India recently reported over 330,000 new COVID cases in a single day, a new world record.
There is a way to dramatically reduce these numbers.
The problem is that India, like most countries, has been following the advice recommended by the recognized authorities (NIH, CDC, WHO, and EMA) for how to prevent and treat COVID. This advice is based on evidence-based medicine (EBM) which takes a relatively long time to discover and rigorously validate effective treatments, especially for generic low-cost repurposed drugs that are off-patent.
For example, for ivermectin, in the past year, there have been 52 studies of ivermectin, 48 of them published in peer reviewed journals, and only one study was negative. However, evidence-based medicine is unable to make a conclusion one-way or the other as to whether the drug might work. A 51/52 success rate is considered “too close to call” since there could be a bias or confounder affecting all these independent studies. The fact that nobody has been able to postulate any such confounder or bias that could explain the consistency is immaterial since it does not prove that there isn’t one. The consistency cannot be explained by publication bias because nobody can identify a single ivermectin study that was not published.
I believe there is a bias in interpreting these results. Had the ivermectin studies all had the same outcomes but in reverse, where 51/52 studies showed a negative effect (where patients fared worse on nearly all metrics), is there any doubt that the same experts would cite this as definitive proof the drug does not work and strongly recommend it should not be used? One need look no further than the hydroxychloroquine (HCQ) data to prove this interpretation bias. With HCQ there have been 29 early treatment studies, 100% positive, and the experts have determined that HCQ should not be used. That’s baffling.
Another example of long lead times associated with EBM is fluvoxamine. It has taken more than one year since Dr. Angela Reiersen first hypothesized it might work for COVID and it is still not through the EBM process yet despite researchers working as fast as possible and spending millions of dollars on running the trials at multiple top institutions.
Today, India doesn’t have the luxury of time for EBM to work. Hospitals are so overloaded now that extremely sick people cannot get in. Waiting another year for definitive data is not a viable option.
It’s clear that it is time for India to forego the EBM-based recommendations and start considering all the evidence (including moderate and lower quality evidence as well as anecdotal evidence) in decision making. Then always select the option which is more likely to produce a superior outcome. This works particularly well with repurposed drugs which all have a known safety profile. If more than 75% of independent studies are positive and the safety profile of the drug is strong, doctors should be able to prescribe the drug without any fear of retribution.
To its credit, India has recently started to do this with the new AIIMS Interim Clinic Guidance for Management of COVID-19 which now explicitly allows the use of ivermectin only in high risk cases (but not fluvoxamine). This is a step in the right direction, but I do not believe that these new guidelines go far enough; they are simply not commensurate with the problem at hand.
Here are some ideas that I believe have the potential to drastically reduce the infection, hospitalization, death, and long-haul COVID rates.
Prevention is the most important thing right now. “An ounce of prevention is worth a pound of cure” and that is true in spades here since all your downstream systems are overloaded.
Short of mass vaccination, the next best scalable way to prevent people from getting COVID is ivermectin. There are 14 clinical trials that support this recommendation. Of course, if you find a drug with more trials and a bigger minimum effect size and better anecdotal data, you should use that drug instead.
People should take a dose of at least .1mg/kg once per week. It won’t prevent all COVID infections, but it should cut the number of COVID infections that need to be treated by a factor of at least 4.
The virus variant prevalent in India today is particularly aggressive and higher dosing may be needed so continuously monitoring patient outcomes is important. The enemy is not static and the treatment shouldn’t be either.
Post-infection early treatment
If someone gets infected with COVID, the most important thing is to remember what David Ho taught us about HIV: hit it fast and hard.
Check out www.c19early.com. Note that fluvoxamine and ivermectin are two widely available drugs that are extremely safe and have the greatest effect sizes.
Why not give both of these drugs together fast and hard? Is there a better option that is more effective?
“Fast” means you deploy these drugs as early as possible. In particular, this means do not wait for symptoms before treating. Viruses are always best treated early. There are no exceptions to this rule. A virus is like a fire. Would you wait until the entire house is on fire before you called the fire department? Of course not! Yet that’s effectively what you are doing if you wait for symptoms. Once you’ve lost your sense of smell or taste, it can be difficult to get it back.
Treating upon confirmation of infection goes against the intuition of doctors who normally want to delay treating patients until they have symptoms. That can be a fatal mistake for this virus.
“Hard” means going beyond standard dosing and treating with a combination of at least one antiviral and one anti-inflammatory.
The normal dose of ivermectin for COVID is .2mg/kg for 3 to 5 days. That’s not hard enough or long enough for the variant you have. Doctors have found that increasing the dose by up to 2X and treating for as long as there are symptoms (minimum 5 days). Ivermectin is safe at that dose and higher. Doctors have found that the later after infection you start treatment, the higher the dose and duration.
An effective dose for fluvoxamine for COVID is 50mg twice a day. Even with the variant you have, this dose has proven to be extremely effective and has a very low side effect profile (fewer than 3% of patients discontinue the drug due to side effects). But if it isn’t normalizing symptoms and lowering the CRP to normal in 5 days in patients, you can up the dose as tolerated, up to double that (i.e., 100mg BID). Fluvoxamine should be continued for 14 days to ensure there is no residual inflammation. Fluvoxamine has a very high safety profile: in the last 35 years, there have been just a couple of reported deaths due to drug overdose.
Amol Kothalkar is a cardiologist in Buldhana India that has been treating COVID patients with both ivermectin and fluvoxamine. He’s treated over 120 patients with ivermectin and fluvoxamine and only two patients had to be hospitalized for respiratory distress due to COVID (both presented late). His protocol is included below. He was so impressed with the improvements when he added fluvoxamine that he told me he thought it was unethical to not give patients the drug.
Other doctors in the US have added fluvoxamine 50mg BID to their ivermectin protocols and all have been uniformly pleased with the results in over 350 cases. I am not aware of any physician anywhere in the world who has tried the combination who has not been extremely pleased with the improvements in outcomes.
Another option is to adopt the FLCCC protocols for inpatient and outpatient treatment. These protocols have now been updated to include fluvoxamine.
Finally, if you treat people early enough, and hit the virus hard enough, you will likely be able to eliminate all long-haul COVID (aka PACS) cases. That will save everyone a lot of pain and suffering, perhaps for the rest of their lives. Early enough means within 4 days of symptoms.
If fluvoxamine is in short supply or becomes too costly, a viable substitute is to use 20mg of fluoxetine daily for 14 days. The mechanisms of action are identical between the drugs. The only reason the clinical trial used fluvoxamine is it had stronger sigma-1 activation than fluoxetine. However, the differences are relatively minor and the overall COVID hospitalization stats for people on either drug are comparable (fluoxetine actually has a slight advantage).
Inhaled budesonide has also shown to be beneficial for patients who develop respiratory symptoms.
Any outpatient (or inpatient) with sustained respiratory distress, rapid respiratory rate, or hypoxemia should be given 8mg TID of cyproheptadine, a low-cost anti-histamine. It has proven to be game-changing for inpatients and should work extremely well for outpatients who present late or fail initial treatment with fluvoxamine. The fluvoxamine should be continued; the cyproheptadine is complementary.
If the CDSCO is open minded, then getting EUA approval to use Interferon Lambda and/or proxalutamide would be completely game changing for early outpatient treatment. Both of these drugs are extremely safe and extremely effective and have excellent results in DB-RCT trials. Interferon lambda is a single subcutaneous injection, and proxalutamide is 14 pills. Both these drugs should be given as soon as possible after infection (i.e., in the ideal case before symptoms) for the best results.
Hospitalized patient treatment
Finally, there will always be patients who will decline and have to be admitted to the hospital.
One approach is to adopt the FLCCC protocols for hospitalized patients which has now been updated to include fluvoxamine.
There are also a number of methods that can be used to reduce their chance of death by 80% or more. One of these methods (inhaled adenosine) has remarkable effects in as little as 10 minutes. Another method, cyproheptadine, has been able to extricate patients from the ICU in as little as 48 hours.
The bad news is that few people know about these techniques.
I created a video and slide presentation describing each technique where the pioneers of each technique describe the technique and how to use it.
Rather than use all the methods described in that link, it would be best to start with the ones that are the simplest and easiest to deploy at scale: inhaled adenosine, cyproheptadine, fluvoxamine or fluoxetine, and cyclosporin. For example, cyproheptadine is very easy: 8mg TID until resolution of symptoms or discharge, whichever comes first.
Leronlimab is an excellent drug for hospitalized patients that reduces fatality risk by more than 85%. It is given just once a week for 4 weeks.
In addition, proxalutamide is also extremely effective for inpatients. But again, the CDSCO would need to immediately issue an EUA for these drugs.
Finally, it is important to keep innovating and try new drug combinations that have proven to be effective in smaller studies including the incorporation of inhaled budesonide, proxalutamide, etc.
India should make various treatment options available to patients, allow the patients to choose, and then centrally track the results and make them publicly available so that the public has the latest information on the most effective treatments.
The FLCCC protocols are widely adopted worldwide, including among doctors in India, and can serve as the baseline standard of care for outpatients and inpatients and physicians should be encouraged to offer newer treatments as options to patients.
In short, India should be executing a real-time adaptive mass clinical trial of treatment options as there is insufficient time to perform the large DB-RCT studies normally required.
Based on everything we know, the above suggestions should make a profound difference in the situation in India if they are widely adopted.
The list above is by no means exhaustive, but simply are the most obvious “low hanging fruit.”
One thing we do know is that doing the same thing over and over and expecting a different result is illogical.
Treating COVID as early as possible means fewer drugs, lower dosing, and better results. Catching COVID before symptoms and treating at that time is optimal. But even if the patient presents late, we have options.
As a world, our biggest challenge is no longer the virus. It is changing our thinking to adopt methods that are more likely to save lives than following the official protocols. The new AIIMS guidelines are a step in the right direction, but they simply aren’t not aggressive enough to mitigate the problem.
The group of doctors I work with who are experts on each of the drugs mentioned in this op-ed are happy to help educate doctors in India.
Amol Kothalkar’s outpatient protocol
Amol works at the Amrut Hrudayalaya and Superspeciality Hospital, Buldhana, India. He takes regular blood work on his patients and can see the effect of these drugs. Here is the protocol he uses to treat his patients. He’s treated over 120 patients with only 2 hospitalizations for patients who showed up very late. Note that this is a lower dose for ivermectin than recommended above.
1) Tab ivermectin 12 mg once a day for five days
2) Tab doxycycline 100 mg twice a day for 5 days
3) Tab Fluvoxamine 50 mg twice a day for fifteen day.
4) Tab sinarest twice a day for 5 days
5) vital D 3 sachet Or tablet 60,000 IU once a day for 4 days
6) Tab BECOSULES Z once a day for 15 days.
7) Tab Pan 40 once a day for 15 days
8) Budecort inhaler 2 puffs BD for five days.
9) Tab rivaroxaban 10 OD for 15 days, if D Dimer more than 1000 ng/ml.