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European Journal of Applied Sciences – Vol. 12, No. 3
Publication Date: June 25, 2024
DOI:10.14738/aivp.123.17113.
Naidu, K., Richards, G. A., Cruickshank, D., Wadee, B., Naidu, J., & Kajee, N. (2024). The Incidence of Fungal Infections in Patients
Treated with Tocilizumab for Severe COVID-19 Pneumonia Requiring High Care or ICU Admission: A Retrospective Cohort Study.
European Journal of Applied Sciences, Vol - 12(3). 378-388.
Services for Science and Education – United Kingdom
The Incidence of Fungal Infections in Patients Treated with
Tocilizumab for Severe COVID-19 Pneumonia Requiring High
Care or ICU Admission: A Retrospective Cohort Study
Kuven Naidu
East Rand Physicians, 36 Park Street,
Benoni, Gauteng, South Africa, 1501
Guy A Richards
University of Witwatersrand, Faculty of Health Sciences,
Johannesburg, Private Bag 3, Wits, South Africa, 2050
Deborah Cruickshank
East Rand Physicians, 36 Park Street,
Benoni, Gauteng, South Africa, 1501
Bilaal Wadee
East Rand Physicians, 36 Park Street,
Benoni, Gauteng, South Africa, 1501
Jayseelan Naidu
East Rand Physicians, 36 Park Street,
Benoni, Gauteng, South Africa, 1501
Nabeela Kajee
East Rand Physicians, 36 Park Street,
Benoni, Gauteng, South Africa, 1501
ABSTRACT
Background: Critically ill COVID-19 patients often experience immune
dysregulation, leading to cytokine release syndrome and an increased
susceptibility to nosocomial infections, including invasive fungal infections. Early
detection and treatment of fungal infections is paramount due to associated high
mortality rates. Tocilizumab, an IL-6 receptor-blocking monoclonal antibody used
in treating COVID-19 patients, has shown efficacy in managing the cytokine storm
but is linked to a heightened risk of secondary fungal infections. Aims: This study
aimed to investigate the association between Tocilizumab use and fungal
infections in COVID-19 patients admitted to an ICU in South Africa. Methods: We
conducted a retrospective cohort study at a private hospital in Johannesburg,
South Africa, from April 2020 to August 2021. Data from 373 COVID-19 patients
admitted to high care or ICU were analysed. Patients were categorized based on
positive fungal cultures. Demographics, Tocilizumab usage, and relevant factors
were collected from electronic databases. Results: Fungal infections were
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Naidu, K., Richards, G. A., Cruickshank, D., Wadee, B., Naidu, J., & Kajee, N. (2024). The Incidence of Fungal Infections in Patients Treated with
Tocilizumab for Severe COVID-19 Pneumonia Requiring High Care or ICU Admission: A Retrospective Cohort Study. European Journal of Applied
Sciences, Vol - 12(3). 378-388.
URL: http://dx.doi.org/10.14738/aivp.123.17113
identified in 15.6% of the patients. Tocilizumab use did not significantly correlate
with fungal infections (OR: 0.342 [95%CI: 0.115-1.019]; P=0.054). Factors
associated with fungal infections included extended hospital stays (OR: 1.098
[95% CI: 1.038-1.163], P=0.050 and elevated D-dimer values (OR:1.20; [95% CI:
1.035-1.390]; P=0.015). Females were less likely to develop a fungal infection
(OR:0.224; [95% CI: 0.054-0.928], P=0.039). Conclusions: Tocilizumab
administration was not significantly linked to an increased risk of fungal
infections in COVID-19 patients in the ICU. This study underscores the
multifactorial nature of fungal infection risk, emphasizing the need for
comprehensive risk assessment.
Keywords: Fungal, Tocilizumab, Covid-19, D-Dimer
INTRODUCTION
The world has recently been in the midst of the worst public health crisis since the 1918
influenza pandemic with COVID -19 officially declared to be a pandemic on March 11th 2020,
by the World Health Organisation (WHO).
It has been previously reported that 5–30% of COVID-19 patients become critically ill and
require intensive care unit (ICU) admission [1] . Severe COVID-19 is associated with immune
dysregulation, affecting both T-helper cell 2 (Th2) and Th1 responses, including the cytokine
release syndrome, which contribute to lung pathology, promote pulmonary microbial
proliferation and a subsequently secondary infection. Critically ill COVID-19 patients have
higher pro-inflammatory (IL-1, IL-2, IL-6, tumor necrosis alpha) and anti-inflammatory (IL-4,
IL-10) cytokine levels and less CD4 interferon-gamma expression, and fewer CD4 and CD8
cells [2] all of which increase the potential for nosocomial infection, including invasive fungal
infections.
Fungal infections, which could be co- or superinfections, have been reported in severely ill
COVID-19 patients admitted to the ICU, with a preponderance of aspergillus and candida
infections[3].
Awareness of the possibility of fungal superinfection in COVID-19 patients is essential to
avoid delays in diagnosis and treatment as these are associated with high mortality [5].
Coşkun et al examined the electronic health records of 627 patients hospitalized in ICU with a
diagnosis of COVID-19 [4].
Opportunistic fungal infections were detected in 32 patients (5.10%) of whom 25 (78.12%)
died and seven (21.87%) were discharged alive from the ICU. Candida parapsilosis (43.7%)
was the opportunistic fungal agent isolated most frequently from blood samples and the
mortality rate with candidemia was 80% [4].
A review of fungal infections in the United States in 2020-2021 revealed that patients
hospitalised with COVID-19 associated fungal infections had a 48.5% mortality rate compared
to 12.3% in those patients who had fungal infections without a concurrent COVID-19 infection
[5].