In December 2019, when there was news of a mysterious viral infection ravaging part of China, little did the citizens of other countries realise that, one day it will enter their homes without so much as a knock and be declared a pandemic. Fast forward to the present day - severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), aka COVID 19, originating in China has affected more than 213 countries, infected nearly 1.8 million people, killed 108,432 and is still unabated!!! It is relentlessly infecting people with no respect to race, gender, colour and affluence. There has been a sense of urgency to discover/develop a treatment for this and research institutes and the pharma companies across the world are burning midnight oil to realise this objective.

COVID 19 – No barriers

(Image courtesy WHO - https://who.sprinklr.com/)

Thanks to the ubiquitous social media and the prolific WhatsApp forwards, everyone has/knows a home-grown solution/therapy/clinical trial that will put an end to this pandemic soon. Alas, this is not the case!! Coronaviruses are a large family of viruses which may cause illness in animals or humans.  In humans, several coronaviruses are known to cause respiratory infections ranging from the common cold to more severe diseases such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). The most recently discovered coronavirus causes coronavirus disease COVID-191 .  Currently there are no known medicine/vaccine to cure or prevent the disease.

Desperate times call for desperate measures:

Given the magnitude of the pandemic, WHO is approaching the situation on a war footing. It is well known that development of a novel molecule aimed at COVID 19, will take years and hence there is sense of urgency to find a solution with the existing cache of drugs.  In an unprecedented effort, on 20th of March, WHO announced a large global trial called ‘SOLIDARITY’ that encompasses a disparate spectrum of therapies: a drug combination used against HIV; a malaria treatment first tested during world war II and a new antiviral that failed against intended use in Ebola2!!

The Solidarity trial will compare four treatment options against standard of care, to assess their relative effectiveness against COVID-19. By enrolling patients in multiple countries, the Solidarity trial aims to rapidly discover whether any of the drugs slow disease progression or improve survival. Other drugs can be added based on emerging evidence. Enrolling patients in one single randomized trial will help facilitate the rapid worldwide comparison of unproven treatments.1.

Treatment Options under SOLIDARITY trial:

Based on evidence from lab, animal and clinical studies following four options were selected:
  • Remdesivir was previously tested as an Ebola treatment. It has generated promising results in animal studies for Middle East Respiratory Syndrome (MERS-CoV) and severe acute respiratory syndrome (SARS), which are also caused by coronaviruses, suggesting it may have some effect in patients with COVID-19
  • Lopinavir/Ritonavir is a licensed treatment for HIV. This trial aims to identify and confirm any benefit for COVID-19 patients. While there are indications from laboratory experiments that this combination may be effective against COVID-19, studies done so far in COVID-19 patients have been inconclusive.
  • Interferon beta-1a is used to treat multiple sclerosis
  • Chloroquine and hydroxychloroquine are very closely related and used to treat malaria and rheumatology conditions respectively. In China and France, small studies provided some indications of possible benefit of chloroquine phosphate against pneumonia caused by COVID-19 but need confirmation through randomized trials

Only those drugs were selected, that had the highest likelihood of working, had the most safety data from previous use, and are likely to be available in supplies sufficient to treat substantial numbers of patients if the trial shows they work2.

Participation in the study1:

The Solidarity trial provides simplified procedures to enable even overloaded hospitals to participate, with no paperwork required. As of now more than 90 countries are working together to find effective therapeutics as soon as possible, via the trial.

The greater the number of participating countries, the faster the results will be generated. WHO is facilitating access to thousands of treatment courses for the trial through donations from a number of manufacturers. WHO is also inviting developers and companies to collaborate on ensuring affordability and availability of the treatment options if they prove effective.

How the trial works1,2:

This is not a double-blind study with ease of enrolment to the trial. With an eligible patient, the physician enters the patient’s data into a WHO website. The participant has to sign an informed consent form that is scanned and sent to WHO electronically. Depending on the availability of drugs at his or her hospital, the website will randomize the patient to one of the drugs available or to the local standard care for COVID-19.

Other options under consideration3:

There are many other investigational therapies also in human clinical trials. To name a few:

  • Early-stage investigational antivirals such as Rintatolimod, Beta-D-N4-hydroxycytidine
  • Immunomodulators and investigational therapies such as:
    • IL-6 inhibitors (sarilumab, tocilizumab), neurokinin-1 (NK-1) receptor antagonist (Tradipitant)
    • Corticosteroids
    • Convalescent plasma (antibody-rich products that are collected from eligible donors who have recovered from COVID-19)
    • Nitric Oxide
    • And more
  • Investigational vaccines such as mRNA vaccines, rDNA vaccines, live attenuated vaccine, PCR based DNA vaccine etc..

Conclusion:

The Spanish influenza of 1918 was the last communicable disease that brought the world to its feet. Although there have been epidemics such as MERS, SARS and Ebola, the world at large had been blissfully ignorant of the havocs wreaked by communicable diseases. The world is now on the lookout for that magic bullet which can end this pandemic. Knowing that brightest of the bright are at work is comforting and lets us peacefully sleep at night with hope of waking up to a cure the next morning.

 

References:

  1. Accessed from WHO website at the URL https://www.who.int/news-room/q-a-detail/q-a-coronaviruses on 13th April 2020.
  2. ‘WHO launches global megatrial of the four most promising coronavirus treatments’ dated 22nd March by Kai Kupferschmidt and Jon Cohen accessed on 13th April 2020 at https://www.sciencemag.org/news/2020/03/who-launches-global-megatrial-four-most-promising-coronavirus-treatments
  3. Treatment of Coronavirus Disease 2019 (COVID-19): Investigational Drugs and Other Therapies – Medscape . Scott J Bergman et al. Accessed on 13th April 2020 at https://emedicine.medscape.com/article/2500116-overview#a2