Researchers provide a guideline regarding who should be actually taking antimalarial drugs as prophylaxis to prevent getting COVID-19. They say health professionals who are being exposed to COVID-19 positive patients and those who test positive but are asymptomatic should be taking drugs such as Chloroquine and Hydroxychloroquine. They explain that these populations remain most in need, and because of limited supply, these individuals need to be prioritized.
A research letter to this effect titled, "To consider or not antimalarials as a prophylactic intervention in the SARS-CoV-2 (COVID-19) pandemic," was published in the latest issue of the Annals of the Rheumatic Diseases.
Chloroquine is one of the standard drugs used against malaria, and hydroxychloroquine is derived from the former and is used in Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE) and other autoimmune diseases. These drugs have been in use for forty more years now, and they are useful in several conditions. Common side effects with these drugs include gastrointestinal upset, severe nausea, and vomiting. Severe side effects include eye damage or retinopathy and cardiac toxicity.
The Italian researchers wrote that there is an acute shortage of these antimalarial drugs, Chloroquine, and hydroxychloroquine due to the recent surge in demand. They explain that these drugs have been included in the Chinese guidelines for the management of pneumonia caused by COVID-19 (int their version 7 released on 3 March 2020). Some small overseas studies found that the drugs could be used as a way to treat COVID-19, sparking a massive uptick in demand, but many experts are skeptical of the evidence. Several new clinical trials have started trying to assess the efficacy of these drugs in preventing more severe disease.
The problem with the use of these drugs as a treatment or as prophylaxis in COVID-19 cases or exposure is unethical since their efficacy is not yet conclusively proven by large scale clinical trials. The team wrote, "Is it permissible to take a controlled risk in the event of a pandemic? In such a case: would it be reasonable to consider antimalarials as primary prophylaxis in healthy subjects living in highest risk regions or, at least, to use them in those testing positive for COVID-19, but still asymptomatic?"
What was found in this review?
The research was undertaken as an observational study collating the available evidence on the issue and was not peer-reviewed. The researchers outline several published studies and the effects of these drugs. For example;
- A study by Wang et al. showed how low concentrations of Chloroquine was able to block the replication of COVID-19. This could be achieved at doses of 500 mg of Chloroquine, they write.
- Another study by Yao et al. showed that hydroxychloroquine has shown an anti-SARS-CoV-2 effect and reduced the replication of the virus. This effect was seen with increasing therapeutic doses in lab studies. Studies reveal that both Chloroquine and hydroxychloroquine can prevent viral entry into the host cell and thus protect the consumer.
- The dose of hydroxychloroquine was 400 mg twice a day on day 1 and 200 mg twice a continued. Hydroxychloroquine was found to be more effective than Chloroquine in this aspect.
- A study by Gao et al. with 100 patients positive with COVID-19 infection treated with Chloroquine has shown beneficial effects. This was a case series, and it showed that chloroquine use could reduce lung complications, improved lung clearance of the disease, shortened the course of the disease, and had minimal adverse effects.
- After six days of use, hydroxychloroquine use in those with COVID-19 infection showed negative nasopharyngeal samples. Among those treated with hydroxychloroquine, 70 percent showed viral clearance and 100 percent of those treated with a combination of hydroxychloroquine and azithromycin showed viral clearance or freedom from the viral load. This was comparable to 12.5 percent viral clearance among those who did not receive hydroxychloroquine. This was a study by Gautret et al.
Conclusions and implications
The authors concluded, "If mass prophylaxis was accepted as an option worldwide, this would raise the question of whether there is enough supply of [chloroquine] and [hydroxychloroquine] to support this approach."
They wrote that The European League Against Rheumatism (EULAR) worries that with a higher demand for hydroxychloroquine by COVID-19 patients during this pandemic, the patients of rheumatoid arthritis who require this drug may suffer. EULAR President, Professor Iain McInnes called for more concrete studies, and EULAR's patient membership group (PARE) also urged increased supply of the drugs to meet the demands of COVID-19 as well as non-COVID-19 patients. McInnes said, "EULAR is concerned, however, that the diversion of drug supplies away from people with rheumatic and musculoskeletal diseases may compromise the health of this important and sizeable group of patients in Europe and beyond." He said, "A balanced approach that meets the imperatives of the ongoing pandemic, but which also takes account of the needs of patients already taking these drugs is essential."
- Spinelli FR, Ceccarelli F, Di Franco M, et al., To consider or not antimalarials as a prophylactic intervention in the SARS-CoV-2 (COVID-19) pandemic, Annals of the Rheumatic Diseases Published Online First: 02 April 2020. DOI: 10.1136/annrheumdis-2020-217367 - https://ard.bmj.com/content/early/2020/03/26/annrheumdis-2020-217367
- Wang M, Cao R, Zhang L, et al. Remdesivir and Chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020;30:269–71. 2 https://pubmed.ncbi.nlm.nih.gov/32020029/
- 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. DOI:10.1093/cid/ciaa237. [Epub ahead of print: 9 March 2020]. https://pubmed.ncbi.nlm.nih.gov/32150618/
- Gao J, Tian Z, Yang X. Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends 2020;14:72–3. https://pubmed.ncbi.nlm.nih.gov/32074550/
- Gautret P, Lagier J-C, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents 2020:105949, https://www.sciencedirect.com/science/article/pii/S0924857920300996