How pandemics originate and evolve

By Prof.Kirthi Tennakone

National Institute of Fundamental Studies

History tells us pandemics have devastatingly interrupted civilizations. They killed millions of humans and brought forth misery and poverty, but never wiped out a civilisation. Epidemics and pandemics begin, escalate and wane or re-emerge. However, the causative agent rarely disappears; it opts for a less vicious coexistence. Smallpox is the only epidemically potent disease that has been eliminated absolutely – not via natural processes but by the intervention of human intelligence.

Life has been created by natural forces endowing an essence for it to reproduce and undergo change. We ourselves and the virus exist because of this, which also enables the virus to adapt itself to the environment, survive and expand causing the pandemic. In ancient times, humans had to await the consequences of the same natural forces to face a pandemic – those who remained fit and immune survived and reproduced.

Today, human intelligent intervention makes things more favourable to us than to the virus, and helps many who lack the natural immunity survive. The eventuality of the present pandemic will be determined by the effort we make to combat it.

How pandemics originate

Persian philosopher Ibn Sina was probably the first to conjecture that living entities in the human body caused diseases. Later, Louis Pasteur proved infections occurred when microscopic organisms entered the body and proliferated and those microbes could pass from one individual to another.

Microbes do not emerge spontaneously; nor do they arrive from the sky. They exist everywhere in the environment as creations of biological evolution. Humans, animals and plants harbour them. Microbes associated with a given species, often symbiotic, pose no danger to the host, whose immunity prevents their undue proliferation. They are selective; those present in one species would not easily move to a different type of host and get established. Nevertheless, the complexity of living things allow exceptions. Occasionally a pathogen or innocuous microbes concealed in animals or found in the environment can jump to a human causing diseases.

An illness acquired from an animal is referred to as a zoonotic disease or a zoonosis. Sometimes, the zoonosis turns out be contagious. Almost all calamitous epidemics and pandemics have arisen from accidental transfer of a bacteria or a virus from an animal species to humans and subsequent evolution- their origin is zoonotic. Ebola, Severe Acute Respiratory Syndrome, Middle East Respiratory Syndrome and COVID-19 are zoonotic diseases. The zoonotic infections such as plague, smallpox, measles and swine flu caused first magnitude pandemics in the past.

Ebola Virus Disease: near pandemic situation 2014-2016

A previously unknown sickness broke out near the Ebola River in Congo in 1976, killing almost 80% of persons who contracted it. The cause of the disease, subsequently named Ebola, was found to be a virus endemically associated with bats. Although the virus does no harm to the bats, when transferred to humans via contact during hunting, a fatal condition, similar to a flu occurs. The exposure to body fluids of the infected persons passes the disease to the community. The Ebola outbreak 2014-2016, spread across West Africa. Some cases were also reported in Europe and the United States.

Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS): The older cousins of COVID-19

Coronaviruses with crown like spikes on the surface exist everywhere. Until early 2000s, they were not considered a threat to humans. In 2002, a new contagious respiratory disease, SARS, emerged in China and spread rapidly to several other countries. International corporation; coordinated by WHO quickly elucidated the nature of the condition. The cause of the disease was identified to be a virus harboured by some bats, transferred to humans by palm civets. Handling civet cat meat in wet markets is believed to have caused the transmission of the pathogen to humans. The epidemic was effectively controlled by isolation of infected persons, use of masks, protective equipment, physical distancing and thermal sensing of passengers in airports. In July 2003, WHO declared SARS had been contained.

Another respiratory viral disease MERS first reported in Saudi Arabia in 2012 crossed continents due to air travel. The second major MERS outbreak occurred in South Korea in 2015. Compared to SARS, MERS is more virulent but less contagious, and spreads through close contacts of infected persons. The origin of MERS virus is zoonotic, bats being the primary source and camels the intermediate which transferred the pathogen to humans. The virus may have undergone genetic change in camels facilitating its adaptation to humans.

How pandemics evolve

Pandemics and epidemics begin when an infectious agent enters a community possessing no immunity to resist. A tragic example is measles epidemic in Fiji. In 1875, an Australian delegation carried the virus to the island whose natives were never exposed to the measles – a disease quite common in Asia and Europe. In a matter of months 30 percent of the population died!

Zoonotic viruses are particularly dangerous because humans are not exposed to them at the beginning. The absence of immunity allowed an epidemic in one locality to expand as a pandemic. Furthermore, when a virus originally found in an animal, genetically and associatively distant from humans, is harboured in an intermediate host closer to humans, some genetic intermingling could occur via processes referred to as recombination and re-assortment. This way, the virus acquires a foreignness needed to evade the human immune response and a kinship favourable for adaptation. Domesticated animals sometimes carry viruses originally derived from humans but genetically modified. A virus found in a wild animal co-infecting a domesticated one can copy genetic information from the latter producing a new kind of virus, adaptable to humans and also withstand host immunity.

The origin of the virus causing COVID-19 named SARS-Cov-2 has been traced to a bat species. The genetic make-up of SARS-Cov-2 tally nearly 95 percent with a virus found in so-called horseshoe bats. It is not conclusive whether the virus passed directly from a bat to humans or through an intermediate host. There exists no evidence to support the conspiracy theories that the virus leaked from a laboratory. Finding out how the virus came into being would shed light on how to control it effectively.

Once a pathogen enters a population devoid of immunity, the number of infected people begins to expand exponentially at a rate proportional to the population density reaching a peak. Thereafter, because of the decrease of susceptible persons owing to acquisition of immunity and deaths, the disease wanes.

Mathematical models predict above behaviour and point to the important concept of the effective reproduction number of a progressing epidemic. Effective reproduction number (RE) is the average number of people who acquire the infection from one infected individual at a given time. The idea of reproduction number was first introduced by the British Physician Ronald Ross, who took up mathematics to find a way to eradicate malaria. Ross showed that in order to control an epidemic RE needed to be kept below one. His suggestions for doing this paved the way for the eradication of malaria epidemics in Sri Lanka. In the initial phases of the COVID-19 pandemic in Wuhan, China RE has been in the range 3-5. Control measures such as physical distancing, wearing masks and isolation reduce RE, but the issue is reducing the number further to reach values below one. The mode of evolution of the COVID-19 pandemic is complicated by human migration by imposition and withdrawal of preventive measures.

Transmissibility and virulence

The virus is not after vengeance to be noxiously virulent and kill as many as possible; evolution in that direction renders no advantage because if a large majority of infected persons die, the virus will be deprived of hosts to feed on and reproduce.

The probability that someone will catch the infection from an infected person depends on the rate and quantity of the pathogen transmitted. A severe infection produces larger progeny of viruses; this has some advantage to the virus. Generally, pathogens compromise between transmissibility and virulence giving a higher weightage to the former. The transmissibility of COVID-19 is high because the infected shred the virus before symptoms fully develop. Contrastingly, in case of SARS; the infected release the pathogen at later stages when symptoms are readily identifiable enabling isolation; this is the main reason why SARS was contained and the COVID-19 transmission continues.

The virus aggressively attacking elderly and sparing younger could also be an advantage to the virus. Severely sick elderly patients release larger quantities of virus, infecting the younger who take care of them. The younger move about and infect others. The virus wants to procreate and exploits everything possible for that purpose!

Variations of the virus

Zoonotic viruses undergo major genetic changes via recombination or re-assortment and adapt to human system. Mutations enable them to fine-tune the traits favourable for adaptation by small genetic adjustments. When viruses replicate, their genetic code is sometimes copied erroneously, resulting in random variations. The process is analogous to typographical errors you make when you retype your essay. Even if you retype thousand times, you would not expect to find an improved version of the essay as result of random typographical errors. However, when a virus replicate trillions of times; a more adaptable one may originate and replicate endlessly – these are new strains of the virus. Recently, more contagious strains have been found to proliferate in the UK, Brazil and South Africa. The British Prime Minister announced that the variant identified in his country seemed to be more virulent.

Convergent evolution of strains

The three strains of the virus (United Kingdom, Brazil and South Africa) seemed to have evolved independently. Yet, all the three variants have undergone similar changes in the spike protein, enabling the virus to attach to host cells more strongly; this is essential for efficient spreading. The qualities acquired indicate that mutations have got selected for the definite purpose of convergence to the same cause – to spread the disease fast.

Convergent evolution is quite common in nature. A prototypical example is the near identical streamlined body shapes of the shark and the dolphin. Shark is classified as a primitive fish, whereas the dolphin has been an evolutionarily modern four-legged mammal that lived on land adapted to the ocean. Both shark and dolphin independently evolved towards the optimum hydrodynamic body features to be able to swim fast.

Future of the Present Pandemic and Future Pandemics

It is too early to determine the degree of effectiveness of existing vaccines to new and emerging strains. Fortunately, some vaccines can be easily reprogrammed to provide immunity to new strains. The world will soon acquire the arsenal of weapons needed to fight it. Efficacious vaccines have been demonstrated, and many are in the pipeline. Antiviral drug research progresses although to date there exist no cure for COVID-19. The virtues of physical distancing, wearing masks, contact tracing and isolation are gaining acceptance. Hopefully wide vaccinations programmes and strict adherence to preventive measures will help subdue the pandemic; a concerted effort is imperative. As pointed out in the editorial The Island editorial of 21^st January 2021 ensuring equitable access to vaccines is an urgency. This the factor determining what lies ahead and how the pandemic will halt.

Doing the needful forthwith is prudent because given sufficient time the virus might mutate in response to a single political decision implemented somewhere, irrespective of the geographical location.

The other issue would be the emergence of new pandemics in the future – most likely those of zoonotic origin. During the past two decades many such diseases have surfaced. Excessive interference with environment; clearing forests, maintaining millions of farm animals in unnatural conditions and climate change resulting from burning fossil fuels probably contribute this dangerous trend.

When humankind turns cruel to animals, destroy flora and engender environment, the return could be a pandemic!