The Race to Find a Cure for COVID-19 by Professor Virander Chauhan
While efforts to develop an anti-COVID-19 vaccine are encouraging, safety issues are paramount, the novel coronavirus has infected more than 8,00,000, people worldwide and led to the deaths of more than 38,000. The epicentre of the pandemic has shifted from Wuhan district in China to the highly developed Western world. Countries such as Italy, Spain, France, Germany, the U.K. and the U.S., which have some of the most advanced health systems in the world, have come under tremendous pressure and seem unable to deal with this health crisis. With no specific therapy or vaccine available at present, it is imperative that we fast-forward the development of efficacious vaccines and drug therapies against COVID-19. However, it must be emphasised that because vaccines are given to large populations, safety issues are paramount. The world is dealing with an unprecedented and unimaginably serious crisis. Therefore, the speed of vaccine development is crucial.
Encouraging developments
The race for developing an anti-COVID-19 vaccine has begun. Reasonable scientific rationale and the information needed for vaccine development are available to all stakeholders in academia and industry. A large number of candidate vaccines based on different vaccine platforms, including delivering the virus genetic materials (RNA, DNA) or using synthetic biology to produce key viral proteins, have already been developed. In fact, Phase-I safety trials of an experimental vaccine, jointly developed by scientists at the National Institute of Health and at Moderna, a biotechnology company, has already been administered to healthy volunteers for its safety and immunogenicity. Although based on some earlier experience of vaccines of other coronaviruses such as SARS and MERS, the speed with which the experimental vaccine has entered safety trials is unprecedented. Another vaccine jointly developed by China’s Academy of Military Medical Sciences and CanSino Biologics has reportedly been cleared for early-stage clinical trials in which more than 100 healthy volunteers are scheduled to receive the vaccine. The Serum Institute of India has also recently announced its readiness to start safety trials following animal experiments. According to a World Health Organization (WHO) report, more than 20 vaccine candidates are in advanced stages of development and will be ready for Phase-I safety trials. While these developments are encouraging, several questions will need to be answered for these candidates to move further.
Although it is quite evident that humans mount a strong immune response and clear the viral load, the nature of the immune response and how to trigger it safely through vaccination will be key questions to address. Some early, but limited, studies from China have suggested that monkeys can be infected with this virus but can be protected from reinfection. How long the acquired immunity in humans will last is another important question to be asked before experimental vaccines move forward. We will need to know this because if the immunity is transient, then humans will be susceptible to reinfections. Before moving to Phase-II trials in a large number of healthy volunteers, we also have to ensure that the immune response induced by vaccination does not lead to any disease enhancement, as has been observed in cases of some experimental vaccines against the dengue virus, and in animal studies with an experimental vaccine against the SARS virus.
It is absolutely imperative that anti-COVID vaccines are developed as fast as possible and by pushing all reasonable vaccine candidates through animal and human clinical trials. However, it is also clear that it will not be possible to roll-out any efficacious vaccine for at least another year. An all-out effort to develop a vaccine against COVID-19 must continue if we have to stop its spread.
With COVID-19 playing havoc across the world, therapeutic interventions, not only for curing severe cases of the disease but also for protecting all front-line healthcare workers, are urgently needed. Since developing new drugs is a complex and lengthy process, scientists and pharmaceutical companies have rushed to investigate and use drugs that have already been approved by regulatory authorities. Using available molecular and structural biology information on the virus, a group of scientists have analysed all interactions of the viral proteins with human proteins that are crucial for the virus to enter human cells and use the host cell machinery to rapidly reproduce itself. Of the nearly 70 short-listed molecules that may interrupt these key interactions, 24 happen to be already approved drugs which can now be tested in laboratory animal models as well as humans. However, the re-purposing of several drugs, alone or in combinations to treat COVID-19 patients, have already been reported. There are many success stories of curing patients of COVID-19 doing the rounds in different parts of the world, but these have managed to create more confusion than hope. Without any appropriate controls, careful dosing and safety concerns, such small experiments can only do more harm than good.
Controlled randomised trials
Given the urgency of finding a cure, it is absolutely necessary to find out unequivocally what works well and what does not. For that conducting carefully controlled randomised trials is the only way to go. In a welcome move, the WHO has announced clinical trials called the ‘Solidarity Project’. Under this four drugs or drug combinations will be tested in many countries around the world. These candidates include the anti-Ebola drug, Remdesivir, Chloroquine, anti-HIV drugs, and the Ritonavir/Lopinavir combination, with or without Interferon-beta. Many countries have already signed up for these trials and all drug companies, including CIPLA from India, have agreed to supply sufficient quantity of drugs needed. The European counterpart of the trial, Discovery, will conduct these trials in countries including France, Spain, Germany and the U.K. The pharma company Roche has also decided to initiate large, randomised Phase-III trials of its arthritis drug Actemra for its safety and efficacy in adult patients with severe COVID-19 pneumonia. It is complex and tedious to conduct randomised, large multi-centric trials. Quickly getting all the stakeholders together is laudable and underscores the notion that everyone needs to fight the deadly virus together. Hopefully, these trials will lead to tangible drug therapies against COVID-19.
It is most heartening to see scientists in academia and industrial partners coming together to fight a monumental public health crisis. The battle between pathogens and humans will continue but let us hope that we win the present one sooner than later.
Virander Chauhan is former acting Chairman of UGC and former Director of the International Centre for Genetic Engineering and Biotechnology where he currently holds the Arturo Falaschi Chair.
Cover Image: Our Gods (Doctors) in Action to Save Us by Praveen Maripelly (Fine Art Awardee, 2012)
