Discussion
In total, three forms of pulmonary aspergillosis, that are chronic
necrotizing pulmonary aspergillosis, aspergilloma and fibrosing
aspergillosis, were found in a patient with no particular history other
than SARS-CoV-2 infection.
By definition, aspergillosis is a fungal infection caused byAspergillus species. The commonly known manifestations are
allergic bronchopulmonary aspergillosis, acute invasive pulmonary
aspergillosis, aspergilloma, and chronic pulmonary aspergillosis. The
latter includes chronic cavitary aspergillosis, chronic necrotizing
aspergillosis, and chronic fibrosis [3,4]. The chronic forms affect
immunocompetent or moderately immunocompromised patients. Chronic
cavitary disease is usually accompanied by the formation of new
(multiple) cavities, but without invasion of the surrounding lung
parenchyma [4]. On the other hand, chronic necrotizing pulmonary
aspergillosis, also called subacute invasive pulmonary aspergillosis, is
more invasive and destroys the surrounding tissue [5]. It is
presented in the form of a single thin-walled cavity enlarging over
several weeks or months, that may contain or not an aspergilloma
[5,6]. In the fibrosing form, the disease progresses quietly with
major fibrosing destruction around the cavity [3,4]. According to
these definitions, our case corresponds to an aspergilloma that
developed in a cavity of chronic necrotizing aspergillosis progressing
to the fibrosing form.
Based on experiences with influenza-associated invasive pulmonary
aspergillosis, cases of aspergillosis superinfection have been
associated with the severe or critical form of Covid-19. However, it is
not clear whether SARS-CoV-2 infection is in itself the main risk factor
for Covid-19-associated pulmonary aspergillosis, or whether other risk
factors, such as corticosteroid therapy frequently used in severe forms,
increase the risk of disease progression [7]. Indeed,
proinflammatory cytokines and chemokines, such as tumor necrosis factor
a (TNFa), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-1b
and monocyte chemoattractant protein-1 were significantly elevated in
patients with severe Covid-19, which would predispose to invasive
aspergillosis [2,7]. In addition, the use of corticosteroids in the
treatment of Covid-19 could also increase the risk of immunosuppression.
In our opinion, both the severity of Covid-19 and the corticosteroid
therapy induced a moderate immunosuppression that put our patient at
risk of chronic aspergillosis.
In the literature, the clinical signs of chronic pulmonary aspergillosis
are nonspecific, with or without Covid-19 [3,4]. Respiratory and/or
general symptoms are often present for one to six months: cough, sputum,
chest pain, dyspnea, hemoptysis with or without long-term fever, altered
general condition with sometimes severe weight loss [4,6]. So
additional examinations are necessary to diagnose aspergillosis. There
are some criteria to make this diagnosis such as clinical signs,
radiological abnormalities, evidence of mycelial filaments, exclusion of
alternative diagnoses, failure of antibacterial therapy, clinical
response to antifungal therapy and exclusion of severe immunosuppression
[8]. Our patient met almost all these criteria.
About the treatment, there is no evidence that the treatment of
aspergillosis is different in patients with or without Covid-19 [7].
Indeed, treatment of chronic aspergillosis with or without aspergilloma
is based on long-term antifungal agents, including in the first instance
Itraconazole 200-400 mg/day or Voriconazole 150-200 mg twice daily,
orally, for 3 to 6 months or longer. Surgery is reserved for patients
who cannot tolerate medical treatment and for patients with active
residual disease despite adequate antifungal treatment [6]. However,
according to the European Respiratory Society in 2016, chronic
necrotizing aspergillosis or subacute invasive aspergillosis should be
treated in the same way as acute invasive pulmonary aspergillosis
because of its rapidly progressive nature [9]. In this case,
treatment is based on intravenous Voriconazole at a dose of 6 mg/kg
every 12 hours on the first day, followed by 3 mg/kg every 12 hours and
then oral therapy for a total duration of at least 3 months. The
evolution of chronic aspergillosis under treatment is variable. The
disappearance of aspergilloma is correlated with a favourable clinical
response to treatment [5].