Of all the possible compounding effects of COVID-19, the disease caused by the novel coronavirus, the cytokine storm is one of the most feared. An immune system overreaction in which the body is flooded with the eponymous signaling molecules, those who suffer a cytokine storm are at risk of dying at the hand of their own immune system, as an indirect effect of the virus they are fighting.
This is the opposite of how we think of our immune system working: if we have a good, strong immune system, we should be safe from the novel coronavirus, right? Unfortunately in this case, too much of a good thing is not a good thing. This is true beyond the example of the cytokine storm, as there are other diseases, often milder ones, caused by a misbehaving immune system; lupus, allergic reactions and celiac disease are all examples of overactive immune responses.
The cytokine storm affects a substantial number of severe COVID-19 patients, enough that it has become the subject of a subset of medical research into COVID-19. Those unlucky enough to experience a cytokine storm will feel cytokines, the immune system helper cells, flood their bodies and especially their lungs as their immune system struggles to fight off the invading virus and the dead lung cells it produces en masse. The overreaction results in the immune system building up too many of these kinds of cells, which can lead to respiratory distress or bacterial pneumonia and ultimately death.
Not everyone who experiences a cytokine storm will die, fortunately. Such is the case of Jonathan Raskin, a 69-year-old pulmonologist who practices medicine in New York City, and who contracted coronavirus a few weeks ago and is currently in recovery. After self-isolating at home, Dr. Raskin's temperature swelled to 102.8°; he spent several days in the hospital in a very bad state (by his own admission) before slowly recovering. As a pulmonologist, Dr. Raskin's insights into what was happening to his own body are particularly keen, as he had a medical understanding of what was happening as it happened to him.
Dr. Raskin was kind enough to be interviewed about recovering from COVID-19 over the phone, from the comfort of his apartment in Manhattan where he continues to recover and is now in better health.
So let's start from the beginning. Do you happen to know how you contracted the virus?
No, I don't. As a pulmonologist, I guess I'm an at-risk population, but I was unable to figure out where and how I acquired it. It was in the community I believe well before people were aware. As we are still unable to test and identify those infected, many of whom are asymptomatic, the issue and concerns remain.
Did anyone else in your office, like any nurses or other doctors get it?
My wife who is also a physician did become positive but she has had a different version of it. Fortunately despite being infected she was asymptomatic. She was offered the test, as she is a physiatrist who oversees a large rehabilitation center.
How did your symptoms progress?
First, I just had this intuition that I had it at some point in late February. Not for any clinical reason — I was feeling low energy, and I'm not a low energy type. There was no fever, there was no cough, I was simply asymptomatic but realized I was at risk so the thought was on my mind a great deal.
[On] Saturday March 7th, I had a chill. I took my temperature and it was over 101. Initially I started Tamiflu, as there was a chance it was influenza but shortly thereafter I realized the symptoms and presentation of influenza is quite different and I knew that the presentation of this virus was unique.
The primary symptoms I had are quite typical for those who find themselves truly afflicted with the illness: high fever, a dry cough and pain in my throat. Not a classic pharyngitis, rather a sort of aching pain which was intermittent. Subsequently, the fevers really took off and averaged 102.5 over the following days. Headaches, nausea, severe muscle and bone pain, change of bowel habits and a loss of taste and smell all evolved.
Three days into it, I began to notice my oxygen level was beginning to go down. I had a oximeter, a device that measures peripheral oxygen levels — as a pulmonologist it comes with the territory — and my oxygen is normally 98 and it declined to about 94, 93. At that point I realized it's time to have someone look at me.
When I went to the emergency room I had not intended to stay. I had been reading that many people will be engaged with home care and realized hospital staff were becoming a bit overwhelmed. I went to the ER primarily to get the test which was not readily available and I was told they were only able to test about 50 patients a day. "Yes, we'll test you," was their response, but they also wanted to check me out, for which I was grateful.
My lab work was stunningly bad. A normal white count might be between 4.5 and 10. My white cell count was at 2,000. My lymphocytes — which are the cells that fight in a virus, normally fall somewhere between 1000 and 1,500 — they were under 200. I don't know if you know the term but the early cells that fight infection are called "bands," and you don't have [them] normally — I had 20% bands. My platelet count was around 100,000, which is low, and I knew I was in trouble.
When they began to tell me some of the data, my eyes widened. They did a CT scan; I had bilateral pneumonia and I was admitted, which was quite fortunate as that night I crashed. I had 103.7° fever, a blood pressure that was 80 over palp, and oxygen levels that were so low I required oxygen support at a level just below that achieved with mechanical ventilation. So it was really serendipity, really tremendous luck that I chose to go over to the ER to be evaluated. I probably would not have made it had I remained home that evening.
That evening, the first evening at the hospital, is a unique memory. I knew I was in trouble but I felt serene, peaceful and while I did not have an out of body experience at no time was I fearful or anxious. Many such as Kubler Ross have written of this, and I guess it was my turn to experience it.
It was the following day that reality returned as the illness really hit me. I was experiencing tremendous headache, nausea, abdominal distention making it harder to breath. I continued with fever to 103°, attendant chills and sweats while breathing at about 30 times per minute. It was challenging but again I didn't feel alarmed or frightened. As a pulmonary physician trained in ICU realities it was more of a funny reality to look at oneself now as a patient and say "Look at you Raskin, now it's your turn!" It was droll and I remembered that God has a sense of humor too.
My infectious disease consultant arrived and said, "We don't really have well documented therapies that are known to work. It's all speculative as to what to do. Let's try to get you through this without pharmacotherapy." I understood the only clinical data that existed in early March was coming from China and consented. First, I knew better than to try and be my own physician and second, I understood that… what she saying was that they didn't really know what to do.
Three to four days later it turns out that wasn't such a great idea because I crashed again and everyone knew that they had to initiate some therapy. Plaquenil (hydroxychloroquine), as well as an IL-6 inhibitor Tocilzumab, to address cytokine storm. Kaletra, an HIV therapy, was also initiated. Fevers abated soon thereafter…
There were a couple of funny moments along the way. While I was so sick, during the time frame before starting therapy, an 87-year old man with a recent stroke and the COVID pneumonia was admitted to the bed next to mine. I look over and I see this man sitting quietly, breathing easily, calling his wife and saying, "things will be okay and not to worry." At which point I just smiled and turned away again reminding myself once again, God has a sense of humor.
So at this point, the cytokine storm hadn't started yet?
Yes, and this was yet another curious moment. The infectious disease physician arrives and shares, "You know there's a lot being written about cytokine storm at this stage of the illness. Do you think you're in cytokine storm?"
I felt a bit like a deer in the headlights… I didn't really know what to say, as the association of cytokine storm is typically associated with medical catastrophes such as sepsis with adult respiratory distress syndrome, severe burns, profound mesenteric ischemia etc. and one hardly finds oneself as a physician asking a patient if they think they are undergoing cytokine storm.
[The question] "Am I in a cytokine storm?" seemed almost absurd, because everybody we've seen in cytokine storm was just a mess and such discussions were unnecessary. But there we were discussing it!
I began to think about all the visceral perceptions I was having and realized the persistence of headaches, nausea, abdominal distention, profound muscle and bone pains, along with my difficulty breathing, might actually qualify me as [some]one who is struggling with cytokine storm! The next day I shared with her that despite the wonderful occasion of my fevers decreasing on current therapy that cytokine storm might be marching to the beat of a different drummer, as I was still experiencing a lot of symptomatology as mentioned.
The normal thinking is that if you're afebrile — no fever — is that we have won the battle and patients can begin healing. In fact I was raging inside. The fire was internal, with gripping headache, profound nausea, waves of pains in my bones and muscles along with the breathing challenges attendant to having pneumonia.
So the next day she comes in and I shared, "You know, there may be two version of afebrile. There's the one that we're used to" in which we are celebrating, thinking we beat this illness — and then there's what I'm feeling, which is a bit distinct. I explained to her some of the visual perceptions I was having. She just looked at me wide-eyed and said, "this is fascinating." I don't think any of us have truly appreciated the spectrum of this clinical state and that there are different manifestations of cytokine storm, even though we do see cytokine dysregulation in various illnesses such as autoimmune disease.
In the current context, we believe we have a biomarker of this condition, a serum level of a non-specific but is an acute phase reactant called serum ferritin. It looks like it may be to be one of the more reliable biomarkers of cytokine dysregulation. A serum ferritin is normally below 400 in our lab, mine was 18,000!
It was stunningly high. When a resident told me the result they were looking at me like, "dude, this is crazy." I agreed, but again felt like the deer in the headlights.
It's amazing you weren't feeling a fever while you experienced cytokine storm.
That's right. It was a remarkable moment because being afebrile, and I believe I became afebrile as a result of the IL-6 therapy, as well as the Tylenol I was getting…. and yet when I was taking the Tylenol I was still spiking fevers over 102 so I believe the impact of the IL-6 therapy brought my fevers down quickly…and perhaps contributed to some of my experience with all the aforementioned symptoms. It really was a unique moment in the world of being afebrile, where you would normally assume you were better but realized you were still struggling. That was curious for sure.
So you're healing at home now. Do you still have symptoms as you recover?
While in the hospital I had profound weight loss — ten pounds in eleven days, and for the first time in my life I looked forward to putting on weight. Also, I evolved with asthma as a result of the pneumonia and still am experiencing this upon my return home.
One daunting symptom is the presence of persistent cough which aggravates the lung and one continues to wheeze. During my stay at the hospital, and after a week of having a dry relentless cough I began to cough up black sputum! I'm coughing up necrotic lung. I've been looking at sputum my whole career, right? People get preoccupied with the color of their sputum and for years patients have brought me sputum collected and preserved in origami like napkins. "Is it okay Dr. Raskin? Is it too yellow, I think I see some it's green…"
But I was coughing up jet black sputum — obsidian black, as black as your cell phone. I thought about it for a moment and then I turned to a physician, whomever was there at the moment and I said, "It's necrotic lung." And they looked at me and went, "Oh my god." That's the only good answer, yes it must be necrotic lung. I love being a teaching attending.
Anyway, that has continued but it's slowly improving, and asthma continues for the moment. As a pulmonary physician, I am completely capable of dealing with it and [am] fine if not bemused by the attendant ironies of it all. Oxygen levels remain a bit low, but I believe this too shall pass.
Many patients have experienced their sense of smell and taste dissipating. Did you feel that?
Yes. It's been written about and I certainly experienced it and perhaps I can share an insight. I am unsure but am guessing that the cranial nerve responsible for taste and smell may not be affected by coronavirus. Early on, I noticed a biofilm in my mouth and I couldn't taste very well at all, even though I knew I should be eating and trying to maintain my nutrition. Physicians at the hospital did examine my mouth but no one saw any pathology. When I finally coughed up sputum, the now infamous black sputum, it grew candida, a fungus associated with the loss of taste but not necessarily smell. My speculation is that this virus immunosuppresses people — remember my white blood count was very low and remained low for quite a while so one is susceptible to a superinfection, in this case a fungal infection possibly causing this clinical finding and concern.
Right. My understanding is that is what thrush is, right? Usually that's an early sign that you may have an HIV infection or something, because you're immunocompromised and can't keep yeast out.
Correct. It happens in diabetics, but it also happens in healthy people. An example are those asthmatics who are using cortisone spray to address their asthma. That's probably where pulmonologists see it most commonly because, as they say, fungus grows where the sun don't shine — the mouth, rectally, vaginally, under armpits, under breasts and skinfolds. Fungus grows in the mouth when you're using cortisone sprays commonly. When I finally coughed up a sputum that had candida in it, I was not on any cortisone inhalation just albuterol therapy. Perhaps the lack of taste and even smell is associated.
That's interesting. So, in theory, perhaps it's not actually the coronavirus that results in the lack of taste, but the compromised immune system that caused candida or other infection?
Right, a superinfection. And this in general is a mild one. It's a surface infection, it's not a system infection. The biofilm that perceived in my mouth is getting better but remains and is improving with therapy addressing the fungal infection.
Just to go back a second, so you were never on a ventilator?
No. Thank god I was on a non-rebreather mask which is the highest version of oxygen support without ventilation.
What happened to the 87-year-old man sitting next to you?
He went home in three days.
I had to laugh…as mentioned, I've always thought God has a sense of humor — make that an ironic sense of humor —so this was one of those moments. "Take that Raskin," I thought. If you are ever very sick, try not to lose your sense of humor, it helps.
And please also remember ones my heart must go out to the people who are caring for you, especially these days when so many are falling ill and getting sick. They are doing God's work. It is so clear.
Do you have any other thoughts on what you went through, medical thoughts you might like to share?
Coronavirus was once a common cold, and no one cared. In 2003 it mutated, and we experienced SARS — 8000 patients were afflicted but we have not seen a recurrence in 17 years. In 2012 MERS [Middle East Respiratory Syndrome] occurred, and it has affected about 2,500 patients but continues to be a human pathogen.
SARS-CoV-2 or COVID-19 is yet another mutation, and clearly is of greater consequence. Each of these mutations should be thought of as a unique illness with different aspects and characteristics. Discussion about the virus — be it about therapy, epidemiology or contact and respiratory droplet spread — is challenged by the fact we are still learning about this illness and truly are early on in our understandings.
An example of this was the comment that the warmer weather will impact on the natural history of the illness. Well, the CDC just reported that the illness is acting the same way in Singapore where the temperatures are currently between 80° and 90° [Fahrenheit]. We must be careful our speculations are not capturing our imagination and remain vigilant as we care for one another.