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.