Does skin inflammation exacerbate COVID-19?

By Tarun Sai LomteOct 18 2022Reviewed by Aimee Molineux

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).

Globally, more than 622 million coronavirus disease 2019 (COVID-19) cases have been recorded, with more than 6.5 million deaths. Moreover, many survivors have reported persistent symptoms for weeks to months after recovering from COVID-19. It is known that inflammation during infection aggravates the clinical severity of the disease.

Aging, diabetes, obesity, metabolic syndrome, and respiratory diseases cause poor COVID-19 prognosis. In contrast, individuals 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, researchers reviewed the fundamental 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 with SARS-CoV-2 infection was identified in December 2019 in Wuhan, China, per official records. However, recent evidence suggests that it might have emerged much earlier than believed. Although the origin of SARS-CoV-2 remains unknown, it is speculated that the virus may have originated from bat coronaviruses (CoVs).

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

Patients experience severe respiratory distress syndrome during the severe phase, and some may also exhibit coagulopathy. Individuals with comorbidities such as diabetes, hypertension, and obesity, among others, have poorer COVID-19 outcomes than those without these conditions. It remains unclear why the disease exacerbates in some subsets of populations.

Nevertheless, inflammation might be responsible for the poor prognosis as these (comorbid) conditions show a low level of chronic inflammation. SARS-CoV-2 uses host angiotensin-converting enzyme 2 (ACE2) for cellular entry. ACE2 has several anti-inflammatory characteristics. SARS-CoV-2 infection might aggravate the inflammatory state by reducing ACE2 expression levels by internalizing the receptor.

Psoriasis and atopic dermatitis

Psoriasis represents one of the significant inflammatory diseases of the skin, affecting 2% to 3% of Westerners and 0.2% to 0.3% of Japanese individuals. Psoriasis is characterized by the elevated T helper (T_H) 1 and T_H 17 cell responses and increased expression of anti-microbial 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 an increased hospitalization risk relative to patients with (other) comorbid conditions. A plausible explanation for this observation would be the small sample size or low statistical power. Another possibility is that psoriasis patients receive biologics and anti-inflammatory and immunosuppressive agents, making them less susceptible to increased risk of severe COVID-19.

A Danish study reported a decreased risk of COVID-19-associated hospitalization and mortality among patients with gastrointestinal or dermatologic disease. Besides, several studies have independently demonstrated that patients with psoriasis using biologics had no elevated risk of SARS-CoV-2 infection.

Apremilast is a phosphodiesterase 4 inhibitor that suppresses inflammation by elevating cyclic adenosine monophosphate (cAMP) levels. 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 the 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 toward the T_H 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 atopic dermatitis and psoriasis treatment. JAK inhibitors have also been approved for treating COVID-19-related cytokine storms. 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 might prove helpful in COVID-19 during the inflammatory phase, despite the possibility of increased risk of COVID-19.

Concluding remarks

The authors postulate that the risk for severe COVID-19 may be highly organ-specific and that the inflammation of the skin does not increase the risk of severe disease. Although the mechanism remains elusive, it is speculated that for cutaneous inflammatory conditions, irrespective of the systemic inflammation, the main site of inflammation is the skin which may influence COVID-19 prognosis. However, more studies are required to delineate the underlying mechanisms.