Abstract

Background

The COVID-19 pandemic has compelled governments and the medical fraternity to make hard choices for its prevention, control and management. The urgent need for decision making regarding treatment, confronted with limited available information, makes it difficult to balance the common good with individual freedoms; and the need to contain its spread against economic losses. These choices ought to be guided by both scientific knowledge and ethical considerations. In the wake of the Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), Ebola and other epidemics, several agencies such as the World Health Organisation (WHO) (1), the Nuffield Council of Bioethics (2), the European Commission (3), Human Health Services, USA (4) and the United States Food and Drug Administration (5) have developed guidance for response in global health emergencies. A few independent frameworks to foster ethical decision making in times of crisis have also been developed (6). The WHO guidance on ethical considerations in developing a public health response to pandemic influenza recommends that policy makers should develop a process for setting priorities and promoting equitable access (7). It is also expected that “duty bearers” should ensure that their decisions are transparent, fair, help in reducing suffering and treat all people as morally equal. Notably, the WHO guidance mentions that the public is entitled to timely and accurate information on the availability of drugs for prophylaxis, treatment, and other measures. Here, we examine the Covid-19 situation in India in the light of this international guidance.

Covid-19 has posed several challenges to the Indian healthcare system. The number of cases and deaths is rising continuously, currently involving more than half of the districts in the country (8). The world’s biggest lockdown was ordered in India, first for 21 days, and then extended further to a total of 55 days. The necessity for a lockdown to ensure compliance with social / physical distancing is resulting in huge economic losses and socio behavioural consequences which may unravel in the near future. The resource-poor healthcare system in India, with persistent shortages of personnel and equipment, may not be able to sustain an emergency response on the scale required for management of the Covid-19 pandemic. Hence, effective prevention, early control and less resource intensive management are most essential for the Indian situation.

Current status of Covid-19 treatment in India

The current therapy for Covid-19 involves only symptomatic treatment, supportive care, and prevention of complications; however, no specific drug or targeted intervention is available yet. The repurposed experimental drugs being tested include hydroxychloroquine (HCQ), remdesivir, lopinavir/ritonavir, in combination with or without Interferon β 1a (WHO Solidarity trial) (9), experimental vaccine, convalescent plasma, manipulated cells and sometimes high dose steroids. These drugs, except HCQ and steroids, are very costly or involve complicated procedures of production, and all of these could cause serious adverse events. Therefore, the best and most cost-effective strategy would be primary prevention by reducing exposure to the pathogen, controlling its spread, arresting progress and enhancing individual immunity by using safer and natural immnunomodulating agents.

HCQ for Covid-19 prophylaxis is under investigation globally. The Indian Council of Medical Research (ICMR) has recommended its use in high-risk individuals including asymptomatic frontline health workers and asymptomatic household contacts of laboratory confirmed individuals (10). In India, the prevention and treatment of Covid-19 has largely been restricted to modern medicine (MM) / biomedicine (BM); whereas, China has successfully integrated Traditional Chinese Medicine (TCM) into mainstream healthcare (11). Historically, India has followed a pluralistic system where the choice to select suitable treatment remains with patients. The Indian government has recognised traditional systems, namely, Ayurveda, Yoga and Naturopathy, Unani, Siddha, Sowa Rigpa and Homeopathy (AYUSH), which are regulated by an independent Ministry of AYUSH. Each of these systems has its own educational policy, standards for professional qualifications, registry of practitioners and research council.

Indian policy makers, since independence, have emphasised the integrative approach involving traditional and modern medicine in preventive and curative services; while the National Health Policy 2017 mentions mainstreaming AYUSH (12, 13, 14). Globally, integrative approaches for health have become increasingly acceptable (15). However, in the context of the Covid-19 epidemic in India, patients are offered only MM treatment (16). A few exceptions are emerging in some states such as Kerala (17) and Gujarat (18) that have boldly adopted an integrative approach, with media reports of success in the prevention and control of Covid-19. The neglect of the integrative approach is not merely pronounced, but is also contradictory to the nation’s policy and to its pluralistic cultural foundation. AYUSH treatments have been kept out of the options available to Covid-19 patients. Besides, AYUSH human resources in the public services have been deprived of opportunities to include these interventions and are almost compelled to follow only MM-based guidelines. As yet, there is no proven standard of care established for prophylaxis or treatment in MM for the new disease, Covid-19. Allopathic drugs are currently used solely on an empirical basis. However, the same principle is not considered for the application of AYUSH systems. This dual standard of practice raises ethical considerations in advancing one particular therapy over the other, and therefore deserves to be examined and revised.

Ethics of neglecting available therapies

Ayurveda recommends local and systemic prophylaxis measures for respiratory diseases that may be beneficial in Covid-19 prevention. These include the use of medicated water, mouth rinse and gargle, steam inhalation, nasal oil application and use of Rasayana as immune strengthening therapy. Reasonably good empirical evidence is available in support of these measures. There are also some age-old traditional practices in popular use. Support for the inclusion of these as public health measures for Covid-19 prophylaxis has garnered international attention (19). Respecting individual autonomy is an ethical principle giving a person the freedom to voluntarily choose a treatment. The person’s preference should be respected by providing all the relevant details about available evidence from the prevalent systems of medicine. Not informing patients of established and available alternatives is unethical. The use of non-pharmacological approaches such as psycho-neuro-immunity for Covid-19 prophylaxis that include diet, sleep and immunity boosting is gaining attention (20). Similar approaches are well reportedin Ayurveda, Yoga, Unani, Siddha and Sowa Rigpa systems. However, despite the supportive evidence of longstanding practice in India, these measures are not integrated with the prophylaxis and management of Covid-19 within the health system. The Ministry of AYUSH has released its independent advisory to people for self -care measures, which has received an enthusiastic response (21).

The Ayurvedic Rasayanas are known for their immunomodulation and rejuvenation properties, which are important in Covid-19 management. Several in vitro, animal and clinical studies have demonstrated the immunomodulatory effects of the Rasayana drugs such as Ashwagandha (Withania somnifera), Guduchi (Tinospora cordifoloia), Amalaki (Emblica officinale) among many others (22, 23). We believe there is convincing evidence of the immunomodulating property of Ayurvedic Rasayana, especially of Ashwagandha and Guduchi, and therefore, they are strong candidates for use in Covid-19 prophylaxis and management. Some classical formulations such as Sudarshan ghana vati and Sanshamani vati are used as safer symptomatic measures for conditions such as coryza and fever. Despite the available empirical evidence, these interventions have not been considered for clinical use during the pandemic. From a moral standpoint, the dangers of not attending to evidence are as significant as ethical issues in its application.

The National Taskforce on Covid-19 constituted by the Indian Council of Medical Research (ICMR) has recommended a protocol for the use of HCQ as prophylaxis for the protection of high-risk individuals against Covid-19. The Drugs Controller General of India has approved this protocol for restricted use under emergency conditions (24). It is important to note that the decision to use HCQ on Covid-19 patients lacks any proof of concept and pharmacokinetic study in the same context. This means there is insufficient evidence to recommend HCQ for Covid-19 prophylaxis. Interestingly, in a well-controlled study in rheumatoid arthritis, the clinical efficacy of HCQ was found to be equivalent to an Ashwagandha formulation (25). Another study has reported that chloroquine was no better than an analgesic in the treatment of chikungunya (26). Several recent articles in scientific journals have raised questions regarding the use of HCQ as prophylaxis in Covid-19 (27). Moreover, the ICMR guidelines are silent on what is to be done by these high-risk individuals after the prescribed seven-week treatment(10). It would be scientifically incorrect to assume that they will be protected beyond this period. It would also be ethically incorrect to leave them to their fate after this period, in the light of the reported possibility of re-infection (28).

There has been longstanding neglect of the Indian systems of medicine (29) until recently. . The AYUSH systems have received increased government support after the establishment of the Ministry of AYUSH. However, this has not translated into drawing on AYUSH resources in tackling the current pandemic, and this may result in huge societal costs. While there is a moral obligation to use all available resources for the greater good, what we are currently witnessing appears to be a refusal to accept empirical evidence in support of the immunomodulatory potential of Ayurvedic Rasayana and other AYUSH measures. This is neither in the people’s interest nor that of science, besides being unethical.

Linking ethical analysis with empirical evidence is important for policy decisions. Norman Daniels, in his framework for priority setting argues that the decision making process of policy makers should be fair and transparent, as they are accountable for the reasonableness of their decisions (30). The procedural conditions to guarantee fair decisions recommended in public health ethics include transparency, reasonable explanation and openness to revision, in addition to adherence to regulation. On this premise, the decision not to include evidence from the Indian AYUSH systems in the search for solutions and management of Covid-19 seems unreasonable and unfair.

In proposing a framework for decision making in public health, Tannahill proposes that while there is a “moral imperative” for evidence-based medicine, an “ethical imperative” for public health with implications for accountability is to use available evidence “appropriately to inform judgements” (31). However, it appears that with the dominance of MM/BM, the search for evidence of effectiveness is skewed towards interventions relating only to MM/BM. Appropriate use of the available evidence calls for breaking down the silos of medical systems and making decisions in the spirit of public health gains. Every medical system should strictly adhere to the principles of quality, safety, science and ethics.

The Ministry of AYUSH is making serious efforts to promote a culture of interdisciplinary collaboration without losing the basic principles of the respective systems. It must be noted that the Ministry of Health and Family Welfare is also encouraging integrative approaches. The establishment of an Interdisciplinary AYUSH Research and Development Taskforce on Covid-19 is a positive step in this direction. Appropriate exploration of AYUSH systems of medicine for solutions to Covid-19 is urgently needed. At this juncture, any delay is bound to cost society and science dearly. The opportunity to undo unfair decisions and to open the door to evidence from the AYUSH systems is not yet lost. Actively promoting the Ayurveda, Siddha, Unani, Sowa Rigpa, Homeopathy medicines, and Yoga and Naturopathy interventions showing empirical evidence might benefit many more, with a minimal potential for harm. More research is certainly needed to confirm this, however, in the exceptional situation of Covid-19, use of these safer options needs to be adopted. There is sufficient rationale, pre-clinical data, and evidence of safety from long-term clinical use for common indications. This can justify the urgent need for systematic clinical research in patients with Covid-19. While intensive care should be left to super specialists from MM, AYUSH doctors should have access to mild to moderate cases of Covid-19 patients. AYUSH doctors should be allowed to work with allopathic doctors under a national level integrative protocol for effective management of Covid-19. The clinical use should either be as per the Monitored Emergency Use of Unregistered Interventions (MEURI) framework by the WHO (32) endorsed by the Indian guidelines (33); or should be based on strong ethical ground. MEURI evolved in the wake of the Ebola crisis when unregistered synthetic drugs were approved for treatment to tackle the epidemic. This framework was expected to be followed in all future epidemics. This principle is also applicable to traditional medicine if evidence of safety and efficacy is available. China has successfully adopted this strategy for integrating Traditional Chinese Medicine. Now is the time to apply the same principle to AYUSH drugs as immunomodulators.

Adhering to scientific standards, integrating simple and safe measures from AYUSH systems in the protocols for prophylaxis and treatment in the early stages of Covid-19 is reasonable and fair from the perspective of the larger public good. Urgent action for such integration would be justified.