In a recent study published in the Internal Journal of Molecular Sciences, researchers discussed inflammation during infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Study: Inflammation Causes Exacerbation of COVID-19: What About Skin Inflammation? Image credit: dimid_86/Shutterstock
Globally, more than 622 million cases of coronavirus disease 2019 (COVID-19) have been reported, with more than 6.5 million deaths. In addition, many survivors have reported persistent symptoms for weeks or months after recovering from COVID-19. Inflammation during infection is known to exacerbate the clinical severity of the disease.
Aging, diabetes, obesity, metabolic syndrome, and respiratory disease all contribute to a poor prognosis for COVID-19. In contrast, people with atopic dermatitis or psoriasis appear to have a less severe course of COVID-19 than people without these skin conditions. In the present study, the researchers revisited the fundamental concepts of SARS-CoV-2, exploring why patients with atopic dermatitis or psoriasis are less likely to suffer from severe COVID-19.
SARS-CoV-2
The first patient with SARS-CoV-2 infection was identified in December 2019 in Wuhan, China, according to official records. However, recent evidence suggests that it may have arisen much earlier than previously thought. Although the origin of SARS-CoV-2 is still unknown, there is speculation that the virus may have originated from bat coronaviruses (CoV).
Infection with SARS-CoV-2 causes mild illness in most people; however, some people have a severe illness that requires ventilation or extracorporeal membrane oxygenation (ECMO). The virus is thought to induce a cytokine storm that common anti-inflammatory agents cannot control. The clinical course of COVID-19 is divided into mild, non-severe and severe stages of infection.
Patients experience severe respiratory distress syndrome during the severe phase, and some may also have coagulopathy. People with comorbidities such as diabetes, hypertension, and obesity, among others, have worse COVID-19 outcomes than those without these conditions. It is not yet clear why the disease worsens in some subsets of populations.
However, inflammation could be responsible for the poor prognosis, as these (comorbid) conditions show a low level of chronic inflammation. SARS-CoV-2 uses the host angiotensin-converting enzyme 2 (ACE2) for cell entry. ACE2 has several anti-inflammatory properties. SARS-CoV-2 infection could exacerbate the inflammatory state by reducing ACE2 expression levels through receptor internalization.
Psoriasis and atopic dermatitis
Psoriasis represents one of the major inflammatory skin diseases, affecting 2% to 3% of Westerners and 0.2% to 0.3% of Japanese. Psoriasis is characterized by elevated T helper (TH) 1 and TH 17 cell responses and increased expression of antimicrobial peptides. Studies have identified associations between psoriasis and diabetes, obesity, cardiovascular disease (CVD), hyperglycemia, and hypertension.
Psoriasis patients with COVID-19 were not found to have a higher risk of hospitalization relative to patients with (other) comorbid conditions. A plausible explanation for this observation would be small sample size or low statistical power. Another possibility is that patients with psoriasis receive biologics and anti-inflammatory and immunosuppressive agents, making them less susceptible to an increased risk of severe COVID-19.
A Danish study reported a decreased risk of hospitalization and mortality associated with COVID-19 among patients with gastrointestinal or dermatologic disease. In addition, several studies have independently shown that psoriasis patients using biologics were not at increased risk of SARS-CoV-2 infection.
Apremilast is a phosphodiesterase 4 inhibitor that suppresses inflammation by increasing levels of cyclic adenosine monophosphate (cAMP). Some researchers have shown that psoriasis patients treated with apremilast have a lower risk of COVID-19. Atopic dermatitis is a chronic inflammatory skin disease. It is often associated with allergic rhinitis, food allergies, bronchial asthma and allergic conjunctivitis.
There are conflicting results regarding associations between atopic dermatitis and COVID-19, with some studies suggesting an increased risk of severe COVID-19 and others reporting a reduced risk. Dupilumab is an antibody against the interleukin (IL)-4 receptor α that restores immunity to the balanced state of TH 1. Several researchers have observed that dupilumab reduces the risk of SARS-CoV-2 infection.
Janus kinase inhibitors
Janus Kinase (JAK) inhibitors are small molecule agents for the treatment of atopic dermatitis and psoriasis. JAK inhibitors have also been approved to treat the cytokine storms associated with COVID-19. JAK inhibitors could block interferon signaling, affecting the host’s defense against viruses. Conversely, the JAK inhibitor tofacitinib has been approved for use in severe COVID-19 to reduce cytokine storms. Thus, JAK inhibitors may be useful in COVID-19 during the inflammatory phase, despite the possibility of increasing the risk of COVID-19.
Final remarks
The authors postulate that the risk of severe COVID-19 may be highly organ-specific and that skin inflammation does not increase the risk of severe disease. Although the mechanism remains elusive, it is speculated that for inflammatory skin conditions, regardless of systemic inflammation, the primary site of inflammation is the skin that may influence the prognosis of COVID-19. However, further studies are needed to delineate the underlying mechanisms.