Therapy for COVID–19 Infection

As there is still no tried and tested vaccine to treat COVID–19 infections, the term “therapy” will be used in this article. The following entries is for information purposes only.

1. Remdesivir

Remdesivir, or GS-5734, is an adenosine triphosphate analog first described in the literature in 2016 as a potential treatment for Ebola.

Remdesivir (GS-5734) is a prodrug which mean that it is a medication or compound that, after administration, is metabolized (i.e., converted within the body) into a pharmacologically active drug.

The pharmacologically active form of Remdesivir is the alanine metabolite, GS-704277. This is then further processed into a monophosphate derivative and ultimately into the active nucleoside triphosphate derivative. Nucleotide analogues are not highly cell permeable, and once in the cell they require di- and then triphosphorylation to produce the nucleoside triphosphate (NTP) that can be utilized by the viral RNA-dependent polymerases (RdRp) for genome replication.

The replication of SARS-CoV-2 requires the viral RNA-dependent RNA polymerase (RdRp), a target of the antiviral drug Remdesivir. Shortly after adding Remdesivir, the enzyme stops being able to add more RNA subunits. This halts genome replication.

DOSAGING OF REMDESIVIR
COMMERCIAL NAME: VEKLURY
DAYS	PHASE	DOSAGE
REQUIRES MECHANICAL VENTILATION AND/OR ECMO
DAY 1	LOADING DOSE	200 mg infused over 30–120 minutes
Day 2 to 10	MAINTENANCE DOSE	100 mg O.D.
DOES NOT REQUIRES MECHANICAL VENTILATION AND/OR ECMO
DAY 1	LOADING DOSE	200 mg infused over 30–120 minutes
Day 2 to 5	MAINTENANCE DOSE	100 mg O.D.
** If clinical improvement not demonstrated, treatment may be       extended for up to 5 additional days (i.e., up to 10 days total)
** ECMO (Extra Corporeal Membrane Oxygenation)

       

2. Dexamethasone

Dexamethasone is classified as a corticosteroid (more precisely a glucocorticosteroid).

Corticosteroids are naturally produced by the adrenal gland in the body. Corticosteroids influence the functioning of most of the body's systems (heart, immune, muscles and bones, endocrine and nervous system).  They exert a wide array of effects including effects on the metabolism of carbohydrates, protein and fats. They help to maintain balance of fluids and electrolytes.

One way that it works is to decrease inflammation (swelling).  It does this by preventing infection–fighting white blood cells (polymorphonuclear leukocytes) from traveling to the area of swelling in the body.

Coronavirus infection triggers inflammation as the body tries to fight it off.

But sometimes the immune system goes into overdrive and it's this reaction that can prove fatal, the very reaction designed to attack infection ends up attacking the body's own cells. Dexamethasone calms this effect.

Dexamethasone is only suitable for people who are already in hospital and receiving oxygen or mechanical ventilation who are the most unwell. The drug does not work on people with milder symptoms, because suppressing their immune system at this point would not be helpful.

The following side effects are common (occurring in greater than 30%) for patients taking dexamethasone:

Increased appetite

         Irritability

         Difficulty sleeping (insomnia)

         Swelling of ankles and feet (fluid retention)

         Heartburn

         Muscle weakness

         Impaired wound healing

Increased blood sugar levels

Dosage:     6mg daily doses (for 10 days)

3. Convalescent plasma

Convalescent plasma therapy uses blood from people who've recovered from an illness to help others recover.

In the United States, the FDA allowed the use of convalescent plasma during the pandemic because there's no approved treatment yet for COVID–19.

The principle behind convalescent plasma is that blood donated by people who've recovered from COVID–19 has antibodies to the virus that causes it. The donated blood is processed to remove blood cells, leaving behind liquid (plasma) and antibodies. These can be given to people with COVID–19 to boost their immunity or their ability to fight the virus.

One of the advantages of convalescent plasma is that it is innate or naturally occurring and doesn’t have to go clinical trials like vaccines.

One of the disadvantage though is that plasma is also a rich source of blood borne infection (i.e. Hepatitis, HIV) thus a need to thoroughly screen the blood prior to therapy.

When convalescent blood was used in Wuhan (China), convalescent plasma needs to have an antibody titer between >1:640 to >1:1,000 and the dosage is between 200 ml to 2400 ml. One blood bag is approximately 450 ml and once red blood cell is precipitated and plasma is expressed, it is only equivalent to approximately 240 ml thus a need for massive sample.