TREATING COVID-19: HOW SCIENCE IS TACKLING THE DEADLY PANDEMIC

Jannis Delaan - September 20, 2021



Managing mild COVID-19 involves many similar things we often do to treat the common cold; sufficient rest, drinking lots of water, and taking medications meant to relieve aches and fever.

However, for people suffering from (or at risk of developing) more intense symptoms or those hospitalised, the US Food and Drug Administration (FDA) has authorised more specific treatments and medicines to help control the progression of COVID-19.

While scientists are still working feverishly to develop more effective regimes, here’s what we know so far about the existing treatments for COVID-19.

The Difficulty in Treating Viral Illnesses


First off, let’s understand why it has been so difficult and time-consuming to develop an effective treatment regime for COVID-19.

An effective antiviral drug must be capable of targeting the particular part of the virus's life cycle that plays a vital role in its reproduction. Also, it must only kill viral cells and not healthy human cells.

Now the problem with viruses is that they are extremely adaptive and reproduce rapidly. This gives them immense opportunity to mutate (change their genetic makeup) and produce a new generation of virus particles, each potentially more resistant to the existing drugs or vaccines developed to destroy them.

COVID-19 Treatment: What Works and What Didn’t


COVID-19 treatment regimens fall under two categories: treatments for severe illness which are administered in a clinical setting to reduce the risk of death, and early treatment which will hopefully reduce the odds of a patient being hospitalised.

Despite the US Food and Drug Administration (FDA) granting emergency authorization to various treatments for COVID-19, not all of them have the same effectiveness and scientific facts to back them up.

Hydroxychloroquine: A Dead End

Probably one of the first drugs highlighted for treating COVID-19 was hydroxychloroquine. 

Hydroxychloroquine is mainly used to treat malaria and various inflammatory diseases, such as rheumatoid arthritis and lupus. 

What made it even popular was that it was low-priced, easily available, and initial reports from France and China suggested that people with severe symptoms improved quickly after taking the medication.

However, an article published in JAMA in December 2020 showed that when compared with a placebo, hydroxychloroquine was not clinically beneficial for adult patients hospitalised with COVID-19. Hence, the National Institute of Health (NIH)issued guidelines against using hydroxychloroquine for treating COVID-19 patients. 

Vitamin D: Possible Protection against COVID-19

It is known that low levels of vitamin D increase susceptibility to upper respiratory tract infections. This is because vitamin D boosts the body's natural defenses against bacterial and viral infections, and it prevents aggravated inflammatory responses which contribute to severe symptoms of COVID-19.

The recommended dietary dosage of vitamin D for adults aged 70 and below is 600 IU per day and 800 IU per day for adults above 70.

Hence, some evidence suggests that vitamin D might offer protection against COVID-19 infection and also from developing severe symptoms. A meta-analysis showed that people taking vitamin D supplements were less likely to develop acute respiratory tract infections as opposed to those who did not.

Ibuprofen and Acetaminophen to Treat Symptoms of COVID-19

Initially, the World Health Organization (WHO) advised using acetaminophen in place of ibuprofen (Advil, Motrin, etc.) to manage symptoms such as fever and pains resulting from COVID-19 infection; however, it now claims that both acetaminophen and ibuprofen are helpful. 

Despite these recommendations, certain doctors do not advise using ibuprofen for managing COVID-19 symptoms. This is based on reports of people positive for COVID-19 but otherwise healthy taking NSAIDs for symptomatic relief and developing severe illnesses, chiefly pneumonia. 

However, these recommendations are based solely on observations and not scientific studies. Hence, if acetaminophen is not available, or taking the maximum dosage still does not provide relief, over-the-counter ibuprofen can be taken.

Medications for Treating People Hospitalised with COVID-19

Dexamethasone

The NIH treatment guidelines for COVID-19 recommend using dexamethasone in certain patients hospitalised with severe symptoms of COVID-19. Corticosteroids such as dexamethasone, prednisone, and methylprednisolone are effective anti-inflammatory drugs that are readily available and affordable.

These recommendations are based on the results of a RECOVERY trial, during which over 6000 hospitalised patients were randomly given standard treatment or dexamethasone. Results revealed that patients receiving supplemental oxygen, or those on ventilators, had a lower mortality rate within 28 days if they took dexamethasone, as compared to those who received standard treatment. 

Tocilizumab

Tocilizumab (Actemra) is an FDA-approved monoclonal antibody (man-made antibodies) used to treat various autoimmune diseases. It was granted emergency use authorization (EUA)for treating hospitalised adults and children under the age of two already receiving either systemic corticosteroids requiring supplemental oxygen or mechanical ventilation or those on a heart-lung bypass machine.

The EUA was issued after reviewing the results of four clinical trials of patients hospitalised with COVID-19. These trials compared using tocilizumab along with routine treatment for COVID-19 with only routine treatment. Within 28 days, tocilizumab alone with usual care decreased the risk of death and being put on a ventilator, and also reduced the duration of hospital stay.

Remdesivir and Baricitinib

In October 2020, the FDA permitted the use of the antiviral drug remdesivir for treating COVID-19. This drug can be used for hospitalised adults and children aged 12 and above and weighing at least 40 kg (88 pounds). Clinical trials show that administering remdesivir to these individuals can discreetly enhance recovery time.

In November 2020, the FDA issued another for using baricitinib along with remdesivir for hospitalised adults and children aged two years and above requiring respiratory support. However, sufficient evidence does not exist to support this therapy.

Fluvoxamine

Most recently, the results of a huge clinical trial have shown that the inexpensive antidepressant fluvoxamine may be effective in treating COVID-19. 

The trial termed the TOGETHER study, included more than3000 patients, of which 800 were given fluvoxamine just within a few days of testing positive for COVID-19. Results showed that this group was 31 percent less likely to being hospitalised, and also less likely to be put on a ventilator.

However, these promising results have been released quite recently, and future research is needed to further cement this exciting development. 

Anticoagulation (Blood Thinner) Drugs 

Low doses of anticoagulants such as heparin or enoxaparin are given to almost all patients hospitalised with COVID-19to prevent the formation of blood clots. 

Certain patients might require higher doses of anticoagulants if they have already developed blood clots or are at a higher risk.


The Use of Monoclonal Antibodies 

Monoclonal antibodies are man-made versions of the natural antibodies our body makes to fight foreign pathogens. Monoclonal antibodies can also be administered in combination with corticosteroids, including dexamethasone, to reduce exaggerated immune responses in critically ill hospitalised patients. 

The three FDA-authorised monoclonal antibodies for COVID-19 infections attack the virus's spike protein and make it difficult to attach and enter human cells. They are:

  • combination of casirivimab and imdevimab(REGN-COV) by Regeneron Pharmaceuticals
  • combination of bamlanivimab and etesevimab by Eli Lilly
  • sotrovimab by GlaxoSmithKline

These treatments must be administered intravenously in a clinical setting, and are currently not authorised for hospitalised patients or those receiving artificial oxygen – they are meant for non-hospitalised adults and children above the age of 12 presenting moderate symptoms of COVID-19, or at a risk for developing severe symptoms.

However, newer research from a pre-peer reviewed study in June 2021 revealed promise for the use of monoclonal antibody treatment in hospitalised patients as well, particularly those with reduced natural immune responses. The review compared using Regeneron’s monoclonal antibody treatment along with routine care to solely routine care in hospitalised patients. In people with minimal natural antibodies, monoclonal antibody treatment decreased the risk of death by 20 percent. 

However, monoclonal antibodies were not beneficial for people who had already produced sufficient antibodies in response to the COVID-19 virus.

Convalescent Plasma as a Potential Treatment 

Convalescent plasma is plasma obtained from recovered COVID-19 patients. It contains antibodies produced to fight the specific virus. Convalescent plasma has been widely used for over 100 years to treat various illnesses and is considered to be effective and safe.

The FDA issued an EAU in August 2020 for using convalescent plasma to treat hospitalized patients with COVID-19.

With regard to this treatment, a randomised, double-blind, and placebo-controlled trial was conducted in January 2021 and published in the New England Journal of Medicine. It involved administering COVID-19 patients aged 65 years and above convalescent plasma after ensuring that it contained increased amounts of antibodies. Results showed that if patients received convalescent plasma within three days of developing symptoms, they had a 48 percent lesser chance of developing severe COVID illness.

However, a meta-analysis of four peer-reviewed randomised clinical trials showed less-promising results. Compared to placebos and standard treatments, convalescent plasma did not significantly reduce the risk of death, period of hospital stay, or risk of the ventilator. But the authors stated that the studies reviewed were small, and further trials could suggest more benefits of this therapy.  


Final Thoughts


The US government declared in June 2021 that it will spend over $3 billion to speed up the development and testing of antiviral drugs and treatments against COVID-19, focusing mainly on oral medications.

While currently available vaccines still play an integral part in the protection against COVID-19, antiviral medications will still play an important role in treating people who do not harvest a significant response to the vaccine, who might experience breakthrough infections, and those who opt to remain unvaccinated. Also, the various treatment regimens authorised by the FDA can, and are, playing an important role in fighting COVID-19 severity.





References:

Mahase E. Covid-19: Regeneron’s antibody combination cuts deaths in seronegative patients, trial finds BMJ 2021; 373:n1570 doi:10.1136/BMJ.n1570

“Solidarity” clinical trial for COVID-19 treatments.World Health Organization.

Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus2019-ncov/solidarity-clinical-trial-for-covid-19-treatments

FDA cautions against the use of hydroxychloroquine or chloroquine for COVID-19 outside of the hospital setting or a clinical trial due to the risk of heart rhythm problems. FDA.

Available from: https://www.fda.gov/drugs/drug-safety-and-availability/fda-cautions-against-use-hydroxychloroquine-or-chloroquine-covid-19-outside-hospital-setting-or

Martineau A R, Jolliffe D A, Hooper R L, Greenberg L, Aloia J F, Bergman P et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data BMJ 2017; 356:i6583 doi:10.1136/BMJ.i6583

Day M. Covid-19: ibuprofen should not be used for managing symptoms, say doctors and scientists BMJ 2020; 368:m1086 doi:10.1136/BMJ.m1086

RECOVERY Collaborative Group, Horby, P., Lim, W. S., Emberson, J. R., Mafham, M., Bell, J. L., Linsell, L., Staplin, N., Brightling, C., Ustianowski, A., Elmahi, E., Prudon, B., Green, C., Felton, T., Chadwick, D., Rege, K., Fegan, C., Chappell, L. C., Faust, S. N., Jaki, T., … Landray, M. J. (2021). Dexamethasone in Hospitalised Patients with Covid-19.The New England journal of medicine, 384(8), 693–704.https://doi.org/10.1056/NEJMoa2021436

Samaee, H., Mohsenzadegan, M., Ala, S., Maroufi, S. S., &Moradimajd, P. (2020).Tocilizumab for treatment patients with COVID-19: Recommended medication for the novel disease. International immunopharmacology, 89(Pt A), 107018.https://doi.org/10.1016/j.intimp.2020.107018

Joyner, M. J., Carter, R. E., Senefeld, J. W., Klassen, S. A., Mills, J. R., Johnson, P. W., Theel, E. S., Wiggins, C. C., Bruno, K. A., Klompas, A. M., Lesser, E. R., Kunze, K. L., Sexton, M. A., Diaz Soto, J. C., Baker, S. E., Shepherd, J., van Helmond, N., Verdun, N. C., Marks, P., van Buskirk, C. M., … Casadevall, A. (2021). Convalescent Plasma Antibody Levels and the Risk of Death from Covid-19.The New England journal of medicine, 384(11), 1015–1027.https://doi.org/10.1056/NEJMoa2031893

The TOGETHER Trial of Fluvoxamine.

Available from: https://ad996812-f908-4f9a-ae29-44e0df5347d5.filesusr.com/ugd/4e5c71_cc113a0bc7e54713a4d5443140234dd5.pdf

 


ALSO READ

Reflections on a Pandemic - Letter by Paddy Palmer

Paddy Palmer and Hugh Palmer - Jan 18, 2022
READ MORE

Censorship in the Medical Field ⎟Who decides what misinformation is?

Andrea Kane - Jan 10, 2022
READ MORE

How To Keep Up With Ever Evolving Knowledge In Medicine?

Dr. Alishba Kainaat - Dec 14, 2021
READ MORE

Expanding Knowledge Beyond Old-school Medicine

Alissa Kivan - Oct 07, 2021
READ MORE

Covid-19 effects on Mental Health of Medical Professionals

Dr. Muhammad Arsalan Sharif - Sep 01, 2021
READ MORE

Thai equivalent of the Family Doctor is non existent

Peter B. Dunki Jacobs MD, PhD - Jul 03, 2020
READ MORE

Essential Knowledge for Healthcare Workers on Respirator Masks

Alinda Jansen - Mar 12, 2020
READ MORE

Prevalence of back pain in UAE residents tops 60%, says expert

Jannis Delaan - Jan 23, 2020
READ MORE

Challenging the Surgical Status Quo

Jeffrey de Jong - Nov 26, 2019
READ MORE