Well, the FDA warning that cautioned against the use of chloroquine or hydroxychloroquine for COVID-19 outside the setting of a hospital:

https://www.covid19treatmentguidelines.nih.gov/whats-new/

and,

All-trans retinoic acid (ATRA) is administered orally and is generally well tolerated but can induce a severe, life-threatening complication called differentiation syndrome, which includes breathing difficulties and fever.

https://www.cochrane.org/CD011960/HAEMATOL_treatment-all-trans-retinoic-acid-addition-chemotherapy-adult-patients-acute-myeloid-leukaemia-non

Then, how can these drugs be used safely at home settings to prevent SARS-CoV-2 infection?!

Yes @Md Rabiul Alam They can not be use outside the hospital

The purpose of this therapy is to reduce susceptibility of target cells to SARS-CoV-2 that causes COVID-19 through altering 3D genome architecture in the target cells. CQ/HCQ can alter 3D genome architecture by intercalating into double-stranded DNA and binding to Pfcrmp. ATRA 's effects on cell differentiation is also associated with alteration of 3D genome architecture, which will augments HCQ's effects on alteration of 3D genome architecture. The altered 3D genome architecture could cause gene expression pattern change, resulting in cellular function change, and thus the susceptibility of target cells to SARS-CoV-2 could be reduced. Since both HCQ and ATRA are administered by inhalation, the drug doses could be greatly reduced. So, there will be no big safety problems.

Many Covid-19 patients have thromboembolic complications increasing in-hospital mortality.

Published - RG:

“Can we manage prophylactic therapy in Covid-19 patients to prevent severe illness complications?”

Authors propose a change in the CHADS-VASC score, including one point for Covid-19 at the score, and, thus, indicates the necessity of prophylaxis of anticoagulant therapy to prevent Covid-19 severe illness complications. Others advantages: to prevent the patient worsening due to thromboembolic problems, as well as the need for ICU, mechanical ventilation and to reduce mortality rate .

There have not been good quality studies on the role of Chloroquine or hydroxychloroquine for the prevention of COVID-19. However, the available data in the management of COVID-19 did not show any improvement in morbidity or mortality but an increased risk of prolonged QT-syndrome when hydroxychloroquine was given either alone or in combination with Azithromycin.

Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State

https://jamanetwork.com/journals/jama/fullarticle/2766117

Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19

https://www.nejm.org/doi/full/10.1056/NEJMoa2012410

Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19).

https://www.ncbi.nlm.nih.gov/pubmed/32356863

Chloroquine (CQ)/HCQ has genotoxicity that is a double-edged sword, on one hand, it causes harm to human cells, on the other hand it plays an important role in antivirus because it can change cellular susceptibility to virus through altering genome structure which causes gene expression pattern change. This is why CQ/HCQ can exert its antiviral effects on all viral infections. Therefore, to reduce CQ/HCQ's genotoxicity, a low-dose CQ/HCQ must be used; to augment low-dose CQ/HCQ's antiviral activities, another less genotoxic agent, such as ATRA, should be used with CQ/HCQ together. To further reduce the drug toxicity, local drug administration is necessary, this is why HCQ-ATRA inhaler is proposed. In a word, CQ/HCQ alone (no matter they are used at a low dose or a high dose) will not help COVID-19 patients a lot. They must be used together with other genotoxic agent.

Using a drug with known side effects and unknown prophylactic effect; by a novel route with unproven bioavailability; to prevent a mild infection; is not justified in accordance of risk benefit ratio

I think that a preliminary eye examination is desirable before taking these drugs.

According to a Lancet paper, there is no evidence on the efficiency of hydroxychloroquine (HCQ) against COVID-19.

https://www.facebook.com/TheLancetMedicalJournal/photos/a.410370953469/10158745332848470/?type=3&theater

Using CQ/HCQ alone will not work well in treatment of covid-19, this is what we have expected. To prevent and treat COVID-19, CQ/ HCQ should be used together with another genotoxic agent, such as ATRA.

That’s a good question. Thanks!!

About prophylaxis to protect against thromboembolic events ?

Can we manage prophylactic therapy in COVID-19 patients to prevent severe illness complications?-RG

Many patients with COVID-19 have thromboembolic complications that worsen their prognosis. Herein, the authors propose a modified version of the CHA 2 DS 2-VASc score, including 1 point for COVID-19, so that prophylaxis to protect against thromboembolic events would be indicated before the condition becomes severe. The advantages of this modification would be prevention of the patient' s condition worsening due to thromboembolic problems and reduction of the likelihood of a need for intensive care and mechanical ventilation, reducing mortality.

Despite its small sample size our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.

Article Hydroxychloroquine and azithromycin as a treatment of COVID-...

We should take any oppurtinity to face Covid and try any drug to keep hope of healing. We should also think deep in malariamedecine and vaccins, it seems to be good

This is a high rise question now a days.

In some study it shows that HCQ has a good impact on patients where others show some abnormal heart bits rate amongs the patients. However WHO currently requested everyone not to use them.

I wish you find your answer

It is unfortunate that the WHO has stopped the proper randomized clinical trials, despite Mehra’s suggestion, “Randomised clinical trials will be required before any conclusion can be reached regarding benefit or harm of these agents in COVID-19 patients.” By stopping the required randomized clinical trials, WHO has done a great disservice to the world.

I think it is becoming clear that these drugs should not be used for TREATMENT. I think it remains unclear whether they can be used for prevention. The latter is being tested now.

Where is the rationale for using the combination of HCQ/ATRA coming from? I presume there is some in vitro and maybe in vivo data published already?

No one has carried out experiment for testing this combination, but I think using 1/3 to 1/2 of normal daily dose of each drug through oral route (could be named as low-dose therapy dose) will be enough. If the drugs are administered via inhaler, the daily dose could be reduced to around 1/100 of the low-dose therapy dose. Since both drugs are already used in clinical practice, trying different dose combitions to treat COVID-19 pateint by doctors should be no big problem.

Hydroxychloroquine is of no benefit against Covid-19

A just-published article shows no advantage of HC for preventing infection.

This case report [1] has supported my hypothesis that to treat COVID-19, chloroquine or hydroxychloroquine should be used together with other genotoxic medicine. Clarithromycin, like ATRA, has genotoxicity [2] , which might augment chloroquine's effects on altering 3D genome structures in the target cells and immune cells and thus reduce the cell's susceptibility to virus and modulate the immune cell's response to coronavirus infection.

.

[1]https://www.researchgate.net/publication/340887454_Successful_recovery_of_COVID-19_pneumonia_in_a_patient_from_Colombia_after_receiving_chloroquine_and_clarithromycin

[2] https://doi.org/10.1508/cytologia.71.5

HCQ no benefit.... and harmful for some.

The only remaining rational was as HCQ a zinc ionophore, for pre-exposure prophylaxis, but quercetin is better and safer for this.

If you're desperate to prescribe something, consider dexamethazone, anticoagulants (carefully) and ivermectin:

https://www.news-medical.net/news/20200427/Ivermectin-alone-not-useful-in-treating-COVID-19.aspx

https://www.newsmax.com/us/ivermectin-covid/2020/06/09/id/971417/

We desperately need larger RCT closed lable study results.

To be honest, if I was admitted needing oxygen, I would accept dexamethazone and ivermectin and anti-coagulants, from a skilled and cautious clinician.

But I would be very wary of any clinician who just proposes anything that "might be helpful" and jacks up the dose without thinking about downsides, and we are seeing that far too much.

I would not accept HCQ, random antibiotics and immune suppressants or morphine or benzos or whatever branded mystery drugs someone thinks "might help" without checking contraindications, trial results or interactions.

Even ibuprofen may be problematic, though this is disputed. Here's a good summary:

https://www.reuters.com/article/uk-factcheck-medication-fever-coronaviru/false-claim-avoid-medications-to-lower-fever-if-sick-with-covid-19-idUSKCN21W259

Anyway, that's enough rationale for me to prefer to play safe and use no analgesic or paracetamol only, especially in early stages.

Administering an anti-viral medication via an inhaler to concentrate on the respiratory epithelium cells is a preferred way for the early prevention of COVID-19, as pointed out months ago in

Preprint Stop COVID-19 with Air Spray of a Hypochlorite Solution

Inhalers are widely utilized in Germany, which could explain why the COVID is now well controlled there.

All use of HCQ should strictly be in RCT as there is no benefit of the drug yet and the drug is being used indiscriminately.

Article Hydroxychloroquine prophylaxis for COVID-19 contacts in India

HCQ should not be used by everyone. This drug is only given to the patients who are in serious condition, as HCQ drug has more harmful side effects.

Why is ‘more harmful’ side effects being aired all the time as a reason not to use HCQ? I am stating it helps, but I know of front line Doctors in India who have been taking ‘prophylactic’ dose like in malaria, without problem. Is there a reason that because no one is going to make lots of money in some quarters that it has been rejected? Only asking, I am not in any camp!

Thanks Reza

Ellen S Vitetta, Rajkumar Rajendram, A. Ray Taylor, Pranav Ish - The major publication asserting that HCQ provides no benefit and is more harmful, which directly resulted in the early termination of many clinical studies, was retracted from The Lancet when they could not furnish any of the data supporting their claims (https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31180-6/fulltext).

The first major peer-reviewed study of HCQ that I've seen demonstrated significant efficacy with early administration (https://www.ijidonline.com/article/S1201-9712(20)30534-8/fulltext).

Could you provide me with any peer-reviewed publications, of comparable scientific rigor, which support the claim that HCQ is not an effective treatment for S.CoV2?

Yes the Lancet paper was retracted after I commented so I must take a step back and reserve judgement.

I now look forward to seeing more well done rigorous studies that support its use ( or not) in different settings (and combos ) AND WITH ALL THE DATA!!

This is a complex disease and things are moving a bit too quickly.... at least for me.

Although there is still no recognized vaccine or drug that can prevent infection, there are a lot of antiviral drugs and excipients (currently available) that have re-profiling potential:

Article A Panel of Broad-Spectrum Antivirals in Topical Ophthalmic M...

We can, however, hydroxychloroquine can increase the risk of arrhythmia, which can be dangerous.

Taking an entirely different direction in perspective, we know that some individuals are asymptomatic or with mild symptoms and that the cytokine storm causing hyper-inflammatory immunology is associated with mast cell activation and expression of inflammatory factors such as histamine. Dengue fever has similar aspects in immunology that can me reduced with antihistamines. Also, the use of dexamethasone for patients with severe symptoms indicates that some early therapy would be advantageous.

Surely advising patients, who test positive for COVID 19, should be advised to take H1 antihistamines that are readily and tolerated as ‘off the shelf’ drugs.

There is theoretical evidence to this concept but no trial data, apart from a small French trial that proved highly effective.

As most patients who have symptoms or test positive do not see a GP but are encouraged to phone 111 or ask for an ambulance with breathing difficulties, how can patients be advised to trial this? Like the public information about vitamin D, should everyone be advised to try taking antihistamine when symptomatic to COVID 19?

As did dexamethasone, in the third of severely affected patients, the concept of prescribing antihistamines to stem the effect of histamine at an early stage, possibly inhibiting the alveolar inflammation and hypoxia, may be highly simplistic but may also reduce some severe symptoms and reduce hospital intake.

How can we test this?