Spray and pray – the COVID-19 version

Kiran Mazumdar-Shaw is the head of Biocon, a company headquartered in Bengaluru and which has repurposed a drug called itolizumab – already approved to help manage severe chronic psoriasis in different markets – to manage cytokine release syndrome (CRS) in COVID-19 patients. Setting aside CRS’s relevance in the COVID-19 pathology (considering it is currently in dispute), Mazumdar-Shaw and a specific coterie of Biocon employees have been aggressively marketing itolizumab despite the fact that its phase II clinical trial seems by all accounts to have been a joke. (I recommend this account.)

Funnily enough, The Print published an article by Mazumdar-Shaw on September 1, in which she describes her experience of the infection (she’s one of The Print‘s funders). Two portions of the article are striking. One is the following paragraph about her treatment, which tacitly implicates a host of drugs and devices in her recovery without providing any additional information of their respective usefulness:

Dr Murli Mohan from Narayana Health, Bengaluru and Dr Shashank Joshi from Lilavati hospital, Mumbai, were my key medical supervisors. I was put on a course of Favipiravir, azithromycin and paracetamol. Apart from this, I continued with my daily dose of Vitamin C, Vitamin D, Zinc, baby aspirin and chyavanprash. Not to mention my twice a week 200mg dose of HCQ. Day two and three were uneventful. I was measuring my oxygen saturation levels six times a day, which were all between 96-98 per cent even after a brisk six-minute walk. My temperature was normal but late evening on Day three, I felt fluish and it extended to Day four and five. No measurable temperature but frequent bouts of sweating, which suggested that my body was fighting the virus. I was also tracking my Cytokine levels.

Reading this brought to mind a terrible period in early 2010, when I had malaria and jaundice together with an unusually strong spate of migraines. I can’t remember the exact drugs and diet that got me feeling better. But after reading what Mazumdar-Shaw went through, I’m inclined to attribute my recovery also to the mug of Bournvita I had every night before bed.

The other striking portion is a list of suggestions that subtly make the case to pay more attention to CRS and treat it with the drugs available in the market for it: “Doctors should not just treat clinical symptoms but rather the cause of the symptoms. If SpO2 (oxygen saturation) reduces, just increasing oxygen flow is not the answer. Treating inflammation caused by cytokines is the answer.” Wonder why researchers don’t yet have consensus… But the Drug Controller General of India has approved two drugs to treat CRS due to COVID-19 in India (through a highly criticised approval process) – and Kiran Mazudar-Shaw’s Biocon’s itolizumab is one of them.

The list is also prefaced by the following statement, among others: “… avoid TV and social media as negative news is bad for fighting Covid-19.” I wonder if this refers to criticism against hydroxychloroquine (HCQ), favipiravir, azithromycin and purported Ayurvedic remedies as well.

India’s missing research papers

If you’re looking for a quantification (although you shouldn’t) of the extent to which science is being conducted by press releases in India at the moment, consider the following list of studies. The papers for none of them have been published – as preprints or ‘post-prints’ – even as the people behind them, including many government officials and corporate honchos, have issued press releases about the respective findings, which some sections of the media have publicised without question and which have quite likely gone on to inform government decisions about suitable control and mitigation strategies. The collective danger of this failure is only amplified by a deafening silence from many quarters, especially from the wider community of doctors and medical researchers – almost as if it’s normal to conduct studies and publish press releases in a hurry and take an inordinate amount of time upload a preprint manuscript or conduct peer review, instead of the other way around. By the way, did you know India has three science academies?

  1. ICMR’s first seroprevalence survey (99% sure it isn’t out yet, but if I’m wrong, please let me know and link me to the paper?)
  2. Mumbai’s TIFR-NITI seroprevalence survey (100% sure. I asked TIFR when they plan to upload the paper, they said: “We are bound by BMC rules with respect to sharing data and hence we cannot give the raw data to anyone at least [until] we publish the paper. We will upload the preprint version soon.”)
  3. Biocon’s phase II Itolizumab trial (100% sure. More about irregularities here.)
  4. Delhi’s first seroprevalence survey (95% sure. Vinod Paul of NITI Aayog discussed the results but no paper has pinged my radar.)
  5. Delhi’s second seroprevalence survey (100% sure. Indian Express reported on August 8 that it has just wrapped up and the results will be available in 10 days. It didn’t mention a paper, however.)
  6. Bharat Biotech’s COVAXIN preclinical trials (90% sure)
  7. Papers of well-designed, well-powered studies establishing that HCQ, remdesivir, favipiravir and tocilizumab are efficacious against COVID-19 🙂

Aside from this, there have been many disease-transmission models whose results have been played up without discussing the specifics as well as numerous claims about transmission dynamics that have been largely inseparable from the steady stream of pseudoscience, obfuscation and carelessness. In one particularly egregious case, the Indian Council of Medical Research announced in a press release in May that Ahmedabad-based Zydus Cadila had manufactured an ELISA test kit for COVID-19 for ICMR’s use that was 100% specific and 98% sensitive. However, the paper describing the kit’s validation, published later, said it was 97.9% specific and 92.37% sensitive. If you know what these numbers mean, you’ll also know what a big difference this is, between the press release and the paper. After an investigation by Priyanka Pulla followed by multiple questions to different government officials, ICMR admitted it had made a booboo in the press release. I think this is a fair representation of how much the methods of science – which bridge first principles with the results – matter in India during the pandemic.