Past and future of Coronavirus Outbreak: Inside humanity's battle to contain pathogen that has paralysed the world

It is hard to comprehend just how quickly coronavirus disease (COVID-19), irreversibly changed the world we live in. On 31 December, 2019 as the world was preparing to usher in another new year, the World Health Organisation China Country Office was notified of multiple cases of pneumonia of unknown cause.

On 7 January, a new coronavirus later dubbed Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) was identified as the cause of the cases of pneumonia in Wuhan, China. Almost as soon as the causative agent of COVID-19 had been identified, cases began to grow exponentially.

 Past and future of Coronavirus Outbreak: Inside humanitys battle to contain pathogen that has paralysed the world

Representational image. AP

The death toll began to mount. China responded swiftly and decisively by building massive temporary hospitals and mobilising doctors and nurses from across the country.

On 23 January, Wuhan, the epicentre of the public health crisis, was put under lockdown. Although many outside of China had never heard of Wuhan, the fact that a major city comparable to Delhi, and more populous than London or New York was shut off from the rest of the world should have prompted the world of the destructive nature of COVID-19.

At that point, it was already known that COVID-19 was a serious disease and around 2 percent of those who were being diagnosed were dying from it. But even a cursory glance of Indian and American newspaper headlines that day do not point out the scale of the challenge on the horizon. National newspapers focused on national political news. Corporate profits were up and the stock markets were rising. COVID-19 was China’s problem.

By the end of the month, as cases began to pop up in other countries, the world rose from its slumber. Travel to and from China was suspended. Unfortunately, as we know now that SARS-CoV-2 is highly infectious and often transmitted by those who show no or minor symptoms.

By mid-January, SARS-CoV-2 had already rapidly spread to many other parts of the world. The true extent of the spread of SARS-CoV-2 will not be known until entire populations are tested for antibodies, but it is safe to conclude that many countries underestimated the scope of the problem.

We cannot say that there were no warning signs. Before the emergence of SARS-CoV-2, virologists and epidemiologists had warned of the high pandemic potential of coronaviruses: after all two other coronaviruses, Severe Acute Respiratory Syndrome (SARS)  and Middle East Respiratory Syndrome (MERS) had jumped from other animals to humans in the past few decades.

Coronaviruses are notoriously promiscuous. They typically have a high propensity to recombine, mutate, and infect multiple species. There are five coronaviruses that are endemic to humans which cause up to 30 percent of common colds. They are with us constantly. And given the rapid spread of SARS-CoV-2, it might end up becoming a sixth endemic coronavirus; it might never be fully eradicated from human populations. But despite repeated credible warnings by experts, they were not heeded by policy-makers.

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The problem with a pandemic response is that it dealt with similar to a one-time disaster, like a cyclone. Something bad happens and then we react to it. However, pandemic preparation should be more of a constant preparedness and preparation for war. No country creates an army only after being attacked.

To be sure, the COVID-19 pandemic is a once-in-a-generation event and while the response by policymakers has often been slow, physicians, scientists, and health-care workers have risen to the challenge. They are heroes and their response has been unprecedented.

Just four days after SARS-CoV-2 was identified as the causative agent of the cases of pneumonia in Wuhan, the genetic sequence was publicly released. This is important because the sequence allows a diagnostic test to be created, mutations to be mapped, the nature of the virus to be gleaned, and certain vaccines and drugs to be developed. Sure enough, the first diagnostic test kit was available only two days later.

On 13 January, the US National Institutes of Health (NIH) and Moderna Therapeutics, used the genetic sequence of SARS-CoV-2 to finalise an mRNA vaccine against the novel coronavirus. On 16 March, the first participant in a clinical trial received a dose of this vaccine. We are moving at an extraordinary pace. At least a dozen other vaccines are in various stages of development.

One of the reasons Moderna was able to develop a vaccine in days is they had experience in creating vaccines for MERS. Similarly, there were initiatives to create vaccines for SARS which could’ve greatly accelerated the process of development of a vaccine to prevent COVID-19. Unfortunately, once the SARS epidemic ended, those initiatives shut down. A vaccine for SARS-CoV-2 will take a minimum of a year, maybe longer, but the lessons are clear. We must invest in vaccine development programs even after the pandemic ends. We cannot repeat the mistakes of the past.

It was never a secret to those in the pharmaceutical and biotechnological industries but the general public is also now realising that vaccine and drug discovery takes years and sometimes even decades. The conventional way to discover drugs is to find small molecules that are effective in low doses in cells and animals first and then work up to humans through phases of clinical trials that demonstrate that the drugs are safe to use and that they work.

We can speed up the discovery process but we can’t speed up (beyond a point) or predict what will happen in clinical trials.  This poses a significant challenge in a pandemic when time is of the essence. Any drugs discovered through the conventional route will not be useful for the current pandemic.

So, in terms of accelerating drugs that can be used to treat those with severe COVID-19, physicians are repurposing drugs for other diseases that have already gone through a regulatory process. These drugs have already been shown to be safe, now they have to work. This process has been fast, and already there are drugs repurposed for COVID-19 from other diseases (malaria, HIV/AIDS, Ebola) that are in clinical trials.

It is important to remember than an antiviral drug doesn’t work the same way as an antibiotic. It typically doesn’t kill the virus but instead stops the virus from hijacking the host cell and making more copies of itself.

Remdesivir, probably the most promising candidate drug right now was created to treat Ebola. The drug looks like adenosine, a building block that would normally be inserted into viral RNA information packets. What Remdesivir does is it gets inserted in the place of adenosine in the viral message and causes a faulty product.

So, the virus cannot make accurate copies of itself and the course of the infection slows down. Chloroquine and hydroxychloroquine are other promising drugs that are thought to change the pH of membrane-bound vesicles inside cells and stop the virus from properly developing. There are some early promising results with these drugs, but we will have to wait for the results of randomised controlled trials underway right now.

There are also treatment options outside of drugs and vaccines that are being pursued. An antibody that “recognizes” SARS-CoV-2 can be used as a biologic therapeutics to treat COVID-19. Already a limited study has shown that a few patients suffering from severe COVID-19 recovered when they were treated with plasma from recuperating patients. This approach will not be useful for all patients, but it expands available treatment options.

In a pandemic treatment is important, but before that comes testing. Diagnostic testing has relied on the real-time reverse-transcriptase polymerase chain reaction, a gold-standard test to detect the presence of viral genetic material in nasal or throat samples, or in sputum.

Modifications of this technology have reduced the wait time from days to hours. In addition, new small platforms will allow testing to be done quickly at the point-of-care. These have the potential to allow for broader testing, diagnosis, and isolation- all key steps in controlling the spread of COVID-19.

Another type of very useful test checks for the presence of antibodies in those who have been infected by SARS-CoV-2. These tests will tell us who has been infected (and might have recovered) in a population and will point out those who have acquired some immunity. Some of these people can return to work. These tests will also let us know how many people have been infected and this, in turn, will help us to get a clearer picture of how fatal COVID-19 actually is. This has real-world consequences. If half of India ends up getting infected by SARS-CoV-2, a difference of 1 percent in the fatality rate translates into 6.5 million lives saved.

All around the world, physicians are working extremely long hours to control COVID-19 and treat severe patients but we also have a part to play. It may seem frustrating to just be sitting at home during a lockdown, but by doing so we are slowing the spread of SARS-CoV-2 through social distancing.

One thing we should all remember is that it takes time for social distancing, even if perfectly done, to reap results. It takes around five days for symptoms of COVID-19 to show up and people can be progressively sick for days after that.  In a world that expects instantaneous results, this can be frustrating, but we must stay the course.

COVID-19 is not unbeatable. SARS-CoV-2 is transmitted by infected humans in very specific ways. By changing our behaviours, we can slow the spread of the disease. These mechanisms such as quarantining, avoiding crowds, and hand-washing are low-tech; they are not glamorous. But they are effective and they buy time for physicians, nurses, and scientists- who are already the heroes in this fight- to control the fallout.

All of us must work together. The pandemic caught many of us by surprise earlier but we have no excuse not to act. The highly infectious nature of SARS-CoV-2, tied with lethality and asymptomatic transmission make it particularly challenging to thwart. But will learn from it, and we will be better prepared for the next pandemic.

The author trained as a microbiologist and is now tracking the coronavirus pandemic while maintaining appropriate social distance.

Updated Date: Mar 29, 2020 20:38:46 IST



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