COVID-19:Flattening The Curve: A Myth Or Reality?

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COVID-19, definitely not a coveted word for Homo sapiens! As 2020 unfolded, never did I, a practicing periodontist and a passionate researcher in oral-systemic health, think that all my scientific interest would be redirected to this miniscule living being, the SARS-CoV 2! My donning dual caps as a clinician and a scientist made me look at this COVID-19 multi-dimensionally! As a periodontist, the aerosol generated from possible disease positive patients/asymptomatic carriers is a huge concern as I have to make choices of treating patients who need emergency dental care! With the surge of cases globally and in India, what with “R naught” statistics in a constant state of flux, there is a genuine concern about how long patients can be guarded from their dental problems! All roads however, lead to one common destination namely, FLATTENING THE CURVE!! Could a mountain predictably become a molehill?
As a periodontist and a scientist, my first response to COVID19 was, “how is the host response to this going to be”? More so, the varying responses to the SARS-CoV-2 and the susceptibility patterns which are so difficult to unveil to date, makes it the most vital factor determining infectivity! In fact, developed nations like the United Kingdom initially took up the stand of “Herd/community immunity” that one would gradually develop immunity to SARS-CoV-2, which was reconsidered following the cataclysmic spread of COVID-19 amongst their population! However, thinking back, or rather ahead, is this the only solution to flatten the curve predictably?

PATHOGENESIS OF COVID-19

We are now familiar with the microscopic structure of SARS-CoV-2 (Figure-1)  and the ensuing pathogenesis of COVID-19 (Fig-2). To recapitulate, the spike glycoprotein “S” which forms a crown around the viral cell, is a heavily-glycosylated, cell-surface protein with two functional domains S1 and S2, both of which are important to mediate viral entry into host cells. S1 which contains the receptor-binding domain for ACE-2 (expressed in the lung, kidney, and gastrointestinal tract), and facilitates entry into the cell and S2 brings about fusion of the cell and viral membranes. The “game-changer” which critically cleaves the S protein is Furin, a host protein-convertase enzyme.

Host responses to COVID-19: A double-edged sword?

 It is notable that not all people exposed to SARS-CoV-2 get infected and not all infected patients develop severe symptoms like Acute Respiratory Distress Syndrome.

There are three stages of this infection,

  1. Stage I, an asymptomatic incubation period with or without detectable virus is the most dangerous because they spread the virus unknowingly
  2. Stage II, non-severe symptomatic period with the presence of virus;
  3. Stage III, severe respiratory symptomatic stage with high viral load

There are two- phases of immune response to COVID-19:

  1. During the incubation period, a specific adaptive immune response is required to eliminate the virus and to preclude disease progression to severe stages. Boosting the immune response at this stage is very vital. A good innate immunity of the host and a genetic background that elicits sufficient anti-viral immunity is important.
  2. However when there is an inadequate immune response, there is an increased expression of the virus on ACE2 receptors such as intestine , kidney and lungs. This can be life-threatening when there is severe inflammation of the lungs leading to respiratory insufficiency and multi-organ shutdown.

Another oft-used termed with COVID-19 is the “CYTOKINE STORM SYNDROME”, which results in adult respiratory distress syndrome and multi-organ failure. This is a consequence of an accentuated immune response to various triggers, including viral infections, resulting in the release of various pro-inflammatory cytokines such as IL2, IL7, IL10, GSCF, IP10, MCP-1, MIP1A and TNF-alpha. When there is an imbalance of the mechanisms regulating pro- and anti-inflammatory balance, a cytokine storm ensues. The treatment of this cytokine storm is the biggest challenge facing COVID-19.

Vaccines and COVID-19

 Long-standing and predictable immunity to COVID-19 can only be a vaccine. An epitope is that part of an antigen to which the antibody binds to fight any infection. Each antigen has several epitopes, to which specific antibodies bind. Five epitopes have been identified in the spike glycoprotein of SARS-CoV-2; two in the membrane protein, which is embedded in the membrane that envelopes the protective protein shell around the viral genome and three in the nucleoprotein, which forms the shell!

Fortunately, as many B and T cell epitopes are highly conserved between SARS-CoV(2002) and SARS-CoV-2, developing a vaccine targeting these regions has already begun! Phase I clinical trials are on for 2 candidate vaccines and 60 vaccines are currently undergoing pre-clincial trials. One of these vaccines includes a “recombinant vaccine” which extracts the sequence for the spike protein of the Sars-CoV-2 antigen, and inserted into bacterial/yeast cells to produce increased levels of the antigen to be purified into a vaccine.

With the current evidence available, it is clear that though COVID-19 is highly contagious, the host response is the determining factor of the susceptibility and severity of this infection.

To conclude, though social distancing and hand hygiene are the two tenets of preventing/ reducing community spread, mass testing would be the ideal solution at this critical juncture of Stage III which our country is moving towards. Because of the unpredictable immune/host responses to COVID-19 infection, mandatory mass testing for Sars-CoV-2 antigen or IgG antibodies to the antigen is now the only measure to identify patients with the disease or at risk to transmit the virus and predictably “Flatten the Curve”!

NONETHELESS, STAY HOME, STAY SAFE!

Author: Dr. Bagavad Gita

Professor and Head,

Dept. of Periodontology, Sree Balaji Dental College and Hospital,

Chennai, Tamil Nadu, India

 

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