Widely Used Drugs And Therapies For COVID-19 Treatment

Oct 27, 2020

The Most Widely Used Drugs And Therapies For COVID-19 Treatment; And The Surprising Non-Drug That Everyone Agrees On

Worldwide, more than 43 million people have been infected by SARS CoV-2 and more than 1.1 million people have lost their lives in the battle against COVID-19. There are no drugs or vaccines approved for the prevention or treatment of COVID-19 yet, except Remdesivir which was approved very recently by the FDA. The urgent need for treatment during the pandemic has led to the widespread use of unproven treatments, supported largely by observational studies.

Here, we discuss the most commonly used investigational drugs and other therapies to treat COVID-19.

Antiviral Therapies

Remdesivir

Remdesivir (GS-5734; Gilead Sciences, Inc) is the first approved drug for COVID-19 treatment by the FDA. This antiviral drug is approved for use in hospitalized adult and pediatric patients 12 years of age and older and weighing at least 40 kilograms (about 88 pounds). The drug has been shown to inhibit replication of other human coronaviruses which include SARS-CoV and MERS-CoV. An in vitro study showed that the drug prevented human cells from being infected with SARS CoV-2. Phase-3 clinical trials of Remdesivir for COVID-19 treatment are undergoing in the U.S., China, and South Korea. This antiviral is also being studied in combination with other medications.

Not all Remdesivir studies have been promising and recently, a study by the World Health Organization called the “Solidarity Therapeutics Trial” found that Remdesivir has little or no effect in hospitalized COVID-19 patients. The results of the study stated that the drug did not reduce mortality, chances for the need of medical ventilation, or the duration of hospital stay as compared with patients without the drug treatment.

Other investigational antivirals:

Favipiravir, also known as Avigan is an oral antiviral medication approved for the treatment of flu in China and Japan. It is approved in Russia for COVID-19 treatment. In Vitro studies have shown that high doses of this antiviral prevent human cells from being infected with SARS CoV-2. Some studies conducted in China for this drug have shown promising results and the first U.S. clinical trials for Favirpiravir were approved to start in Boston.

Tamiflu, also known as Oseltamivir is an antiviral medication used to treat and prevent influenza A and B virus. Several clinical trials are currently undergoing for Tamiflu in combination with other drugs to treat COVID-19.

Galidesivir is a new antiviral drug that is currently being developed and clinical trials for this drug are starting in Brazil soon.

The NIH currently recommends against using these antiviral drugs – Azithromycin, Hydroxychloroquine, chloroquine, Kaletra (lopinavir/ritonavir), and Ivermectin for COVID-19 which were earlier used for COVID-19 treatment.

Corticosteroids

Dexamethasone

Dexamethasone is a corticosteroid drug used to treat various conditions such as arthritis, blood/hormone/immune system disorders, and allergic reactions. This drug showed promising results in the UK’s national clinical trial RECOVERY where it was tested in hospitalized patients of COVID-19. The medication seemed to benefit patients who were critically ill.

Based on the preliminary findings shared with WHO, the drug was shown to reduce mortality by about one third for patients on ventilators, and about one fifth for patients requiring only oxygen. Additionally, a prospective meta-analysis from the WHO rapid evidence appraisal for COVID-19 therapies (REACT) pooled data from 7 trials (for ex. RECOVERY, REMAP-CAP, CoDEX, CAP COVID) and found that the mortality rate was significantly lower in hospitalized patients who took one of three different corticosteroids — dexamethasone, hydrocortisone, or methylprednisolone, compared to those who took none (32% vs. 40%)

Immune-based therapies

Convalescent plasma

On Aug 23, 2020, the FDA granted emergency use authorization for the use of convalescent plasma in hospitalized COVID-19 patients. Convalescent plasma therapy involves transfusing antibody-rich plasma from the blood of people who have been infected with the virus and recovered into people who are infected with the virus or vulnerable to the virus. It is also known as passive antibody therapy and is known to be used in various infectious disease outbreaks such as diphtheria, influenza, and, more recently, SARS, MERS, and Ebola.

Some studies showed a reduced mortality rate in patients treated with convalescent plasma, however, there is no conclusive evidence on the benefits of the plasma therapy yet.

IL-6 inhibitors

IL-6 or Interleukin-6 is a pro-inflammatory cytokine produced by a variety of cell types, including lymphocytes, monocytes, and fibroblasts. Inflammation and respiratory failure caused by COVID-19 can be related to cytokine storms, as indicated by elevated blood levels of IL-6, C-reactive protein (CRP), D-dimer, and ferritin. It is hypothesized that modulating the levels of IL-6 or its effects might alter the course of disease.

IL-6 inhibitors such as Tocilizumab, Sarilumab block the IL-6 and are believed to help in managing cytokine storms. However, the NIH currently recommends against the use of such IL-6 inhibitors for COVID-19 treatment.

Kinase inhibitors

The kinase inhibitors are proposed as treatments for COVID-19 because they can block the cytokine signaling pathways and are believed to have a potential role in managing the cytokine storms. Acalabrutinib (Calquence), baricitinib (Olumiant), ruxolitinib (Jakafi), tofacitinib (Xeljanz) are some of the kinase inhibitors that are being tested for COVID-19. However, the NIH recommends against the use of these inhibitors for COVID-19 treatment as they broadly suppress the immune system and so make it difficult to fight off the infection.

Monoclonal Antibodies

Antibodies are proteins that are produced by the immune system in response to the entry of toxic substances into the body. They bind to these toxic substances and help to fight off the infection. Artificially developed antibodies (i.e. made in a lab) are called monoclonal antibodies. Since our body can take several weeks to develop antibodies, using monoclonal antibodies can help the body to fight off the infection sooner.

REGN-COV2 and LY-CoV555 are two monoclonal antibodies that are currently being developed for COVID-19 treatment, by Regeneron and Eli Lilly respectively. Clinical studies for both these drugs are still undergoing and the full results are not available yet.

Immunity Boosters

With no coronavirus vaccine approved yet, many people are turning to vitamins and other supplements to boost their immune system. One of these supplements, Vitamin D is being explored by many scientists around the world as a potential therapeutic agent for COVID-19.

Vitamin D

Past studies showed that Vitamin D reduces the risk of respiratory tract infections. More recent research suggests that people with sufficient vitamin D levels in the U.S. had a reduced risk of getting infected with COVID-19. In fact, Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said in an Instagram live, “If you are deficient in vitamin D, that does have an impact on your susceptibility to infection”.

For months now, we have been claiming that Vitamin D is as important to COVID-19 treatment  as any pharmaceutical; the evidence is substantial:

  • Vitamin D is critical to immune system function and therefore affects outcomes; many research studies show that COVID patients with higher Vitamin D levels had better outcomes. 
  • Vitamins D helps regulate Bradykinin levels; a Bradykinin storm could be at the core of the now-infamous cytokine storm. 
  • Lower mortality rates in countries like India can partly be due to vitamin D being a standard part of treatment as opposed to the US where until recently, Vitamin D was not part of CDC protocol.

According to the NIH and WHO, there isn’t enough evidence as of now to recommend the use of Vitamin D as prevention or a therapeutic agent for COVID-19. However, we believe this has more to do with the large scale insurance and cost dynamics of implementing any new element to the treatment regimen, and possibly, the politics of the message that a simple supplement could be more powerful than the firepower of US pharma.  On the ground the reality is different; President Trump received vitamin D immediately as part of his treatment. 

And on a personal note, Girish Khera, the founder of COVIDIndia.org, had a brother in the ICU who didn’t respond after 3 days of Remdesivir, or to convalescent plasma, but was released from ICU 36 hours after getting vitamin D. It’s not scintillating science but we need more studies on vitamin D treatment for Covid-19!

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