BREAKING COVID-19 News! Indonesian Researchers Warn That SARS-CoV-2 Infections Can lead To Oral Pemphigus Vulgaris In Post-COVID Phase!

COVID-19 News: In an alarming revelation, researchers from the Department of Oral Medicine at Universitas Trisakti, Jakarta, and the Faculty of Dentistry at Universitas Padjadjaran, Bandung, Indonesia, have issued a stark warning regarding the potential development of oral pemphigus vulgaris (PV) in individuals during post-COVID-19 infection phases. This autoimmune life-threatening mucocutaneous disease, characterized by widespread bullae and ulceration on the skin and mucosa, has been observed in a case series of four patients, raising concerns about the broader implications of COVID-19 on autoimmune health.


Clinical presentation of oral Pemphigus Vulgaris. Case # 1 (a, b); Case #2 (c, d); Case #3 (e, f); Case #4 (g, h). Courtesy of Prof. Amtha and Dr. Gunardi

As of November 2023, the official global tally of confirmed COVID-19 cases has surpassed 710 million, with over 7.1 million reported deaths. The pandemic has displayed a varied spectrum of health manifestations, with the immune system emerging as a pivotal factor in determining the outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections.
 
The Indonesian study covered in this COVID-19 News report, points to an alarming trend of increased cases of oral pemphigus vulgaris or PV following COVID-19 infection, suggesting a potential link between the uncontrolled immune response triggered by the virus and the onset of autoimmune diseases.
 
A few other published case reports and studies have also corroborated the fact that SARS-CoV-2 infections are indeed triggering pemphigus vulgaris.
https://www.cureus.com/articles/127261-pemphigus-vulgaris-possibly-associated-with-covid-19-infection#!/
 
https://link.springer.com/article/10.1007/s42399-021-00971-8
 
https://pesquisa.bvsalud.org/global-literature-on-novel-coronavirus-2019-ncov/resource/pt/covidwho-1995309
 
https://onlinelibrary.wiley.com/doi/10.1111/dth.14398
 
https://www.biolifesas.org/EN/10.23812/j.biol.regul.homeost.agents.202236.2S4.1
 
The Indonesian study presents a case series involving three females and one male, aged between 33 and 57, all of whom had no history of drug-induced illness or allergies. Notably, each patient had previously contracted SARS-CoV-2, emphasizing the temporal relationship between COVID-19 infection and the subsequent development of PV. Treatment for the observed lesions included systemic and oral corticosteroids, with the addition of immunomodulator agents to mitigate the side effects of steroids and reduce PV severity.
 
The researchers emphasize the need for vigilance among clinicians regarding the potential emergence of autoimmune reactions in the aftermath of the COVID-19 pandemic. The exact mechanism behind PV induced by SARS-CoV-2 remains unclear, prompting a call for further investigation into the genetic aberrations that may be triggered by viral infections, potentially leading to autoimmune diseases beyond PV.
 
COVID-19's Varied Impact on Health
The COVID-19 pandemic has showcased a diverse range of case severities and outcomes, influenced by factors such as population density, healthcare infrastructure, and public health measures. Beyond the immediate respiratory impact of the virus, emerging evidence suggests a connection between COVID-19 and autoimmune diseases, raising questions about the long-term health consequences for survivors.
 
A systematic review of reported cases indicates that COVID-19 has been linked to various autoimmune diseases, shedding light on a potential relationship between the infection and autoimmunity. The severity of SARS-CoV-2 infection appears to correlate with the type of immune-related manifestations observed, with evidence of autoantibodies further supporting the association between COVID-19 and autoimmune diseases.
 
Pemphigus Vulgaris: A Closer Look
Pemphigus vulgaris, an autoimmune mucocutaneous disease, manifests as widespread bullae and ulceration on the skin and mucosa. Identified risk factors include genetics, drugs, viral infections, allergens, and stress. The production of autoantibodies against desmoglein-1 and desmoglein-3 induces intraepithelial acantholysis, damaging the keratinocyte layer and posing a life-threatening risk. Early identification is crucial, as patients with oral PV may experience limited physiological function due to extensive ulceration and prolonged pain.
 
Case Reports Highlighting the Link
The researchers present four compelling case reports detailing individuals who developed oral PV post-COVID-19 infection. In Case Report #1, a 48-year-old woman exhibited persistent oral ulceration, ultimately diagnosed as PV. Treatment included systemic corticosteroids and immunomodulator agents, resulting in complete healing after five months.
 
Case Report #2 involved a 57-year-old woman with oral and skin lesions post-COVID-19, managed successfully with a combination of medications over 15 months.
 
Case Report #3 featured a 56-year-old man with oral ulceration and subsequent skin lesions, diagnosed as PV one-month post-COVID-19 recovery. Treatment included oral and topical medications administered by specialists in oral medicine and dermatology.
 
Case Report #4 involved a 33-year-old woman with oral ulceration four months post-COVID-19, showing significant improvement with oral and topical corticosteroids.
 
Unraveling the Mechanism: From Viral Spike Proteins to Autoimmune Response
The researchers delve into the potential mechanism linking SARS-CoV-2 infections to autoimmune diseases like PV. The binding of viral spike proteins to cellular receptors, primarily angiotensin-converting enzyme 2 (ACE2), serves as a key entry point for the virus into target cells. High levels of ACE2 expression in the oral mucosa and skin may contribute to the development of lesions in these areas.
 
The proposed pathways for autoimmunity activation include molecular mimicry, bystander activation, and epitope dissemination. In molecular mimicry, the structural similarity between virus antigens and self-antigens triggers a cross-reactive immune response, causing tissue injury. Bystander activation involves an overreactive antiviral immune response inducing a pro-inflammatory environment, leading to the release of self-antigens and subsequent tissue injury.
 
Epitope dissemination suggests that persistent viral infections may continue tissue injury, releasing more self-antigens and activating autoreactive cells targeting additional self-epitopes.
 
Future Directions: A Call for Further Investigation
The researchers acknowledge the limitations of their case series, with data on COVID-19 infection based solely on medical records. The specific type of SARS-CoV-2 virus and drugs consumed by the patients were not considered, potentially playing a role in PV development. Despite these limitations, the emergence of PV following the COVID-19 pandemic is proposed as a vital element in risk assessments for COVID-19 infections.
 
In conclusion, clinicians are urged to closely monitor patients for signs of autoimmune reactions post-COVID-19, with oral lesions potentially serving as early indicators. The unclear mechanism of PV induced by SARS-CoV-2 underscores the need for comprehensive research to understand the genetic anomalies triggered by the viral infection, establishing a definitive link between COVID-19 and autoimmune diseases. As the world grapples with the ongoing challenges of the COVID-19 pandemic, this research adds a critical dimension to the long-term health implications for survivors.
 
The study findings were published in the peer reviewed Journal of Oral & Maxillofacial Pathology.
https://journals.lww.com/jpat/fulltext/2023/27030/the_emerging_concern_of_oral_pemphigus_vulgaris.26.aspx
 
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