COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Understanding its pathophysiology involves examining how the virus interacts with the human body to produce illness. This includes the mechanisms of infection, the resulting damage to various organ systems, and the body’s complex immune responses.
How the Virus Enters and Replicates
The SARS-CoV-2 virus initiates infection by targeting specific receptors on human cells. Its outer spike (S) protein binds to the angiotensin-converting enzyme 2 (ACE2) receptor, which is abundant on the surface of various human cells, particularly in the lungs. This binding facilitates the virus’s entry into the host cell. The SARS-CoV-2 spike protein demonstrates a 10 to 20-fold higher binding affinity to ACE2 compared to SARS-CoV-1, which may explain its increased transmissibility.
For successful entry, the viral spike protein also requires priming by host cell proteases like TMPRSS2. Once inside, the virus releases its genetic material, a positive-sense single-stranded RNA, into the cell’s cytoplasm. The host cell’s machinery is then hijacked to replicate the viral RNA and produce new viral proteins.
These newly synthesized viral components assemble into new SARS-CoV-2 virions within the host cell. These new viral particles are then released, ready to infect neighboring cells and continue replication. The initial sites of infection commonly include cells in the upper respiratory tract, such as those lining the nose and throat.
Impact on the Respiratory System
The lungs are the most frequently affected organ system in COVID-19, with the virus causing a range of respiratory issues. Viral replication within lung cells, particularly type II alveolar cells, leads to direct cellular damage. This damage, combined with the subsequent inflammatory response, impairs the lungs’ ability to function effectively.
Infected individuals often develop pneumonia, where the air sacs (alveoli) in both lungs fill with fluid, limiting oxygen uptake. This fluid buildup and tissue thickening make it harder for oxygen to pass into the bloodstream, leading to symptoms like cough and shortness of breath. The type of pneumonia associated with COVID-19 can be severe and may result in lasting lung injury.
In severe cases, COVID-19 can progress to acute respiratory distress syndrome (ARDS), a life-threatening form of lung failure. ARDS occurs when the lung lining is extensively damaged, causing fluid to accumulate in the air sacs and leading to their collapse. Patients with ARDS experience severe hypoxia, a dangerously low level of oxygen in the blood, often requiring mechanical ventilation to support breathing.
Effects Beyond the Lungs
COVID-19 is a systemic disease that can affect multiple organ systems beyond the respiratory tract. The widespread inflammation and damage to blood vessels are often responsible for these broader effects. The virus can directly invade cells in various organs that express the ACE2 receptor, including the heart, kidneys, and gastrointestinal tract.
Cardiovascular complications are common, including heart inflammation (myocarditis), irregular heart rhythms (arrhythmias), and the formation of blood clots (thrombosis). Blood clots can lead to serious events such as strokes or heart attacks. Acute kidney injury is frequently observed in hospitalized COVID-19 patients and is associated with a poor prognosis.
Neurological manifestations can also occur, ranging from “brain fog” and headaches to more severe conditions like seizures, strokes, and encephalitis. Elevated liver enzymes, indicating liver injury, are also common. Gastrointestinal symptoms, such as diarrhea, have also been reported, although they are less common than other systemic effects.
The Body’s Immune Response
The human immune system’s reaction to SARS-CoV-2 infection is complex, involving both protective mechanisms and responses that can cause further tissue damage. Upon infection, the innate immune system provides an immediate, non-specific defense. This involves the release of various signaling molecules, including interferons, which attempt to control viral replication.
Following the innate response, the adaptive immune system mounts a more specific attack. This includes the activation of B cells to produce antibodies that can neutralize the virus and T cells that target and destroy infected cells. A well-coordinated immune response is important for clearing the virus and preventing severe disease.
However, in some patients, the immune response becomes overactive, leading to a phenomenon known as a “cytokine storm.” This involves an excessive and uncontrolled release of pro-inflammatory cytokines, such as IL-6, IL-1, and TNF-α, by various immune cells. This hyperinflammation can cause widespread tissue damage, multi-organ dysfunction, and contribute to the severity of COVID-19.