Does skin inflammation exacerbate COVID-19?

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 recorded, with more than 6.5 million deaths. Additionally, many survivors have reported lingering symptoms for weeks or months after recovering from COVID-19. Inflammation during infection is known to aggravate the clinical severity of the disease.

Aging, diabetes, obesity, metabolic syndrome, and respiratory disease lead to poor COVID-19 prognosis. 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 current study, researchers reviewed basic concepts of SARS-CoV-2, exploring why patients with atopic dermatitis or psoriasis are less prone to severe COVID-19.

SARS-CoV-2

The first patient infected with SARS-CoV-2 was identified in December 2019 in Wuhan, China, according to official records. However, recent evidence suggests it may have emerged much earlier than expected. Although the origin of SARS-CoV-2 remains unknown, it is speculated that the virus may have originated from bat coronaviruses (CoV).

SARS-CoV-2 infection causes mild illness in most individuals; however, some people have severe illness requiring ventilation or extracorporeal membrane oxygenation (ECMO). The virus is thought to induce a cytokine storm that regular anti-inflammatory agents cannot control. The clinical course of COVID-19 is divided into mild, non-serious and severe stages of infection.

Patients suffer from severe respiratory distress syndrome during the severe phase, and some may also present with coagulopathy. People with comorbidities such as diabetes, hypertension, and obesity, among others, have lower COVID-19 outcomes than those without these conditions. It remains unclear why the disease worsens in certain subsets of populations.

Nevertheless, 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 characteristics. SARS-CoV-2 infection could worsen the inflammatory condition by reducing ACE2 expression levels by internalizing the receptor.

Psoriasis and atopic dermatitis

Psoriasis is one of the main inflammatory skin diseases, affecting 2 to 3% of Westerners and 0.2 to 0.3% of Japanese. Psoriasis is characterized by elevation of T helper (TH) 1 and TH 17 cellular 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 did not have an increased risk of hospitalization compared 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 are receiving 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 in patients with gastrointestinal or dermatological diseases. Additionally, several studies have independently demonstrated that psoriasis patients using biologics do not have an elevated risk of SARS-CoV-2 infection.

Apremilast is a phosphodiesterase 4 inhibitor that suppresses inflammation by raising 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 disease of the skin. It is often associated with allergic rhinitis, food allergies, bronchial asthma and allergic conjunctivitis.

There are mixed results on 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 directed against the α interleukin (IL)-4 receptor that restores immunity against TH 1-balanced state. 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 for the treatment of cytokine storms related to COVID-19. JAK inhibitors might block interferon signaling, affecting host defense against viruses. Conversely, the JAK inhibitor, tofacitinib, has been approved for use in severe cases of COVID-19 to reduce cytokine storms. Thus, JAK inhibitors might prove useful in COVID-19 during the inflammatory phase, despite the possibility of an increased risk of COVID-19.

Final remarks

The authors posit 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 hypothesized that for inflammatory skin conditions, regardless of systemic inflammation, the primary site of inflammation is the skin which may influence the prognosis of COVID-19. However, further studies are needed to delineate the underlying mechanisms.

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