COVID-19 Drug: Sorry Oxford, TN Government Doctors Beat You To It
The announcement of Oxford University’s preliminary trials on corticosteroid Dexamethasone was made with much fanfare and excitement, as a possible “wonder drug” in the treatment of COVID-19.
While international media hailed this as the “first life-saving drug”, the fact remains that government doctors in Tamil Nadu seem to have beaten Oxford to the finish. Because a full two months before the June 16 announcement by Oxford, Tamil Nadu had already begun using methylprednisolone to critically ill patients and witnessing wondrous results.
Unfortunately though, since all hands are on deck in saving lives, doctors in Tamil Nadu have not been able to get down to researching, conducting double blind studies and publishing papers on their findings.
Dexamethasone Versus Methylprednisolone
“Both dexamethasone and methylprednisolone are steroids,” said Dr Raghunandan, Professor of Medicine at Madras Medical College in an interview with The Lede. “Methylprednisolone is faster acting. Both drugs produce anti-inflammatory effects. Whenever an infection occurs, some pro-inflammation markers called cytokines are released into the system. They are the culprits in creating further consequences.”
Cytokines are normally part of the body’s immune response but when too many are released too quickly, it can be harmful. This is what is referred to as a cytokine storm and is seen in severe COVID-19 patients. These steroids control inflammation in the lungs caused by this cytokine storm and lack of oxygen.
“They are like sisters. The younger sister is brighter than the older sister,” laughs Dr Paranthaman, Professor of Medicine at the Kilpauk Medical College and Hospital. “Methylprednisolone is the younger sister. Dexamethasone is longer acting and cheaper. Its effect can be felt for 36 to 48 hours. Methylprednisolone is a short duration steroid and works for 24 to 36 hours.
The advantage to the Methylprednisolone action is that it is more concentrated on the lungs. I think many people are not aware of this,” said Dr Paranthaman.
Doctors and researchers at the Kilpauk Medical College and Hospital decided to use Methylprednisolone for this very reason – its targeted action.
“The advantage of Methylprednisolone is that its action on the lungs is more than Dexamethasone. Dexamethasone will spread and act all over the body but the receptors on Methylprednisolone will target the lungs. So since in COVID, there is pneumonia and lung injury involved, Methylprednisolone is the best choice compared to Dexamethasone. Otherwise both can be both. Four mg of Dexamethosone is equal to 16 mg of Methylprednisolone. So you can use both as a daily dose.
If you see action-wise, there is no superior action. Both are the same, except that the younger sister is more specialised than the older sister,” said Dr Paranthaman. “If you consider the cost and availability, Dexamethasone is cheaper and available everywhere. That is the only advantage.
So instead of Methylprednisolone, we can use Dexamethasone. But there is no superiority of Dexamethasone over Methylprednisolone,” he said.
Tamil Nadu’s Treatment Protocol
Tamil Nadu has witnessed a low death rate compared to states like Maharashtra, Delhi and Gujarat.
Part of this at least, is attributed to the treatment protocol formulated by doctors.
Tamil Nadu has been using a combination of two drugs as part of its treatment protocol for the past two months, which has been yielding rich results, according to them.
This has been accompanied by a change in protocol as well, as doctors recorded more observations.
“The secondary COVID infections like the injury to the lungs caused by the virus - that can be addressed only by two drugs,” said Dr Paranthaman of Kilpauk Medical College and Hospital. “The blood becomes thick and gets clotted inside the small blood vessels in the lungs – this is called localised pulmonary thrombotic micro angiopathy. That is the main problem occurring in COVID.
Due to this the blood does not carry oxygen into the lungs, a situation called hypoxia. Low molecular weight heparin releases the block in the lungs, thereby leading to better oxygenation.
The second event is (lung) consolidation,” he said.
Lung consolidation is when lung tissue has filled with liquid instead of air. This is marked by swelling or hardening of a normally aerated lung.
“Pneumonia caused by the occlusion (blocking) of the blood vessels by increased thrombosis which in turn causes increased opacity in the lungs, is called consolidation. There is an inflammation caused by this consolidation which leads to release of toxic substances,” said Dr Paranthaman.
This inflammation is treated with the steroid Methylprednisolone.
The treatment protocol adopted in the past two months by Tamil Nadu’s doctors is called PALM therapy.
“P stands for prone position (lying on the stomach), A for avoiding activity, L for low molecular weight heparin and M for Methylprednisolone,” explained Dr Paranthaman.
“Prone position may seem like an ordinary thing but it is very very useful for the management of COVID. Oxygenation is improved because one particular part of the lung is activated and becomes better oxygenated.
The other most important thing to watch out for in COVID is activity. A patient may not know that he has hypoxia (low oxygen level in the blood). Despite having hypoxia, he may not have breathlessness or chest pain, so he will continue to do his regular activities.
These activities tend to sharply increase hypoxia and the patient will suddenly collapse. That is the reason many patients are suddenly collapsing. Sudden death is due to activity. If he doesn’t exert himself, he will not collapse. That is the reason we have added A for avoid activity in the therapy regimen,” he said.
This PALM therapy has been formulated by professors in Tamil Nadu, especially those in the Kilpauk Medical College.
The earlier treatment protocol being used was called LAMP. L for low molecular weight heparin, A for azithromycin (an antibiotic), M for Methylprednisolone and P for prone position.
It was only in the past two months that doctors found out that activity and exertion is causing COVID patients to collapse. The PALM strategy was then developed.
“PALM therapy is very effective and we are very happy with the outcome,” said Dr Paranthaman.
“We use Methylprednisolone whenever we see lung lesion, even a mild lesion. We immediately start PALM treatment. We shift from LAMP to PALM when a patient is stable, is not aware that he has the sickness, but has low blood pressure or low oxygen saturation (below 80-85%) but the patient is conscious and oriented. Then we shift them from LAMP to PALM,” explained Dr Paranthaman.
“We should have some evidence for pro-inflammatory markers before using the steroids,” added Dr Raghunandan of the Madras Medical College. “We test the blood for C-reactive protein, serum serotonin, interleukin-6 – these are the inflammatory markers. If they are high, we will use Methylprednisolone.
There is a lot of literature on these. The expert committees meet every week and decide on the course of treatment. So far nothing is officially approved. All are being used on a trial basis. There are more than 10 drugs that are being tried in various stages. Considering the overall system, these two drugs are the only ones really yielding results,” he explained.
Tamil Nadu doctors are testing 10 drugs both as part of the World Health Organisation’s protocol as well as their own findings.
Four of these drugs are part of the WHO’s Solidarity trial being conducted worldwide. These drugs are anti-viral drugs Remdesivir, Lopinavir-Ritonavir, anti-malarial drug Hydroxychloroquine and Lopinavir-Ritonavir-Interferon beta-1a.
Apart from these four drugs, Tamil Nadu is also testing tocilizumab, an immune modulator. Other drugs on trial are ivermectin (viral inhibitor), doxycycline (antibiotic), azithromycin, low molecular weight heparin and Methylprednisolone.
“Every country is trying combinations and coming out with reports. Methylprednisolone needs double blind studies for approvals. We don’t have time to do these,” admitted Dr Raghunandan.
Dr Paranthaman agrees. “We are just focussed on saving lives, we are not looking to publish papers,” he said.