Dr Dhananjay Bakhle, a physician treating COVID patients but also leading medical research for a pharmaceutical company, has agreed to respond to our questions regarding the recent crisis in India. In March, we published the article “The Mystery Behind India’s Success in Flattening the Curve,” which he co-authored. While infections and mortality remained low, per capita, in the first wave, the recent rapid increase in cases and mortality has taken the country by surprise. In this interview, Dr Bakhle helps us understanding what is going on, and why some states appear to fare much better than others.
(the interview was done in writing, through email exchanges on April 23-29; some edits were done for readability purposes).
1. There has been a dramatic increase in new cases starting mid-march, with 23,000 new daily confirmed cases on March 15, and 281,000 new daily confirmed cases on April 22, according to World in Data. What do you think of these numbers?
These numbers have been outstripped as of today. India has crossed 346,000 new cases in a single day. In last 3 days close to million cases and yesterday crossed the death toll of 2000 in a single day.
2. What is the geographic spread of these new infections? Which states are the most affected? Is it mostly an urban phenomenon?
There are 7 states which contain 67% of all active cases in India as of today. The adjoining graph shows the break-up. One would expect some correlation between the number of active cases & cases per million but it doesn’t correlate in 4 states.
This led me to look at the population density against the cases per million to see which states are outliers. The graph shows these numbers on two different axes. It shows that Uttar Pradesh is doing something right whereas Chattisgarh, Maharashtra & Karnataka are not on track.
Since the whole country is following all standard methods of prevention like masks, sanitization & social distancing, the differences are likely to be attributed to the differential treatments being received by the patients in these states.
3. Similarly, there is a huge increase in daily deaths, from less than 200 per day to now about 1800 per day. Can you confirm these figures? Can you comment?
This figure has crossed 2000 per day for the last 4 days.
Today, most leading doctors in India are themselves not promoting the Ministry of Health guidelines that includes the use of hydroxychloroquine, ivermectin and inhaled budesonide (see below).
Another change from the first wave is that people from the upper middle class and the elite have been more involved in this wave, while they had escaped the first wave when people from lower socio-economic strata were mostly involved.
The people from the slums who got hit by the first wave were treated in the govt and municipal dispensaries, and got hydroxychloroquine and zinc regimen. This helped keeping the death rate very low.
This time the upper class are being treated by the elite doctors in their private clinics/nursing homes who don’t use HCQ but use more expensive drugs like favipiravir and remdesivir. This has led to a huge demand and supply gap for remdesivir that did not occur in the first wave.
These people also get admitted as inpatients much earlier than their lower socio-economic counterparts. The demand for hospital beds this time far exceeds availability in most urban areas of India.
Also noteworthy is that, when remdesivir is used, HCQ is stopped even if it was given by a family physician.
The net result of this whole situation is a higher death rate in major cities like Mumbai where it crossed 2% CFR.
4. Today, are there states where early treatment is being given more pro-actively?
This is clearly the case looking at the example of Uttar Pradesh, which has double the population of Maharashtra but 2.5 times less the number of active cases as seen from the graph below: This is simply because UP is providing home treatment kits containing Ivermectin to each positive case.
Goa is another state, though much smaller than any of the 7 states listed above, that is providing Ivermectin home treatment kits as shown in the picture below.
This has made it possible for both states to avoid lockdowns whereas Maharashtra is in full lockdown. Even as compared to Mumbai, its twin metropolis of Thane has a much wider use of Ivermectin and lower fatality rates.
Another feature of the second wave is that number of affected districts are more clustered in urban areas as compared to the first wave. The number of districts comprising the top 50% of cases has dropped from over 40 at the time of the last peak, to less than 20 currently, indicating a much more concentrated pandemic.
This has left treatment in the hands of fewer frontline doctors as compared to the last wave and also a change in the type of doctors treating the disease, from crowded localities to more housing societies and more plush areas of the cities. This has reduced the use of drugs such as hydroxychloroquine and Ivermectin as stated before
5. If early treatment is being given, how can you explain this dramatic increase in mortality?
Firstly, treatment is not necessarily comprising of HCQ & Ivermectin as much as Favipiravir & Remdesivir in small private hospitals and nursing homes.
Also some of the state government establishments have written off the use of HCQ like what Pune Municipal Corporation did by issuing a statement not to use HCQ.
Note also that the Lancet Covid-19 commission India Task Force does not give particular attention to outpatient treatment as a means to reduce the pressure on hospitals and ICUs.
6. Can you comment on the vaccination campaign in India?
There is a clear increase in the number of cases associated with the vaccination campaign, which has brought out all the elderly from a lockdown-like situation directly into hospitals, which became spreading centres.
Several patients that me and my colleagues have treated in the second wave had been recently vaccinated.
Vaccination can’t cope up with the much faster spread of this wave and thus the campaign has so far not been able to impact the case increases. The following graph shows the fully vaccinated people vs. cases/million to see if there is some correlation.
From the graph, there appears to be some advantage to Gujrat and Rajasthan in keeping cases/million lower than Maharashtra where vaccinated people/million are low and the cases/million is the largest.
Uttar Pradesh again beats this trend and despite lowest vaccinated people, its cases/million are also the lowest. I believe this may be an “Ivermectin effect.”
7. With the “double mutant” variant, is there evidence that early treatment with Ivermectin, doxycycline, etc. is still effective?
Since Ivermectin and HCQ are hos mediated drugs they work irrespective of the mutant strains. HCQ works on the ACE2 receptors and endosomes which normally work in acidic environment to facilitate endocytosis. Whereas, Ivermectin is the positive allosteric modulator of 7 alfa-nicotinic receptors that is attacked by SARS-CoV2.
Doxycycline is a known inhibitor of IL-6, TNF-alfa and MMP enzymes which play a pathological role in Covid-19. These mechanisms are independent of viral strains and hence have been found to remain effective in the second wave also.
Some doctors in a twin city of Mumbai called Thane have been using Ivermectin in double dose (12 mg twice daily) for 5 days, relatively free from side effects.
The typical treatment that I have been using in the second wave has been primarily Ivermectin 12 mg once daily for 5 days along with elemental Zinc 50 mg once daily for 7 days. In patients with fever I add Doxycycline 100 mg twice daily for 5 days. Vit D3 either 60,000 units weekly or 4000 Units daily for at least 10 days.
If the fever doesn’t settle by 5-6 days I start dexamethasone 4 mg for 3 days and then wean off. Dexamethasone has been doing wonders for the second peak of fever which is generally due to inflammation rather than viremia and appears sometimes after the first peak is resolved after Ivermectin/Doxycycline combination.
For patients with cough, I prefer to add Budesonide inhalation by dry powder inhalation in a dose of 400 micrograms twice daily to be increased upto 800 mcg twice daily if required. I recently treated a patient of Asthma with Covid whose cough and breathlessness was not resolving with repeated inhalations with Albuterol to whom Budesonide resolved it completely in a dose of 600 mcg twice daily.
Many young patients who show higher blood markers of inflammation like CRP, IL-6 and D-dimer have responded very well to HCQ and Zinc combination with or without Doxycycline.
If such a treatment is given to all patients, no hospital admission is necessary. This dramatically reduces the burden on hospital resources, including oxygen. The issue is that early home treatment is not being promoted by the medical task forces or in the media.
8. On social media, the most common requests are for oxygen and remdesivir. How do you explain the continued use of remdesivir while the SOLIDARITY trial and the WHO concluded it is not effective for COVID-19?
Remdesivir is touted as a life saving drug by most elite medical doctors and the media. I haven’t heard of any doctor giving the real data, which don’t show any mortality benefits. A sort of hype of unavailability of the drug created a huge demand with all patients wanting it.
Since the Indian government had restricted the use of Remdesivir to only those patients who require oxygen support, the demand for the drug may have even led to more usage of oxygen in all these patients whether required or not. This may have led to an artificial shortage of oxygen.
Of course the mammoth new cases exploding every day also put additional pressure on the oxygen capacity of the hospitals.
9. From the data, or from your contacts with medical doctors on the frontline, are there indications that some outpatient treatments are working particularly well in India, at least in some states?
Yes, many doctors at district level in states such as Uttar Pradesh, Gujrat & Goa are treating patients with the early home treatments mentioned above. The ministry of health guideline continues to suggest HCQ and Ivermectin.
It is very important to know that health is a state and not a central government responsibility. Hence, there are bound to be differences among states.
While the giant second wave in India is associated with the double mutant, its management in different states shows variance. States like Uttar Pradesh have stuck to Ivermectin and show low numbers despite high population density. Maharashtra, where the use of these drugs declined, shows on the other hand very high numbers.
If our assessment of how India tamed the first wave is correct, the 2nd wave will also be brought under control by the frontline doctors at district levels who use early home treatments. We hope to see that happening soon just like the first wave faded away just a few months back.
10. Concretely, what are the solutions, from a public health policy perspective, for India to again flatten the curve?
We need to replicate the policies of the largest state in India – Uttar Pradesh – to provide early treatment kits to people in states like Maharashtra.
India should remove the taboo around the use of hydroxychloroquine simply because there has not been a single death reported in the world due to HCQ while 2000 people are dying every day.
While Ivermectin is a great drug for early treatment, it may not work as well as HCQ, from the experience of many of us in the second wave. The kit should also include Zinc supplement in the dose of 50 mg elemental Zinc along with Doxycycline.
A pulse Oxymeter and a chart to indicate how to measure and record the readings should likewise be provided. It goes without mentioning that a good thermometer should be provided like being done by the Goa government.
There should be clear criteria provided about who should seek hospital admission. When the patient gets into hospital, the early outpatient treatment should be continued and not stopped, as is being done today.
This will ensure that many patients will then complete at least 5 days of either HCQ or Ivermectin-based treatment, which stabilizes the immune response, thereby reducing the chances of cytokine release syndrome.
All governmental media contact points should promote the early home treatment and the government should promote telemedicine initiatives as acceptable for CSR expenditure for corporates who will then come forward and initiate them.
The telephone services can run a tune before each call is picked up to say that there is effective home treatment and primary care doctors should be contacted in case of symptoms.
Early home treatment is no competition for vaccines and hence both have to co-exist, which can play a major role in reducing stretch on the hospital resources in the country. However, a lopsided massive emphasis on vaccinations has led to the current situation without a plan B for this new wave.
If such a plan B for early home treatment were to be implemented, it can supplement the governmental ambitious plans for vaccinating the entire huge population of India in the next few months in a calculated and planned manner rather than struggling to cope with both at the same time.