Govt of India had released advisory regarding the chemoprophylaxis of HCW involved in treatemnt of COVID-19 positive patients with HCQ. Hydroxychloroquine and chloroquine drugs have in-vitro activity against SARS-CoV, One small study reported that hydroxychloroquine alone or in combination with azithromycin reduced detection of SARS-CoV-2 RNA in upper respiratory tract specimens compared with a non-randomized control group but did not assess clinical benefit.

Both CQ and HCQ are weak bases that are known to elevate the pH of acidic intracellular organelles, such as endosomes/lysosomes, essential for membrane fusion. In addition, CQ could inhibit SARS-CoV entry through changing the glycosylation of ACE2 receptor and spike protein. Time-of-addition experiment confirmed that HCQ effectively inhibited the entry step, as well as the post-entry stages of SARS-CoV- .

Thanks Malangori Parande for your valuable comments.

The available study o HCQ and azithromycin from France can be criticized in many aspects, but clinical trials on HCQ are now ongoing.

Thanks Christian G Meyer for your useful contribution.

Article Acquired Long QT Syndrome: A Review of the Literature

This review discussed the points I outline below.

Several medications that have been recommended for the treatment of Covid-19 are associated with prolongation of the QTc interval and therefore torsade de pointes and sudden cardiac death.

The Italian National Institute for Infectious Diseases recommends treatment with hydroxychloroquine in combination with another antiviral agent. Hydroxychloroquine is affordable, widely available and there is well established data on the safety profiles. The evidence of the potential benefit of chloroquine and hydroxychloroquine in the treatment of Covid-19 is increasing.

Other medications which may be used in this cohort include the macrolide antibiotics (e.g. azithromycin). These can also prolong the QTc interval.

Administering several medications that may prolong the QT interval is associated with a high risk of complications.

In medicine risks and benefits must be balanced. Safety netting is important whenever there is a great potential benefit but also a very significant risk. In that context QTc intervals, renal and liver function must be monitored closely in patients treated with chloroquine and or macrolides. They should probably not be started if the baseline QTc is more than 450 ms. It should probably be stopped if the QTc increases 25% above baseline. It should definitely be stopped if QTc is above 500 ms. This is an evolving situation and recommendations may change as the potential risks and benefits become clearer.

Beta-blockade is used in the treatment of congenital and acquired long QT syndrome, so may be beneficial in this setting.

Thanks RajKumar Rajendram for your comments and valued information that you shared especially in this COVID-19 situation when there is a definite trend of prescribing HCQ/CQ and Azithromycin in the treatment of Novel coronavirus infected patient.

In an open-label study of 36 patients with COVID-19, use of hydroxychloroquine (200 mg three times per day for 10 days) was associated with a higher rate of undetectable SARS-CoV-2 RNA on nasopharyngeal specimens at day 6 compared with no specific treatment (70 versus 12.5 percent) . In this study, the use of azithromycin in combination with hydroxychloroquine appeared to have additional benefit, but there are methodologic concerns about the control groups for the study, and the biologic basis for using azithromycin in this setting is unclear.

Here is the link of the study.

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

Thanks, Farzaneh Sadeghi for your valued addition to the discussion.

Please see this article when considering treatment for Covid-19

Ventricular Arrhythmia Risk Due to Hydroxychloroquine-Azithromycin Treatment For COVID-19

https://www.acc.org/latest-in-cardiology/articles/2020/03/27/14/00/ventricular-arrhythmia-risk-due-to-hydroxychloroquine-azithromycin-treatment-for-covid-19

Criticisms on the French study could include the usage of a control group to emphasize the difference between the treated and untreated. However, electrocardiograms were used to exclude participants from treatment concerning their risk to the therapeutics, based on their QT interval. The cycle threshold value was set at >34 to be virally cured, I am not completely sure if that is a standardized value. The study also terminates with a number of cases that are still under oxygenation, that leaves room for doubt. The study is also non-randomized, what is often not preferred but possibly more achievable than a controlled study given current conditions. However, the study also includes many cases with underlying chronic conditions, who typically have a significantly higher mortality rate. Azithromycin was utilized to avoid early stage infections before they progress to an irreversible condition. Finally, some may have wanted a test statistic to generate a probability value comparing hydroxychloroquine against hydroxychloroquine in combination with azithromycin.

Thanks Sarah Joseph for your worthy addition to the discussion.

No Evidence of Rapid Antiviral Clearance or Clinical Benefit with the Combination of Hydroxychloroquine and Azithromycin in Patients with Severe COVID-19 Infection

Jean Michel Molina et al.

PII: S0399-077X(20)30085-8

DOI: https://doi.org/doi:10.1016/j.medmal.2020.03.006

Reference: MEDMAL 4279

To appear in: Médecine et Maladies Infectieuses

Received Date: 28 March 2020

Thanks Christian G Meyer for very important information at this COVID-19 situation when there is a trend of prescribing Hydroxychloroquine and Azithromycin in severe SARS-CoV2 infection. This will certainly help to prevent the misuse of these drugs.

When considering the benefit of Hydroxychloroquine to the fight against SARS-CoV2, one should be thus familiar with this paper, from 2005, by the CDC:

Article Chloroquine is a potent inhibitor of SARS coronavirus infect...

I wish one day scientists would be able to prove the efficacy of Chloroquine/ Hydroxychloroquine against coronavirus in human beings.

Observational study of Hydroxychloroquine in Hospitalized Patients with Covid-19 results do not support the use of hydroxychloroquine at present, outside randomized clinical trials testing its efficacy.

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2012410?query=RP

The Chinese "Handbook of COVID-19 prevention and treatment" has their national protocol.

Thanks Sarah Joseph for valued information.

Zinc likely affects activity of HCQ+AZM. To see if there's real, useful effect as either treatment or prophylaxys, Zinc needs to be included (w/o Zn results so far are ambiguous at best). Ideally, any study should measure Zn status at baseline.

The EVMS protocol includes Zn & quercetin (which acts as a Zn++ ionophore) along with other measures including methylprednisolone was claimed (in testimony to US Senate by Pierre Kory) to reduce ICU mortality to ~2%.

https://www.evms.edu/media/evms_public/departments/internal_medicine/EVMS_Critical_Care_COVID-19_Protocol.pdf

Thanks Amelia Carolina Sparavigna for the important links you shared.

Yes, hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin. Ref: Article Hydroxychloroquine and azithromycin as a treatment of COVID-...

Again these findings are reverse: Among patients hospitalized in metropolitan New York with COVID-19, treatment with hydroxychloroquine, azithromycin, or both, compared with neither treatment, was not significantly associated with differences in in-hospital mortality. Ref: Article Association of Treatment With Hydroxychloroquine or Azithrom...

Thanks Amelia Carolina Sparavigna for your interest in the topic and the important link you shared.

These are some of the treatment protocols collected, not everyone is using HCQ + AZM.

Please have a look..

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

Thanks Amelia Carolina Sparavigna, Sarah Joseph, Talha Bin Emran for useful links you shared. These would definitely enrich me in this field.

Both are used from the very beginning here like a blind therapy. Now Remdesivir got approval in many countries.

Thanks Muhammed Ashraful Alam for your interest in the topic and your valued addition to the discussion. Yes, Remdesivir has been authorized for emergency use in the US, India, Singapore, and approved for use in Japan for people with COVID-19 severe symptoms. It also received approval in the UK in May 2020. It may shorten the time it takes to recover from the infection.

Ref: https://en.wikipedia.org/wiki/Remdesivir