Chloroquine and hydroxychloroquine in covid-19
BMJ 2020; 369 doi: https://doi.org/10.1136/bmj.m1432 (Published 08 April 2020) Cite this as: BMJ 2020;369:m1432Read our latest coverage of the coronavirus outbreak
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Dear Editor
I have never seen such a short-sighted medical response. Citing President Trump seems churlish - perhaps a more inquisitive mind would be asking "why" the President might have made these remarks.
The efficacy of HCQ on Coronaviruses generally has been known since c.2005.
In view of the claimed "essentially untreatable" nature of COVID19 - it would, in the absence of other treatments be a reasonable point of departure for any doctor seeking to try and save lives.
Moreover the anecdotal data and research, certainly as prophylactic and early stage treatment is highly promising:
https://www.sciencedirect.com/science/article/pii/S0924857920300996?via%...
Only this week, an new paper, published: 27 May 2020, in the American Journal of Epidemiology, by Harvey A Risch
https://doi.org/10.1093/aje/kwaa093 - Early Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key to the Pandemic Crisis -
urges that Hydroxychloroquine and azithromycin which have been used as standard-of-care in more than 300,000 older adults with multicomorbidities, with estimated proportion diagnosed with cardiac arrhythmias attributable to the medications 47/100,000 users, of which estimated mortality is <20%, 9/100,000 users, compared to the 10,000 Americans now dying each week. - need to be widely available and promoted immediately for physicians to prescribe.
Perhaps we should be listening rather more intently to President Trump - and perhaps we should be asking how he knows what he claims to know.
Competing interests: No competing interests
Mark T Sullivan1, Carl M Kirkpatrick2, Edward J Mills3, Craig R Rayner4
1. Medicines Development for Global Health, Melbourne, and University of New South Wales, Sydney Australia
2. Monash Institute of Pharmaceutical Sciences, Melbourne, Australia
3. Cytel Inc., Boston, Massachusetts, USA
4. Certara Inc., Princeton, New Jersey, USA
Dear Editor
The rapid response to this article from Professor Hoy(1) suggests that the evaluation of ivermectin as a potential therapeutic option for SARS-CoV-2 should be prioritised.
The pivotal question in the repurposing of a licensed therapy for a new disease is determining the well tolerated and effective dose. Rayner et al submitted a letter to the editor of Antiviral Research in response to Caly et al's paper on in vitro effects of ivermectin on SARS-CoV-2. In this, it was determined that the in vitro inhibitory concentration in 50% of Vero cells (IC50) was >9-fold and >21-fold higher than the day 3 human plasma and lung tissue maximum concentrations (Cmax), respectively, simulated using a high dose ivermectin regimen of 600 μg/kg dosed daily for 3 days. The same reference includes cautionary comments from the United States Food and Drug Administration and Dr François Noël on safety associated with high dose ivermectin (2) .
Our greatest risk in the urgency of the pandemic is to fill the gap between the data we have and what we want to achieve clinically with hope instead of evidence. With rare exceptions, scientific advancement requires iteration of learning through data generation. The fundamental principles of pharmaceutical medicine are, for compounds with promise, to identify an effective dose range through in vitro then in vivo models of the disease and pharmacokinetic/pharmacodynamic modelling before clinical evaluation(3). We still have only the most rudimentary data about ivermectin’s effect on SARS-CoV-2, achieved in vitro at biologically implausible concentrations. Until such time that new peer reviewed scientific evidence presents an alternate and credible argument for translating the in vitro pharmacology for patients, we should avoid exposing patients infected with SARS-CoV-2 to ivermectin.
Health claims database analyses and other real-world assessments should not be a substitute for establishing a sound scientific basis for translation to the clinic. Nor should such evidence be combined to argue for skipping key steps in the drug development process including dose finding and proof of concept. It is this type of decision making that has led to an inefficient clinical trials process with COVID-19 to date, as evidenced by 126 largely redundant trials with hydroxychloroquine, examined alone or in combination, involving approximately 180,000 participants(4,5).
Our desire to provide therapeutic options is understandable but we should guard against moving straight to the clinic because we have familiarity with the agent. Clinical trials should not be undertaken lightly (6). All interventions have risk and inconvenience for the participant and cost for society. Even randomised, controlled trials, our highest standard of evidence, rely on more than just the design to be meaningful - the arms of the study, the endpoints chosen, the presence or absence of blinding, the scope of safety data collected, which patient population included, clinical and statistical methodologies employed, amongst other factors, are critical factors for success.
Professor Hoy is right to suggest the use of existing tools to address an important medical issue. However, we must bring rational design to our work or else these good intentions will squander our opportunity for credible science and meaningful outcomes.
1. Ferner RE, Aronson JK. Chloroquine and Hydroxychloroquine in covid-19. BMJ. 2020 Apr 8;369:m1432. doi:10.1136/bmj.m1432
2. Bray M, Rayner CR, Noel F, Jans D, Wagstaff K. Ivermectin and COVID-19: A Report in Antiviral Research, Widespread Interest, an FDA Warning, Two Letters to the Editor and the Authors' Responses. Antiviral Res. 2020 Apr 21;178:104805. doi: 10.1016/j.antiviral.2020.104805)
3. Hartman D, Kern S, Brown F, Minton SK, Rayner CR. Time to step up: A call to action for the clinical and quantitative pharmacology community to accelerate therapeutics for COVID-19. Clin Transl Sci. 2020 May 22. doi: 10.1111/cts.12824
4. Thorlund K, Dron L, Park J, Hsu G, Forrest JI, Mills EJ. A real-time dashboard of clinical trials for COVID 19. Lancet Digit Health. 2020
5. https://www.covidpharmacology.com/clinical-trial-tracker/
6. World Medical Association. World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. JAMA. 2013;310(20):2191–2194. doi:10.1001/jama.2013.281053
Competing interests: No competing interests
Dear Editor
Clarification:
We regret any inference that the intended dose of Ivermectin in potential controlled trials of post-exposure prophylaxis for COVI-19 should try to emulate the high concentrations that were virocidal in the in-vitro studies. Our intent was to promote consideration of Ivermectin doses known to be easily and safely administered, such as used for scabies treatment or control. This was clearly stated in an earlier response we wrote on the same topic (https://www.bmj.com/content/369/bmj.m1432/rr-26). We hope that no harm has been done by misguided administrations caused by our communication.
Best regards
Competing interests: No competing interests
Dear Editor
Both Chloroquine and Hydroxychloroquine has been used intensively in India both for Malaria and Rheumatoid arthritis. [1][2][3] The dose used also is almost the same as proposed for Covid19 chemoprophylaxis and treatment. [4] The adverse effects of these drugs are not as common as depicted in the editorial. Especially in the context of Rheumatoid arthritis where patients are usually prescribed 200 mg twice daily for at least three months, the frequency of cardiac or ophthalmological adverse events are not alarming. [5] Even in malaria the National Vector Borne Disease Control Programme of India advocates a dose of 600mg (10mg/dl) stat chloroquine followed by a dose of 5mg/dl. [6]
Almost 140 doctors and 300 healthcare workers of our institution took Hydroxychloroquine as chemoprophylaxis for covid19 in the dose prescribed by Indian Council of Medical Research (ICMR ) [7]. In an yet unpublished study involving the same group of people most of them did not face any severe adverse effects with nausea and dizziness as the most common reported side effects.
It’s too early in the pandemic to rule out the effectivity of Chloroquine and Hydroxychloroquine in the treatment and chemoprophylaxis for covid19. Nevertheless the cardiac and ophthalmological adverse effect looms large on the population and even a single patient who suffers from these effects is a failure on our part to prevent it. Usually the ophthalmological adverse effects occur only after chronic intake of Chloroquine and Hydroxychloroquine. [8] Hence we advocate atleast a baseline ECG to rule out any cardiac conduction defects and baseline fundus examination to rule out preexisting maculopathy before prescribing Hydroxychloroquine to Covid19 patients or before taking Hydroxychloroquine as chemoprophylaxis for covid19. These simple measure should ensure the concern of the authors regarding the toxicities of Chloroquine and Hydroxychloroquine.
REFERENCES
1. Anvikar, A. R., Arora, U., Sonal, G. S., Mishra, N., Shahi, B., Savargaonkar, D., Kumar, N., Shah, N. K., & Valecha, N. (2014). Antimalarial drug policy in India: past, present & future. The Indian journal of medical research, 139(2), 205–215.
2. Guerin P J, Dhorda M, Ganguly N K, Sibley C H. Malaria control in India: A national perspective in a regional and global fight to eliminate malaria. J Vector Borne Dis 2019;56:41-45.
3. Misra R, Sharma BL, Gupta R, Pandya S, Agarwal S, Agarwal P et al. Indian Rheumatology Association consensus statement on the management of adults with rheumatoid arthritis. Indian Journal of Rheumatology 2008 November, Volume 3, Number 3 (Suppl); pp. S1–S16.
4. Gautret, P., Lagier, J. C., Parola, P., Hoang, V. T., Meddeb, L., Mailhe, M., Doudier, B., Courjon, J., Giordanengo, V., Vieira, V. E., Dupont, H. T., Honoré, S., Colson, P., Chabrière, E., La Scola, B., Rolain, J. M., Brouqui, P., & Raoult, D. (2020). Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. International journal of antimicrobial agents, 105949. Advance online publication. https://doi.org/10.1016/j.ijantimicag.2020.105949.
5. Modi JV, Patel KR, Patel ZM, Patel HR, Dhanani SS, Shah BH. Dose response relationship of hydroxychloroquine sulphate in the treatment of rheumatoid arthritis: a randomised control study. Int J Pharm Sci Res. 2017;8(2):856–858. doi: 10.13040/ijpsr.0975-8232.8(2).856-858.
6. https://nvbdcp.gov.in/WriteReadData/l892s/Guidelines%20for%20Diagnosis20... Last assessed on 13/05/2020 22.42hrs.
7. https://www.mohfw.gov.in/pdf/AdvisoryontheuseofHydroxychloroquinasprophy... Last assessed on 13/05/2020 22.45hrs.
8. Yusuf, I. H., Sharma, S., Luqmani, R., & Downes, S. M. (2017). Hydroxychloroquine retinopathy. Eye (London, England), 31(6), 828–845. https://doi.org/10.1038/eye.2016.298.
Competing interests: No competing interests
Dear Editor
A careful analysis of the alleged experimental proof for HCQ’s efficacy for SARS-CoV2 has led us to conclude that it lacks validity.
The widely adopted dosage, 400 mg daily, was derived from an in-vitro study with virus-infected Vero cells showing EC50 of 6.14 μmole/L at 24 hours, values impossible to achieve with 400 mg/day; as this dosing has been shown to produce peak plasma-levels of 1.22 μmole/L and 0.5 μmole/L in hour 24 hours, respectively. Free drug concentrations in plasma must be adjusted down by 40% for protein-binding, and interstitial concentration further reduced by rapid uptake of HCQ into cells. In contrast, HCQ concentrations of cell culture medium would hardly decrease despite drug uptake into cells, since fluid-volume of culture-medium is more than a million-fold greater than volume of cultured cells. Aided by computer simulation, the authors concluded that tissue HCQ concentrations would far exceed EC50 values, due to extensive drug accumulation in the lung.
However, extensive tissue-accumulation of HCQ is shown to occur in all organs and cells except red blood cells, most probably including the Vero cells; which are cultured African green monkey kidney cells used in the study, due mainly to extensive binding of HCQ to many cellular biochemicals such as DNA, phospholipids, and ganglioside. In theory, high HCQ concentrations in the lungs would impede, rather than aid, its antiviral effect, as these chemical binders of HCQ would compete for free drug; as what matters ultimately would be cytoplasmic free-drug concentration. Thus, if we were to trust the in vitro results, the 400 mg/day dosage would be grossly inadequate for COVID-19. Substantially higher HCQ doses have been used in 2 clinical studies; 1200 mg daily for 6 weeks and 1600 mg daily for one week. However, interpolating the pharmacokinetic data of 400 mg/day dose to higher doses suggests that even by quadrupling the dose, free HCQ concentrations of lung interstitial fluid would still be far less than EC50 of in-vitro studies.
In conclusion, evidence for effectiveness of HCQ against Covid-19 fails at the first stage of experimental proof, i.e. at the level of in-vitro studies.
1. Yao X, Ye F, Zhang M, et al. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis 2020.
2. Lim H-S, Im J-S, Cho J-Y, et al. Pharmacokinetics of hydroxychloroquine and its clinical implications in chemoprophylaxis against malaria caused by Plasmodium vivax. Antimicrob Agents Chemother 2009;53:1468-75.
3. Furst DE, Lindsley H, Baethge B, et al. Dose-loading with hydroxychloroquine improves the rate of response in early, active rheumatoid arthritis: a randomized, double-blind six-week trial with eighteen-week extension. Arthritis Rheum 1999;42:357-65.
4. Loudon JR. Hydroxychloroquine and postoperative thromboembolism after total hip replacement. The American Journal of Medicine 1988;85:57-61.
Competing interests: No competing interests
Dear Editor
Might I request Prof Ferner and Prof Aaronson to make clear that:
Chloroquin and hydroxychloroquin have different actions.
And Chloroquin is dangerous to those with 5 Hydroxydehydrogenase deficiency.
That both can cause retinal damage?
I ask the professors, because I may have got wrong end of the stick. Also, I trust the doctors treating patients in India, Pakistan and the Mediterranean as well as Arab countries may pay attention them.
Thank you.
Competing interests: Old chap
Dear Editor,
As of 8th May , a total of 37,916 (thirty seven thousand nine hundred and sixteen ) active Covid 19 cases are present in the country along with a casualty score of over one thousand patients as per the Ministry of Health and Family Welfare, Government of India website ( https://www.mohfw.gov.in/ last accessed on 8th May, 2020). The Indian government has taken many proactive steps to halt the rapid spread of the pandemic in this nation of 1.3 billion people. Measures include implementation of a 40 days complete lockdown of all academic and commercial activities in the country and restricting citizens to their home. (https://www.bbc.com/news/world-asia-india-52277096). One of the other measures taken by the Indian Council of Medical Research (ICMR), the premier Medical Research body in India which has been the guiding force of the management of Covid 19 pandemic is to issue an advisory on the prophylactic use of Hydroxychloroquine (HCQ) for preventing Covid 19 infections. (https://www.mohfw.gov.in/pdf/AdvisoryontheuseofHydroxychloroquinasprophy...).
India is the first country to recommend the usage of HCQ as a chemoprophylaxis in Covid 19. As per the advisory, tablet hydroxychloroquine (HCQ) can be given to “high risk population” to prevent the disease occurrence in asymptomatic healthcare workers taking care of suspected or confirmed Covid 19 cases. A dose of 400 mg Twice daily for day 1 followed by 400 mg once weekly for next 7 weeks has to be taken by these healthcare workers. The second group which can receive HCQ are the asymptomatic household contacts of laboratory confirmed cases. The household contacts are advised to take 400 mg of HCQ twice on day 1 followed by 400 mg weekly for next 3 weeks. ICMR has recommended that this chemoprophylaxis is contraindicated in any children below 15 years of age and in persons with history of retinopathy or with known hypersensitivity of HCQ.
HCQ is an old drug used primarily for the treatment of malaria and in other chronic inflammatory conditions like Rheumatoid arthritis and Systemic lupus erythematosus (SLE). In an in vitro pre-clinical study by Yao et al. (https://doi.org/10.1093/cid/ciaa237), HCQ has exhibited better activity than Chloroquine (CQ) against anti-SARS-CoV-2 in Vero cells derived from the African green monkey kidney. Some of the clinical trials reported from China and France have inferred that HCQ usage alone or in combination with Azithromycin has been associated with improvement of virological clearance and improvement of clinical symptoms in Covid19 patients (https://doi.org/10.1016/j.ijantimicag.2020.105949).
The ICMR advisory was based on the efficacy found in laboratory and in-vivo studies. Following the advisory there was a rush among the common mass to buy this medication resulting in scarcity of drug availability in some parts of the country (https://timesofindia.indiatimes.com/city/kolkata/not-for-public-but-key-...). However, with timely Government intervention the indiscriminate sale was stopped and situation was brought under control.
As a patient safety professional, the question which comes to my mind is, “Is this data sufficient enough to safely recommend chemoprophylaxis to large number of “high risk” Indians?” We probably need to more evidence for answer this critical question. A systematic review found that although pre-clinical results with HCQ are promising, there is a dearth of evidence to support the clinical efficacy of HCQ in preventing COVID-19. (https://doi.org/10.1111/1756-185X.13842). One of the major limitations of this review was that it did not include any prospectively designed study as none were available. Recently, ICMR has approved the first observational study to analyze the effectiveness of HCQ prophylaxis in 10,000 (ten thousand) Indian healthcare workers. (https://www.livemint.com/news/india/covid-max-hospital-group-to-study-us...)
Another issue is about the safety aspect of HCQ. According to this editorial (https://doi.org/10.1136/bmj.m1432) “no drug is guaranteed to be safe, and wide use of hydroxychloroquine will expose some patients to rare but potentially fatal harms”. Serious adverse effects include retinopathy, chronic cardiomyopathy and carcinogenic potential (https://www.medicines.org.uk/emc/product/1764/smpc). However, these toxicities have been witnessed with long term usage of HCQ. It is very difficult to predict what kind of toxicities would be experienced at the dosage recommended for short term prophylaxis for Covid 19 and to understand it better, a premier Government Medical college and research institution in Kolkata, India has initiated a Covid 19 chemoprophylaxis registry for healthcare personnel. (http://www.ipgmer.gov.in/chemoprophylaxis.php).
Recently, the Indian government has revised the management strategy of Covid 19 positive cases in lieu of increase demand of hospital beds and has allowed the domiciliary management of patients with mild to moderate symptoms. (https://www.mohfw.gov.in/pdf/GuidelinesforHomeIsolationofverymildpresymp...). These patients need to be with a caregiver who must be on HCQ prophylaxis. This is a welcome step which would help to optimize the utilization of beds for moderate to sick Covid 19 patients. It would be interesting to note if HCQ reduces the viral transmission amongst the caregivers of these domiciliary Covid 19 patients as this step would be the game changer in Covid numbers in the country. Results from the pharmacovigilance registry and the large observational study would yield real time evidence for prophylaxis use of HCQ in the long run not only for India but for the rest of the world.
Competing interests: No competing interests
Dear Editor:
In their review on the use of chloroquine and hydroxychloroquine in COVID-19, Ferner and Aronson (1) elegantly address the matter of these repurposed drugs which have a known risk of QTc prolongation. This risk is potentially compounded by the adjunctive agent azithromycin and the antivirals lopinavir/ritonavir, all having an association with torsades de pointes (2).
Consideration must be given to additional QTc-prolonging factors prior to the prescription of these COVID-19 treatments, such as underlying congenital long QT syndrome, concomitant drugs known to prolong the QTc, electrolyte abnormalities and underlying cardiac disease (2,3). QTc prolongation and arrhythmogenic potential is further enhanced by a viral-induced high-grade systemic inflammatory state, associated with acute myocardial injury, cytokine-driven modulation of cardiomyocyte ion channels and cardiac sympathetic hyperactivation (3).
The recommendation of baseline electrocardiography (ECG) to interrogate the QTc before and after the commencement of chloroquine and hydroxychloroquine is essential, due to their hERG potassium channel blocking capabilities and potentially fatal arrhythmogenic consequences (1,2). In general, ECG surveillance for QTc-prolonging medications should occur when the drug has reached steady-state. However, due to the long half-lives of these two agents (20 to 60 days and 22 days for hydroxychloroquine and chloroquine respectively) and steady-state concentrations not being achieved for 3 to 4 months, it should be noted that QTc prolongation can occur at any time during the treatment period (4,5). Torsades de pointes has been reported in patients who have been taking hydroxychloroquine on a chronic basis (6). Despite the usual course of these medications being approximately 10 days for COVID-19 purposes, such long half-lives mean these patients are likely to require ongoing QTc monitoring after course completion.
Thus, a single ECG performed early in the treatment course cannot exclude the risk of QTc prolongation later on. Guidance on the frequency of ECG monitoring is provided on the basis of an individual’s risk stratification, understanding that the safety of healthcare workers is paramount, and clinicians may need to rely on telemetry or mobile devices to limit contact with patients and preserve personal protective equipment (2).
As the pandemic continues and these drugs are prescribed “off-label” as treatment or as prophylaxis, correct QTc interpretation is a fundamental clinical skill for all physicians to minimise morbidity and mortality caused by ventricular arrhythmias. This requirement introduces an important challenge, given the inaccuracies of automated QTc measurement on ECG and correct identification of QTc prolongation having reported rates of below 50% for cardiologists and 40% for other physicians (7,8).
We recommend the following practical measures to enhance QTc assessment (7):
• Select ECG lead II or V5, or if they are unsuitable, the lead with the most clearly-defined consistent T wave.
• Use the tangent method to manually determine the true end of the T wave, delineated by the point where the tangent of the distal slope of the T wave intersects the isoelectric line.
• Correct for heart rate using an appropriately selected formula. The Bazett and Fridericia formulae, while commonly used, are unreliable in tachycardic patients (i.e. HR > 70 bpm, which is likely in septic or unwell patients). We would recommend the Framingham or Hodges formula in this instance.
• For a broad QRS (>120 ms), the modified Bogossian formula or the wide QRS complex-adjusted QTc formula: QTc – [QRS – 120 ms] (2) may be applied.
• The “half R-R interval” can be useful for screening in the presence of atrial fibrillation, followed then by averaging over five consecutive beats.
Continuous cardiac monitoring should be commenced if the QTc is found to be >500 ms or ΔQTc of >60 ms, with a review for reversible causes and consideration of therapy cessation if appropriate (2,7). In closing, consistent, replicable QTc measurements will be vital for patient safety while the efficacy of these drugs remains to be elucidated.
REFERENCES
1. Ferner RE, Aronson JK. Chloroquine and hydroxychloroquine in covid-19: Use of these drugs is premature and potentially harmful. BMJ 2020;369:m1432 doi: 10.1136/bmj.m1432
2. Giudicessi JR, Noseworthy PA, Friedman PA, Ackerman MJ. Urgent guidance for navigating and circumventing the QTc prolonging and torsadogenic potential of possible pharmacotherapies for COVID-19. Mayo Clin Proc 2020. doi: https://doi.org/10.1016/j.mayocp.2020.03.024
3. Lazzerini PE, Boutjdir M, Capecchi PL. COVID-19, arrhythmic risk and inflammation: Mind the gap! Circulation 2020. doi: https://doi.org/10.1161/CIRCULATIONAHA.120.047293
4. Pastick KA, Okafor EC, Wang F, et al. Review: Hydroxychloroquine and chloroquine for treatment of SARS-CoV-2 (COVID-19). Open Forum Infect Dis 2020;7(4). doi: https://doi.org/10.1093/ofid/ofaa130
5. Tett S, Cutler D, Day R. Antimalarials in rheumatic diseases. Balliere’s Clinical Rheumatology 1990;4(3):467-489. doi: https://doi.org/10.1016/S0950-3579(05)80004-4
6. O’Laughlin JP, Mehta PH, Wong BC. Life threatening severe QTc prolongation in patient with systemic lupus erythematous due to hydroxychloroquine. Case Rep Cardiol 2016;2016:4626279. doi:10.1155/2016/4626279
7. Indraratna P, Tardo D, Delves M, Szirt R, Ng B. Measurement and management of QT interval prolongation for general physicians. J Gen Intern Med 2019;35(3):865-873. doi: https://doi.org/10.1007/s11606-019-05477-7
8. Viskin S, Rosovski U, Sands AJ, et al. Inaccurate electrocardiographic interpretation of long QT: the majority of physicians cannot recognize a long QT when they see one. Heart Rhythm 2005;2:569-574. doi: 10.1016/j.hrthm.2005.02.011
Competing interests: No competing interests
Dear Editor,
I am extremely troubled by the contamination of politics into the arena of science in general and medicine specifically. Everyone of us should be. COVID-19 has challenged the world by its rapid ascent to pandemic status, initial and to this date unknown mortality risk and severe global economic impact. Naturally, world scientists and political leaders are scrambling to reverse its deleterious course, rapid and widespread as it has been. Time stress often does not bring out the best in us. Methodical and slow, careful study designs and evaluation of methodology is ideal, but not affordable with this epidemic. People are dying quickly.
Sadly, and I believe I am not the only physician in this camp who tries to analyze and make use of medical research, I am left uncertain as to the study analyses and expert opinions regarding treatment options for COVID-19. Many commentaries reek political bias. Front and center are the strong political opinions from the world of the president of the United States, Donald Trump. Three years of multi-pronged attempts to oust him from office provides the backdrop for suspicion that anything he may opine or support initiates frantic attempts by his detractors to refute, often at all costs.
Which brings us to this article and the potential benefits of hydroxychloroquine. I emphasize that I do not know the heart, political tilt or intention of this author but the point is suspicion of political bias cannot be helped. Trump is mentioned specifically. My criticism is this: reference to the dangers of hydroxychloroquine. The two references mentioned, ventricular arrhythmias and hepatic failure are so weak that this article in general cannot be taken seriously. Corrected QT prolongation isn’t always a straightforward measurement and besides, the point of assessing this measurement when using drugs known to prolong it is to discontinue the medication to avoid arrhythmia development. This is standard fare and increases the safe use of such drugs when monitored.
Regarding the reference to hepatic toxicity...I’m shocked such a reference is even mentioned. Even the reference states that severe hepatic toxicity hasn’t been reported in its widespread use since 1963.
The conclusion: I am left suspicious that the author is grasping desperately to suggest that proponents of hydroxychloroquine are being reckless and creates yet another criticism of Mr Trump. For those of us personally and our patients particularly who fall prey to rapidly worsening symptoms from COVID-19, an illness thus far without a definitive cure, denying any reasonable attempt at today’s “possible “ treatment modalities that statistically are clearly low risk is, in my opinion, reckless and irresponsible. Ask yourself this question, posed to you on this date, May 2, 2020: if you were COVID-19 positive, febrile and developing worsening dispensa or already hypoxia, would you consent to therapy with hydroxychloroquine, remdesivir, neither or both?
Competing interests: No competing interests
Re: Chloroquine and hydroxychloroquine in covid-19
Dear Editor
Readers my be interested in what has taken place with ivermectin over the year since this article.
Researcher Mika Turkia has compiled a timeline.
See
https://doi.org/10.13140/RG.2.2.13705.36966
Geoff Taylor
Wendy E. Hoy
Competing interests: No competing interests