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Effective medicines against Covid-19 from daily practice

Last updated on 17/05/2021

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Even after more than a year of experience with Covid-19 disease, there is often a general feeling of powerlessness due to the conviction that no drugs exist against this disease. Indeed, provisional approval of a novel vaccine is only permissible if there are no effective drugs on the market. However, there are many well-known molecules that have proven themselves in the daily practice of practising physicians and whose effectiveness against covid-19 has been demonstrated in numerous studies. Their risks and side effects are – in contrast to the provisionally approved vaccines – well known.

As long as they are not officially recognised as medicines against Covid-19, they are considered “off-label use”. This means that the doctor and patient use them without official authorisation. A well-known example of such off-label use is aspirin. This drug, officially approved as a painkiller, was discovered to have blood-thinning properties. Although aspirin was not originally “invented” for this purpose, it is often used for this “practical side effect”. There are many molecules that are successfully used in such an off-label use. 

Here is an overview of the effective drugs and the corresponding studies

IVERMECTIN

NIH (National Institute of Health): https://www.covid19treatmentguidelines.nih.gov/antiviral-therapy/ivermectin/

Since the last revision of this part of the official treatment guidelines, the results of several randomised trials and retrospective cohort studies on ivermectin use in patients with COVID-19 have been published in peer-reviewed journals or made available as manuscripts prior to peer review. 

Some clinical trials showed no benefit or worsening of disease after ivermectin use, while others reported shorter time to resolution of disease manifestations attributed to COVID-19, greater reduction in inflammatory marker levels, shorter time to viral clearance, or lower mortality rates in patients receiving ivermectin than in patients receiving comparator drugs or placebo.

As for the 4 “negative”, or inconclusive studies, these are:

  • A study in Bangladesh (72 patients), https://pubmed.ncbi.nlm.nih.gov/33278625/. Symptoms of fever, cough and sore throat were identical in the 3 groups, including the placebo control group, viral load decreased on day 5 in the ivermectin group. No side effects.
  • A Pakistani study (50 patients, 32 of whom were asymptomatic), https://www.ijsciences.com/pub/article/2378 Statistically, there was no significant difference between the case group that received ivermectin along with symptomatic treatment and the control group that received only symptomatic treatment without ivermectin and was asymptomatic on day 7 of follow-up.
  • A study in Bangladesh (116 patients) https://assets.researchsquare.com/files/rs-38896/v1/3ee350c3-9d3f-4253-85f9-1f17f3af9551.pdf. In two comparison groups, the ivermectin-doxycycline group performed slightly better than the hydroxychloroquine-azithromycin group.
  • A Peruvian study (retrospective analysis study of 5,683 patients in Peru, pre-printed and not peer-reviewed.) https://www.medrxiv.org/content/10.1101/2020.10.06.20208066v3. Result: no effect. Note: Studies that are not controlled by other scientists should not be used, especially not by the NIH.

Now to the positive studies

https://ivmmeta.com/

50 studies with 15,838 patients, 26 of which were RCTs (randomised controlled trials, the gold standard).

Result :

  • With early treatment: 81% efficacy
  • With late treatment: 46 % effectiveness
  • In prophylactic treatment (e.g. for other elderly people in homes): 88% effective.
  • Mortality: 74% Efficacy.

Vitamin D

Conseil supérieur de la Sante (Belgique) CCS 9620 : On page 9, the authors refer to a study by the University of Angers. The same group has started a randomised controlled trial comparing the effect on outcome of two doses of vitamin D (50,000 vs. 200,000 IU) administered at intake (https://clinicaltrials.gov/ct2/show/NCT04344041). The results are announced for May 2021.

Spanish study, 95 % effectiveness

https://www.sciencedirect.com/science/article/abs/pii/S0960076020302764?via%3Dihub

Of 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50%) p-value X2 Fischer test p

A study in a French nursing home

certifies an 89% reduction in mortality

https://www.sciencedirect.com/science/article/abs/pii/S096007602030296X

A retrospective British study

with approximately 1000 hospitalised Covid patients found an 80% reduction in mortality with high-dose vitamin D. https://www.mdpi.com/2072-6643/12/12/3799

Results: 70 studies can be found on vitamin D, of which 20 are treatment studies with 14,808 patients Result: 62% improvement in these 20 studies 69% improvement in the mortality studies (11 studies).

Hydroxychloroquine

There is often a lot of controversy about the drug hydroxychloroquine, but out of 232 studies, 177 show a very positive effect.

Factors that negatively influence the results:

  • The timing of the start of the treatment (the later you administer it, the less effective it is).
  • The countries doing the studies (USA and England show the most negative studies, the other countries almost no negative study)
  • The conflicts of interest (QR:1.15, IHU Marseille)

Regarding safety, here is a statement from the European Society of Cardiology: https://doi.org/10.1093/europace/euaa216 with the following conclusion:

HCQ administration is safe for short-term treatment of patients with COVID-19 infection, regardless of the clinical setting of administration, and causes only modest QTc prolongation and no directly attributable arrhythmic deaths 

https://doi.org/10.1093/europace/euaa216

One of the main reasons for the criticism of this drug (and the subsequent attempted character assassination of Prof. Dr. Didier Raoult), one of Europe’s leading virologists and infectiologists, was provided by the extremely negative study RECOVERY, which must be strongly rejected for the following reasons:

The authors used doses, at least at the beginning of the treatment (4 times the normal dose), which must definitely be classified as highly toxic! The normal dosage according to Prof. Dr. Raoult is 600 mg. With 2.4 gr in this recovery study, demonstrably toxic doses were administered. The estimated lethal dose for this drug is between 3-5 grams, depending on body weight!

At the IHU in Marseille, which remains THE reference centre in infectiology, the results are as follows:

(Use of HCQ + azithromycin + Zn directly at onset of symptoms):

Out of 8,439 patients (9/3/2021)

  • No mortality under 60 years
  • Mortality of 0.2% of 60-70 year olds (standard in France: 0.6%)
  • Mortality from 70-80 years: 0.2 % (norm 2.8 %)
  • Mortality 80-90: 3.2% (norm: 5.9%)
  • All-cause mortality reduced by 75% (P
  • IHU mortality 7/10000
  • World: (Worldometer) 270/10000

No side effects if contraindications and 2 ECGs (beginning and middle of treatment) are observed.

Treatment must be started early. If hospital doctors say it doesn’t help (or helps only a little) then that’s absolutely true, because you must administer these drugs beforehand, before you have to go to hospital.

Other medicines

Budesonid (inhalation corticosteroid)

https://www.medrxiv.org/content/10.1101/2021.02.04.21251134v1

Early administration of inhaled budesonide reduces the likelihood of needing acute medical care and shortens the time to recovery after COVID-19 infection treated early.

Bromohexin (Bisolvon)

https://bi.tbzmed.ac.ir/Article/bi-23240

Study result: A total of 78 patients with comparable demographic backgrounds and disease characteristics were included. There was a significant reduction in intensive care admissions (2 of 39 vs. 11 of 39, P = 0.006), intubation (1 of 39 vs. 9 of 39, P = 0.007) and death (0 vs. 5, P = 0.027) in the bromhexine-treated group compared with the standard group. No patient was excluded from the study due to adverse effects.

Carvedilol

https://doi.org/10.1371/journal.pbio.3000970

In this study, it was found that carvedilol use was significantly associated with a lower likelihood of a positive laboratory test result for SARS-CoV-2 (OR= 0.74,95% CI 0.56-0.97) after adjusting for age, sex, race, history of smoking and various disease comorbidities.

Famotidine :

https://www.gastrojournal.org/action/showPdf?pii=S0016-5085%2820%2934706-5

In the raw data analysis, the use of famotidine was significantly associated with a reduced risk of the combined outcome of death or intubation.

Aspirin: 

https://www.medrxiv.org/content/10.1101/2020.12.13.20248147v1

Among COVID-19-positive patients, prescribing aspirin before diagnosis was associated with a statistically and clinically significant decrease in all-cause mortality at 14 days (OR 0.38, 95% CI 0.32-0.46) and at 30 days (OR 0.38, 95% CI 0.33-0.45), reducing the mortality rate by more than half (62%). The results showed that aspirin prescription before diagnosis was strongly associated with a lower mortality rate.

Here is an overview of existing studies on natural products

Melatonin

https://doi.org/10.1371/journal.pbio.3000970

In this study, it was found that melatonin use was associated with a 28% reduction in the likelihood of a positive laboratory test result for SARS-CoV-2 (odds ratio [OR]= 0.72, 95% CI 0.56-0.91; Figure 8a).

doi: 10.1016/j.virusres.2020.198108. Epub 2020 Aug 5.

The potential of melatonin against viral infections including COVID-19: Current evidence and new insights.

If you search the ncbi database (official US database of scientific data), you will find 779 articles about melatonin essentially reducing the storm of inflammation in the second phase of the disease.

Zinc

https://doi.org/10.1101/2020.10.07.20208645

Study result: this study shows a correlation between serum zinc levels and COVID-19 outcome. Serum zinc levels below 50 µg/dl at admission correlated with worse clinical situation, longer time to reach stability and higher mortality. Our in vitro results indicate that low zinc levels favour viral spread in SARS-CoV2 infected cells.

Quercetin

DOI: 10.1128/JVI.78.20.11334-11339.2004

As an FDA-approved drug substance, quercetin offers great potential as a possible drug for the clinical treatment of SARS.

Dr. Martin König