We lack medical oxygen. We lack hospital and ICU beds. More than a year into the COVID-19 pandemic, we lack an evidence-based treatment protocol too! Every state, every hospital, every medical practitioner, even AYUSH practitioners, and also ministers and others, have their own protocols and treatment strategies for COVID-19 in India.
It’s the same new coronavirus and the same human species in all the countries, and therefore, the same scientific treatment protocol shall hold good for all the countries. Such simple, clear and evidence-based treatment protocol can minimise confusion, prevent misuse, and stop unscrupulous elements from taking advantage of the difficult situation.
In fact, most countries, and the World Health Organisation (WHO), have published nearly similar COVID-19 treatment guidelines since March-April 2020 and kept them updated on the basis new studies and emerging evidence. The guidelines of the WHO, the US, the UK, and even of our neighbours such as Bangladesh, Sri Lanka and Pakistan either do not even mention or explicitly recommend against the use of drugs such as hydroxychloroquine (HCQ), ivermectin, azithromycin, doxycycline, oseltamivir or favipiravir for treating COVID-19. All these guidelines recommend very restricted use of remdisivir and tocilizumab and suggest careful use of steroids and anticoagulants in severe cases while cautioning against the use of steroids in mild and non-severe cases.
The Union Ministry of Health and Family Welfare did publish the first guidelines on March 17, 2020 and revised it later, but these are neither comprehensive nor on par with the guidelines of other countries nor enforced nationally. A recent write-up in the British Medical Journal has termed India’s slow moving treatment guidelines to be misleading and harming patients. As a result, we now have very many different treatment protocols, by many state governments and organisations, enlisting many drugs and tests that are unnecessary, unproven, potentially dangerous and expensive. With revisions to these different protocols appearing every now and then, and the old ones too circulating, there is complete confusion in investigating and treating COVID-19 cases.
It is now a free-for-all kind of situation, with some physicians prescribing, on their own, experimental drugs like bevacizumab for moderately severe cases. The Drugs Controller General of India (DCGI) has also recently given emergency use authorisations for pegylated interferon alpha-2b in moderate cases, without any reliable data to support such a decision. It seems as if we are trying to latch onto any available straws, however weak or ineffective or harmful, only to show to the people that something is being done to save them from COVID-19. Such directionless and uncontrolled treatment methods are also resulting in panic buying, hoarding and black marketing of drugs such as remdisivir.
Added to this, promotion of AYUSH products such as kashaya, kwatha, turmeric milk etc., and of fake claims of squeezing lemon drops into nostrils, drinking animal urine, chanting mantras etc., repeatedly made by ministers, MPs, MLAs and the media have created more confusion and panic, while also causing adverse effects such as allergies and reactions to these products.
The first guidelines from the Union Ministry of Health and Family Welfare, published on March 17, 2020 had clearly advised against the use of corticosteroids and any other specific antiviral treatment for COVID-19, stating lack of adequate evidence. However, the Indian Council for Medical Research (ICMR) recommended HCQ for pre-exposure prophylaxis for all healthcare workers in its directives on March 23, 2020, and again on May 22, 2020, even after reports in medical journals questioned its utility and safety.
Kerala government published its interim guidelines on March 24, 2020, and contrary to the Union government guidelines published in the previous week, it recommended symptomatic treatment for mild disease, chloroquine or HCQ plus azithromycin and oseltamivir for moderate disease, chloroquine/HCQ and azithromycin plus oseltamivir plus ritonavir/lopinavir for severe disease, along with corticosteroids and tocilizumab.
The Karnataka government published its first clinical protocol for COVID-19 cases on May 15, 2020. It suggested a whole battery of investigations, including CT scans, echocardiography, chest X Ray, and other expensive blood tests, even for mild and asymptomatic cases and recommended oseltamivir, HCQ, azithromycin, zinc, vitamin C, anticoagulation for all cases, mild to severe, and suggested, in addition, remdisivir, tocilizumab, ritonavir/lopinavir, convalescent plasma and as yet unproven drug named sepsivac, and discretionary use of steroids, for severe cases. Almost all of these were arbitrary and without any support of evidence for efficacy.
The MoHFW’s updated guidelines (version 5), published on July 3, 2020, classified COVID-19 cases into mild, moderate and severe. The mild cases were advised institutional care at COVID Care Centres, First Referral Units etc., and were recommended paracetamol for symptomatic relief, and HCQ for high risk cases. Moderate cases were recommended supplemental oxygen, anticoagulation, corticosteroids, HCQ and conditional use of remdisivir and plasma therapy. For severe cases, these guidelines recommended oxygen, anticoagulation, corticosteroids, and conditional use of tocilizumab. These revisions too had no basis in evidence.
The second version of the Kerala guidelines, published on August 15, 2020, added favipiravir, remdisivir, anticoagulants and plasma therapy to the list. Later, the interim guidelines for management of COVID-19 (version 1.5), released by the All India Institute of Medical Sciences (AIIMS) on September 8, 2020, suggested home isolation for mild cases, instead of institutional care, and recommended HCQ for high risk cases. For moderate cases, it suggested HCQ or remdesivir, plus steroids and anticoagulants and hospitalisation and for the severe cases, it suggested ICU admission and use of steroids, tocilizumab and anticoagulants. And now, on April 22, 2021, AIIMS/ ICMR-COVID-19 National Task Force/Joint Monitoring Group has published a new clinical guidance, modifying the earlier AIIMS guidance, with ivermectin or HCQ along with inhaled budesonide for mild cases isolated at home, and restricting the use of remdisivir and tocilizumab for specific cases of moderate and severe disease. Neither the National Insitutes of Health (NIH), US nor the National Institute for Health and Care Excellence (NICE), UK recommend budesonide for COVID-19 of any severity.
The guidances issued by the states have also changed accordingly. The third version of Kerala guidelines, published on April 25, 2021, replaced choloroquine, azithromycin, and antivirals (except favipiravir) with ivermectin, and also added inhaled budesonide for moderate cases, on the lines of ICMR’s new guidelines. Karnataka too revised its guidance on April 20, 2021, recommending home isolation along with ivermectin, favipiravir, zinc and vitamin C for mild and moderate cases; and remdisivir, tocilizumab, itolizumab, corticosteroids, anticoagulants, antibiotics, and a big list of expensive investigations for more severe cases. Yet again, on May 1, 2021, Karnataka’s guidance was modified, with ivermectin, favipiravir and HCQ along with inhaled budesonide, as suggested by the ICMR, plus paracetamol, pantoprazole, zinc, vitamin C, cetirizine being recommended for home isolated cases.
COVID-19 manifests in two phases; the first one being the entry of the virus and its amplification, followed by the body's immune response clearing the virus; these happen during the first week. The second phase is the overdrive of the immune response, the so-called cytokine storm, that causes injuries to the lungs and disturbs the clotting pathways. In most, or almost all, of the patients, the immune system itself clears the viral load and none of the available or recommended drugs offer any help. It’s the second phase that leads to all the complications, and it should be identified early by monitoring the oxygen saturation, and treated early with oxygen supplementation. Steroids and anticoagulants have shown some benefit in only severe cases, when used under medical supervision. Indiscriminate or early use of steroids, in the first phase or in non-severe cases, can worsen the infection by hampering the immune system’s efforts to clear the infection.
These being the facts, the confusing multitudes of guidelines in India may be doing more harm than good, and may be contributing to the chaos that is being witnessed today. For example, both HCQ and azithromycin are well known to prolong the QT interval (of heart's electrical activity) and precipitate heart arrhythmias and sudden deaths, and both being long acting drugs, the risk is higher, particularly when used in combination or one after another, in repeated doses. It's a common practice now in India to co-prescribe a proton pump inhibitor with a drug called domperidone, supposedly to prevent gastritis, and this domperidone is also known to prolong the QT interval, and therefore co-prescription of HCQ, azithromycin and domperidone can be quite dangerous.
As mentioned earlier, unnecessary and premature use of steroids in mild cases can aggravate the infection and worsen the outcomes, and can worsen coagulation problems, particularly on prolonged use.
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But the wide coverage given to the reports of the RECOVERY trial, that showed benefits of steroids in severe cases, and irrational and indiscriminate prescriptions by doctors and civic authorities, could have contributed to worsening of the infection in some, if not many. The Bruhat Bengaluru Mahanagara Palike (BBMP) and Shivamogga district hospital have printed Home Isolation Medicine Kits for COVID-19, and have enlisted dexamethasone for 12 days and prednisolone for 5 days, respectively, for mild cases on home isolation, contrary to all the recommendations, of foriegn countries or of our own Union government or of Karnataka government!
Thus, it is evident that there is no rational and scientific and safe treatment policy in India and each and every institution or even medical practitioner seems to have one’s own treatment plan, most of them being wrong and potentially dangerous. With no clear guidance to the people on the need to stay home and monitor for development of potential complications, scaremongering by the media, rumours on social media, no official plan or facilities in place for oxygen supply and arrangements of hospitals and ICUs, it is all hell broken loose. Therefore, it is now urgently needed to publish a nationally applicable, evidence-based treatment protocol for COVID-19 in India, and such guidelines published by the WHO, NIH, USA, NICE, UK, and our neighbouring countries can be immensely useful.
Dr Srinivas Kakkilaya is a physician and public health specialist based in Mangaluru.