Background: During the COVID-19 epidemic, we have witnessed numerous manifestations and complications after contracting this disease. One of these complications in patients with COVID-19 is the increased risk of invasive fungal infections due to the suppression of the immune system caused by the disease or due to the use of suppressive drugs such as corticosteroids.
Case presentation: Here we report three cases of invasive fungal sinusitis after contracting COVID-19 with recurrence after primary treatment and the measures taken for these patients.
Discussion: Invasive fungal sinusitis with involvement of orbit or brain is a known complication in COVID-19 patients especially in diabetics. Recurrence of manifestations of fungal infection after primary treatment and hospital discharge may be related to uncontrolled underlying disease and residual fungal infection especially in necrotic soft tissue or bone.
Conclusion: Early diagnosis and management with antifungal drugs and surgical debridement and also close follow up after discharge from hospital is essential for treatment and achieving higher survival in patients with invasive fungal sinusitis

Dehghani Firouzabadi, Amrollah

Ghorbani, Jahangir

Karimi Galougahi, Mahboobeh

Raad, Nasim

English

Journals Portal, Shahid Beheshti University of Medical Sciences

CASE REPORT Journal of Otorhinolaryngology and Facial Plastic Surgery 2022;8(1):1-5. https://doi.org/10.22037/orlfps.v8i1.41572  ------------------------------------------------------------------------------------------------------------------  This work is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 License (CC BY-NC 4.0). 1 Chronic or Recurrent Invasive Fungal Sinusitis after    COVID-19 Infection  Jahangir Ghorbani1,2*, Nasim Raad1, 2, Mahboobeh Karimi Galougahi3,2,1, Amrollah Dehghani Firouzabadi1 1. Department of Otolaryngology, Masih Daneshvari Hospital, Shahid Beheshti University of Medical Sciences Tehran, Iran. 2. Chronic Respiratory Disease Research Center, National Research Institute of Tuberculosis and Lung Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 3. Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Article Info  Abstract  Article Note: Received: October, 2022  Accepted: November, 2022  Publish Online: December, 2022  Corresponding Authors: Dr. Jahangir Ghorbani   Email: jghorbani@sbmu.ac.ir   Keywords: COVID-19;  Invasive fungal infection;  Opportunistic infection;  Diabetes;  Fungal sinusitis.    Background: During the COVID-19 epidemic, we have witnessed numerous manifestations and complications after contracting this disease. One of these complications in patients with COVID-19 is the increased risk of invasive fungal infections due to the suppression of the immune system caused by the disease or due to the use of suppressive drugs such as corticosteroids.  Case presentation: Here we report three cases of invasive fungal sinusitis after contracting COVID-19 with recurrence after primary treatment and the measures taken for these patients. Discussion: Invasive fungal sinusitis with involvement of orbit or brain is a known complication in COVID-19 patients especially in diabetics. Recurrence of manifestations of fungal infection after primary treatment and hospital discharge may be related to uncontrolled underlying disease and residual fungal infection especially in necrotic soft tissue or bone.  Conclusion: Early diagnosis and management with antifungal drugs and surgical debridement and also close follow up after discharge from hospital is essential for treatment and achieving higher survival in patients with invasive fungal sinusitis. Conflicts of Interest: The Authors declare no conflicts of interest. Please cite this article as: Jahangir Ghorbani, Raad N, Karimi Galougahi M, Dehghani Firouzabadi M.  Chronic or Recurrent Invasive Fungal Sinusitis after COVID-19 Infection. J Otorhinolaryngol Facial Plast Surg 2022;8(1):1-5. https://doi.org/10.22037/orlfps.v8i1.41572  IntroductionCoronavirus 2019 (COVID-19), caused by the Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can cause mild to severe respiratory disease and lead to an emergency pandemic in the world (1). COVID-19 may lead to acute respiratory distress syndrome (ARDS). In these patients, corticosteroids such as Dexamethasone and Methylprednisolone are prescribed to reduce lung inflammation caused by the disease and prevent its progression (2). Because these drugs suppress the immune system of COVID-19 patients, they are likely to cause opportunistic infections (3, 4). Studies have shown that the rate of opportunistic infections are higher in patients with severe form of COVID-19 among them, about 10 to 30 percent are related to fungal infections (5). The most commonly reported fungal infections in patients with COVID-19 include aspergillosis, invasive candidiasis, and mucormycosis (6–8). Antifungal-resistant infections have also been described in patients with severe COVID-19 (9).  Uncontrolled diabetes and overuse of steroids are important risk factors in treating COVID-19 (10).  Herein we present three cases of chronic or recurrent invasive fungal sinusitis in patients CASE REPORT Journal of Otorhinolaryngology and Facial Plastic Surgery 2022;8(1):1-5. https://doi.org/10.22037/orlfps.v8i1.41572  ------------------------------------------------------------------------------------------------------------------  This work is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 License (CC BY-NC 4.0). 2 referred to our otolaryngology department with history of COVID-19 infection. Case Presentation Case 1 A 42-year-old diabetic male with right pre-septal cellulitis referred from ophthalmology department. He had no past medical history. His past surgical history was also insignificant. He claimed that before developing ophthmological symptoms, he had an episode of COVID-19 infection.  Except for pre-septal cellulitis, every other physical examination was normal. He had normal neurological examination and his eyes movements were normal.  Except for inflammatory markers, laboratory investigations were otherwise normal (Table 1). Table 1. shows the details of laboratory investigations of the discussed patients Laboratory investigation  Case 1 Case 2 Case 3 White blood cell count  5823 7625 6254 Hemoglobulin  13.2 12.8 14.1 Platelet  398500 423000 345000 Fasting blood sugar  98 87 129 Erythrocyte sedimentation rate  78 66 48 C-reactive protein  Positive Positive Positive COVID-19 IgM Negative Negative Negative COVID-19 IgG Negative Negative Negative  Endoscopic examination showed necrosis of parts of right middle turbinate. There was opacity in the anterior and posterior ethmoids and right frontal sinus in CT images (Figure 1).   Figure 1. Bilateral opacity of maxillary sinus.  Right antrostomy and posterior and anterior ethmoidectomy was performed for the patient, and the necrotic tissue was completely removed. Pathology findings in this stage showed invasive fungal rhinosinusitis. Six weeks later, the patient again developed right periorbital edema and erythema, which again underwent endoscopic sinus surgery. In the second stage, the sphenoid sinus was opened and cleared of fungal secretions and pterygopalatine space was examined and cleared of necrotic tissue. The pathology findings from the second stage showed sinonasal mucoromycosis associated with mucromycotic osteomeilitis.  Case 2 A 58-year-old diabetic male with a history of COVID-19 referred to us. He complained of pain and decreased sensation of left cheek and decreased visual acuity of left eye. He had insignificant past medical and surgical history. He consumed no medication.  Except for the mentioned abnormal examinations, neurological examinations were otherwise normal. The eyes movements were normal.  Sensation, strength, reflexes, and tone were unremarkable in the trunk and extremities. The patient's gait was normal. High inflammatory markers were evident in his laboratory investigations (Table 1). Endoscopic examination showed necrosis in the left middle turbinate. Opacity of maxillary sinus, anterior and posterior ethmoids and left sphenoid sinus was evident on CT images. In the first stage, the necrotic mucosa of the left anterior ethmoid and CASE REPORT Journal of Otorhinolaryngology and Facial Plastic Surgery 2022;8(1):1-5. https://doi.org/10.22037/orlfps.v8i1.41572  ------------------------------------------------------------------------------------------------------------------  This work is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 License (CC BY-NC 4.0). 3 maxillary sinuses were removed. Pathology findings showed invasive fungal rhinosinusitis. After the first surgery, serial endoscopic examinations with debridement of remained necrotic tissue were performed in 3 sessions. After 8 weeks of antifungal treatment and with significant improvement of symptoms, including vision, the patient discharged from hospital. He came back with complaint of swelling of the left periorbital area after 3 months. Then he underwent endoscopic sinus surgery again. Pathology findings of the second stage showed tiny necrotic tissue associated with some broad pauci-septateted hyphae. Case 3 A 49-year-old diabetic male with a history of COVID-19 came to our clinic with complains of nasal obstruction and pain.  He had no other medical illness. His past surgical history was insignificant. His drug history consisted of Metformin.  On physical examination, the only evident abnormal finding was nasal congestion. His facial movement and sensations were normal. There was necrosis of mucosa of right inferior turbinate during nasal endoscopy. The details of laboratory data are mentioned in Table 1. Imaging findings showed opacity of the right and left maxillary sinuses (Figure 2).   Figure 2. Bilateral opacity of sinuses.    In the first stage, the patient underwent endoscopic sinus surgery and debridement. Pathology findings showed invasive fungal rhinosinusitis. The patient returned to the hospital after 2 months of discharge with symptoms of lip numbness and pain on the right side. Then he underwent endoscopic debridement again. In the second stage, bone sequestrations were removed from inside of right maxillary sinus. Pathology findings in the second stage showed invasive fungus in favor of Mucorales. Discussion COVID-19 is a viral disease that can lead to a global emergency epidemic. This disease has killed more than 1 million people worldwide. The treatment of this disease varies according to the symptoms and severity. Along with specific antiviral treatments, supportive care plays an important role in controlling the disease of COVID-19. One of the treatments for these patients is the administration of glucocorticosteroids. These drugs improve the lung inflammation and reduce the mortality caused by it in patients suffering from hypoxia (11). Due to the reduction of CD8+ T and CD4+ T cells, COVID-19 suppresses the immune system in patients. Administering glucocorticosteroids further suppress  the immune system in these patients (12). Therefore, it causes a susceptibility to opportunistic infections. One of the most common opportunistic infections is fungal infection. Chronic Invasive Fungal Sinusitis (CIFS) is a subset of Invasive Fungal Rhinosinusitis (IFS) occurs due to the inhalation of fungi and their invasion of the sinuses. It  caused by saprophytic fungi such as Zygomycetes (Mucor, Rhizopus, Rhizomucor) and numerous Aspergillus species (13). Among them, Aspergillus species such as Aspergillus flavus or Aspergillus fumigatus are the most common cause of CIFS in humans (14). CIFS is classified into granulomatous and non-granulomatous forms, which can be distinguished mainly based on the presence of CASE REPORT Journal of Otorhinolaryngology and Facial Plastic Surgery 2022;8(1):1-5. https://doi.org/10.22037/orlfps.v8i1.41572  ------------------------------------------------------------------------------------------------------------------  This work is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 License (CC BY-NC 4.0). 4 submucosal granuloma with fungal hyphae and multinuclear giant cells on histopathology (15). CIFS is a fatal but rare infection that usually manifests in immunocompetent patients or patients with mild immunosuppression, such as patients taking corticosteroids for a long time or patients with mild diabetes mellitus (16). In immunocompetent individuals, phagocytes destroy inhaled fungal spores, but in immunocompromised patients, these spores may act as opportunistic pathogens and cause disease. In diabetic patients, increased blood sugar levels facilitate the germination and formation of hyphae, followed by vascular invasion with local tissue proliferation (17). The rate of progression of CIFS is slow, often progressing gradually over weeks or months. A period of less than 4 weeks separates the acute form of the disease from the chronic form (18).  Therefore, we think our patients cannot be categorized as classic CIFS cases because of different clinical course and especially existing underlying immunocompromised state. Presentation of invasive fungal sinusitis after initial resolution of manifestations and control of disease may be related to poor control of underlying disease or residual disease in tissues, like case 1, with fungal osteomyelitis. Thus, close follow up of patients in outpatient setting for early symptoms of recurrence of disease is important. Complete eradication of invasive fungus may be difficult and complicated and may need more prolonged periods of antifungals, drugs originally have many side effects and on the other hand more aggressive surgical debridement while preserving viable tissue. Early diagnosis and treatment of this disease is very necessary, especially in patients with immunodeficiency. Treatment for invasive fungal sinusitis includes reversal of any immunosuppression, surgical debridement, and systemic antifungal therapy such as amphotericin B.   Conclusion In summary, physicians should be aware of the serious infections that can affect patients with COVID-19. Early diagnosis of invasive fungal disease in COVID-19 patients and appropriate measures are necessary to cure the disease. It is also essential to follow patient for early symptoms of recurrence along with control of underlying conditions.   Acknowledgments Not declared.  Conflicts of Interest The authors declare no conflicts of interest.  Financial Support The authors declare there was no funding support for this study.  Authors' ORCIDs Jahangir Ghorbani  https://orcid.org/0000-0001-6209-1081  Nasim Raad  https://orcid.org/0000-0003-1372-3710   Mahboobeh Karimi-Galougahi https://orcid.org/0000-0001-9880-3802  References 1. Peng Zhou, Xing-Lou Yang, Xian-Guanf Wang, Ben Hu, Lei Zhang, Wei Zhang, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;  2. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021;384(8):693–704.  3. Tabarsi P, Khalili N, Askari E. COVID-19 associated rhinosinusitis mucormycosis due to Rhizopus oryzae: A rare but potentially fatal infection occurring after treatment with corticosteroids. 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Chronic or Recurrent Invasive Fungal Sinusitis after COVID-19 Infection

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Chronic or Recurrent Invasive Fungal Sinusitis after COVID-19 Infection

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