Over the last three months, the world has changed irrevocably. The most-mentioned words around the world in recent weeks have to be coronavirus and COVID-19 .
Let’s recap the history of this pandemic. The first known case of the viral infection later called COVID-19 was noticed in the Wuhan City of People’s Republic of China on December 1, 2019. It was dubbed an outbreak on December 12 by the Chinese state broadcaster, and the WHO was notified on December 30 and the viral genome sequence was decoded on January 3, 2020. The events since then are well-known – the virus has spread to 200 countries (areas, territories), resulting in over 4,65,900 confirmed cases as on date.
In India, the first case was detected in Kerala on January 30, 2020, in a student who had come back from China. By this time, it had spread to several countries outside of mainland China, and the WHO declared coronavirus as a ‘public health emergency of international concern’ on January 31.
Till February 29, 2020, three cases were reported in India, all in Kerala. They were swiftly identified and quarantined. This period was the first and perhaps the most important window of opportunity for the research experts and public health specialists to come together and contextualise the available evidence as applicable to the Indian setting in terms of testing, treatment, prophylaxis and mathematical models of transmission and help guide policy.
Given that India has a long history of dealing with infections and the existence of a disease surveillance programme for epidemic detection and response since 2004, and the wide expectation that such a pandemic was inevitable (Bill Gates spoke about exactly such a scenario in a 2015 TED talk), the failure of the Indian research community to respond to this imminent threat with sufficient alacrity is surprising. The first reports of coronavirus being noticed by the Indian research community appear in the third week of February. Still, there seems to be little urgency amongst the Indian public health community in trying to predict the impact of this pandemic.
During this time, modelling exercises were going on around the world. The impact of science on policy became apparent when the publication of the Imperial College modelling study forced the British government to abruptly change its policy position from attempting to ‘ride out the storm’ and allowing the population to develop herd immunity to taking urgent steps to suppress the pandemic. In the U.S., the calm visage of Dr Anthony Fauci has had a reassuring effect on the American public, even as the bumbling political response has led to a crisis situation.
The Indian reaction relied heavily on the reactionary approaches to scout for evidence in the middle of a pandemic. To date, only one data modelling on COVID-19 has been published from India. However, this analysis did not focus on predicting the burden or behaviour of COVID-19 but to identify the effect of intervention strategies that were unlikely to work anyway. There was enough evidence that close to 50% of infected individuals would not be detected through the airport thermal check-based screening (the prevalent screening approach in India), and that simply quarantining symptomatic individuals would miss large numbers of infected but asymptomatic individuals. Thus, this report had little likelihood of informing policy development. An editorial in British Medical Journal on the COVID-19 response in South Asia noted “for a region that has sent rockets to Mars and includes two nuclear powers, lack of a single academic centre with the epidemiological expertise to model a rapidly progressing epidemic seems remarkable.”
During this time, global public health experts, including those in the WHO, were stressing of the need to make the testing criteria liberal and adopting strict isolation policies of identified cases, but the official response from the Indian health authorities was to reassure the Indian public that all was well.
It was only after the mayhem in Europe, the drumbeat of voices from the U.K. and U.S., and the appearance of expert opinions on alternative media portals, that the response changed, and the national lockdown was implemented. The official Indian position still denies the existence of community transmission, based on data from random testing. The design and the data that supports this conclusion has been widely questioned, largely on the basis of the small number of subjects samples, which does not truly represent the large and diverse Indian population.
The importance and need of the lockdown at this time is not in doubt. At the time of writing, on the fourth day of lockdown, the number of cases in India stands at 873, with 149 new cases in a single day, a 50% jump over the rise in the previous day. Further, it is unclear whether we are substantially expanding our testing capability. Serological tests are available now, which allow results to become known in a matter minutes. The lockdown will end some day, and its benefits can only be sustained only through a policy of aggressive testing, contact tracing and isolation.
During these testing times, even as the scientific research activity has ground to a halt, coronavirus researchers must remain busy. The basic scientists around the world including in India are trying to understand the fundamental organism and disease biology, developing simple and affordable test kits and vaccines.
We need to find safe and effective intervention strategies, for prevention and treatment of COVID-19. The global standard for finding such strategies is through randomised clinical trials. Based on anecdotal experience and pre-clinical data, one candidate molecule for such a trial is hydroxy-chloroquine, used currently for treatment of malaria and certain autoimmune diseases.
In violation of the principle of recommending interventions only after establishing the safety and efficacy, the national taskforce for COVID-19 issued a recommendation advocating empiric use of hydroxychloroquine for prophylaxis of this infection in asymptomatic individuals including healthcare workers. The purported evidence they use to support this recommendation is highly speculative, has been criticised as being bad in science, and riddled with conflicts of interest. Standing next to, and despite exhortations from U.S. President Donald Trump, Dr Fauci declined to support its use, pointing out the need for a randomised clinical trial.
The U.K. has restrained the use of this compound outside of a trial. Under pressure, the French authorities allowed the use of hydroxychloroquine and another antiviral drug to treat patients infected with the coronavirus. The recommendation is highly contextual, with the statement from France’s Director General of Health allowing “a temporary authorisation to allow certain patients with coronavirus to benefit from this therapeutic route.” It needs to be emphasised, however, that the authorisation is for treatment of infected individuals, and not prophylaxis.
This advisory has led to a run on this compound, making it disappear from market, putting patients who legitimately need for treatment for other conditions at risk. Moreover, reports of self-medication leading to complications and even deaths have been reported. The Ministry of Health and Family Welfare has declared hydroxychloroquine as a Schedule H drug, suggesting that it intends to double down on this poorly conceptualised recommendation.
Moreover, this recommendation puts in jeopardy any planned clinical trial of this intervention by removing equipoise (a state of genuine uncertainty regarding the comparative therapeutic merits) which is essential for such investigation. This is at a time when research groups around the world, including the WHO, have started large trials in order to find effective interventions. We have possibly lost an opportunity because the advisory will prompt healthcare providers to adopt this approach, more so to compensate for the shortage of personal protective equipment for healthcare workers, with potentially tragic consequences.
There can indeed be genuine tension between research and the urgent desire to help patients with whatever is available during public health emergencies. Some caregivers may feel that providing clinical care and conducting clinical research are incompatible. However, there is a difference between opinion-based advice by a doctor and recommendation from an authoritative body.
During the recent G20 Virtual Summit, India’s Prime Minister underscored the need to put people at the centre, freely and openly share the benefits of medical research and development, develop adaptive, responsive and humane health care systems, and promote new crisis management protocols. U.S. Democratic Presidential contender Joe Biden said in a tweet – “If I'm elected president, I will always lead the way with science. I will listen to the experts and heed their advice”.
As the country cowers in fear of COVID-19 and hopes that the lockdown will suppress the spread of the infection and prepare to provide appropriate care to those who might develop its ill-effects, the Indian research community must join the fight and shine the light on the path that leads to good health.
(Vivekanand Jha is the Executive Director and Oommen John is a Senior Research Fellow at the George Institute for Global Health India.)
