Sunday, June 21, 2020

Ch 6. Candidate treatments - immunity to coronaviruses in context of COVID-19

What medications are candidates for COVID-19 treatment?
  1. Medicines the attack the virus, such as remdesivir.
  2. Medicines that boost an APPROPRIATE immune response.
  3. Medicines that calm down an INAPPROPRIATE immune response, and
  4. Medicines that can do both 1 and 3 such as hydroxychloroquine (HCQ).



COVID-19 virus, immune response and medication options


1. Medicines the attack the virus
REMDESIVIR

Why is Remdesivir a candidate to treat COVID-19?
This medicine has shown anti-virus activity. It binds and blocks an enzyme needed for the virus to make more copies of itself (Chapter 1). In experiments, animals treated with remdesivir had lower lung virus levels. They also had less lung damage than those who did not receive it.
Others like favipiravir are also being tried out.

2. Medicine that boost an APPROPRIATE immune response.
CONVALESCENT PLASMA

What is convalescent plasma?
When a person has recovered from COVID-19 infection, their blood has antivirus antibodies (Chapter 3). Plasma is part of blood that is rich in antibodies. Purifying plasma of such person provides COVID fighting antibodies.

How could convalescent plasma help?
Antibodies to the virus interfere with virus in several ways. Antibodies can bind to a virus particle. They can block a virus from entering new healthy cells. They can also activate immune cells to kill virus containing cells.

3. Medicines that calm down an INAPPROPRIATE immune response
MEDICINES TO TREAT CYTOKINE STORM (chapter 5)

How could medicines that calm down an INAPPROPRIATE immune response help?
A cytokine storm is an excessive immune response that can damage organs (Chapter 5). Medicines to calm an overactive immune system are helpful. Dexamethasone (a corticosteroid, also known as steroid) acts in this manner. Other medicines (tocilizumab, tofacitinib, ruxolitinib) act to block effects of specific cytokines involved in cytokine storm. Azithromycin a common antibiotic also has immune regulating properties.

4. Medicines that can do both 1 and 3 
HYDROXYCHLOROQUIN (HCQ).

Why is HCQ a candidate to treat COVID-19?
HCQ interferes with virus sticking to its receptor on cell (ACE2). It interferes with blending of virus with membranes of lung cells. These actions reduce entry of virus into cells. It can also block virus leaving the cell (Chapter 1). Finally, HCQ has effects on immune system, which may be beneficial in a cytokine storm (Chapter 5).

How does HCQ affect immune function?
Hydroxychloroquine (HCQ) can pass into our cells with ease. HCQ accumulates inside parts of the cell called lysosome. In immune cells, lysosome deals with processing and secretion of proteins. By increasing in the lysosome, HCQ interferes with its function in immune cell. HCQ can also block proteins recognizing "danger signals". This reduces the activation of early immune cells (Chapter 3). This is the reason patients with certain autoimmune diseases like SLE (lupus) take HCQ. It is the reason for treating joint inflammation in rheumatoid arthritis.

Why is HCQ used in prevention or treatment of malaria?
The same principle of lysosome interference works malaria parasite. In the lysosome of malaria parasite HCQ interferes with digestion of blood proteins. Thus, it is effective anti-malarial.

The medications listed above are all under trials to see which of these actually makes an impact on outcome of COVID-19 infection.


Reference
COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment Guidelines. National Institutes of Health. Available at https://www.covid19treatmentguidelines.nih.gov/. Accessed [6-21-2020].

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