Discussion
Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 coronavirus, has infiltrated our planet during the last three years, generating one of the deadliest pandemics in history. Granulomatosis with polyangiitis (GPA) is a systemic disease that produces vasculitis in multiple organs. It primarily affects white persons between the ages of 40 and 65, affecting around one in every 100,000 people each year[13].GPA and COVID-19 both have a high rate of pulmonary involvement. GPA has a wide range of clinical symptoms, and diagnosis is sometimes overlooked or delayed.The development of GPA after COVID-19 infection is extremely rare[14].
We herein report a case of GPA that developed following COVID-19 in an adolescent boy. This is the first reported case of GPA with DAH in an adolescent boy in Hunan proveince of China, which developed shortly after COVID-19 infection,presented with pneumonia and DAH, directly responded to steroids,rituximab and plasmapheresis.We summarize the clinical characteristics of new-onset GPA following COVID-19 infection by searching the database (PubMed,Wanfang Data,CNKI) and comprehensively analyze the literature results.Results show commonly seen clinical manifestations were cough,dyspnea,and Arthralgia/Myalgia,the rare symptoms are gastrointestinal bleeding and DAH, and renal involvement is rare, which is different from other causes of GAP. Of these patients, c-ANCA and PR-3 antibody were all positivity.The CT findings of GPA were various, including consolidation, multiple nodules, mass shadows, ground glass opacities and cavitary nodules, but multiple nodules and ground glass opacities were the most common. Most patients were treated with methylprednisolone and rituximab, and the prognosis was good with early diagnosis and treatment.
Clinicians may struggle to differentiate GPA from COVID-19 pneumonia because they share many clinical and radiological characteristics. Previous case reports have shown that individuals with undetected GPA who are treated as COVID-19 pneumonia improve with steroid therapy, obscuring the true diagnosis[10]. This means that, especially during epidemics, new-onset GPA can be readily misinterpreted as pneumonia.The COVID-19 epidemic has made it more difficult to diagnose newly diagnosed GPA. As a result, clinical data and serologic tests are advised to differentiate COVID-19 infection from underlying GPA.Granulomatous polyangiitis (GPA) is an anti-neutrophil cytoplasmic antibody(ANCA)-related vasculitis (AAV) with a wide range of clinical, imaging, and laboratory manifestations[15].Although the mechanism of GPA development remains unknown, numerous causes such as genetic factors, drugs,infections, and environmental exposures, may be involved in the pathogenesis of the disease by triggering autoimmunity[1, 2].
Since the COVID-19 pandemic, several reports have described the occurrence of AAV after COVID-19 [8, 16], suggesting that COVID-19 has the potential to trigger the development of AAV.In susceptible individuals, autoimmunity may be generated by a combination of genetic, hormonal, and environmental factors[17]. One such environmental factor is viral disease.Studies have shown that there is a causal relationship between viral infection and the pathogenesis of autoimmune diseases. Epstein-barr virus, cytomegalovirus and human immunodeficiency virus are viruses that have been clearly associated with a variety of autoimmune diseases[18].Since the COVID-19 pandemic, several reports have described cases of GPA after COVID-19,and there have been many mechanistic analyses of the development of GPA after COVID-19. Increasing evidence suggests that SARS-CoV-2 is another virus that can induce dysregulation of the immune system and the development of autoimmune diseases in adults [19].
There are currently two conjectures about the mechanism of COVID-19 inducing GPA:
The first speculation:autopsies have revealed that patients affected with SARS-CoV-2 can develop small, medium and large vessel vasculitis within multiple organ systems [20],there are some speculations that the virus could be a direct invader of endothelial cells,and may cause vasculitis.
The second speculationIn:the debate between COVID-19 and GPA, the possibility that SARS-CoV-2 infection could be a ”trigger” for vasculitis is an intriguing topic and a preferred speculation. Firstly, the time relationship between COVID-19 infection and the symptoms of GPA suggests that there may be a causal relationship between them. As described by Garlapati et al[21], many viruses have been shown to reveal potential GPA propensity by increasing serum levels of inflammatory mediators. We also know that SARS-CoV-2 increases levels of the same mediators, some of which play a role in the pathogenesis of GPA. Thus, it is conceivable that the presence of an excess of inflammatory mediators provides a substrate for neutrophil priming and ANCA-induced degranulation, leading to the development of GPA in patients.
Following vaccination with SARS-CoV-2 mRNA vaccines, AA V has been the subject of numerous reports[22, 23]. The finding of AA V following SARS-CoV-2 infection and vaccination further supports the theory that an immune response to SARS-CoV-2 may serve as a catalyst for the onset of GPA.
The immunological etiology of GPA is complicated, with roughly 80% of GPA patients producing PR3-ANCA[24]. Although positive ANCA is not required for the clinical diagnosis of GPA, it is pathogenic and plays a crucial role in the disease’s etiology. ANCA titers rose with COVID-19, according to several publications. Lee et al. measured serum myeloperoxidase (MPO)-ANCA and PR3-ANCA levels in 178 SARS-CoV-2 patients[22]. There were 22 cases of MPOANCA (12.4%) and 14 cases of PR3-ANCA (7.9%). GPA was diagnosed in 12 patients (6.7%). They came to the conclusion that SARS-CoV-2 infection could increase ANCA positivity. Because the prevalence of ANCA positivity in the general population is 0.9%, the prevalence of ANCA in COVID-19 patients is much higher.
In COVID-19, SARS-CoV2 binds to angiotensin-converting enzyme 2, invades endothelial cells and causes microvasculitis. Because inflammatory cytokines and coagulation markers are elevated during and even after infection, the persistent inflammatory response and hypercoagulable state are associated with the development of vascular disease and other complications[8]. In AAV,increased inflammation caused by cytokines and macrophages leads to microvasculitis and endothelial damage, and some studies also speculate that there is cross-reaction between SARS-CoV-2 antigen and autoantibodies in autoimmune diseases[23] . These studies suggest a causal relationship between SARS-CoV-2 infection and vasculitis.
It is worth considering the role of SARS-CoV-2-induced alterations in the nasopharyngeal and pulmonary microbiota in the performance of GPA in patients after covid-19. There is good evidence that SARS-CoV-2 alters the microbiome and that microbial dysbiosis is significantly associated with increased TNF-α, which is a key mediator of granulomatous lesion formation.