Angioedema is a condition of rapid, pronounced swelling that occurs in the deep layers of the skin. This swelling can affect various body parts, most notably the face, lips, tongue, and throat. Observations have linked the occurrence of angioedema to both COVID-19 infections and the vaccinations developed to combat the virus. These connections have prompted scientific inquiry into the underlying mechanisms driving these reactions.
Angioedema Triggered by COVID-19 Infection
The SARS-CoV-2 virus, which causes COVID-19, can provoke angioedema through several proposed biological pathways. A primary theory focuses on the virus’s interaction with the angiotensin-converting enzyme 2 (ACE2). SARS-CoV-2 uses the ACE2 receptor to enter human cells, and this process can downregulate ACE2, disrupting its normal function in breaking down a protein called bradykinin. An accumulation of bradykinin leads to increased vascular permeability, allowing fluid to leak from blood vessels into surrounding tissues, which manifests as swelling.
Another potential mechanism involves the immune system’s response to the virus. The infection can trigger a widespread inflammatory response, leading to the activation of mast cells. These immune cells release histamine and other inflammatory mediators, which can also cause blood vessels to become leaky, resulting in swelling. Angioedema can appear during the acute phase of a COVID-19 infection or may emerge as a lingering issue in individuals experiencing Long COVID.
Angioedema Following COVID-19 Vaccination
Cases of angioedema have also been reported following COVID-19 vaccination, although this is an infrequent event. The reaction has been most studied in relation to mRNA vaccines. In these instances, the angioedema is often categorized as a hypersensitivity reaction, an exaggerated immune response to a component of the vaccine. The onset can be immediate, occurring within hours, or delayed, appearing more than 24 hours after the shot.
One of the vaccine ingredients investigated as a potential trigger is polyethylene glycol (PEG). PEG is a compound used to stabilize the lipid nanoparticles that deliver the mRNA into cells. While allergies to PEG are not common, prior sensitization through exposure to other products containing it, like cosmetics, could lead to a reaction upon vaccination.
It is also proposed that the reaction may not always be a true IgE-mediated allergy. Instead, it could be a manifestation of the body’s strong inflammatory response to the vaccine, a sign that the immune system is being activated. For most individuals, the protective benefits of vaccination against severe COVID-19 are considered to outweigh the small risk of such rare side effects.
Symptoms and Diagnosis
The swelling from angioedema commonly appears on the eyelids, lips, tongue, hands, feet, or genitals. The affected skin often feels firm and is not typically itchy, though some individuals may experience a burning or painful sensation. In some cases, angioedema is accompanied by urticaria, which are raised, itchy welts on the skin’s surface, but it can also occur on its own. When swelling affects the throat, tongue, or larynx, it can obstruct the airway, leading to difficulty breathing or a change in voice.
Diagnosis is primarily clinical, based on a physical examination and a thorough patient history. A physician will assess the swelling and ask detailed questions to identify a potential trigger. This includes inquiring about recent illnesses, such as a confirmed COVID-19 infection, or the timing of a recent vaccination. The doctor will also ask about any medications the patient is taking and whether there is a personal or family history of similar swelling. Blood tests may be ordered to check for inflammatory markers or to rule out hereditary forms of angioedema, but these are not always necessary for diagnosis.
Management and Treatment Options
Treatment for angioedema depends on its severity and the suspected cause. For milder cases, especially those associated with histamine release, second-generation antihistamines are often the first line of treatment. If swelling is more significant, a course of oral corticosteroids, such as prednisone, may be prescribed to reduce inflammation. These medications are often effective for angioedema that is accompanied by hives.
Angioedema that involves the tongue, throat, or causes any difficulty breathing is a medical emergency. In these severe situations, immediate medical attention is required to secure the airway. Emergency treatment may include an intramuscular injection of epinephrine, which can quickly reduce swelling and open the airways.
Patients with severe symptoms are often hospitalized for observation to ensure the swelling does not return as the medication wears off. Depending on the situation, intravenous antihistamines and corticosteroids might also be administered.