If you want to understand what a virus is, please start here.  Dr. Bendebury has dug into the concept at length. In brief, a virus is the often pathological, yet evolutionarily integral, process by which a biological entity called a virion is produced and extruded from the cells of a live host. 

When an organism encounters a virion for the first time, several pathologies may or may not arise ranging from the common cold and flu to cancer and autoimmunity.  The coronavirus epidemic of 2020 is an example of such a viral pathology whereby a virion is absorbed into human tissue and the host creates more copies of the virion, which are detectable in the blood by RT-PCR.

Do viruses make you sick or does your immune system react to make you sick?

Viruses cause sickness through two basic means and yet the contributions of each mechanism to pathology are generally unclear.  Today I want to explore the literature a bit and see if I can somehow compare the weight of these two basic pathological devices in the progression of viral pathology.  I submit to you that while a virus may incite dysfunction and cellular or even organismal death through one of two following basic modes, these are by no means the only roles of viruses in biology:

1)  Viral replication variably stresses critical cellular machinery; this results in mis-function, and dysfunction of your vital tissues.

2)  The virus elicits immune responses which variably culminate in cellular damage throughout your body.

Let’s look at the first case:  direct viral damage.  For those of you with college level biological knowledge, you are may remain under the impression that viruses destroy their hosts by proliferating to the point of literally bursting open their hosts, like the parasitic Face-Huggers of the film, Aliens.  This direct lytic mechanism is, in fact, surprisingly rare among viral infections in animals.  There are just a few anecdotes of animal viruses assisting in the permeabilization of host membranes, for example.   Generally if direct lysis occurs in animals, it is usually after a prolonged period of latency whereby the virus lurks within the host’s genome.  What is more likely is that viruses in eukaryotic tissue have evolved to be less directly virulent, promoting longer-term, rather than immediate cellular failure.    

Think about it.  Virions cannot survive for very long outside of a body.  They certainly cannot replicate without a host; and generally, they are well-suited to a fairly specific host-type.  Since virions are highly simple structures, they rely of a very few genes to accomplish a great deal and this inherently restricts and regulates their spread among species.   And while in pools of bacteria, viruses must play a numbers game and infect as many as possible, as quickly as possible, literally to the point of bursting open the cell so as not be out-divided.  But such an approach is not so effective in slow-moving, slowly dividing, cellularly complex animals like you, the hairless ape.  So in the case of a typical cold, flu, or even the coronavirus epidemic of late, lytic action is unlikely to be a primary contributor to most viral pathologies.   

In alternative, there are several means by which a virus can overwhelm molecular machinery directly, eventually leading to cellular death.  For instance, the virus can certainly divert critical energies by clogging up ribosomes and other native replication infrastructure like polymerases.  It seems that these sorts of resource-throttling behaviors are the real danger when it comes to direct viral pathology.  Human viruses appear, in general, existentially invested in keeping your cells functional.   At least long enough to be stably integrated into an often-dispersed, peripatetic population.  So what kills you if your cells aren’t exploding under viral load?

A virus can turn your body against you.

Viral success in an animal depends upon availability of appropriate cellular machinery within the host, as well as host-cell surface patterning, ambient temperature, pH, the presence of oxygen tension enzymes, and a wealth of other non-specific factors in body secretions.  Your immune system is capable of adjusting many, if not all, of these conditions for better or worse during an infection.  Furthermore, your immune system is fully capable of making you sick in its own right.  When you actually feel sick during a fever, you are indeed feeling the inflammatory molecules used by your immune soldiers to do battle.  And this is where the real, tangible, pathology of a viral infection begins.  

Let’s talk about that fever we’ve all had.  The overwhelming majority of fevers are caused by infections of some sort and in some rare cases can be hormonal, or due to various tissue occlusions, drugs, or malignancies.  This is the primary symptom being screened fo by hospitals during admission under standard COVID19 precautions. You know the feeling too well: You’re hot and you’re cold; perhaps your hands feel like two balloons.  You’re delirious and can’t seem to rest.  Sleep doesn’t make sense and your dreams are as maddening as they are nonsensical.  What’s going on in your body?

During a fever, your body attempts to rig the home court to its advantage for some impending battle against a perceived threat.   Fever is marked by elevated core body temperature.  This seems to offer the feverish individual a protective advantage for several reasons.  First, infectious pathogens seem to demonstrate optimal replication at temperatures below 37C.  Raising the temperature of your body therefore slows expansion of the pathogenic population.   The rise in temperature also seems to favor innate immune weaponry within your body.  Your body’s immune tools are simply more chemically effective at that elevated temperature.  The fever also serves to thermodynamically stress the actual pathogens:  the heat actually shakes their structures and threatens their integrity.

The hypothalamus of your brain decides to fever.

The fever is a centrally adjudicated process.  The decision to instigate a febrile response occurs at the bottle-neck level of the Hypothalamus and pre-optic area of the brain.  There, alarms initiated by various sentinel cells throughout the body arrive in the form of molecules called prostaglandin and ceramide are integrated.  Then the brain instructs the body to fever.

Once a fever is initiated, mild to severe symptoms accompany the elevation in core body temp.  Serious tissue damage can occur expressly due to the fever itself, including cell-membrane disruption, mitochondrial and DNA damage, disruption of cell-signaling, and gut bacteria translocation with associated endotoxemia. In other words, a fever has many ways to kill you in its own right.  What is remarkable is that the eventual death of your cells during a fever is due to cellular stress, much like mechanism #1 for our viral pathology dichotomy.  Just as the heat from a fever is itself toxic to pathogens, it also hurts your own tissue.  Your cell’s building blocks are shaken to the core.  Once cells are weakened sufficiently by this litany of insults, they implement a process of apoptosis or are otherwise found necrotic, in which case the body’s immune soldiers are likely to have cleaned out the failing corpse.  

Bear in mind that there may also be silent immune responses in the absence of fever.  Not having a fever does not mean your body is taking no action, but it certainly implies that there is less immediate danger.  What is truly fascinating is that even if viruses do, indeed, directly reprogram cells to necrose or apoptose, the contribution from your host immunity to these very same outcomes will be indistinguishable.  Certain febrile response, like bacterial translocation, are much more immediately dangerous than any sort of direct insult to your tissues.  Even if a virus converts your healthy tissue into malignant tissue, or modulates autoimmunity, it is unlikely that these potentially deadly consequences constitute the same degree of immediate threat that the primary fever response could indicate.

Sometimes you take on a virus and don’t get sick.

Only about 70% of persons directly infected with influenza viruses appear to develop symptoms.  Only 40% develop fever.  It has been noted that even in highly virulent diseases like the Ebola epidemic in Africa, persons associated with the care of sick individuals will become infected with the virus but remain asymptomatic.  This is a fascinating piece of the puzzle and really goes to show just how little we know for certain concerning viral pathology.  So many questions remain:  are these asymptomatic carriers as infectious as their sick counterparts?  Many of the Ebola patients had very low levels of virus in their system after infection.  Does their lack of inflammation potentially make them more prone to cancerous viral transformations down the line?  

Much work is needed on this topic, yet patients studied are generally available at hospitals.  It is highly unlikely that patients will offer themselves up for study if they aren’t symptomatic and this unavoidably skews the numbers concerning virulence of a pathogen.  When we talk about morbidity and mortality in an epidemic like COVID19, we can only really speak to the percentage afflicted within the population that has already presented itself to the medical community; almost unanimously, this is a symptomatic group.  Studying the actual impact of infection on the population at large requires random sampling throughout the world and finding persons agreeable to such intrusion seems problematic at best.  So unless citizens can come to volunteer themselves in dedication to answering for these epidemiologic blind spots, it’s unlikely we will ever know the answers precisely.

What is dangerous about COVID19?

The first reports we received concerning COVID-19 pathology involved lung biopsies from malignant tissue, of which separating the source of tissue damage proves impossible.   Other early reports implicate the overwhelming contribution of inflammatory immune responses, akin to our discussion of fever, in the pandemic Coronavirus pathology.  A 2016 Cell Microbiology review examined different types of coronaviruses and found similarly ambiguous pathologies including malignant neoplasia and various immune cell infiltrations into the lung tissue.  

Corona viruses have also been used to mimic multiple sclerosis, which is thought of as an auto-immune disorder.  While COVID19 has not been implicated specifically in such autoimmune dysfunction, this should illustrate the extent to which these types of viruses are capable of reprogramming one’s immune system.  In any case, it should be apparent by now that our immune reaction is potentially our biggest enemy in this worldwide battle against COVID19.  The most common symptom among the Italian patients at the beginning of the pandemic was fever, and we’ve already seen how deadly fever be.  About half of the patients examined exhibit some form of toxic cytokine overload- the “cytokine storm” effect.

In general the inflammation to COVID19 appears tolerable to healthy individuals but much of the world’s population is already suffering from inflammatory disorders and adding a viral infection to those pathologies often proves too much for afflicted individuals to bear.  This “tipping point” where the immune system becomes overloaded appears to be the critical junction where the disease goes from bad to unstoppable.  The data from Spain and Italy suggest that almost all of the victims display advanced co-morbidities.  Since co-morbidities are common in aging groups, a large portion of the western population is indeed at serious risk during this otherwise tolerable infection.  

For those of us lucky enough to remain healthy as of yet, we would be very much served by maintaining close vigilance over our inflammation.  There are countless ways to promote a healthy balance with inflammation: avoiding glycemic diets, maintaining regular exercise regimens, and generally chasing lifestyles that won’t stress us without respite from day to day.  With this temper, we might suffer future viral epidemics without serious fear of complication.