Dr. Anil Pareek is India's evangelist-in- chief for Hydroxychloroquine. He was instrumental in getting the first regulatory approval in the country for Hydroxychloroquine in Rheumatoid Arthritis patients. Hydroxychloroquine, a generic low-cost molecule was first approved by USFDA in 1955 and is emerging as a potential treatment option for COVID 19. Dr. Anil Pareek spoke to Dr. Sudhir Bhandari, Principal, SMS Medical College and a leading diabetologist. Dr. Bhandari has successfully treated three seriously ill COVID19 patients

Dr. Anil Pareek: Everybody wants to know how to manage COVID-19 patients. Can you please elaborate on what treatment was given to these patients?

Dr. Sudhir Bhandari: We were well aware of the Corona issue. COVID-19 is spreading all around, so we were very sensitized. If you recollect, we had a great experience of handling swine flu epidemic seven or eight years ago and we have been getting a lot of cases of swine flu, most of them being the terminal, respiratory and pneumonia patients. We were prepared for this much before the first COVID-19 patient came.

We have a core team of consultants at SMS Medical College. We studied a lot of literature; we checked a lot of trials before handling the first three patients. The patients included one Italian couple and an elderly Indian person from Dubai, second and third were the senior citizens with high-risk groups. The second patient was a 69-year-old Italian with emphysema, third was an 85-year-old Indian with renal failure. So, it was a real challenge for us.

Whenever a COVID patient comes, it requires intense medical and supportive management and definitely we had to work upon anything which we can do to reduce viral replication and the virus load. At the moment when these patients came, they were corona positive, tested twice. They had significant medical issues of breathlessness, high fever, and respiratory distress. Along with the standard medical management and the supportive treatment we started working on the antiviral drug. Our bottom line was to reduce viral load.

Having seen a lot of literature for Chloroquine and Hydroxychloroquine along with a lot of trials that are going on the combination of Chloroquine and Hydroxychloroquine along with two antiviral drugs lopinavir as well as ritonavir. We started using a combination of Hydroxychloroquine which we gave for five days then we coupled this with lopinavir and ritonavir. Patient’s consent was taken before treatment. We started this protocol and we were monitoring the side effect, if at all any.

Dr. Anil Pareek: How soon were COVID19 patients introduced to the combination of the three drugs?

Sudhir Bhandari: We introduced three drugs the moment the patients tested positive, and there is a definite indication of giving antiviral drugs because they were significantly symptomatic. They were symptomatically symptomatic, saturation was little compromised and they were having breathing difficulty, so the moment the second sample confirmed that they were Corona positive, we introduced the three drugs combination.

Dr. Anil Pareek: Did you consult the Indian Council of Medical Research (ICMR) for treating these patients. Are there any guidelines for practitioners from ICMR on this?

Sudhir Bhandari: Coincidentally, the ICMR team happened to be in our institute on the same day the COVID-19 positive case was reported. We discussed with ICMR that we intended to reduce the viral load and we want to use this protocol. It was consented by them. We used Hydroxychloroquine coupled up with lopinavir and ritonavir.

Dr. Anil Pareek: What is the benchmark to consider if the patient has been treated successfully?

Dr. Sudhir Bhandari: It was our initial experience, so we were closely monitoring if at all there are any side effects. On day one along with Hydroxychloroquine coupled up with lopinavir and ritonavir and other supportive treatment, the patient started improving.

The first patient, who was 50 plus years of age, became Corona negative within seven days. Two successful testing was required to label her Corona negative. The second patient who was an advanced cardiac and Chronic obstructive pulmonary disease (COPD) patient because of being a chain smoker, also became Corona negative in the next 10 days. The third patient, who was a senior citizen, 85 years old man with renal failure also became Corona negative.

All three patients were discharged happily. I have a feeling that along with giving standard medical treatment, we need to act in a direction to reduce virus load, and viremia and this will be documented by fast recovery along with Corona being negative.

Currently, we have six more COVID-19 positive patients, which is the very beginning of our experience. We have put them on the same regime. First, we started Hydroxychloroquine and then we couple it with antiviral. All six patients have given consent for the treatment. Patients on this regime take lesser time to be Corona negative. They have faster recovery, better recovery of respiratory symptoms, clearing of the pneumonia patch on x-ray, improvement of oxygen saturation requiring lesser oxygen and lesser of Bilevel Positive Airway Pressure (BIPAP) support. I am sure, over a period of time all these parameters are going to make our conviction stronger that we should be able to reduce the virus load by using these new drugs.

Dr. Anil Pareek: There is a study from China where Chloroquine has been used and it has improved pneumonia. There is also a study from France where they have used Hydroxychloroquine with azithromycin on COVID19 patients. What are your views on this?

Dr. Sudhir Bhandari: Chloroquine was used in Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). There was every valid reason that we could use Chloroquine or Hydroxychloroquine in our patients. A similar shorter study from France with only 26 patients found out that patients whom they gave Chloroquine and Azithromycin, recover much faster and the patient became Corona negative. Although we do not want more patients to come, but we have been following this protocol.

As we are entering phase three, we started getting more patients. We have been giving this combination of Chloroquine or Hydroxychloroquine coupled with lopinavir which helps the patients to recover faster and reduce the morbidity and mortality. Even a mildly symptomatic patient can be given only Hydroxychloroquine or Chloroquine coupled with azithromycin. If a patient has significant symptoms, we could combine later the newer antiviral drugs which are very safe. Preliminary observation is that it is worth giving the drugs to these patients because we have got all positive results.

Dr. Anil Pareek: I think there is an in vitro study which suggests the use of Hydroxychloroquine since it has a little longer half-life and better concentration in the respiratory secretions?

Dr. Sudhir Bhandari: Even an in vitro data is worth considering but more important is that the toxicity of Hydroxychloroquine is much lesser and it is better tolerated. We need to take into consideration the in vitro study definitely but equally important is the lesser toxicity of the drug. The level of confidence in using Hydroxychloroquine is much more than a simpler Chloroquine. I think another thing is that we have been using Hydroxychloroquine in a number of other conditions. I have a feeling that having used even for longer and longer duration the toxicity becomes very less and late.

Dr. Anil Pareek: What is your advice to uncontrolled diabetic patients?

Dr. Sudhir Bhandari: The use of Hydroxychloroquine was an integral part of my anti-diabetic treatment study. To be honest, it has so many strengths, it is economical, it has lesser toxicity, it brings about very good diabetic control and it increases insulin sensitivity and reduces insulin resistance, so I feel it has a proven anti-inflammatory advantageous effect in this metabolic disease.

Dr. Anil Pareek: How should a practitioner should deal with COVID19? What is the current situation in Rajasthan, since there is community spread? What measures should be undertaken to prevent it's further spread ?

Dr. Sudhir Bhandari: First of all, I must tell you we are entering phase three of Corona spread. So far, COVID-19 had come from international travelers or from identified countries and some of the people who came in contact with international travelers. Now we are fearing the interpersonal or community spread.

Dr. Sudhir Bhandari: First of all, I must tell you we are entering phase three of Corona spread. So far, COVID-19 had come from international travelers or from identified countries and some of the people who came in contact with international travelers. Now we are fearing the interpersonal or community spread.

The honorable Prime Minister Narendra Modi has been motivating for quarantine. I have a feeling that if each and every citizen of our country follows these basic principles like total isolation for the next two to three weeks, frequent hand washing, preventing the congregation, not going into public places, we could prevent the interpersonal community spread.

Now, if we look at the other countries also, the first three weeks was almost a flat curve, fourth and fifth week it zoomed up like anything. I have an appeal to all my fellow Indians, fellow colleagues that please maintain quarantine, especially to my senior citizen colleagues, who have diabetes, hypertension, kidney problems, immunocompromised, COPD patients, on steroids or inhalers, and for any other reason if they have low immune status.

Dr. Anil Pareek: Do you recommend any prophylaxis for this disease?

Dr. Sudhir Bhandari: There have been fewer studies of prophylaxis with Hydroxychloroquine. I would wait for some more time before giving definite value to this prophylactic proposal. I would let an authenticated journal like the New England Journal publish about it. Theoretically, I would say, sooner or later, it will be included in the prophylactic armamentarium.

We stay in such a country that there has to be a rock-solid evidence for any advice, otherwise little misuse or overuse of any prophylactic medication will be disastrous. I would recommend people to consult a doctor if they have a travel history, contact history and now even without history because we are entering into phase three. Also, if someone has a fever or cold, and suspected symptoms it will be better to consult a doctor.

The new ICMR guidelines state that any person who has a cough, cold, fever, even without contact with the suspect or in contact with the patient, needs to get himself investigated because we started having community cases.

If you are COVID positive then I would still feel Hydroxychloroquine is a great drug to begin in mild patients. With the newer studies, we may combine Hydroxychloroquine with azithromycin which is again a harmless drug in moderate and severe symptoms. If it is a patch of pneumonia on an x-ray or a falling oxygen saturation, falling blood pressure, tachypnea breaths, general condition is low, I think we can club Hydroxychloroquine with antiviral therapy which is very safe and effective.

Dr. Anil Pareek: Finally, what is your advice to practitioners in rural areas.

Dr. Sudhir Bhandari: My advice to practitioners in rural areas will be two-fold. The first advice in the present situation of COVID-19 to practitioners is that we have to protect our country from entering into phase three. Ensure complete isolation, do not see non-critical patients. If at all you see any critical patients with respiratory symptoms, better protect yourself using N95. N95 mask is not essential for the public at large. There has been a rat race of acquiring an N95 mask by the public which is not required. N95 mask should be used by doctors only.

Rural colleagues, please educate people that a simple three-layer surgical mask is enough if someone is coughing. Otherwise, for a common population, I again repeat there is no need for a mask, maintain a distance of five to six feet from any person whom you are talking to. Normal people do not require any mask. If someone has a cough, cold, sneezing he can use a triple layer mask. N95 is only for medics, paramedics or consultants who see a patient. The second one of the most important things is that this virus spreads when someone coughs or sneezes. The virus settles down on any of the surfaces. Thus, frequent hand washing is very important.

One important advice I would like to give to my rural colleagues is that the first station, where this virus enters the body, is the throat mucosal lining and the virus grows in the mucosal lining of the sinuses. So, if you can take warm water and steam inhalation through your nose and mouth a few times a day you deactivate the virus. I would strongly recommend my colleagues and my countrymen in rural areas to drink warm water, to take steam and not to worry about the mask.

Now if a patient develops the symptoms like cough, fever, little breathlessness, the doctor should make sure before testing the patient for COVID19, otherwise, consult with a higher center or a senior consultant, get him examined for the COVID-19 if symptoms are prominent. The moment you find a positive case it will be logical and prudent to start Hydroxychloroquine combined with azithromycin in mild cases, moderate to severe cases you can combine antiviral drugs.