November 01, 2020

The Corona Century: Looking Backward, Looking Forward

For over, 50 years, epidemiologists had been expecting “the big one.” Like earthquakes in California, influenza epidemics have become an inevitable part of the landscape. From year to year, influenza mutates; every so often the strain is particularly virulent and it produces a world-wide pandemic, as happened in 1918 and, on a smaller scale, in 1957, 1968, and 2009. Every year, scientists scrutinize the prevailing type of influenza, anticipating that one day we will see the resurgence of a virus as virulent as the one that killed upwards of 50 million people in 1918-1919. Granted, we have vaccines today that prevent or attenuate many cases of the flu, we have antiviral medications with modest degree of efficacy against influenza, and we have sophisticated supportive respiratory treatments such as ventilators, none of which were available in 1918. As a result, any new influenza pandemic is unlikely to be as devastating as its counterpart 100 years ago—but nonetheless, could wreak havoc in our globalized world. So, it was very surprising when, in March, 2003, scientists in search of the causative agent of the newly described respiratory illness known as SARS (Severe Acute Respiratory Syndrome) peered through their electron microscope and discovered, not influenza, but corona virus.

Coronaviruses had first been identified in the 1960s; they were known to infect cattle, pigs, rodents and chickens; in humans, they were associated with about fifteen percent of colds, but not with any more illnesses. But there it was, with its characteristic crown-like ring of proteins—the agent responsible for the mysterious disease that had killed clusters of health care workers, families, and residents of an apartment complex, principally in China and Hong Kong.

Once the genetic identity of the virus had been established, the race was on to figure out where it came from. It was pretty clear that the virus had jumped species, making SARS a “zoonosis.” What species it came from was never definitively established, though palm civets and raccoon dogs sold in the wild meat markets of Guangdong province, China, to consumers eager for an “exotic” meal are the leading candidates. Growing evidence suggests that the true animal reservoir of the SARS virus (SARS-CoV-1) is the bat, with animals such as civets serving as an intermediary.

Due to good epidemiologic practice, the biology of SARS-CoV-1, and luck, SARS disappeared. The World Health Organization (WHO) announced the containment of the epidemic in early July, 2003, less than four months after it first issued an international alert about the dangers of the disease, and less than a year after it first appeared in China in November, 2002. A total of 8098 people developed the illness, of whom 774 died, or just under 10 percent.  All told, the virus appeared in 39 countries. Only China, Hong Kong, Singapore, and Canada had 50 or more cases each. The world breathed a sigh of relief; epidemic prevention programs were developed on paper—and shelved.

And then, in 2012, coronaviruses were back. Or rather, a new coronavirus made its debut: MERS-CoV (for Middle East Respiratory Syndrome). Originally found in Saudi Arabia, it soon travelled to the rest of the Middle East. And stayed there, with the only significant outbreak anywhere else in the world found in Korea in 2015 after the index case had travelled to the Middle East. Unlike SARS, MERS has never disappeared. It remains endemic in the Middle East, where it kills 35 percent of those it infects. Its animal reservoir is probably also a bat, but from bats it infects is camels, and from camels it reaches people. By limiting contact with camels and using case isolation and contact tracing, the total number of confirmed cases in the last eight years is only 2500. More lethal than its SARS-CoV-1 cousin, but less easily transmitted, MERS put coronavirus firmly on the map as a pathogen to be reckoned with, but a relatively minor one, compared to, say, the viruses causing Ebola or AIDS.

Until November, 2019, when yet another atypical pneumonia appeared in China, an illness that would prove to be caused by another coronavirus, this one dubbed SARS-CoV-2. The rest is history, although history that is still unfolding. As of October 30, 2020, according to WHO-COVID Dashboard, there have been a total of 44.59 million cases worldwide, with 1.18 million deaths.  In the US alone, there have been 8.83 million cases and 227,045 deaths. The pandemic is far from over, with the US reporting 81,599 new cases per day. This latest variant of the coronavirus has proved far more successful than its relatives: it seems to have found the ideal balance of transmissibility and lethality, which has enabled it to achieve far more extensive community spread than any previous coronavirus. COVID-19 (the name given to the disease caused by SARS-CoV-2) kills roughly 2.5 percent of those who are diagnosed with the condition, less than SARS (10 percent) and much less than MERS (35 percent), though in all three cases, the mortality is far higher in individuals over age 65. In addition, it ingeniously developed the ability to spread from asymptomatic hosts, allowing it to escape prompt detection and thus limiting the effectiveness of isolation to contain its spread.

Supported by governments and the WHO, several pharmaceutical companies along with university research labs are scrambling to produce a safe and effective vaccine. But with cases of COVID-19 continuing to rise in many parts of the world including the US and Europe, the prospects for an end to the pandemic any time soon are not good.  Several nations have reintroduced lockdowns: France just announced it would shut down from October 30 until December 1 and Germany declared a partial shutdown for roughly the same period. With the whole world suffering from pandemic fatigue—except, perhaps, Taiwan, which just celebrated its 200th day in a row without a single locally transmitted COVID case—it’s hard to even think about life-after-COVID except in terms of “going back to normal.” Odds are that when the disease finally goes into retreat, we will breathe a collective sigh of relief and not want to think about viruses. But that would be a grave mistake.

The current century has already seen three coronavirus epidemics, each with a different variant of this wily microorganism. Most likely, all three normally live in bats and jumped from bats to non-flying mammals and from those mammals to humans. Coronaviruses are RNA viruses, known for their extraordinarily high mutation rates—as much as a million times higher than human mutation rates, which means they will continue to develop new variants. And these new variants will now and then develop the capacity to infect people, both because humans have encroached on the territory of animals with whom we previously had little contact and because global warming drives animals out of their traditional habitats and into new arenas that are occupied by humans. The really successful ones, like COVID-19, will be transmissible from asymptomatic individuals. They will have the ability to spread to other humans quickly, without or before killing their new human host. And then they will be spread by humans from person to person, from household to household, from country to country, from continent to continent.

In short, there is no reason to believe that even if we manage to kill or contain SARS-CoV-2, we will have seen the last of the coronaviruses. However appealing it will be to resume normal life, we must not let down our guard. We have to begin now to plan for the next outbreak. We must be sure to learn from our experiences. That means, first and foremost, taking basic preparedness measures such as stocking up on personal protective equipment. It means replenishing the supply of masks and gowns, even if we go for ten years without an epidemic, just in case. 

Planning for the future, as explained by public health lawyer Lawrence Gostin, entails investing in a robust public health system. Such a system must be able to institute traditional measures such as quarantine of those exposed to disease, isolation of cases, social distancing, and mask-wearing. We have to support scientific research so that new pathogens can be identified, tests developed, and treatments tested in a timely fashion. We must restore the FDA and the CDC to their former grandeur, two organizations that, until the current pandemic, were the envy of the world because of their sophistication, wisdom, and integrity. We have to engage in surveillance, constantly monitoring bats and other species for new diseases. 

We must recognize that we live in an interconnected world, which means collaborating with other researchers and laboratories across the globe, including those of China and of the World Health Organization. And when a new, disease-causing virus appears, we need to demand transparency from our leaders and our scientists: an informed public, armed with the tools of public health and the fruits of medical science, is crucial to combatting the threats that will inevitably appear. 

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