Content uploaded by Mariangela Cernera
Author content
All content in this area was uploaded by Mariangela Cernera on Jan 02, 2024
Content may be subject to copyright.
https://doi.org/10.1177/23247096231217823
Journal of Investigative Medicine High
Impact Case Reports
Volume 11: 1–5
© 2023 American Federation for
Medical Research
DOI: 10.1177/23247096231217823
journals.sagepub.com/home/hic
Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-
NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction
and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages
(https://us.sagepub.com/en-us/nam/open-access-at-sage).
Case Report
Introduction
Severe acute respiratory syndrome coronavirus 2 (SARS-
COV-2) causes the coronavirus disease 2019 (COVID-19)
which led to a pandemic of more than 650 million cases and
6 million death as of January 2023 in the course of nearly 3
years. The most common signs of COVID-19 are respiratory
distress, gastrointestinal (GI) and hepatic diseases, and neu-
rological complications.1 This infection could develop in
fatal outcomes, especially in patients with underlying comor-
bidities, such as diabetes mellitus, hypertension, obesity, old
age, trauma, organ transplant, hematopoietic malignancies,
or cardiac, respiratory, or renal disorder.2,3
The physiopathology suggests that in infected COVID-19
patients, the absolute number of T lymphocytes, and CD4+
and CD8+ T cells are lower than healthy individuals while
various inflammatory markers, including interleukin (IL)-2,
IL-6, IL-10, tumor necrosis factor-alpha (TNF-α) are at
higher levels.4
This immune dysregulation is exacerbated in patients
with metabolic disorders, including hypertension and diabe-
tes and other chronic medical conditions, such as respiratory
system disease and cardiovascular disease as well as patients
taking drugs, such as steroids and Tociluzimab during
COVID treatment.5,6
Following COVID-19 infection, individuals are prone to
other infections, especially those infections for which cell-
mediated immunity constitutes an important host defense.
Recent studies suggest that some people may develop sinus
infections after COVID.7 The weakened inherent immunity
predisposes the patient to fungal and bacterial infections.
Fungal infections were observed in SARS patients in earlier
studies and were considered the leading cause of death in
25% to 73.7% of patients.8-10
Other studies have found a higher percentage of secondary
pulmonary infections (8%-15%) in COVID-19 patients, but
it is not clear whether it is bacterial or fungal infection.11,12
A rare kind of bacterial infection is caused by Actinomyces
israelii that could be associated with COVID infection.
The aim of the present study is to present a rare case of
actinomycosis and perform a review of literature on post-
COVID-19 occurrence of actinomycotic infection.
1217823HICXXX10.1177/23247096231217823Journal of Investigative Medicine High Impact Case ReportsMoaddabi et al
case-report20232023
1Department of Oral and Maxillofacial Surgery, Dental Research Center,
Mazandaran University of Medical Sciences, Sari, Iran
2Department of Neurosciences, Reproductive and Odontostomatological
Sciences, University of Naples “Federico II”, Naples, Italy
3Department of Oral and Maxillofacial Radiology, Dental Implants
Research Center, Dental Research Institute, School of Dentistry, Isfahan
University of Medical Sciences, Isfahan, Iran
*These authors contributed equally to the work.
Received August 30, 2023. Revised November 5, 2023. Accepted
November 12, 2023.
Corresponding Author:
Mariangela Cernera, University of Naples Federico II, Via Pansini 5,
80131 Naples, Italy.
Email: mariangela.cernera@icloud.com
Actinomycotic Sinomaxillary Infection
in a COVID-19 Patient: A Case Report
and Review of the Literature
Amirhossein Moaddabi, DDS, MSc1,*, Mariangela Cernera, DDS2,*,
Niccolò Giuseppe Armogida, DDS2, Parisa Soltani, DDS, MSc2,3,
and Gianrico Spagnuolo, DDS, PhD2
Abstract
Individuals with COVID-19 are prone to a variety of infections due to immune dysregulation. The present report presents
a case of actinomycotic infection in the maxillary bone and sinus region in a patient with a history of COVID-19. This case
report highlights the importance of considering bacterial infections including actinomycosis when encountering destructive
lesions resembling more prevalent fungal infections due to different therapeutic medication protocols. In addition, a literature
review of the existing reports of similar post-COVID-19 actinomycotic infection is presented.
Keywords
actinomycosis, actinomycete, COVID-19
2 Journal of Investigative Medicine High Impact Case Reports
Case Presentation
A 62-year-old Iranian female attended the office of an oral
and maxillofacial surgeon with a chief complaint of pain in
the maxillary and zygomatic region. The patient had a his-
tory of controlled hypertension and cardiac problems and
was taking the following medications: aspirin 80 mg, clopi-
dogrel 75 mg, bisoprolol 2.5 mg, indapamide 1.5 mg, and
losartan 12.5 mg. She tested positive for COVID-19 in
August 2021 using real-time polymerase chain reaction
(RT-PCR) technique. After 10 days, she felt an intense, dull,
pulsating pain in the maxillary and zygomatic region. She
claimed that the pain was alleviated only with diclofenac.
After 1 month, the patient was referred to an otolaryngolo-
gist who performed endoscopic sinus surgery. However, the
pain did not resolve and was exacerbated. The patient was
then referred to a dentist after 20 days who extracted the right
maxillary second premolar. However, the pain was not alle-
viated and the extracted socket was not healed. Finally, 2
months after the diagnosis of COVID-19, the patient was
referred to the oral and maxillofacial surgeon.
Extraoral clinical examination was normal with a normal
range of mouth opening and no extraoral swelling. In the
intraoral examination, necrotic bone was observed in the
posterior right maxillary alveolar bone. The roots of the right
maxillary first molar were exposed and inflammation was
noted in the surrounding gingiva (Figure 1). The right maxil-
lary first molar had severe mobility.
Cone-beam computed tomography (CBCT) was obtained
from the maxillary region and paranasal sinuses. In the
CBCT views, a lytic and destructive lesion was observed on
the right side of the maxilla. Destruction of the posterior
alveolar process, medial wall, anterior wall, lateral wall, and
floor of the right maxillary sinus was seen. The right maxil-
lary sinus was completely opacified with soft tissue density
and fragments of bone were also seen in the sinus. Evidence
of endoscopic sinus surgery was observed in the nasal and
paranasal regions. Loss of bone support of the involved teeth
was detected without root resorption (Figure 2).
Under general anesthesia, the right maxillary first molar
was extracted and a biopsy was obtained from the necrotic
bone and granulation tissue in the maxillary sinus and sinus
mucosa. The samples were stored in 2 different containers:
one with normal saline for culturing and another one with
formalin for histopathological examination. Bacterial smear
and culture revealed a tangled mass of elongated, rod-shaped
cells that branched into filaments about 1 to 2 µm in diame-
ter. Gram staining revealed gram-positive rods and thiogly-
colate broth growth showed non-acid fast bacteria indicating
Actinomyces. Histopathological evaluation using hematoxy-
lin and eosin staining also demonstrated areas of bone necro-
sis along with inflammatory infiltration and bacterial rods
(Figure 3).
Figure 1. Intraoral photograph depicting exposed roots of the
right maxillary first molar with surrounding inflammation.
Figure 2. Cone-beam computed tomographic images in (A)
coronal and (B) axial sections depicting the lytic and destructive
lesion on the right side of the maxilla.
Moaddabi et al 3
The patient was prepared for surgery by a team contain-
ing an oral and maxillofacial surgeon, an oral and maxillo-
facial radiologist, and an otolaryngologist. Half an hour
before the surgery, 1 g of cefazolin was administered via
intravenous injection. First, endoscopic sinus surgery was
performed to clear the nasal cavity and sinus ostium.
Afterward, curettage and removal of necrotic bone was per-
formed using intraoral open sinus surgery with buccal
advancement flap and buccal fat grafting to close the oroan-
tral connection. After the operation, cephalexin 500 was
administered every 8 hours for 1 week. Routine non-steroi-
dal anti-inflammatory drugs (NSAIDs) were administered
in case of pain. Chlorhexidine 0.2% mouthwash was also
administered 3 times a day for 1 week. The patient then
received high-dosage penicillin G for a period of 6 months
administered by the infectious diseases specialist.
The patient was followed 1 week, 1 month, 3 months, 6
months, and 8 months after the surgery. The clinical signs
and symptoms started to improve after the surgery. The sur-
gical site and the extraction socket have been completely
healed. No evidence of pus discharge and secretions and
oroantral fistula was observed in clinical examination
(Figure 4).
Discussion
Actinomycosis is a rare anaerobic bacterial infection caused
by gram-positive, non-motile, non-acid fast filamentous bac-
terial rods. Actinomyces are part of the normal flora com-
monly seen in the human oral cavity, female urogenital tract,
and GI tract. The organism has low virulence and only
invades the body to cause deep-seated infections when there
is tissue injury or following a break in the normal mucosal
barrier. Clinically, actinomycotic infection has 3 subtypes;
cervicofacial, thoracic, and abdominal. Cervicofacial type is
the most common type of actinomycotic infection. Infection
is mostly polymicrobial, established with the help of a com-
panion bacteria by inhibiting host defense, reducing oxygen
tension, or by toxin production that facilitates the inoculation
of actinomycoses.13
The infection is characterized by contagious spread,
suppurative and granulomatous inflammation leading to
multiple abscess formation, and sinus tracts that may dis-
charge yellow-colored sulfur granules. In the jaw bones, it
can result in osteomyelitis if untreated. Imaging findings are
nonspecific and are non-contributory in diagnosing fungal
or bacterial osteomyelitis, but will help in assessing the
degree of soft tissue and bone involvement. Only the biopsy
specimen of the involved tissue could confirm the diagnosis
in which the filamentous shape of the microbes that resem-
ble fungal hyphae could be observed.
There are only a few reported cases of actinomycosis sec-
ondary to COVID-19 infection in the literature (Table 1). All
of them report male patients, with a mean age of 49-year-old,
with a history of COVID-19 for 1 to 4 months before the start
of the bacterial infection and with other comorbidities, such
as type II diabetes and other predisposing conditions, includ-
ing dental extractions. Hyperglycemia in diabetic patients is
associated with impairment of immune response and inter-
ference with the wound healing process. Therefore, resis-
tance to bacterial infection is lower in diabetic individuals
compared with those without diabetes.19,20 Similarly, admin-
istration of corticosteroids can lead to immune suppression,
in turn increasing the susceptibility of the individuals to
infective diseases.21 The reported cases mostly revealed
co-infection of actinomycosis and mucormycosis in the
individuals. A systematic review in 2021 revealed 101 cases
of post-COVID-19 mucormycosis, of which 82 were from
India. Diabetes, extensive use of corticosteroids, and a
background of COVID-19 appears to increase incidence
of mucormycosis.19 Therefore, mucormycosis is one of the
most important differential diagnoses to consider in such
Figure 3. Histopathological hematoxylin and eosin staining of
the sample indicating focus of actinomycosis with surrounding
inflammatory response.
Figure 4. Intraoral photograph depicting resolution of
inflammation and favorable healing of the infection.
4 Journal of Investigative Medicine High Impact Case Reports
cases. Another bacterial infection that needs to be considered
is nocardiosis. Nocardia are gram-positive aerobic filamen-
tous bacteria with similar cytomorphologic features with
actinomycete. However, they differ most prominently in
their ability or lack thereof to retain acid-fast staining.22
Infections with the two microorganisms also may show simi-
lar clinical manifestations. In addition, nocardiosis has been
reported in COVID-19 patients.23 However, since the bacte-
rial tests in the present case revealed non-acid-fast features, a
diagnosis of actinomycosis was made.
The current report presented a case of actinomycosis in
a 62-year-old female patient with a history of controlled
hypertension and cardiac problems and showing clinical
symptoms 10 days after testing positive for COVID-19. The
radiographic appearance of bone destruction and necrosis in
the sinonasal region of COVID-19 patients rises the more
common possibility of fungal infections including mucormy-
cosis. Improper diagnostic tests and culture can lead to mis-
diagnosis and thus hinder adequate and timely treatment
with antibiotic therapy. Therefore, it is important to consider
the possibility of imitating bacterial infections, such as acti-
nomycosis in these cases.
Typical management of cervicofacial actinomycosis con-
sists of conservative debridement and intravenous antibiotic
therapy.24 The same regimen used in our case report allowed
for the resolution of infection.
Conclusion
This case reports highlights the importance of histopatho-
logical diagnosis in routine clinical practice. The prevalence
of actinomycosis in COVID-19 patients is considerably less
than mucormycosis. Definitive treatment cannot be provided
in cases of misdiagnosis, which can lead to substantial mor-
bidity and mortality. Histopathological examination of these
lesions is crucial for a definitive diagnosis and prognosis of
the lesion.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, author-
ship, and/or publication of this article.
Ethics Approval
Our institution does not require ethical approval for reporting indi-
vidual cases or case series.
Informed Consent
Written informed consent was obtained from the patient for their
anonymized information to be published in this article.
ORCID iD
Mariangela Cernera https://orcid.org/0000-0001-6356-6536
References
1. Weiss SR, Leibowitz JL. Coronavirus pathogenesis. Adv Virus
Res. 2011;81:85-164.
2. Ng WH, Tipih T, Makoah NA, et al. Comorbidities in SARS-
CoV-2 patients: a systematic review and meta-analysis. mbio.
2021;12:e03647-20.
Table 1. Characteristics of Previous Cases of Head and Neck Actinomycotic Infection After COVID-19.
Year Authors Sex Age Comorbidities Medication Chief complaint
Histopathologic
examination Treatment Recurrence
1. 2021 Jagtap etal14 M 46 Type II diabetes mellitus
COVID-19
1 month ago
Steroid
Amphotericin B
Headache, bilateral nasal
obstruction, swelling mid-
face region, foul-smelling
nasal discharge, fever
Necrotic tissues
aseptate fungal hyphae
actinomycotic colonies
None Not reported
2. 2021 Mishra etal15 M 37 None except for
aggressive debridement
for mucormycosis
(dental extraction)
COVID-19
2 months ago
Amphotericin B
Posaconazole
Pain around eyes
Nose bleeding
Sinus tenderness
Ulcerated hard palate
Necrotic tissue
Aseptate fungal hyphae
Ampicillin Not reported
3. 2021 Prajwal16 M 38 Type II diabetes mellitus
(dental extraction)
COVID-19
3 months ago
Dexamethasone Swelling right middle third
face
Paresthesia over the right
cheek and right lateral
wall of the nose
Acute on chronic
inflammatory lesion
with bacterial
colonies
Oral clindamycin
Chlorhexidine
mouthwash
Imipenem
Ceftriaxone
Not reported
4. 2022 Jawanda etal17 M 70 Type II diabetes mellitus
COVID-19
4 months ago
Metformin
Ivermectin
Remdesvir
Tocilizumab
Pain in the right side of the
maxilla for 3 months
Oroantral communication
Necrotic bone
Aseptate fungal hyphae
Actinomycotic colonies
Candidal hyphae
Surgery
Posaconazole
Clindamycin
Not reported
after 3 months
5. 2022 Arshad etal18 M 56 Type II diabetes mellitus
Hypertension (dental
extraction)
COVID-19
4 months ago
Steroid Non-remitting facial pain Necrotic bone
Inflammatory infiltrate
Actinomycete colonies
Surgery and
adequate
antibiotic
Not reported
Moaddabi et al 5
3. Wolff D, Nee S, Hickey NS, Marschollek M. Risk factors for
Covid-19 severity and fatality: a structured literature review.
Infection. 2021;49(1):15-28.
4. Chen G, Wu D, Guo W, et al. Clinical and immunological
features in severe and moderate forms of coronavirus disease.
J Clin Invest. 2019;82:137244.
5. Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities
and its effects in patients infected with SARS-CoV-2: a sys-
tematic review and meta-analysis. Int J Infect Dis. 2020;94:
91-95.
6. Nuñez DDF, Leon L, Mucientes A, et al. Risk factors for
hospital admissions related to COVID-19 in patients with auto-
immune inflammatory rheumatic diseases. Ann Rheum Dis.
2020;79:1393-1399.
7. El-Kholy NA, El-Fattah AMA, Khafagy YW. Invasive fun-
gal sinusitis in post COVID-19 patients: a new clinical entity.
Laryngoscope. 2021;131(12):2652-2658.
8. Yin C-H, Wang C, Tang Z. Clinical analysis of 197 patients
with critical severe acute respiratory syndrome in Beijing
areas. Chin J Crit Care Med. 2004;24:248-249.
9. Li CS, Pan SF. Analysis and causation discussion of 185 severe
acute respiratory syndrome dead cases. Chin J Crit Care Med.
2003;15(10):582-584.
10. Tommi JAJ, Reddy LS. Post COVID-19 mucormycosis-the
horizon. Indian J Otolaryngol Head Neck Surg. 2023;75(2):
517-522.
11. Huang C, Wang Y, Li X, et al. Clinical features of patients
infected with 2019 novel coronavirus in Wuhan, China. Lancet.
2020;395:497-506.
12. Ruan Q, Yang K, Wang W, et al. Clinical predictors of
mortality due to COVID-19 based on an analysis of data
of 150 patients from Wuhan, China. Intensive Care Med.
2020;46:846-848.
13. Ge M, Fu Y, Zhou H, et al. Clinical feature analysis of 30
cases with pulmonary actinomycosis. Zhonghua Yi Xue Za Zhi.
2019;99:3617-3621.
14. Jagtap SV, Hulwan A, Vartak S, et al. Co-infection of mucor-
mycosis and actinomycosis in COVID-19 infection. Int J
Health Sci Res. 2021;11:127-130.
15. Mishra N, Mutya V, Irfan K, et al. Post COVID-19 invasive
mucormycosis and actinomycosis co-infection: a case report.
Int J Otorhinolaryngol Head and Neck Surg. 2021;7:1537-
1539.
16. Prajwal K. Post COVID-19 recovery-a focus on opportunistic
infections of maxillofacial region: report of two cases. South
Asian Res J Oral Dent Sci. 2021;3:54-59.
17. Jawanda MK, Narula R, Gupta S, et al. Mixed infections
(Mucormycosis, Actinomycosis and Candidiasis) leading to
maxillary osteomyelitis in a diabetic mellitus patient in post
COVID phase: first case report. Acta Med. 2022;64:218-223.
18. Arshad W, Mahmood Kamal M, Rafique Z, Rahat M, Mumtaz
H. Case of maxillary actinomycotic osteomyelitis, a rare post
COVID complication-case report. Ann Med Surg (Lond). 2022;
80:104242.
19. Singh AK, Singh R, Joshi SR, Misra A. Mucormycosis in
COVID-19: a systematic review of cases reported worldwide
and in India. Diabetes Metab Syndr. 2021;15(4):102146.
20. Agarwal P, Chug A, Kumar S, Jain K. Palatal actinomycosis
osteomyelitis–complication of impacted tooth in a diabetic.
Spec Care Dentist. 2019;39(3):319-323.
21. Tokunaga A, Sugiyama D, Maeda Y, et al. Selective inhibition
of low-affinity memory CD8+ T cells by corticosteroids. J Exp
Med. 2019;216:2701-2713.
22. McHugh KE, Sturgis CD, Procop GW, Rhoads DD. The cyto-
pathology of Actinomyces, Nocardia, and their mimickers.
Diagn Cytopathol. 2017;45(12):1105-1115.
23. Stamos DB, Barajas-Ochoa A, Raybould JE. Nocardia pseu-
dobrasiliensis co-infection in SARS-CoV-2 patients. Emerg
Infect Dis. 2023;29(4):696-700.
24. Stájer A, Ibrahim B, Gajdács M, et al. Diagnosis and manage-
ment of cervicofacial actinomycosis: lessons from two distinct
clinical cases. Antibiotics. 2020;9:139.