Ask the Pharmacist

Q) There is much talk about the symptoms of long COVID but really nothing about why it happens in some people. Is there any information you can pass on about this?

A) Last week, we restarted our conversation about the constellation of symptoms that make up the new medical disorder that has been called long-COVID or post-COVID syndrome or long-hauler’s disease among other monikers.

Hopefully, we are nearing the end of the acute phase of this infection in terms of the amount of people becoming infected and getting sick enough to warrant hospitalization and/or dying. COVID, much like the flu, will likely be with us indefinitely but perhaps in a less lethal way as vaccination rates and natural immunity inches upwards.

Given the relative frequency of this new condition, it has been postulated that once we are finally finished with this acute phase of this infection it will vie with other health care crises for the top reasons for seeking medical help. Some of the other health care crises competing for this are mental health, drug addiction and all the diagnoses that were missed during our shut-downs.

We know COVID itself is a viral infection, but the question remains as to why some people remain sick for so long whereas most others do not? This situation is not unique to COVID. Doctors have known for years that a multitude of viruses can lead to chronic illness. A case in point would be one of COVID’s predecessors, the SARS virus where there are records of patients battling symptoms for years after they were first infected.

When it comes to COVID (and possibly other viruses as well) there are three biological explanations. The first is that the infection itself never really leaves. The virus perhaps mutates within our body or is somehow otherwise changed, possibly by components of our immune system, into an altered form that is most likely no longer infectious or replicating and is, therefore, undetectable by the usual tests we use to diagnose COVID. We see this with other viruses such as the measles and Ebola.

Direct proof to support this theory is lacking but an article in the magazine Nature spoke of how traces of the virus have been detected in the urine and intestines of some people months after they had seemingly recovered from their infection. Hence, in this theory, the virus does not die as most viruses usually do but instead changes and continues to create havoc within our body and manifesting itself in a variety of symptoms that persist for an indefinite period of time.

Another possible biological explanation for long COVID is that it is in fact an autoimmune disorder. We are already aware of a bevy of autoimmune disorders such as lupus, Crohn’s disease and rheumatoid arthritis to name just a few. In this theory, as the virus enters our body, our immune system activates, as it is supposed to, to kill of the invading virus molecules. But alas, something goes awry with our normal immunological response and our various infection fighters start to attack our own body’s tissues leading to a host of symptoms depending on the tissues under assault.

Evidence to support this theory comes from blood and tissue samples taken from long-haulers which show macrophages that are behaving maliciously and B-cells that appear abnormal in their activity. Other markers of abnormality include unusually high levels of auto-antibodies, low levels of interferons and T-cells which act, as one scientist described them, as being exhausted. Further evidence comes from a study in which those patients complaining of brain fog seemed to have T-cells that responded differently than would normally be expected. Researchers theorize that perhaps these long-haulers were already genetically susceptible to acquiring an autoimmune disorder and that the immune activation that goes with the initial infection perhaps “pushes” them over the edge and into this chronic disease type.

A third possible mechanism behind long-COVID is that the symptoms are simply the lingering results of tissue damage that was caused by the widespread inflammation that we know occurs during the acute infection. Cytokines are immune system proteins that have been found in very high amounts in the blood samples of some patients with COVID-19. High levels of cytokines are associated with rampant inflammation and it is speculated that this inflammation perhaps damages parts of our autonomic nervous system or the cells that line our blood vessels leading to the symptoms that so many of these people experience. For instance, changes to the lining of our blood vessels would alter the flow of blood to our target organs such as the brain and could well affect their function which might give rise to a symptom such as brain fog.

Most experts believe that these three theories are not mutually exclusive and that there is a chance that all three mechanisms may well be playing a role in this large group of patients. It is more probable than not that long-COVID is in fact a term that embraces several unique conditions all with differing causes in much the same way that the word cancer connects a number of very unique diseases.

Needless to say, studies are underway to get a better understanding of just what is going on inside the bodies of these patients. Until we get a better grasp on the underlying physiological process, we will struggle to adequately treat these unfortunate people, which is a wonderful segue to what we are going to discuss next week. For more information about this or any other health condition, contact your pharmacist.