Concerning the Coronavirus Disease (2019), hydroxychloroquine post-exposure prophylaxis for malaria was tested at CMH, Lahore, Pakistan. However, the primary objective of the 2016 chloroquine pilot study by Waqar, Khushdil, and Haque was to assess the efficiency of the tablets as a first-line agent in treating malaria among Pakistanis. The central element required while considering the old malaria drug is testing efficacy for COVID-19 by conducting clinical trials in Pakistan. Hydroxychloroquine and chloroquine are typically used for treating malaria, inflammatory conditions such as rheumatoid arthritis, and amebiasis. The two drugs have sufficient data to confirm anti-viral activity in vitro. However, clinical efficiency is yet to be established in the treatment of coronavirus.
Chloroquine and hydroxychloroquine appear to work via the glycosylation of the ACE2 receptor, which decreases the ability of SARS-CoV-2 to center cells. The acidification of endosomes is impaired which interferes with virus trafficking in the cells. Immunomodulatory effects may attenuate cytokine storm reactions in the severe form of coronavirus (2019) disease. The immunomodulatory effects may be harmful to the viral disease.
A drug shortage of hydroxychloroquine phosphate emerged in Pakistan’s major cities of Karachi and Lahore during March after news began circulating online that the drug was effective in treating patients who test positive for the novel coronavirus. During a press conference on 19 April 2020 in Islamabad following the federal cabinet meeting, Dr. Firdous Ashiq Awan, the Special Assistant to the Prime Minister said Pakistan is set to export chloroquine to ‘friendly countries.’ Dr. Awan states,
“Pakistan has a surplus stock of around 40 million [chloroquine] tablets and sufficient raw material to produce the drug in great number… the export of drugs will not cause a shortage of domestic consumption. One million chloroquine tablets each will be dispatched to Saudi Arabia and the United States, half a million each to Turkey and Italy. In addition to this, 5 million will be dispatched to the United Kingdom, 700,000 to Kazakhstan, and 300,000 to Qatar.”The Express Tribune
Pakistan’s Young Scientists and Students
Scientists Against COVID-19 Pakistan (SACP-19): A virtual network of 3000+ young scientists from across Pakistan.
Pakistan’s youth is beaming with ideas and useful strategies to beat the coronavirus, some of which may be implemented with affordable costs. The country is currently undergoing one of its biggest health challenges. While COVID-19 has led to increased despondency and immense fear among the public, researchers are working collectively to ensure that the country fights the virus in the strongest manner possible.
“There is an astounding number of people who are ready to volunteer and assist with the effort,” says Mohammad Ismail who is a 25-year-old bio-technologist.Dawn News
He started the platform with Lahore-based research immunologist Maryam Ahmed, Peshawar-based physiology student Adil Salim, and Karachi-based microbiologist Sadia Khalil a week ago.
“We want universities and labs in Pakistan to donate their equipment for use to scale up testing. This is something that’s already happening in the US,” says Ismail.Dawn News
However, he noted that there is a Disconnect between various sectors in Pakistan, which makes it much more challenging to execute these ideas in Pakistan.
Student Taskforce Against Covid-19 (Stac-19): Another youth-led group started by final year medical students at the Aga Khan University Hospital, Karachi.
The group has now turned into a community with over 500 members, which comprises of non-medical students as well. Dawn News reports one of its founders, Kaleem Ahmed’s statement,
“The challenge is managing the rapid growth of our task force… It’s novel and interesting to see this implosion in just a week. We are not turning anyone away but are trying to offer tasks in batches so everyone remains engaged while ensuring that no one gets burnt out.”Dawn News
Stac-19 has also been assisting the Sindh government in contact tracing. This means that the status of all those in contact with COVID-19 patients is determined by tracking patients and counseling them. They are informed about the two-week period of isolation that merits further observation.
The taskforce is also volunteering at the Expo Centre isolation ward at Karachi to help the Pakistan Medical Association.
SARS-CoV-2, previously named as 2019-nCOV, causes the clinical illness COVID-19. It is a novel virus that belongs to the coronavirus family. With over 5.3 million cases worldwide, various treatment options are undergoing evaluation or are being applied clinically. To prepare for in-patient treatment of COVID-19, evidence for therapies and recommendations are shared. The use is divided among various groups such as Internal Medicine, Medical Microbiology, Infectious Diseases, Emergency Medicine, Pharmacy, and Long Term Care.
Until 22 May 2020, Pakistan has 52,437 confirmed cases, 2,603 recovered patients, and 1,101 dead. A fatality rate of 2.1% is noted in the total cases of COVID-19 in Pakistan. The recovery rate is 31.8% of the total cases. 111 patients, 0.2% of total cases, are critically treated in the ICU. Daily cases that are being treated are 34,683 in number, which is 66.1% of total cases. The daily confirmed cases are 238 per million population.
COVID-19 Report until 22 May, 2020: Coronavirus cases continue to rise.
Hydroxychloroquine Trials Across the World
- Observational study, New England Journal of Medicine: Hydroxychloroquine is claimed to be a life-saving drug to patients with COVID-19. However, there is no robust evidence supporting its use. Geleris et al. examined the association between Hydroxychloroquine use and intubation or death at a large medical center in New York City. Data were obtained regarding patients hospitalized with COVID-19. The authors compared outcomes in patients who received Hydroxychloroquine with those who did not receive the treatment. The conclusions of the original article were presented after an analysis of admitted patients was conducted. No association was found with a greatly increased or lowered risk of the composite endpoint of intubation or death. The observational study noted that randomized clinical trials are further required to confirm trends of the drug.
- Q-PROTECT: Hamad Medical Corporation enrolled 456 participants for a randomized clinical trial for their study “Qatar Prospective RCT of Therapy Eliminating COVID Transmission.” The estimated start date was 14 April 2020 until 30 May 2020. The Double-Blinded Trial highlighted that a reduction in viral load is key in reducing viral transmission between humans. Further, observation data suggests that Azithromycin and Hydroxychloroquine may lead to a reduction in the viral load. The study uses random ambulatory patients with COVID 19 that are confirmed via PCR and who show clinical symptoms. They receive Hydroxychloroquine and Azithromycin OR Hydroxychloroquine and placebo for seven days. Between the days 2-14, the participants are reviewed by research team members, and samples are obtained for the viral load with physical examination and an ECG recording. On days 15-20 of the study, all patients are reviewed via semi-structured questionnaires on the telephone. On the 21st day, participants are examined in person and by using oro-nasopharyngeal swabs that are analyzed by the PCR method. These participants are then followed for 6 months.
- Istinye University, Turkey: An observational case-control prospective study enrolled 80 participants. The study started on 20 March, 2020 and the estimated date of completion is 1 September 2020. The title is “Prophylaxis for Healthcare Professionals Using Hydroxychloroquine Plus Vitamin Combining Vitamins C, D and Zinc During COVID-19 Pandemic: An Observational Study.” Healthcare professionals who started taking Hydroxychloroquine 200 mg known as Plaquenil repeated single doses every three weeks. Vitamin C in addition to zinc was taken once a day during the study. The Turkish study aims to find measures of protection against COVID-19 by taking the drug.
- SOLIDARITY clinical trial for COVID-19 treatment: The World Health Organization writes about the solidarity international clinical trial that aims to find an effective treatment for the coronavirus. The trial is set to be completed in four treatment options against the standard of care and assess relative efficacies against the virus. Patients from multiple countries are to be enrolled and the effects of drugs on disease progression noted. The treatment options under study are Remdesivir; Lopinavir/Ritonavir; Lopinavir/Ritonavir with Interferon beta-1a; and Chloroquine or Hydroxychloroquine. While RCTs typically take years to design, the solidarity trial has reduced the time by 80%. As of 21 April 2020, over 100 countries are gearing themselves towards finding effective treatment options. Chloroquine and hydroxychloroquine are closely related, and have formerly been used to treat malaria and rheumatology conditions respectively. In France and Chance, selected studies have indicated the possible benefits of chloroquine phosphate against pneumonia caused by COVID-19 but require confirmation through randomized trials.
The Case for Chloroquine
James Todaro, a blockchain investor tweeted on 14 March 2020 that the 85-year-old drug named chloroquine was preventative against the novel coronavirus.
People have been pitching chloroquine as an antiviral drug for many years. Researchers in the 1990s proposed the drug as an adjunct, in treating HIV/AIDS, to early protease inhibitor drugs. Stuart Nichol led a team at the Centers for Disease Control and Prevention and published a paper in 2005 stating that chloroquine is effective against SARS-infected primate cells. This was the first-ever coronavirus known to affect humans. The test was in-vitro, that is, it was carried on cells and not live animals.
A CDC spokesperson emailed,
“CDC is aware of reports of various medications being administered for either treatment or prophylaxis for COVID-19, including those demonstrating in vitro activity against SARS-CoV- 2. At this time, it is important to ensure robust clinical data, gathered from clinical trials, are obtained quickly in order to make informed clinical decisions regarding the management of patients with COVID-19.”Wired
Sunit K. Singh, PhD, a professor of molecular immunology & virology and head of the molecular biology unit at Banaras Hindu University’s Institute of Medical Sciences in Varanasi, India states,
“The combination therapy of azithromycin and hydroxychloroquine was thought to be better over the monotherapy of hydroxychloroquine to control the mixed infection of virus and bacteria.”Forbes
It is further articulated that Hydroxychloroquine currently used to treat rheumatoid arthritis and lupus is slightly different from chloroquine phosphate, a drug that primarily treats malaria.
Mel Thomson, Ph.D., an emerging infectious disease expert and founder at VeraQ Pty Ltd in Australia states,
“Many intensive care clinicians are willing to ‘try anything once’ in these unprecedented times.”Forbes
The Pursuit of Clinical Trials For COVID-19 Vaccine in Pakistan
Around a dozen drugs to treat the coronavirus are undergoing clinical trials in China. Remdesivir, the antiviral drug was previously undergoing clinical trials in the US. No clinical trials for Hydroxychloroquine or Chloroquine were found registered in Pakistan.
In this regard, Dr. Attaur Rehman, the chairman of the task force on Science & Technology hopes that clinical trials for anti-viral drugs including chloroquine will start soon. A massive 93% success rate was noted for using antiviral drugs in France where patients recovered from COVID-19.
Dr. Rahman also said that scientists need more time to determine if the drug is safe and effective.
“In France, it will only be available under strict hospital supervision and patients are warned that it should not be taken under any other conditions,” he mentioned.Pakistan Today
It was stated that the University of Health Sciences (UHC) Vice-Chancellor Dr. Akram was to lead the clinical trials for a possible coronavirus vaccine in Pakistan. Dr. Rahman also stated that virologists and scientists across the world and in Pakistan are working hard to develop a cure or a vaccine.
Khalid Mahmood, CEO and MD Getz Pharma, said,
Under this initiative, we are supporting the University of Health Sciences, Lahore, for research that includes clinical trials of the hydroxychloroquine. The virus is mutating as it moves from one population. There is a need to examine the coronavirus in Pakistan more. This initiative would help on all these lines and lead to better results and other initiatives.Pro Pakistani
Dr. Rehman further notes that his task force has established Karachi University as a testing center for COVID-19. He shares that 25-30% of the surrounding regions are positive for the virus. In this regard, the task force has been monitoring and identifying cases as briefed by the National Command Center.
“The only way we can stay safe is to cooperate with the government-induced lockdown and ensure precautionary measures. As of now, infected patients receive the utmost care and medications that help alleviate the system. The topmost priority is to support vital organ systems.”Pakistan today
Chloroquine has been in the news since the outbreak ensued around the globe. The anti-malarial drug must be tested for treating COVID-19 by conducting different clinical trials in Pakistan. Global trials are still underway with inconclusive findings related to the virus. While both drugs are closely related to each other, hydroxychloroquine is used widely during the COVID-19 pandemic in Pakistan. If UHS and Getz Pharma prove that hydroxychloroquine or chloroquine is effective against the coronavirus, WHO may promote the FDA’s emergency approval of the drug.
© 2020 Zouina Sarfraz
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Post by: Zouina SarfrazMs. Zouina Sarfraz is a final year student at Fatima Jinnah Medical University.
She is an associate editor at Pakistan Journal of Surgery and Medicine and PJSM Blog. Zouina strives to present new findings in the realm of medicine by promoting research at an undergraduate level.
Cite This Work
Sarfraz, Z. (2020, May 23). Hydroxychloroquine and Chloroquine for COVID-19 in Pakistan. PJSM Blog. Retrieved from: https://blog.pjsm.com.pk/2020/05/23/hydroxychloroquine-and-chloroquine-for-covid-19-in-pakistan/.