A recent piece over at New York magazine touches on something not talked about enough in the mainstream media: the wildly hard-to-predict clinical course of your typical Covid-19 infection. Why does one healthy middle-aged patient have few-to-no symptoms, while another has been on a ventilator for weeks and has had kidney failure and an amputated leg?
We know enough to know that Covid’s favorite target is the respiratory system, and cases range from the completely asymptomatic, to something resembling a typical upper respiratory infection, to a pneumonia demanding hospitalization, to total respiratory failure and death, with the latter two far more likely in elderly patients. In fact, this is the same as the garden-variety flu, although at a vastly higher mortality rate.
But unlike influenza, Covid-19 isn’t satisfied with merely battering the lungs. Nobody knows why, but Covid-19 displays tropism for an astonishing array of human tissue compared to other respiratory virii. Here are what else I have witnessed first-hand, treating many, many Covid inpatients at a public hospital in NYC:
- Acute kidney injury. Enough people come in with elevated serum creatinine (one of the most reliable lab tests for kidney injury or failure) that I wonder if hospitalized Covid+ patients with kidney damage outnumber those without. The sheer numbers cannot be adequately explained by dehydration or previously undiagnosed chronic kidney problems. More likely, the virus attacks the kidneys directly.
- GI problems. This is less common, but nausea, vomiting, and diarrhea happen with a good number of my patients. In one case, uncontrolled throwing up was in fact the primary cause of hospitalization for a Covid+ patient.
- Coagulation problems and inflammed blood vessels. Many of my patients have had elevated INR numbers, a marker of how well your blood clots. They also usually have high “D-Dimer,” a marker of active blood clotting, to the point that some have obscenely sky-high numbers that more experienced colleagues have never seen before in their careers. Some say that this lab number is the most important one to follow, although I disagree: see below.
- Heart failure and acute decompensation. Now this may happen just from respiratory failure, but scientists also believe this happens because the virus itself may attack the heart.
And, what I believe is most important:
- Very low numbers of a type of an infection-fighting white blood cell called lymphocytes (aka lymphopenia). Almost all of my Covid patients have this (and, correspondingly, usually have higher numbers of non-lymphocyte WBCs). If this sounds familiar, it is: HIV attacks one specific type of lymphocyte, leading eventually to failure of the immune system. The lymphopenia picture in Covid is more indiscriminate, although literature suggests a type of lymphocyte called the “natural killer” cell, which works by killing virus-infected cells, is particularly vulnerable to depletion.
Here’s why this is critical.
There are two main components of the immune system: what we call “innate” immunity, one that is unfocused and generalized, mediated by cells like neutrophils and macrocytes, and “acquired” immunity, which consists of lymphocytes and antibodies. The latter is far smarter and more sophisticated and, while innate immunity is important in the beginning of any infection, your body depends on acquired immunity to eventually kill the bug — and, hopefully, prevent future infections, which is also how vaccines work.
Also, and critically, acquired immunity generally causes far less collateral damage to your body. If innate immunity is indiscriminate carpet bombing, acquired immunity consists of snipers and laser-guided bombs.
The fact that Covid causes suppression of the acquired immune system is, in my opinion, *the* most important reason why some people get incredibly sick from this thing, to the point that the coronavirus has a free hand to even attack non-respiratory organs like the kidneys, gut, blood vessels, and heart. It is also, I believe, *the* most salient reason why some people experience an out-of-control innate immune response, leading to chronic lung damage (some of my otherwise-recovered patients go home on portable oxygen tanks) and that “cytokine storm” thing you may have heard of — it’s like, if the body tries calling in laser-guided bombs but nothing happens, it resorts to mass carpet-bombing instead.
Perhaps take my opinion with a grain of salt — I’m just an ordinary MD, not an infectious disease specialist, hematologist, or virologist with high-falutin’ Ivy cred. If Dr. Fauci is a four-star general, I’m just a 1st lieutenant.
But I strongly believe it’s the lymphopenia that lets this beast out of its cage. And besides HIV, there is another precedent to bolster my case: leprosy. Yes, leprosy.
Like Covid, the symptoms of leprosy, aka Hansen’s Disease, range in a wide spectrum, from mild disease on one end to the real old-Testament version on the other. (Or “tuberculoid” vs. “lepromatous,” to use the traditional medical terms.) And we’ve known for quite some time now that what really determines the course of this disease is the acquired, aka the adaptive, immune system. Mild leprosy is associated with a well-functioning acquired immune system, with antibodies and natural killer cells keeping the germ in check (although this grouping of patients is more likely to experience sensory loss, similar to how losing one’s sense of smell seems to happen more often in mild cases of Covid-19).
But for less fortunate leprosy patients, for some reason, the acquired immune response doesn’t work correctly. The lymphocytes wind up using the wrong methods, or incorrectly going with what scientists call the “TH2” pathway, which is ineffective in this condition, instead of going with what the leprosy bacteria is vulnerable to, the “TH1” response. Thus, leaving the victim’s body with only the innate immune system to fight off the invader — and as with Covid, we all know how well that works out.
Also, this is why one of the scariest drugs in all of medicine, thalidomide, has been used in the past in lepromatous leprosy. By dampening the body’s innate immune system, it eases some of the symptoms, but without also weakening the acquired immune system the way steroids like prednisone do. Nowadays nobody in their right mind prescribes the drug, but if Covid-19 had hit in, say, 1962, I bet thalidomide would have soon been part of every hospital’s standard regimen.
Finally, returning to the flu, it too may be a precedent. Severe cases of the flu also are marked by lymphopenia. Although the cause-effect relationship remains unproven, smart money bets on low lymphocyte numbers being what can lead the flu to become a killer. Similarly, it is precisely because Covid somehow weakens the body’s acquired immune system that it may become so deadly.
Now how, exactly, the coronavirus does in the body’s lymphocytes is an open question. Perhaps it suppresses the body’s “factories” of blood cells, the bone marrow. Maybe it targets some lymphocytes directly, the way HIV does. It could confuse the body into killing its own lymphocytes. Or perhaps it tricks the body into producing the wrong type of immune response. Or some combination thereof — that’s definitely above-my-pay-grade material.
But in my mind, where there is no question is that this characteristic lymphopenia is the key to figure out. Prevent, or at least treat, that, and you prevent the bug from further damaging so many organ systems.
The silver-bullet solution is to pre-activate the general population’s acquired immune system so that the virus may not get a foothold, i.e., make and distribute a vaccine; but that’s a long way’s off. In the meantime, if scientists are finally able to figure out specifically what causes lymphocyte numbers to crater in serious Covid-19 infection, we might be able to come up with a more effective drug to help patients like mine.