Since its initial outbreak in December of 2019, the COVID-19 pandemic has been shrouded by uncertainty. Because transmittance of the virus is new in human populations, there is limited research on it, and clinical and experimental data leads to new conclusions on almost a daily basis. However, as the disease continues to spread at a rapid rate, it is important to understand how the disease spreads, as well as how infection leads to disease in order to develop effective preventative measures and treatments.
The main way SARS-cov-2, the virus that causes COVID-19 disease, is transmitted is through droplets produced when an infected person sneezes or coughs. These droplets can enter the body through the eyes, nose, or mouth. Another less common method of transmission is contact with contaminated objects or surfaces and subsequent touching of the eyes, nose, or mouth; however, studies have shown that the virus can only survive for 72 hours on plastic, 48 hours on stainless steel, 24 hours on cardboard, and 4 hours on copper, and by the end of these periods of time, less than 0.1% of virus material remains.
Once the virus enters the body, the viral particles travel to the back of the nasal passage and to the mucous membrane at the back of the throat. At this point, the anatomy of SARS-cov-2 proves to be the reason behind the virus’s pervasiveness. Coronaviruses are unique in that they have spike proteins on their surfaces that enable the viruses to recognize and bind to host cells. SARS-cov-2 specifically has spike proteins, or S proteins that seem to be optimized to human Angiotensin-Converting enzyme-2 (ACE2) receptors, which exist on the surfaces of respiratory cells that line the airway.
But this is the same mechanism that was utilized by SARS-cov, the virus that caused the 2002 coronavirus epidemic, which raises the question: what gives SARS-cov-2 the unique ability to spread so fast, to the point where a pandemic has arisen?
First, genetic sequencing has shown that the SARS-cov-2 strain has six amino acid residues that differ from the SARS-cov strain that give it a higher binding affinity with human ACE2 receptors. In fact, studies show that SARS-cov-2 is 10-20 times more likely to bind to ACE2 receptors than SARS-cov.
Second, SARS-cov-2 takes advantage of a protein, furin, made by human cells to enter the host cell upon recognition and binding. The S proteins consist of two subunits, called S1 and S2: the S1 subunit contains the receptor binding domain and is responsible for initiating the virus’s entry into the host cell, and the S2 subunit enables fusion between the host cell membrane and the viral membrane so that the virus can actually enter the host cell. In order for this fusion to take place, the S protein must be cleaved such that the amino acid sequences on the S2 subunit are exposed for the host cell membrane to attach to. Between the S1 and S2 subunits of the SARS-cov-2 spikes is a cleavage site specific to furin, a structure that is not present between the SARS-cov subunits. It is hypothesized that the ability of the virus to infect both the upper and lower respiratory tract is a result of the presence of furin in both regions. Moreover, furin is found in particularly large concentrations in the lungs, which explains the severe respiratory symptoms COVID-19 patients may experience.
After entering the host cells, the virus begins its replicative cycle. Coronaviruses are RNA viruses, and their genetic material is made up of single-stranded RNA (ssRNA). The SARS-cov-2 ssRNA can directly serve as mRNA in the host cell, meaning that the virus can exploit host cell machinery to produce viral proteins and replicate its genome almost immediately after infection. Using the newly translated viral proteins and replicated genome, new viruses self assemble and leave the host cell to infect other cells.
Initially, when the virus is located in the upper respiratory tract, in the nasal passage and at the back of the throat, it may cause acute symptoms such as sore throat and dry cough, but as the virus replicates more and more, the symptoms become more severe. As the virus replicates, more cells are infected, and dying cells begin to fill the airways, pushing the virus to the lower respiratory tract, particularly the lungs. At this point dead cells and fluid fills the lungs, making breathing more labored. The immune system will try to fight against infection, but, in some cases, this only further damages the lungs and exacerbates symptoms. For example, blood vessels may open up to provide entryway to cytokines, which are secreted by T cells in the body in order to regulate the immune response. Problems arise when a cytokine storm occurs: blood vessels may open up to allow too much fluid to enter the lungs, which only worsens difficulty breathing, or inflammatory cytokines may cause the immune system to attack the body itself due to a lack of ability to precisely locate and aim at target viruses. These cytokine storms can lead to inflammation of the lung’s mucous membranes, which damages the alveoli, hindering the exchange of carbon dioxide and oxygen in the lungs, and can even cause pneumonic symptoms and organ failure.
Ultimately, it is evident the SARS-cov-2 has evolved to be extremely precise and successful in infection and pathogenesis. The virus’s ability to exploit human cells and metabolic machinery so effectively and affect both upper and lower respiratory tract are major causes for concern, but, perhaps, we can find solace in the likelihood that it can’t get worse than this. Since the start of the pandemic, 100 mutations have been documented, but none have risen to dominance, showing that there is no evolutionary pressure for the virus to be better.