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Ring around the rosie,

Pockets full of posies,

Ashes, ashes

We all fall down

This common nursery rhyme is familiar to most children, sometimes with the lyrics switched changed slightly (in Britain, they say “achoo” instead of “ashes”). But this innocent song has a darker origin— some folklorists say it’s about the infamous Black Death, one of the most well-known plagues in history.

In the mid-1300s, word arose of a mysterious ailment in Central and Western Asia: patients were afflicted with blackish-bluish boils, swelling, and in serious cases, infection of the lungs and blood. The disease was unwittingly shipped to the Sicilian port of Messina in 1347, spreading the pestilence to millions more. Some estimates suggest that the plague, which we now know as Yersinia pestis, killed as much as one-third of Europe’s population. 

Today, we are faced with the COVID-19 pandemic. 

Disease outbreaks have been a constant throughout human history. Even with the evolution of our technology and knowledge — from antibiotics to vaccines to germ theory — humans can’t quite escape the grasp of pathogens. During the “Age of Exploration,” a period in the late 1400s and early 1700s, European nations brought devastation to the Native American populations in the form of smallpox, influenza, and measles, which infected millions and wiped out entire civilizations. By some estimates, as much as 90% of the Native American population were killed by various introduced diseases. In the 1980s, doctors in the United States began noticing rare lung infections and cancers in previously healthy men. The HIV/AIDS virus killed more than 34.7 million people around the world in the 1980s alone. 

So, what’s next? 

It may be premature to ask, especially considering much of the world is still deep in the trenches of COVID-19, but pathogens are all around us. In some scenarios, COVID-19 could even lead to our next pandemic. 

Enter the fungus. Spoilers: He’s not such a fun guy. 

Mycologists estimate there could be more than 5.1 million fungi species, and fungi are responsible for more than 150 million serious infections annually. “Black Fungus” has been making rounds in the news lately, in the midst of India’s bout with Covid. Also called mucormycosis, this fungal infection is caused by a number of species of environmental moulds in the scientific order Mucorales. Although generally harmless, in patients with impaired immune systems, the fungi spread rapidly, causing fever and lesions in the soft tissue. The infection has a mortality rate of over 50%. Fighting off any disease, including COVID-19, temporarily weakens the immune system, allowing infections— in this case, black fungus— to set in. 

Fungi are also becoming superbugs — pathogens that have evolved to resist typical treatments. Candida auris is a fungus that is classified as a serious global health threat by the CDC. Some strains of C. auris have grown resistant to all three forms of antifungal drugs, making treatment nearly impossible. Like many other superbugs, Candida can hide within a hospital, meaning that vast numbers of patients within a hospital could be exposed to it. Worse yet, many strains can even survive exposure to typical cleaning chemicals. 

Superbugs – microbes that have become resistant to antibiotics – are rapidly becoming one of the most prolific pathogenic threats. In a 2019 report, the CDC recorded that there were 2.8 million antibiotic resistant (AR)-caused illnesses in the United States, leading to more than 35,000 deaths. Diseases once considered all but conquered thanks to the triumph of antibiotics are now making a comeback. Tuberculosis, which has long been treated with antibiotics, has developed AR strains that are immune to the most powerful medications available. As many as 10% of TB infections in Estonia, Latvia, and parts of Russia and China are now antibiotic resistant.  

Superbugs are also notorious for their ability to spread within healthcare facilities. As a result, individuals who are often susceptible to infection as a result of treatments, wounds, or illness, may easily catch these bugs while in the hospital.

The next great pandemic might not emerge from a hospital tough. It could come from animals. In fact, coronaviruses are generally thought to have originated in bat species. Zoonoses are pathogens that originated in animals that “jump” onto humans. The World Health Organization estimates that around 61% of all human diseases are zoonoses, making the shift from animals to humans at some point in their evolution. Poxviruses are a prime example of this: chickenpox, one of the most well-known childrens’ illnesses, actually originated in chickens. 

Many animal species have a form of poxvirus that may infect it, from cows to crocodiles (Crocodylidpoxvirus, in case you were wondering). Humans also had a poxvirus, smallpox (which may have originated in rodents 10 million years ago), which was declared eradicated in 1980.

In recent years, monkeypox has gathered attention as a possible zoonosis that could wreak havoc on humans. In 2019, Nigeria experienced an outbreak of the virus, with more than 300 people falling ill. More concerningly, however, was that the monkeypox demonstrated human-to-human transmission. In the four decades since smallpox’s eradication, many individuals have lost their immunity to the illness. Immunity from smallpox also often guarded people against the monkeypox virus, as they are both forms of orthopoxvirus, but the loss of immunity could be telling of a darker future for monkeypox. 

These potentially catastrophic, could-be pandemics may have some cures, however.

Recently, researchers at the University of Sheffield created a compound capable of treating antibiotic-resistant superbugs. Bacteria fall into two categories, gram positive and gram negative, and are distinguished by the structure of their cell walls. Gram negative bacteria are notoriously difficult to treat, as their cell wall is much harder to penetrate. However, the Sheffield team’s findings could change everything: it has worked in killing both gram positive MRSA as well as gram negative E. coli. 

Probiotics— yes, the stuff in your favorite morning Chobani or Lifeway Kefir yogurt— have also shown potential in beating the pandemics of the future. Lactic Acid Bacteria have long been used to treat a variety of infections, from oral infections to gastrointestinal infections.  

And now, we’re seeing them treat COVID-19. 

Scientists have noticed that in COVID-19 patients, important sources of probiotics (beneficial bacteria), Lactobacillus and Bifidobacterium spp., have been disappearing from the intestines. These probiotics are essential to preventing infection and ensuring gastrointestinal health. As a result, the study suggests that taking probiotics and prebiotics (substances that promote the growth of beneficial bacteria) could have the potential in preventing post-COVID infections.

Gene editing could also provide a method for fighting COVID-19 and similar viruses. At Stanford University, researchers have developed a CRISPR-based system to precisely target and destroy the COVID-19 virus and its genome. The method could help protect patients from lung infections, as well as dramatically reduce viral load within the body— by as much as 90%. This method could also be used to protect patients from 90% of existing and emerging coronaviruses, helping to prevent a variant coronavirus pandemic.

Now, we’re even repurposing the agents of pandemia to help us. In other words, we’re using viruses to cure deadly diseases.   

The Maraba virus (MG1) has been used as an oncolytic virus: it can infect and kill cancer cells. However, researchers noticed that cancer cells weren’t the only type of cell that MG1 could identify; it could also target dormant HIV-infected cells. Currently, we don’t have a way to completely eliminate dormant HIV-infected cells, so if an individual stops taking their antiviral medications, the dormant cells activate, and the illness rebounds. However, MG1 could change this by locating and destroying the infected cells. 

Fungi, superbugs, and zoonoses, Oh My! While there is no way to predict with 100% accuracy where or when the next global pandemic will occur, we can be certain that another planet-wide pathogen will emerge at some time to threaten the human population. Thankfully, with advances in science and technology, we’ll be ready to engineer new solutions, and even engineer pathogens to cure current deadly illnesses like cancer. 

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