Hydroxychloroquine (upper left), chloroquine (lower left), and risk-reward scale. [Credit: Nancy R. Gough, BioSerendipity, LLC]

What You Should Know about Chloroquine and Hydroxychloroquine

No one should be self-administering these or any other experimental treatments for COVID-19.

Although data from a small trial were encouraging and showed that hydroxychloroquine reduced viral load in patients with COVID-19, hydroxychloroquine and the related chemical chloroquine are not without adverse effects. That small study also did not have any data on patient outcome. Did the treatment reduce the number of deaths or reduce time of hospitalization? It was too soon to tell. Since these findings were made public and mentioned by President Trump, deaths from ingestion of high concentrations of chloroquine have occurred in the US and in Nigeria.

Chloroquine and hydroxychloroquine are not without serious side effects in some people and can even be lethal. So, even though these are widely approved for treating malaria, as well as lupus and rheumatoid arthritis, these drugs need to be taken under the care of a physician.

For the COVID-19 pandemic caused by SARS-CoV-2, there is a need to carefully weigh potential benefit against potential harm from administering these (and any other) drugs broadly throughout populations either as a prophylactic agent (to prevent symptoms or infection) or as a therapeutic agent (to treat symptoms and disease). In a rapidly spreading pandemic with a high incidence of serious illness, there is also the need for rapid action. That is why the World Health Organization (WHO) established a simple randomized clinical trial for testing chloroquine and the related molecule hydroxychloroquine, as well as 3 other possible treatments for COVID-19.

Although not common, cardiovascular complications and hypoglycemia are two of the potential life-threatening hazards associated with chloroquine and hydroxychloroquine. Given that COVID-19 appears most lethal to patients with underlying medical conditions of cardiovascular disease, kidney disease, and diabetes, doctors need to carefully consider which patients will likely benefit from the use of these drugs to treat COVID-19 and which could be harmed.

Additionally, these drugs can be dangerous in people with a genetic deficiency in the enzyme G6PD, and dosing may need to be adjusted in people with liver or kidney disease. Administration broadly throughout a population could result in severe consequences, if these complicating factors are not considered and understood by the population and the prescribing physicians.

Clinical trials testing these drugs are in progress. No one should be self-administering these or any other experimental treatments for COVID-19.

Public health officials and healthcare professionals need to proceed with caution, carefully examining the evidence and the potential for harm against the risk associated with delaying potential treatments. An interesting idea that was mentioned in the AAAS Member Community was to evaluate data related to patients currently taking chloroquine and hydroxychloroquine for malaria or as an immunosuppressant and the frequency of these patients among people who test positive for COVID-19 and among the COVID-19 patients requiring hospitalization. This type of retrospective analysis could help inform clinical and public health decisions.

Related Reading

N. R. Gough, WHO Testing 4 Possible Treatments for COVID-19. Medium (23 March 2020)

Md. Abdul Alim Al-Bari, Chloroquine analogues in drug discovery: new directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases. J. Antimicrob. Chemo. 70, 1608–1621 (2015) DOI: 10.1093/jac.dkv018

Abdulaziz N, Shah AR, McCune WJ. Hydroxychloroquine: balancing the need to maintain therapeutic levels with ocular safety: an update. Curr. Opin. Rheumatol. 30, 249–255 (2018). DOI: 10.1097/BOR.0000000000000500

Colson P, Rolain JM, Lagier JC, Brouqui P, Raoult D. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19 [published online ahead of print, 2020 Mar 4]. Int. J. Antimicrob. Agents 105932 (2020). DOI: 10.1016/j.ijantimicag.2020.105932

Mohammad S, Clowse MEB, Eudy AM, Criscione-Schreiber LG. Examination of Hydroxychloroquine Use and Hemolytic Anemia in G6PDH-Deficient Patients. Arthritis Care Res. 70, 481–485 (2018). DOI:10.1002/acr.23296

Information for Clinicians on Therapeutic Options for COVID-19 Patients. Centers for Disease Control and Prevention https://www.cdc.gov/coronavirus/2019-ncov/hcp/therapeutic-options.html (accessed 24 March 2020)

Hydroxychloroquine sulfate. Prescribers’ Digital Reference https://www.pdr.net/drug-summary/Plaquenil-hydroxychloroquine-sulfate-1911 (accessed 24 March 2020)

Hydroxychloroquine Post Exposure Prophylaxis for Coronavirus Disease (COVID-19)

Clinical Trials (as of 24 March 2020 and listed on ClinicalTrials.gov)

Efficacy and Safety of Hydroxychloroquine for Treatment of Pneumonia Caused by 2019-nCoV ( HC-nCoV )

Hydroxychloroquine Post Exposure Prophylaxis for Coronavirus Disease (COVID-19)

Norwegian Coronavirus Disease 2019 Study (NO COVID-19)

Post-exposure Prophylaxis for SARS-Coronavirus-2

Hydroxychloroquine Treatment for Severe COVID-19 Pulmonary Infection (HYDRA Trial) (HYDRA)

Hydroxychloroquine Chemoprophylaxis in Healthcare Personnel in Contact With COVID-19 Patients (PHYDRA Trial) (PHYDRA)