boiled for an hour under high pressure to kill any microorganisms.
The only living thing that leaves the facility is the scientist.
An exterior view of the Eva J. Pell BSL-3 containment laboratory at Penn State. Penn State, CC BY-ND
Training and Oversight
Many of the safety precautions around working in a high containment facility happen long before a researcher steps foot on the site. To gain access to this laboratory, I underwent an extensive FBI and police background check.
I was subject to a medical exam, and my lung capacity was tested. I was vaccinated against influenza. I'm sure when a COVID-19 vaccine becomes available, I'll get that shot as well.
A rigorous training and testing process made sure I know how to handle agents like SARS-CoV-2 safely, as well as things like what to do during a fire, a bomb threat and even a tornado. Regardless of my over 10 years experience working with viruses, everyone entering the facility is trained from scratch.
Every high containment lab in the U.S. is subject to regular inspections by the U.S. Department of Agriculture, the Centers for Disease Control and Prevention or both. Once open, a facility is reinspected and certified every three years. During the interim, inspectors arrive unannounced to review all aspects of the facility, including maintenance records, inventories of agents and operating procedures. My university also provides oversight.
In addition, there is a myriad of other security features. One of my colleagues once joked that during a zombie apocalypse, the containment lab would be the best place to hide.
Ultimately, all these precautions are in place to help us understand how the SARS-CoV-2 virus is transmitted in animals and determine the optimal vaccine formulation that will prevent transmission. The facility at Penn State, like others throughout the U.S., was built for this type of research so scientists could quickly and safely respond during a pandemic. With a bit of luck, the work done by dedicated researchers in these facilities will help bring the COVID-19 pandemic to an end, sooner than later.
Troy Sutton is an Assistant Professor of Veterinary and Biomedical Sciences, Pennsylvania State University.
Disclosure statement: Troy Sutton receives funding from Centers of Excellence for Influenza Research (CEIRS), the National Institute of Allergy and Infectious Diseases (NIAID), and The Huck Institutes of Life Sciences at Pennsylvania State University.
Reposted with permission from The Conversation.
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By Ana Maldonado-Contreras
- Your gut is home to trillions of bacteria that are vital for keeping you healthy.
- Some of these microbes help to regulate the immune system.
- New research, which has not yet been peer-reviewed, shows the presence of certain bacteria in the gut may reveal which people are more vulnerable to a more severe case of COVID-19.
You may not know it, but you have an army of microbes living inside of you that are essential for fighting off threats, including the virus that causes COVID-19.
How Do Resident Bacteria Keep You Healthy?<p>Our immune defense is part of a complex biological response against harmful pathogens, such as viruses or bacteria. However, because our bodies are inhabited by trillions of mostly beneficial bacteria, virus and fungi, activation of our immune response is tightly regulated to distinguish between harmful and helpful microbes.</p><p>Our bacteria are spectacular companions diligently helping prime our immune system defenses to combat infections. A seminal study found that mice treated with antibiotics that eliminate bacteria in the gut exhibited an impaired immune response. These animals had low counts of virus-fighting white blood cells, weak antibody responses and poor production of a protein that is vital for <a href="https://doi.org/10.1073/pnas.1019378108" target="_blank">combating viral infection and modulating the immune response</a>.</p><p><a href="https://doi.org/10.1371/journal.pone.0184976" target="_blank" rel="noopener noreferrer">In another study</a>, mice were fed <em>Lactobacillus</em> bacteria, commonly used as probiotic in fermented food. These microbes reduced the severity of influenza infection. The <em>Lactobacillus</em>-treated mice did not lose weight and had only mild lung damage compared with untreated mice. Similarly, others have found that treatment of mice with <em>Lactobacillus</em> protects against different <a href="https://doi.org/10.1038/srep04638" target="_blank" rel="noopener noreferrer">subtypes of</a> <a href="https://doi.org/10.1038/s41598-017-17487-8" target="_blank" rel="noopener noreferrer">influenza</a> <a href="https://doi.org/10.1371/journal.ppat.1008072" target="_blank" rel="noopener noreferrer">virus</a> and human respiratory syncytial virus – the <a href="https://doi.org/10.1038/s41598-019-39602-7" target="_blank" rel="noopener noreferrer">major cause of viral bronchiolitis and pneumonia in children</a>.</p>
Chronic Disease and Microbes<p>Patients with chronic illnesses including Type 2 diabetes, obesity and cardiovascular disease exhibit a hyperactive immune system that fails to recognize a harmless stimulus and is linked to an altered gut microbiome.</p><p>In these chronic diseases, the gut microbiome lacks bacteria that activate <a href="https://doi.org/10.1126/science.1198469" target="_blank" rel="noopener noreferrer">immune cells</a> that block the response against harmless bacteria in our guts. Such alteration of the gut microbiome is also observed in <a href="https://doi.org/10.1073/pnas.1002601107" target="_blank" rel="noopener noreferrer">babies delivered by cesarean section</a>, individuals consuming a poor <a href="https://doi.org/10.1038/nature12820" target="_blank" rel="noopener noreferrer">diet</a> and the <a href="https://doi.org/10.1038/nature11053" target="_blank" rel="noopener noreferrer">elderly</a>.</p><p>In the U.S., 117 million individuals – about half the adult population – <a href="https://health.gov/our-work/food-nutrition/2015-2020-dietary-guidelines/guidelines/" target="_blank" rel="noopener noreferrer">suffer from Type 2 diabetes, obesity, cardiovascular disease or a combination of them</a>. That suggests that half of American adults carry a faulty microbiome army.</p><p>Research in my laboratory focuses on identifying gut bacteria that are critical for creating a balanced immune system, which fights life-threatening bacterial and viral infections, while tolerating the beneficial bacteria in and on us.</p><p>Given that diet affects the diversity of bacteria in the gut, <a href="https://www.umassmed.edu/nutrition/melody-trial-info/" target="_blank" rel="noopener noreferrer">my lab studies show how diet can be used</a> as a therapy for chronic diseases. Using different foods, people can shift their gut microbiome to one that boosts a healthy immune response.</p><p>A fraction of patients infected with SARS-CoV-2, the virus that causes COVID-19 disease, develop severe complications that require hospitalization in intensive care units. What do many of those patients have in common? <a href="https://www.cdc.gov/mmwr/volumes/69/wr/mm6912e2.htm" target="_blank" rel="noopener noreferrer">Old age</a> and chronic diet-related diseases like obesity, Type 2 diabetes and cardiovascular disease.</p><p><a href="http://doi.org/10.1016/j.jada.2008.12.019" target="_blank" rel="noopener noreferrer">Black and Latinx people are disproportionately affected by obesity, Type 2 diabetes and cardiovascular disease</a>, all of which are linked to poor nutrition. Thus, it is not a coincidence that <a href="https://www.cdc.gov/mmwr/volumes/69/wr/mm6933e1.htm" target="_blank" rel="noopener noreferrer">these groups have suffered more deaths from COVID-19</a> compared with whites. This is the case not only in the U.S. but also <a href="https://www.washingtonpost.com/world/europe/blacks-in-britain-are-four-times-as-likely-to-die-of-coronavirus-as-whites-data-show/2020/05/07/2dc76710-9067-11ea-9322-a29e75effc93_story.html" target="_blank" rel="noopener noreferrer">in Britain</a>.</p>
Discovering Microbes That Predict COVID-19 Severity<p>The COVID-19 pandemic has inspired me to shift my research and explore the role of the gut microbiome in the overly aggressive immune response against SARS-CoV-2 infection.</p><p>My colleagues and I have hypothesized that critically ill SARS-CoV-2 patients with conditions like obesity, Type 2 diabetes and cardiovascular disease exhibit an altered gut microbiome that aggravates <a href="https://theconversation.com/exercise-may-help-reduce-risk-of-deadly-covid-19-complication-ards-136922" target="_blank" rel="noopener noreferrer">acute respiratory distress syndrome</a>.</p><p>Acute respiratory distress syndrome, a life-threatening lung injury, in SARS-CoV-2 patients is thought to develop from a <a href="http://doi.org/10.1016/j.cytogfr.2020.05.003" target="_blank" rel="noopener noreferrer">fatal overreaction of the immune response</a> called a <a href="https://theconversation.com/blocking-the-deadly-cytokine-storm-is-a-vital-weapon-for-treating-covid-19-137690" target="_blank" rel="noopener noreferrer">cytokine storm</a> <a href="http://doi.org/10.1016/S2213-2600(20)30216-2" target="_blank" rel="noopener noreferrer">that causes an uncontrolled flood</a> <a href="http://doi.org/10.1016/S2213-2600(20)30216-2" target="_blank" rel="noopener noreferrer">of immune cells into the lungs</a>. In these patients, their own uncontrolled inflammatory immune response, rather than the virus itself, causes the <a href="http://doi.org/10.1007/s00134-020-05991-x" target="_blank" rel="noopener noreferrer">severe lung injury and multiorgan failures</a> that lead to death.</p><p>Several studies <a href="https://doi.org/10.1016/j.trsl.2020.08.004" target="_blank" rel="noopener noreferrer">described in one recent review</a> have identified an altered gut microbiome in patients with COVID-19. However, identification of specific bacteria within the microbiome that could predict COVID-19 severity is lacking.</p><p>To address this question, my colleagues and I recruited COVID-19 hospitalized patients with severe and moderate symptoms. We collected stool and saliva samples to determine whether bacteria within the gut and oral microbiome could predict COVID-19 severity. The identification of microbiome markers that can predict the clinical outcomes of COVID-19 disease is key to help prioritize patients needing urgent treatment.</p><p><a href="https://doi.org/10.1101/2021.01.05.20249061" target="_blank" rel="noopener noreferrer">We demonstrated</a>, in a paper which has not yet been peer reviewed, that the composition of the gut microbiome is the strongest predictor of COVID-19 severity compared to patient's clinical characteristics commonly used to do so. Specifically, we identified that the presence of a bacterium in the stool – called <em>Enterococcus faecalis</em>– was a robust predictor of COVID-19 severity. Not surprisingly, <em>Enterococcus faecalis</em> has been associated with <a href="https://doi.org/10.1053/j.gastro.2011.05.035" target="_blank" rel="noopener noreferrer">chronic</a> <a href="https://doi.org/10.1016/S0002-9440(10)61172-8" target="_blank" rel="noopener noreferrer">inflammation</a>.</p><p><em>Enterococcus faecalis</em> collected from feces can be grown outside of the body in clinical laboratories. Thus, an <em>E. faecalis</em> test might be a cost-effective, rapid and relatively easy way to identify patients who are likely to require more supportive care and therapeutic interventions to improve their chances of survival.</p><p>But it is not yet clear from our research what is the contribution of the altered microbiome in the immune response to SARS-CoV-2 infection. A recent study has shown that <a href="https://doi.org/10.1101/2020.12.11.416180" target="_blank" rel="noopener noreferrer">SARS-CoV-2 infection triggers an imbalance in immune cells</a> called <a href="https://doi.org/10.1111/imr.12170" target="_blank" rel="noopener noreferrer">T regulatory cells that are critical to immune balance</a>.</p><p>Bacteria from the gut microbiome are responsible for the <a href="https://doi.org/10.7554/eLife.30916.001" target="_blank" rel="noopener noreferrer">proper activation</a> <a href="https://doi.org/10.1126/science.1198469" target="_blank" rel="noopener noreferrer">of those T-regulatory</a> <a href="https://doi.org/10.1038/nri.2016.36" target="_blank" rel="noopener noreferrer">cells</a>. Thus, researchers like me need to take repeated patient stool, saliva and blood samples over a longer time frame to learn how the altered microbiome observed in COVID-19 patients can modulate COVID-19 disease severity, perhaps by altering the development of the T-regulatory cells.</p><p>As a Latina scientist investigating interactions between diet, microbiome and immunity, I must stress the importance of better policies to improve access to healthy foods, which lead to a healthier microbiome. It is also important to design culturally sensitive dietary interventions for Black and Latinx communities. While a good-quality diet might not prevent SARS-CoV-2 infection, it can treat the underlying conditions related to its severity.</p><p><em><a href="https://theconversation.com/profiles/ana-maldonado-contreras-1152969" target="_blank">Ana Maldonado-Contreras</a> is an assistant professor of Microbiology and Physiological Systems at the University of Massachusetts Medical School.</em></p><p><em>Disclosure statement: Ana Maldonado-Contreras receives funding from The Helmsley Charitable Trust and her work has been supported by the American Gastroenterological Association. She received The Charles A. King Trust Postdoctoral Research Fellowship. She is also member of the Diversity Committee of the American Gastroenterological Association.</em></p><p><em style="">Reposted with permission from <a href="https://theconversation.com/a-healthy-microbiome-builds-a-strong-immune-system-that-could-help-defeat-covid-19-145668" target="_blank" rel="noopener noreferrer" style="">The Conversation</a>. </em></p>
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