Ask the Pharmacist

Q) How come sometimes I feel fine even though a urine test or throat/ nasal swab proves that I am indeed carrying an infection?

A) By this time, we all know at least one person who has tested positive for COVID but felt absolutely fine, without even the hint of a runny nose or a fever. At the same time, this same virus is still killing 3,000 people in the U.S. each week and it wasn’t long ago that those numbers were significantly worse. Why is it that some people get through an infection unscathed and others find their lives irrevocably altered. There is much we don’t know about the answer to this question, but we do know that it’s not specific to COVID.

The flu, urinary tract infections, SARS, MERS, Epstein-Barr and even some of the most feared names in the world of viruses such as Ebola, dengue, yellow fever and Japanese encephalitis can all be deadly to one person and asymptomatic in the next. A wide range in terms of severity is the norm, rather than the exception when it comes to viruses. One reason this variance exists lies in the fact that viruses are constantly evolving, just as every other living organism is. Given their short life spans, viruses fundamentally change in nature much quicker than say mammals do.

We have seen this with the COVID virus which has evolved to new forms with names such as Delta and Omicron. This process occurs because, in general, viruses do not wish to harm their human hosts. A dead host also equates to a dead virus. As such, viruses mutate, in some cases over millions of years to become better and better at infecting us while at the same time making us feel less and less sick.

A classic example of this is human cytomegalovirus which can be found in most of the world’s population (including you more likely than not) but is almost always asymptomatic since it has developed a host of tricks to evade our immune system, at least to some degree. Scientists believe that by the time we become seniors, nearly a quarter of our killer T cells (perhaps the most important part of our many layered immune system) are devoted to fighting this virus. The pathogen and the immune system are in constant battle, keeping each other in check. This war almost always occurs in the background (except rarely in some immunocompromised hosts when the virus simply overpowers our defences) as we go about our lives blissfully unaware of the potentially deadly virus within us.

There are however other reasons some of us feel sick and others do not. To further unravel the mystery we need to look at the delicate dance between pathogens and our immune system that is performed each and every time a virus enters us.

The first factor that determines just how sick we get is the “viral load” that we are exposed to. This term refers to the sheer number of virus particles that enter our body. The more particles that land in your throat or nose, the more likely it is that the virus will overwhelm your immune system thereby increasing the odds that you will feel sick. Within hours of a typical infection, those virus particles that are not initially killed off enter cells and begin to produce molecules known as interferons. Interferon’s purpose is to alert both our nonspecific innate immune system and our adaptive immune system to these invaders.

Our innate system responds by causing widespread inflammation which acts as our first line of defence but also unfortunately also usually leaves us feeling fevered and sick. Our adaptive system will over a series of days crank out antibodies and T cells that will more precisely target the invading virus. If these targeted attacks succeed in minimizing the infection, we will likely go symptom free. If, however, they are not enough of a defence on their own, eventually the blunt instrument that is our innate immune system will need to continue to ramp up its activity destroying both viral and healthy human cells in the process. This will inevitably leave us with many of the classic symptoms of an infection.

As such, scientists have wondered for years if part of the answer to why some people feel sick and others do not lies within our genetic ability to produce T cells and antibodies rapidly.

To investigate this, researchers in Singapore during the COVID era recruited 478 workers who volunteered to have their immune responses tracked through periodic blood samples over a six-week period. About a third of the study participants contracted COVID during this interval with most cases being termed asymptomatic. When the blood samples were compared, the symptom free group seemed to have an adaptive immune system that was more robust. Their samples displayed more specific and coordinated T-cell responses along with higher levels of an antiviral molecule and another molecule that serves to help regulate our T cells. The sicker patients in contrast showed greater amounts of molecules that are associated with inflammation which is evidence that their innate immune system had to do the heavy lifting when it came to battling the infection.

We also know that T cell responses weaken with age which helps explain why COVID and most other viruses cause far more symptoms in the older demographic as well as substantially higher mortality rates. To sum up, how you feel after an infection depends upon the person who sneezes near you (i.e. the viral load you are exposed to), the nature of the virus (has it evolved to the point that it doesn’t want to harm you, it just wants to borrow you) and then the immune system that genetics has gifted you.

There are undoubtedly a host of other factors that play a role that scientists have yet to fully understand. For more information about this or any other health related questions, contact your pharmacist.