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\begin{document}

\title{Pulmonary Aspergillosis After Covid-19, A Case Report}



\author[1]{: Seray  Hazer}%
\author[1]{Gülşen Göktepe}%
\author[1]{Leyla Acar}%
\author[1]{Selim Şakir Erkmen Gülhan}%
\affil[1]{Ankara Kecioren Sanatoryum Ataturk Gogus Hastaliklari ve Gogus Cerrahisi Egitim ve Arastirma Hastanesi}%


\vspace{-1em}



  
  \date{May 20, 2024}


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\begin{abstract}
This study presents a 57-year-old male patient with COVID-19 who had had
no lung disease before COVID-19 pneumonia. However, after COVID-19
pneumonia with sequels and treatments that include corticosteroids and
IL-6 receptor antagonists, an invasive pulmonary aspergillus (IPA)
cavity occurred immediately.%
\end{abstract}%



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\textbf{Pulmonary Aspergillosis After Covid-19, A Case Report}

\textbf{Summary}

COVID-19 is an infectious disease that spreads worldwide, can progress
rapidly, affect individuals of all ages, and cause death, especially in
the elderly and people with chronic diseases. It has predisposed a
relatively high number of patients to acute respiratory distress
syndrome, and co-infections are a frequent complication, especially
during prolonged hospital stays. Bacterial or viral co-infections with
SARS-CoV-2 have been reported in many studies, but knowledge of
Aspergillus co-infection in patients with COVID-19 is limited.

This study presents a 57-year-old male patient with COVID-19 who had had
no lung disease before COVID-19 pneumonia. However, after COVID-19
pneumonia with sequels and treatments that include corticosteroids and
IL-6 receptor antagonists, an invasive pulmonary aspergillus (IPA)
cavity occurred immediately.

In addition to the fact that COVID-19 infection progresses with
destructive parenchymal damage and sequelae, the effectiveness of
treatment is limited, and treatment-related side effects and
complications can be examined. Therefore, clinical and radiological
follow-up of patients whose symptoms persist after infection is
essential.

\textbf{Introduction}

Coronavirus disease 2019 (COVID-19) is caused by severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2), which appeared in China
in late 2019. Several opportunistic infections as~\emph{Aspergillus}
~spp\emph{.} ,~\emph{Candida} ~spp\emph{.} ,~\emph{Cryptococcus
neoformans} ,~\emph{Pneumocystis jiroveci} ~(\emph{carinii} ),
mucormycosis,~\emph{Cytomegalovirus} ~(CMV),~\emph{Herpes simplex virus}
~(HSV),~\emph{Strongyloides stercoralis, Mycobacterium tuberculosis,}
~and~\emph{Toxoplasma gondii~} have been identified following severe
respiratory viral infections in COVID-19 patients (1, 2). Especially the
incidence of fungal infections is high (3).

\textbf{Case Report}

A 57-year-old male patient, who applied to our clinic with complaints of
hemoptysis, was hospitalized for further examination and treatment due
to a cavitary lesion in the right upper lobe. Nine months ago, he was
treated for 55 days as non-intubation in the intensive care unit for
five days due to COVID-19 pneumonia (Figure-1). During this period,
steroid treatment and four flacons of 162 mg Tocilizumab (a monoclonal
antibody against the interleukin-6 receptor) was given because of
respiratory symptoms and sequelae COVID\_19 pneumonia (Figure-2).
Pulmonary rehabilitation and steroid therapy were continued for three
months because dyspnea continued in the patient whose treatment was
terminated (Figure-3). In thorax Computed Tomography (CT), a cavitary
lesion was observed in the right upper lobe who administered with
complaints of swelling in the legs and hemoptysis in the fourth month of
his treatment (Figure-4). After taking a nonspecific culture, the
patient continued prophylactic fungal treatment and steroid treatment
due to dyspnea. Blood culture, sputum culture, urine culture, fungal
culture, and tuberculosis tests, Aspergillom specific IgE, was negative,
Total IgE was normal. On the 12th day of his treatment, the patient's
general condition was good, and he was discharged after colchicine and
steroid treatment were arranged. In the control HRCT after antibiotic
treatment, the cavity persisted in the right upper lobe (Figure-5). Due
to intermittent complaints of hemoptysis, right upper lobectomy via
thoracotomy was performed. The postoperative pathology result was
reported as Aspergilloma (Figure-6) and discharged on the seventh
postoperative day without complications. He is in the third month of his
follow-up, and any complications occurred.

Figure-1: First hospital admission Chest X-Ray\selectlanguage{english}
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Figure-2: Thorax CT when the patient applied to the hospital for the
second time, on 15th day: bilateral ground glass were determined\selectlanguage{english}
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Figure-3: Thorax CT on the 45th day. Ground glass and fibrotic lesions,
right upper thin-walled cystic lesion were determined\selectlanguage{english}
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Figure-4: Right upper lobe cavitary lesion was detected in Thorax CT
angiography

Figure-5: Right upper lobe cavity persisting on control thorax CT,one
month after the treatment\selectlanguage{english}
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Figure-6: The macroscopic appearance of Postoperative specimen of right
upper lobectomy with aspergilloma\selectlanguage{english}
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\textbf{Discussion}

Since the new pneumonia was first recognized in Wuhan, China, at the end
of 2019, the causative pathogen SARS-CoV-2 has been identified, and its
associated infection, COVID-19, has rapidly evolved worldwide. While
SARS-CoV-2 is responsible for severe pneumonia and ARDS, COVID-19 is
associated with a wide variety of extrapulmonary complications; many
other organs can be affected, including cardiovascular, immune, nervous,
and gastrointestinal systems, therefore, can be considered a systemic
disease. In addition to common bacteria and viruses, Aspergillus can
cause co-infection in COVID-19 patients, especially in severe/critical
illnesses. The possibility of co-infection with bacterial or fungal
infections is higher in patients who require follow-up in intensive care
units or require mechanical ventilation(4). Among the possible pathogens
in COVID-19 patients, Invasive pulmonary~aspergillosis ~(IPA ) carries
more attention to Aspergillus as it is challenging to diagnose and can
be associated with high morbidity and mortality. In particular,
respiratory samples for mycological studies such as fungal culture,
galactomannan test, and PCR from respiratory tract samples can help
early diagnosis. In our case, the culture results of the patient who was
followed up and treated with the non-intubated high flow for five days
in the intensive care unit during this period were typical.

All studies of COVID-19 fungal infections have reported that they occur
during COVID-19 infection, mostly 14 days after the onset of COVID-19
symptoms(5). In this case, a cavitary lesion in the right upper lobe was
observed in the fourth month of the patient's COVID-19 treatment.

In COVID-19-associated pulmonary aspergillosis, diabetes,
immunosuppressive drug use, steroid therapy, and intubating are risk
factors for patients followed. It also increases the risk of pulmonary
aspergillosis in COVID-19 patients using IL-6 antagonists (6). In our
case, four vials of 162 mg tocilizumab were given on the 12th day of the
patient's treatment. The patient had fibrotic lesions on the thorax CT,
and dyspnea continued. The patient was followed up under steroid and
colchicine treatment for about four months after discharge, and a
cavitary lesion in the right upper lobe was observed in the fourth-month
tomography.

Aspergillosis is one of the most common opportunistic fungal
co-infections caused by certain Aspergillus species, mainly affecting
immunocompromised individuals such as COVID-19 patients. It can
critically affect the respiratory system, leading to a mild/serious lung
infection known as pulmonary aspergillosis, a severe form of
aspergillosis that worsens over time and has no effective treatment.

\textbf{Conclusion}

In patients with severe acute respiratory disease associated with
SARS-CoV-2, invasive aspergillosis should be suspected in case of
clinical worsening, even in immunocompetent patients. At the same time,
aspergillosis should not be forgotten in patients with worsening after
steroid and immunomodulator therapy.

Pulmonary aspergillosis is a severe complication of COVID-19 patients
that may not respond well to medical therapy. Pulmonary resection is the
most effective treatment to control the disease.

\textbf{Author Contributions:}

Authors 1: Have made substantial contributions to conception and design,
or acquisition of data, or analysis and interpretation of data

Authors 2: Been involved in drafting the manuscript or revising it
critically for important intellectual content; and

Authors 3: Given final approval of the version to be published. Each
author should have participated sufficiently in the work to take public
responsibility for appropriate portions of the content

Authors 4: Agreed to be accountable for all aspects of the work in
ensuring that questions related to the accuracy or integrity of any part
of the work are appropriately investigated and resolved

\textbf{References}

Talento A.F., Hoenigl M. Fungal Infections Complicating COVID-19: With
the Rain Comes the Spores.~\emph{J. Fungi.~} 2020;6:279.
doi:~10.3390/jof6040279.

Abdoli, A., Falahi, S., \& Kenarkoohi, A. (2021). COVID-19-associated
opportunistic infections: a snapshot on the current
reports.~\emph{Clinical and experimental medicine} , 1-20.

Mulet Bayona J.V., Tormo Palop N., Salvador Garc\selectlanguage{ngerman}ía C., Fuster Escrivá
B., Chanzá Aviñó M., Ortega García P., Gimeno Cardona C. Impact of the
SARS-CoV-2 Pandemic in Candidaemia, Invasive Aspergillosis and
Antifungal Consumption in a Tertiary Hospital.~\emph{J. Fungi.~}
2021;7:440.

Bassetti M., Giacobbe D.R., Grecchi C., Rebuffi C., Zuccaro V.,
Scudeller L. Performance of existing definitions and tests for the
diagnosis of invasive aspergillosis in critically ill, adult patients: a
systematic review with qualitative evidence synthesis.~\emph{J.
Infect.~} 2020;\textbf{81} (1):131--141.

Marr K.A., Platt A., Tornheim J.A., Zhang S.X., Datta K., Cardozo C.
Aspergillosis complicating severe coronavirus disease.~\emph{Emerging
Infect. Dis.~} 2021;\textbf{27} (1):18.

Bartoletti M., Pascale R., Cricca M., Rinaldi M., Maccaro A., Bussini L.
Epidemiology of invasive pulmonary aspergillosis among COVID-19
intubated patients: a prospective study.~\emph{Clin. Infect. Dis.~}
2020;\textbf{1} (1)\selectlanguage{english}
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