COVID-19: Where lies the treatment?

Daily: The Pulse
Date: 28.03.20

Much has already been talked about the epidemiology (the mode of spread) of the disease
produced by COVID-19, a type of virus that is virulent enough to cause the Acute
Respiratory Distress Syndrome. The virus is considered contagious and hence is the focus
of attention on preventing its spread by active intervention. The virus is dangerous not only
because of its contagious nature owing to its being a droplet infection (through an airborne
route) directly (by cough and sneeze) or indirectly (by touch), but also because of its
virulence (i.e. the ability to cause harm) mostly to the respiratory system of the patient.
Nevertheless, this article will address the prospective areas of treatment for the
understanding of all including lay public.

It is known that a healthy human body develops a full immune response against a virus on
fifth day (or maximum on seventh day). An under-nutrition human body may develop a full
immune response by fourteenth day. Pakistanis witnessed this phenomenon during the
Dengue virus outbreak in 2011.

It is known that COVID-19 is a strain of Severe Acute Respiratory Syndrome-Corona Virus
(SARS-COV) called SARS-COV-2. Chinese scientists have already done its genetic
sequencing, which gives an idea what is present on the outer coat of the virus to make it so
virulent. COVID-19 shares about 85 percent of its genetic material (Ribo-Nucleic Acid, or
RNA, lying inside an outer layer of protein) with the SARS virus (transferred from animals to
humans) that gave an outbreak of epidemic proportion in 2002-2003 originating from
China. COVID-19 has also Chinese origin and it mutates slowly but it has attained a
pandemic proportion affecting most countries of the world. For both kind of viruses, dry
weather with low humidity and bright Sun-shine are lethal. Both factors significantly reduce
the contagious character of the viruses, though not their virulence.

Two main factors award COVID-19 high virulence: first, patients with a weak immune
(defence) system because of old age, some immunity related diseases such as AIDS, and
under-nutrition; and second, patients on the treatment of hypertension (high blood
pressure).

The receptors (or projections) existing on the protein surface of any virus determine its
virulence. On its protein surface, COVID-19 has three known glycoprotein receptors, E-
protein, S-protein and M-protein, which help the virus identify the cells it would enter. One
of identification markers on the recipient cell is Angiotensin-Converting Enzyme 2 (ACE-2)
receptor that are present on the cells of the respiratory system (and also the digestive
system). Now, patients of hypertension who take anti-hypertensive therapy based on ACE
inhibitors (ACEIs) or Angiotensin receptor blockers (ARBs) develop a higher number of
ACE-2 receptors on their cells in the respiratory system inviting S-protein of COVID-19 to
bind to them and let the virus enter the respiratory cells quickly and abundantly. That is,
patients taking ACEIs (of the Sartan family such as Losartan) and ARBs (of the Pril family
such as Captopril) are at a high risk of getting the virulent effect of COVID-19. Instead of
stopping the medicines, these patients should be more careful not to contract the virus.

There are two types of treatment for a COVID-19 infected patient: first, direct treatment
through vaccination; and second, indirect treatment through reducing the intensity of
inflammation damaging respiratory cells. Regarding the direct treatment, latest reports
suggest that more than one kind of vaccines (to develop active immunity against the
disease) have been developed, but they are passing through various stages of clinical
trials to determine the efficacy, before being marketed. Regarding the indirect treatment, all
anti-inflammatory drugs compete with one another for grabbing attention of clinicians. The
most favoured are two: first, quinine derivatives; and second, anti-interferon gamma
therapies.

Quinine derivatives such as Chloroquine and Hydroxy-Chloroquine are known drugs for
treating malaria. Recently, problems emerged when lay public started using them for
prophylaxis (or prevention) of COVID-19, for which these drugs created side effects.
Quinine derivatives may help in the treatment of COVID-19 to control cytokines (hormones
of short duration influencing short distance) that create a pro-inflammatory cytokine storm,
which, along with killing the virus, kills respiratory cells. Quinine derivatives are already in
use to dampen the pro-inflammatory cytokine storm that appears in certain inflammatory
diseases such as rheumatoid arthritis and systemic lupus erythematosus, which are
autoimmune diseases. As a preventive medicine, quinine derivatives may cause adverse
effects including quinine poisoning when there is present no pro-inflammatory cytokine
storm in the body, but this may not be the case during the active phase of COVID-19. That
is, quinine derivatives do not kill COVID-19 but these drugs diminish the pro-inflammatory
cytokine storm and protect respiratory cells from dying during the course of the disease by
the time the patient’s body develops its natural immune response against COVID-19.

Interferon gamma is one of the pro-inflammatory cytokines found active in human body
especially against invading viruses and it is the major contributory cytokine to any pro-
inflammatory cytokine storm evoked in response to any foreign agent including COVID-19.
Interferon gamma has been effectively used against Hepatitis C viral infection. In the case
of COVID-19, however, an anti-interferon gamma therapy is required to diminish the pro-
inflammatory cytokine storm. Anti-interferon gamma (monoclonal) antibodies are already in
use as a therapy against autoimmune diseases such as rheumatoid arthritis and the lupus
disease. That is, an anti-interferon gamma therapy offers a neutralizing effect on the pro-
inflammatory cytokine response to protect the patient’s respiratory cells by the time the
patient’s body develops its natural immune response against COVID-19.

There is no harm in exploiting anti-inflammatory properties existing in herbs used in
alternative medicine such as Unani medicine. Any such herb may protect the respiratory
cells to ensure lives of patients.

In short, before any vaccine emerges successful out of clinical trials, to save the life of
COVID-19 infected patients, anti-inflammatory drugs individually or in combination may be
administered to protect the respiratory cells to ensure the survival of COVID-19 patients.
The dose can be the same which is already in use for treating autoimmune diseases.
Pakistani doctors are equally capable of making such a treatment possible.

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