by William B. Miller, Jr. M.D.*

The COVID-19 global pandemic has created a major crisis in health and economics. Societal disruption has been universal with a consequential unraveling of intimate human connections. Its total impact has been likened to global near paralysis. Its toll on morbidity and mortality across the planet is rightfully regarded as devastating. At least 2.5 million have died globally.  In the United States, that number is over 500,000 and still climbing. The statistics are naturally chilling and from that, many might assume that this experience is unique in human history. It is in some ways. There’s never been a comparable all-encompassing simultaneous global response to an epidemic in human history.

Homo sapiens have been on the planet for an estimated two hundred thousand years. Yet, it is only in the last one hundred years that transformative technologies have enabled the type of coordinated trans-global response that we are undertaking. Although surely painful and dramatic, it would be a mistake to surmise that this event is of any inordinate scale compared to similar events in recorded human history. In reality, though dreadful in its own right, it is merely a small-scale event (Fig 1).

Fig 1.   A visual history of the impact of the deadliest pandemics in history(derived from and courtesy of https://www.visualcapitalist.com/history-of-pandemics-deadliest/

Certainly, the graphic is startling. The COVID-19 pandemic is featured in the second row from the bottom. Certainly, it must be regarded as a major pathogenic episode. However, the comparative scale of the Bubonic Plague (1347-1351), with 200 million deaths, should be regarded as the jolting factor. Yet, even as startling as it first seems, that raw number must be put into the context of a total global population that was much smaller then it is today. The estimate of world population in 1300 was fewer than 375  million. When placed in this applicable context, the death toll from the Black Death was at least 200 times greater than has been experienced so far in the United States with COVID-19. This is an unimaginable differential.

Some historians have assessed the death toll in medieval Europe between 1346-1353 might have been as high as 60% of the population. Indeed, of the estimated 80 million living in Europe at that time, it has been calculated that 50 million died.  In Florence, one contemporaneous survivor wrote: “ All the citizens did little else except to carry dead bodies to be buried […] At every church they dug deep pits down to the water-table; and thus those who were poor who died during the night were bundled up quickly and thrown into the pit. In the morning when a large number of bodies were found in the pit, they took some earth and shovelled (sic) it down on top of them; and later others were placed on top of them and then another layer of earth, just as one makes lasagne with layers of pasta and cheese.”  (as quoted in Benedictow, O.J. The Black Death: The Greatest Catastrophe Ever, History Today. March 3, 2005. https://www.historytoday.com/archive/black-death-greatest-catastrophe-ever). Whole families were wiped out in days. A surviving parent might bury a spouse and all five children.

Most are generally familiar with the typical range of symptoms of COVID-19:  fever and chills, a dry cough, shortness of breath, fatigue, muscle aches and a headache. Less commonly, some have experienced sore throat, some congestion, nausea, or diarrhea. These resemble the symptoms of the common flu.  Importantly though, a great many individuals who are infected with  COVID have no symptoms at all or just trivial ones. Obviously, COVID-19 can be fatal, but trying to get an accurate estimate of the Infection Fatality Rate (IFR- the chance of dying if you get infected) is very difficult. With COVID, no definite answer has been derived since no one knows what percentage of the total population has been infected but have remained asymptomatic. Estimates of the IFR vary from 0.2% to over 7%, dependent on geographic locality (Ritchie et al. Mortality Risk of COVID-19. Our World in Data. March 1, 2021, https://ourworldindata.org/mortality-risk-covid)/).

Pertinently, the risk of death is highly stratified by age. For the very young, mortality is negligible but for the elderly (over 80 years of age), especially those with preexisting conditions, mortality can reach 15% or more. Overall, COVID’s IFR is very likely well-under 2%. This is not trivial when compared to seasonal flu, which has a significantly lower mortality of approximately 0.2%. On the other hand, COVID mortality is itself minimal compared to Ebola with an estimated IFR of 50%.

What might it have been like to contract bubonic plague?  The Black Death was gruesome and truly terrifying in its inexorable swift mortality. In its bubonic form, it’s first appearance was an ominous swelling in the armpits or groins. These were enlarged lymph nodes (buboes) that would rapidly increase to the size of an apple, rupture, and ooze pus and blood. These swellings were accompanied by headaches, painful aching joints, and fatigue.  Shortly thereafter, black spots would appear on the arms or thighs, quickly followed by very high fevers and vomiting blood. If you discovered a buboe or black spot on yourself, you knew your future. You would almost certainly be dead after 2 to 7 days of agony. Some victims avoided the bubonic manifestations of plague and alternatively contracted its pneumonic form with symptoms of fever, cough, and a copious blood-tinged flow of mucus and saliva. On the bright side, you didn’t need to worry about buboes. But, this was only because you wouldn’t live long enough to develop them. You’d would be dead that day or the next. Unlike COVID-19, all ages appear to have been equally vulnerable, and the healthy and the frail all fell to this unsparing pathogen.

Of course, there were many attempts at finding a cure to combat the disease. Necessarily, there were no Centers of Disease Control or World Heath Organizations, no idea of germ theory, and no concept of vaccinations. Instead, medieval medical practitioners relied on potions, like Four Thieves Vinegar ( a combination of vinegar, wine, spices, and cider, perhaps with a pinch of opium), bloodletting, enemas, fumigations, ground-up animal body parts, or pastes (especially ‘theriac’, a syrup or paste with lots of opium). Others counseled bathing in urine or smearing oneself with feces. Of course, none of these worked.

Bad air was considered dangerous and medieval doctors would costume themselves for protection with a beak mask containing specialized mixtures of herbs (Fig 2).

Fig 2.    Medieval costume worn by physicians for protection from plague. This odd-appearing mask was designed to cover the physician’s face, nose, and mouth to keep at a distance from an infected patient.

When these failed, some tried a variety of religious cures including public flagellation, prayer, fasting, or religious processions.

There were actions that might have had marginal effectiveness. Those who could took flight from areas with high infection rates to improve their chances. Some cities practiced rigid quarantines which may have helped marginally. Then, as now, social distancing might have had some degree of effectiveness.

How might we gauge the societal impact of this terror?  In our circumstances, we are appropriately discontented with the many compromises that each of us has made toward a cohering societal compact to deal with the COVID epidemic. However,  how many of our current accommodations are likely to reverberate over any significant length of time? Surely, the continuation of Zoom meetings can hardly be considered a continuing hardship. What was the state of medieval society as a consequence of the Black Death?

The social ramifications from this event were colossal and reverberated for centuries. World population dropped precipitously. Europe’s total population was halved and didn’t recover for 150 years. Consequently, wars ceased. Law and social order deteriorated. Trade plummeted. The amount of land under cultivation dropped since there were so few laborers. Wages rose. Society became somewhat more fluid but human behavior became exaggerated with extremes of  religious devotion, self-isolation, dietary restrictions, alcoholism, and a breakdown of traditional societal mores. On a psychological level, the arts became preoccupied with death and the afterlife. Although religion thrived, there was a concomitant rise in mysticism as an alternative to Roman Catholic Church doctrine.

It should be pointed out that epidemics serve an evolutionary purpose. They are a form of immunological culling. It is biology’s adherence to the well-worn adage, ‘that which does not kill you makes you stronger’. There is objective evidence that those that survived the epidemic were actually healthier and longer-lived than medieval European populations were before the tragedy (DeWitte SN. Health in post‐Black Death London (1350–1538): Age patterns of periosteal new bone formation in a post‐epidemic population. American Journal of Physical Anthropology. 2014 Oct;155(2):260-7).

How does this apply to our still unfolding experience with COVID. In that regard, an aphorism that has often been attributed to Mark Twain puts it best: “History doesn’t repeat itself, but it often rhymes”.  The same applies to the intersection of pathogenic microbes with human populations.  Evolutionary forces produce variants. They are the ‘rhyme’. Yet, the basic manner in which they interact with human populations is through repetitive commonalities. Most devastating pathogens arise by jumping from other animals to humans, termed ‘zoonotic’ infections. These account for at least 70% of emerging diseases on the planet. It is believed that Bubonic Plague was spread globally by rats infested with disease-bearing fleas carried on ships. At that time, ships were the primary mechanism of long-distance global commerce. In contrast, COVID-19 spread with uncommon alacrity through international jet travel and human to human transmission.

In the Middle Ages, nearly 90% of the population was rural. Since the primary vector is believed to have been flea-ridden rats (although airbornes spread as pneumonic plague also occurred) it rapidly disseminated throughout the countryside. Rats are believed to have been monumental disease carriers (500-1000 times the number of plague bacilli compared to a human) and their wanderings could inflict catastrophic damage. With today’s dominating urbanized environments,  the respiratory transmission of COVID-19 is the modern effector of person-to-person transmission.

What then should be gleaned from the past? There is only a single certainty. Large-scale epidemics will happen again. It is our good fortune to have modern tools that can be utilized for our benefit that permit us to combat this threat in a previously unheralded manner. To that end, we can only hope that the correct lessons are learned from our current trials.

Although each pandemic has its idiosyncratic trajectory and eventual amplitude of grief and suffering, the essential patterns remain constant over time as they must. The elemental drama is always the same. It is the limitless expression of the eternal balance of forces that perpetually exists between microbes and humankind.

*Dr. Miller is a graduate of Northwestern University in Biology, Northwestern Medical School, and is a member of the medical honor society, Alpha Omega Alpha.  He currently serves as a scientific consultant to the microbiome industry. He is the author or co-author of three books  and over a dozen peer reviewed articles on evolutionary biology and the science of the microbiome.