About the virus
The pathogenic virus, SARS-CoV-2, is a member of the coronavirus family which includes the viruses responsible for SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) infections. The virion, which is a single virus particle, consists of a small set of genes encoded in the virus’ genetic material, RNA that is enclosed by a spherical membrane made up of a layer of lipid molecules. Since the lipid molecules can be easily destroyed by soap, it is recommended that a thorough washing of hands is sufficient to break apart the viral particles.
The membrane is covered by spiky protrusions resembling a crown, hence the name, ‘coronavirus’. COVID-19, which is the disease caused by SARS-CoV-2 is an abbreviation for coronavirus disease (year) 2019. It is a zoonotic disease, which means that it jumped from an animal species into humans with the first cases reported in December 2019 in the province of Hubei, China, of which Wuhan is the capital. Early evidence indicates that the virus jumped from bats to humans due to their close living proximity since in China, bats are traditionally symbols of good luck and happiness.
How does it enter human cells?
Most respiratory viruses infect either the upper or lower part of the respiratory airways but this novel coronavirus seems to infect both. Infection of the upper tract only results in milder symptoms but when the virus infects the lower tract, the symptoms become more severe.
The spike (S) protein on the SARS-CoV-2 surface attaches to the ACE2 protein on our cells. This is the first stage to an infection. The fusion of both viral and human cell membranes allows the virus’ RNA to enter the cell. Like other viruses, it hijacks our cell’s protein-production machinery to make new copies of the virus from the RNA template. In just hours, our cells are forced to produce several thousand new virions, which can then exit and infect other healthy cells.
ACE2, or angiotensin converting enzyme-2, is a receptor protein present in many cell types and tissues including the lungs, heart, blood vessels, kidneys, liver and gastrointestinal tract. Scientists have discovered that the protein is also present in cells that line the nose and mouth, which would explain the virus’ primary entry point in humans.
In 2003, during the first SARS epidemic, Michael Farzan and team discovered that ACE2 was responsible for opening the door to the SARS-CoV virus (1). The protein has again garnered increased attention due to the current pandemic and the recent emergence of the novel SARS-CoV-2 virus. In a recent research article published in the journal Nature, the structural features of the virus-receptor interaction were discovered for the first time, which could lead to antiviral interventional strategies (2).
Immune response against the intruder
Our immune response to an infection, in broad terms, is categorized into two branches – the innate immune response and the adaptive immune response.
The innate system is the initial ‘quick response’ and more generalized line of defense consisting of immune cells such as macrophages, dendritic cells and natural killer cells. These ‘always on’ cells can recognize and ward off a variety of foreign pathogens by recognizing common molecular patterns on the pathogen. However, if viral particles outnumber the innate defense team, the second branch, the adaptive system needs to be mobilized.
The adaptive system, or acquired immune response as it is commonly called, consists of lymphocytes – B cells and T cells – the body’s lethal professional pathogen killers. B cells produce antibodies that bind to the virus particles in the blood and mucosal surfaces and can block the spread of the infection, and T cells recognize and kill infected cells.
An article published in May 2020 in the journal, Cell, suggests that SARS-CoV-2 uses a completely new mechanism to take over the host’s cellular machinery. In the pre-clinical study, scientists found that the virus uniquely manipulates the host cell’s genome by blocking one set of immune system genes that are responsible for fighting the virus while activating other virus-fighting genes, thus altering the host’s ability to effectively defend itself (3).
Why do we get sick?
The infection is dependent on who wins the race – virus or immune system. The milder the viral load, or the number of virions that are produced, the better our immune system can limit its uncontrollable spread.
If the virus wins the race, lung cells get severely damaged and can no longer deliver oxygen to the rest of our body and thus a person requires a ventilator.
Our immune system produces molecules called cytokines, which are proteins that coordinate the body’s response against an infection and triggers inflammation. Sometimes this response goes into overdrive and the overproduction of these molecules creates what is called a ‘cytokine storm,’ leading to hyperinflammation (4). This can cause serious harm or even be fatal. In the 2005 outbreak of the “bird flu,” the high fatality rate was associated with an out-of-control cytokine response. This phenomena is not unique to COVID-19 and people with autoimmune diseases and cancer patients receiving immunotherapy also can experience a similar hyperactive response. This might explain why some patients already having a chronic disease end up with secondary complications besides the lungs.
Coronoavirus tends to be a winter virus similar to influenza. This is because the cold and dry air makes the liquid ‘mucus’ layer that coats our lungs and airways to become very thin and the hair-like projections on the cells that line the airway find it hard to get rid of the viruses. In the summer, however, the heat and humidity reverses this effect and as the Northern hemisphere enters the Summer season, we could see a slowdown in the infection rate.
Treatments
There are over 200 clinical trials of therapeutics and vaccines for COVID-19 that are slated to yield study results in Summer 2020, just a few months after COVID-19 was declared a pandemic by the WHO. There are some front-runner companies in the race to find a solution, developing novel vaccines and therapies tailored to SARS-CoV-2. Other companies are repurposing drugs to treat COVID-19 in an attempt to fast track potential options. A good resource for finding more information is here.
Only time will tell which treatment option(s) will work but I am very optimistic seeing the combined and focused efforts of the global academic, biotech and pharma institutions towards this pandemic.
Additional resources
https://www.en.fondazione-menarini.it/Home/Coronavirus-Library
https://www.who.int/emergencies/diseases/novel-coronavirus-2019
Coronavirus information in Germany: https://www.deutschland.de/en/corona-virus-germany-overview
Coronavirus information in India: https://www.mygov.in/covid-19/
