Scientists Believe Bradykinin (Huh?) Is Causing Trouble In COVID-19 Patients
Shortness of breath. Loss of smell and taste. Sore throat. Fatigue. Muscle aches. Diarrhea.
The list of COVID-19 symptoms goes on and on, with severity ranging from minor annoyances to life-threatening.
Since the beginning of the pandemic, these symptoms of COVID-19 have stumped scientists and medical professionals across the globe. Researchers have been thrust into a search for answers, with the stakes higher — and the timeline tighter — than ever before.
As the pandemic has unfolded, discoveries about the mysterious nature of the virus have sprung up in laboratories around the world.
One of the latest of these discoveries was born in the Oak Ridge National Lab in Tennessee. The Summit supercomputer in this lab analyzed over 40,000 genes from 17,000 genetic samples. Despite being the second fastest computer in the world, it took more than a week to complete.
Researchers analyzed the results from Summit and developed a model that could explain how COVID-19 impacts the body: the bradykinin storm hypothesis.
What Is Bradykinin?
Let’s back up for a moment and define some key terms needed to understand the bradykinin storm hypothesis.
The renin-angiotensin system (RAS) is responsible for controlling many parts of the body’s circulatory system. This includes bradykinin, which is a chemical that helps regulate blood pressure.
It might seem like extra bradykinin wouldn’t be harmful and would further the body’s ability to control blood pressure — but that’s not the case. Bradykinin can also induce pain and cause blood vessels to expand and leak, which can then lead to swelling in the surrounding tissue.
ACE And ACE2
Angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme-2 (ACE2) are enzymes within the RAS, and are directly involved in regulating bradykinin.
The SARS-CoV-2 (the novel coronavirus) enters cells in the body through ACE2 receptors. This usually occurs in the nose, since the nose is home to an abundance of these receptors.
The Bradykinin Storm Hypothesis
The recent study found that the SARS-CoV-2 virus tweaks the RAS. It decreases ACE levels while increasing ACE2 ones. This causes bradykinin production into overdrive, creating a “bradykinin storm.”
As bradykinin levels increase, blood vessels — the tubes that carry blood throughout the body — become leaky. When blood vessels leak during a bradykinin storm, the lungs can fill with fluid. Also, immune cells can make their way into the lungs and cause inflammation. With fluid and inflammation in the lungs, breathing becomes difficult — and that could be one explanation of why cough and difficulty breathing are effects of COVID-19.
Bradykinin Might Be Why Ventilators Aren’t Helping Everyone With COVID-19
Ventilators are machines that are like external lungs. They breathe for someone who can’t breathe on their own and reduce the amount of energy their body uses on breathing, allowing that energy to be redirected toward fighting an illness.
At the beginning of the COVID-19 pandemic, when it became clear that severe difficulty breathing was a potentially deadly side effect of the virus, ventilators were in hot demand. Hospitals across the country feared that they would not have enough of these machines.
As it turned out, the ventilator shortage wasn’t as devastating as originally thought — not because hospitals suddenly had enough of them, but because providers learned that ventilators were not helping as much as anticipated. Ventilators were still life-savers for some patients, but were not too effective in others. In fact, some researchers have argued that ventilators can actually do more harm than good in patients with COVID-19.
This begs the question: If ventilators are supposed to help people breathe, why aren’t they working as well as expected?
One potential reason is the combination of the bradykinin storm and hyaluronic acid.
Bradykinin Storm + Excess Hyaluronic Acid (HA) = Disaster
Hyaluronic acid (HA) is a substance produced naturally by your body and found in many areas, including your skin, eyes, and synovial fluid in the joints. It can absorb 1,000 times its own weight in liquid. HA is often used in addressing cosmetic concerns, from lifting cheeks to rejuvenating earlobes. It’s also frequently used in lotions and soaps.
Similar to bradykinin, HA is helpful in the right doses. In addition to its skin and cosmetic benefits, it’s also involved with wound healing. However, too much HA can wreak havoc on the body.
HA levels can increase when someone has COVID-19. As HA in the lungs combines with fluid leaking in from the bradykinin storm, the two substances form a hydrogel that is very difficult to breathe through. Regardless of how much oxygen gets pumped into the body via a ventilator, it can’t make it through the hydrogel in the lungs. A patient can suffocate even while hooked up to a ventilator.
The Bradykinin Storm Hypothesis May Explain COVID-19’s Unique Symptoms
The bradykinin storm hypothesis doesn’t just explain the breathing problems that come with COVID-19 and why ventilators aren’t as successful as expected — it also may shed light on why some of the other symptoms occur.
For example, a bradykinin storm could be behind some of the heart damage seen in 1 in 5 patients who are hospitalized with COVID-19. While some of the damage may be due to the virus infecting the heart directly, it could also be due to the fact that the renin-angiotensin system (RAS) controls certain cardiac functions and a bradykinin storm could cause arrhythmias or low blood pressure — the heart problems seen in COVID-19 patients.
A bradykinin storm could also be why some COVID-19 patients experience neurological effects, like dizziness, delirium, or seizures. Excess bradykinin can break down the blood-brain barrier (the filter between the brain and the rest of the circulatory system). If this happens, harmful cells could make their way into the brain, where they could cause inflammation, brain damage, and the neurological effects associated with COVID-19.
Additionally, too much bradykinin could explain other symptoms, such as fatigue, diarrhea, headaches, and decreased cognitive function. These symptoms are common in other conditions involving high levels of bradykinin, so it would be reasonable to hypothesize that these symptoms in COVID-19 patients may be the result of excess bradykinin.
Some researchers have even theorized that a bradykinin storm could be the culprit behind the more “bizarre” effects, from bruised toes to thyroid disease.
What Does All Of This Mean?
The bradykinin storm hypothesis might mean a lot — but it could also mean nothing at all.
Any time we learn more about how a disease works, the more information we have at our disposal for finding a vaccine or a cure.
For instance, there are already medications approved by the FDA for treatment of other conditions that involve overproduction of bradykinin. These drugs may be able to fight off potentially fatal bradykinin storms in patients with COVID-19. (Of course, the drugs still need to be tested in clinical trials — but it’s a good starting point). In fact, the researchers who developed the bradykinin storm hypothesis identified more than 10 of these possible treatments.
There are also medications that can reduce HA levels and stop hydrogel from forming in the lungs, as well as supplements for vitamin D — a vitamin that is involved with a healthy RAS and could possibly thwart bradykinin storms.
However, while the bradykinin storm hypothesis may be the key to unlocking the mystery of COVID-19 and finding a cure, it is far from being the definitive answer. There have been other promising theories circulating since the beginning of the pandemic, so the bradykinin storm hypothesis is not the first possible explanation.
Still, there is reason to celebrate. With each new promising theory like the bradykinin storm hypothesis, we inch closer toward a return to normal — from attending concerts to going out without masks to hugging our loved ones.
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Virtual Meeting Bingo: From, “Wait, Is My Camera On?” To “Sorry, That Was My Cat”
It has been a few months since COVID-19 basically made physical office spaces obsolete. And while the country has slowly started reopening, many offices still remain closed — or are allowing employees to continue to work from home if they’re more comfortable with that.
If you’re one of the millions of Americans who now work from home, you’ve probably become familiar with the world of virtual meetings. Whether it’s via Zoom, Google Meet, or Skype (so old-school), online meetings make working from home easier and allow you to still connect with your coworkers.
You know what else virtual meetings do?
They set the stage for really lame jokes and plenty of snafus that no one will let you forget.
How many of these have you experienced?
So, we really do focus on healthcare content. But sometimes, you just need a little dose of something fun — and we are all about that, too.
My First Time Using Telemedicine
It was a Tuesday night when I started to feel the burn. And no, I’m not talking about politics. I’m talking about the unmistakable burn of a urinary tract infection (UTI).
Having had a couple before, I knew exactly what I was in for. So, I booked the first available appointment for the next day at a clinic by my apartment, took some Advil and a sleeping pill, and went to bed.
The pain woke me up at 3 a.m. I won’t say I was in agony, because that’s a bit dramatic. But it was as close to agony as you can be in without actually being in agony.
No matter what I tried, I could not get comfortable and I couldn’t fall back asleep. I knew that there was no way I could sit there sobbing from the pain until my 11 a.m. appointment.
I logged into the patient portal on my insurance provider’s website to see if I had coverage at any 24-hour clinics. The first thing that popped up was “MDLIVE.”
MDLIVE Called To Me
MDLIVE is a telemedicine smartphone app. Even though I’ve written about telemedicine before—and about how great it is for patients who have limited access to physicians—I was still skeptical about using it myself.
But, the nagging pain made up my mind for me. I downloaded the app and got started.
When you download MDLIVE, you begin by setting up a profile. You fill out a brief medical history form, including chronic medical conditions and allergies to medications. I don’t remember putting in my insurance information but, to be honest, that night is a bit blurry from the pain.
MDLIVE also lets you add in a picture of yourself when you’re setting up your account because hey, why not make telemedicine just like Facebook?
For the record, I chose this picture. I think it’s kind of cute.
Next, you click on “Find a Provider” and choose the type that will best meet your needs: family physician, therapist, or psychiatrist. (For a brief moment, I flirted with the idea of choosing “therapist” to discuss the emotional disaster that is my dating life, but decided I should probably go with the type of provider I actually needed in that moment.)
The next thing you do is enter your symptoms. Once you start typing, it gives you a list of suggestions (kind of like Google’s autocomplete feature).
On this page, you can also upload a photo if you have a rash or cut. I decided against including a photo for my particular ailment.
You then get taken back to your medical history page, just so you can be sure you didn’t miss any important details. Once you’ve double checked your pre-existing conditions and allergies, and marked down any medications you’re currently taking, you’re good to go on to the next step: confirm your pharmacy.
You can get help locating a nearby pharmacy on the app. Fortunately, I found one near me that was open 24 hours, or this whole experience would have been for naught.
Next, you’re asked to choose between a “visit” by video call or phone call. (I chose a phone call … I was in my pajamas and not at my best.)
At this point, you can choose “See the First Available Family Physician,” or you can pick a specific provider—not that you probably know any of them (unless you’re a frequent caller), but they do have pictures. This felt like it was just one step away from a swiping, Tinder-like app for telemedicine.
The Waiting Room (From My Bed)
You’re supposed to get a call within the hour, but the app says it usually takes less than 10 minutes. Luckily, when it’s 3 a.m., you get a call back pretty quickly.
A wonderful doctor (let’s call him Dr. Saverofpelvicpain) called me within 2 minutes. I told him my symptoms, and that I was 99% sure I had a UTI since I’d had one before and had experienced the same symptoms. The doctor agreed and sent off a prescription to the pharmacy I had chosen.
I was happy that Dr. Saverofpelvicpain made a point to mention that he was giving me a second-choice drug, since I’m allergic to the mainstay for UTIs. I’ve been to clinics before where I’ve told them about my allergies, and was still almost prescribed a drug that my body would not have appreciated.
The call lasted all of 3 minutes. I drove to the pharmacy, picked up my prescription, and was back in bed with an on-the-mend pelvis by 4 a.m. I woke up the next morning feeling refreshed, and ready to go about my day, burn-free.
Musings Of A Patient
So, what were my overall impressions of my first telemedicine experience?
- 24/7 access to care—you can’t beat those hours.
- Really, really, really easy and quick.
- The physician had clearly looked at my medical history.
- I received a prescription almost instantly.
- You don’t get any lab testing. For this type of appointment, that was fine. You don’t even always get a urine test when you go to see someone in person about a UTI—they just give you a prescription. But it does make me nervous about using telemedicine for other illnesses.
- Dr. Saverofpelvicpain was very nice, but he seemed rushed. I’m not sure why he was so rushed at 3 a.m.—maybe there was an onslaught of cross-country UTIs?
- The pricing was a bit unclear. I couldn’t figure out if this was considered a primary care visit or a specialty visit, so I didn’t know exactly how much I was going to be paying. The app did guarantee it would be cheaper than the urgent care copay, so I knew I was scoring a good deal. I just wish I’d had a bit more information about the cost upfront.
- The in-person physicians I’ve seen since then have had mixed reactions. My primary care provider thought it was cool, and great for things like UTIs. The emergency room doctor I saw the next night (for an unrelated issue) was very wary about it.
Overall, I was very pleased with my first experience with telemedicine. In the future, I’d still like to try to see someone in-person. I think that that’s usually ideal because an in-person provider can run lab tests, see if anything on your body looks abnormal, etc.
However, for things like UTIs where the pain is really bad, I’m almost positive I know what it is, and I just want a prescription as soon as possible, I would absolutely use telemedicine again. It’s really easy, quick, and less expensive than urgent care.
Plus, it just feels kind of cool to have a telemedicine appointment. It’s like you’re getting a house call. (Get it?)
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