The SARS-CoV-2 virus, better known as COVID-19, has presented the global community with a medical, economic, and social crisis, raising considerable concern over its virality. Since the start of the pandemic, symptoms have varied in intensity, with some patients experiencing “long COVID, ” lasting effects that persist past recovery stages, while others encounter quick recoveries. More recently, the development of the vaccine strategy to effectively curb the disease by repressing its deadly manifestations has been attributed to aiding in the recovery from SARS-CoV-2. Still, important mechanisms such as innate and adaptive immune responses are the front-line for attacking the virus and affecting the severity of infection. To understand the role of the innate immune response and why symptoms vary in severity, the mechanisms behind the SARS-CoV-2 infection must be investigated.
Viral Infection
SARS-CoV-2 is a positive sense, a single-stranded RNA molecule that belongs to the coronavirus family. The mechanisms of attack for this virus are conducted through the use of proteins found in the lipid bilayer, the membrane of the cell.
The S or spike protein is the primary protein that allows the virus to gain entry and attach to a host cell. Additional molecular structures including the E (envelope) and M (membrane) proteins contribute to the formation and stability of the viral envelope which protects the genetic material of the virus as it travels between host cells. One domain within the S protein - the S1 division - interacts with the angiotensin-converting enzyme 2 (ACE2) receptor on the cell surface allowing for viral interaction with the host cell. The virus utilizes a lock-key mechanism to bind to the ACE2 receptor, using it as a doorway to enter the cell. Under normal conditions, the ACE2 receptor regulates the angiotensin II (ANG II) protein that can result in increased inflammation and cell death, especially in the alveoli - the site of gas exchange. When SARS-CoV-2 binds to the ACE2 receptor, its function is inhibited making the modulation of ANG II extremely difficult. As a result, the risk of lung and heart injury increases substantially in COVID-19 patients. Following entry into the cell, the viral RNA genome undergoes replication from which new viral particles are formed through the creation of a new viral envelope.
Innate Immunity
Before the targeted immune response begins, the mucosal lining acts as the first line of defence to prevent viral particles from travelling down the respiratory tract. Once the RNA molecules are identified by the body, infected epithelial cells produce interferons that allow for the innate immune response to occur. Dendritic cells (skin cells), macrophages (cells that perform phagocytosis to destroy bacteria), and neutrophils initiate the immune response and contain receptors that activate signalling cascades to amplify the secretion of cytokines.
However, because cytokines are proinflammatory in order to localize and eliminate infected tissues, overactivation of the inflammatory immune response could deteriorate the recovery of COVID-19 patients. In addition to the cytokines, targeted immune response through secretion of T-cells which kill virus-infected cells, and B-cells that produce virus-specific antibodies add to the inflammatory response.
Variations in Immune Responses
Questions remain in regards to the variations in the severity of the viral infection. While much remains undiscovered, current researchers point to the role of autoimmune responses in determining the severity of the symptoms. Autoantibodies, proteins that target the body’s own tissues by mistake, are commonly found in autoimmune diseases making patients suffering from such diseases more susceptible to severe symptoms and harsher recoveries. In fact, studies have shown that autoantibodies present before the coronavirus infection may account for 20% of fatal COVID-19 cases (National Institutes of Health). Furthermore, 50% of hospitalized COVID-19 patients had autoantibodies compared to only 15% of healthy controls. Autoimmune diseases set up a weaker immune system, making inflammatory immune responses dangerous and often contribute to a longer and more strenuous recovery period. With this in consideration, maximizing protection by adhering to protocol, staying informed, and getting vaccinated remain pertinent concerns.
Author : Sanjana Perungalam
Pictures:
Comentários