Fungal Infections Other Than Invasive Aspergillosis in COVID-19 Patients
Abstract
:1. Introduction
2. Pathophysiology of COVID-19 Lung Disease
3. COVID-19 Therapies and Risk of IFD
4. Scope and Pathogens
4.1. COVID-19-Associated Pulmonary Aspergillosis (CAPA)
4.2. Invasive Candidiasis
4.3. Pneumocystis Pneumonia
4.4. Non-Aspergillus Mould Infections
4.5. Endemic Mycoses
4.6. Cryptococcosis
5. Approach to Diagnosing a Suspected Fungal Co-Infection in COVID-19 Patients
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Drug Category | Drugs | Mechanism of Action | Fungal Infections Reported |
---|---|---|---|
Antiviral drugs | remdesivir, (Veklury®, Gilead Sciences Inc.) | Nucleoside anti-proviral drug Inhibits SARS-CoV-2 replication via RNA-dependent RNA polymerase (RdRp) | Nil reported |
Immune modulators | Glucocorticoids e.g., predinisone prednisolone dexamethasone | Decrease vasodilation, permeability of capillaries, and leukocyte migration Inhibit neutrophil apoptosis and demargination; inhibit phospholipase A2 function, and inhibit NF-Kappa B and inflammatory transcription factors Promote expression of anti-inflammatory genes such as that for IL-10. | Candidiasis Pneumocystosis Invasive aspergillosis Mucormycosis [41,42] |
baricitinib, (Olumiant®, Eli Lilly and Company) | JAK inhibitors: Bind to JAK, which prevents the activation of the JAK–STAT signalling pathway, which reduces the production of proinflammatory cytokines | Candidiasis Pneumocystosis Histoplasmosis Cryptococcosis ** [43,44] | |
tofacitinib, (Xeljanz®, Pfizer) | Oesophageal candidiasis Cryptococcosis [45,46,47] | ||
Monoclonal antibodies (mAb) | tocilizumab, (Actemra®, Roche) | IL-6 receptor antagonist. Results in reduction in cytokine and acute phase reactant production. | Invasive candidiasis Cryptococcosis Pneumocystosis [47,48,49] |
sotrovimab, (Xevudy®, GlaxoSmithKline) | Engineered human IgG1 monoclonal antibody that binds to the spike protein receptor binding domain (RBD) of SARS-CoV-2 | Nil reported to date | |
sarilumab, (Kevzara®, Sanofi and Regeneron Pharmaceuticals, Inc.) | IL-6 receptor antagonist. Results in reduction in cytokine and acute phase reactant production. | Candidiasis Pneumocystis. ** [50] | |
casirivimab and imdevimab (REGEN-COV™, Regeneron Pharmaceuticals, Inc.) | Casirivimab (IgG1κ) and imdevimab (IgG1λ) bamlanivimab (IgG1κ) and etesevimab (IgG1κ) Recombinant human monoclonal antibodies that bind to the spike protein RBD of SARS-CoV-2, which leads to the blocking of binding to the human ACE2 receptor, thereby preventing viral attachment to host cells | Nil reported to date | |
bamlanivimab and etesevimab (Eli Lilly and Company) |
CAPA | IC | PCP | Cryptococcosis | Endemic Mycoses | Non Aspergillius Mould Infections | CAM | ||
---|---|---|---|---|---|---|---|---|
RISK FACTORS | ||||||||
Corticosteroid receipt | X | X | X | X | X | X | X | |
ICU MV or non MV + (clinical deterioration) | X | X | X | X | X | X | X | |
IL-6 inhibitor therapy | X | X | X | |||||
HIV/severe lymphopenia | X | X | ||||||
Receipt of immunosuppressive therapies | X | X | X | X | X | X | X | |
Poorly controlled diabetes mellitus | X | |||||||
Major trauma | X | X | ||||||
Travel to endemic region or previous infection with endemic mycoses | X | |||||||
DIAGNOSTIC APPROACHES | ||||||||
Histopathology | Characteristics findings using standard stains | • | • | • | • | • | • | • |
Hyaline, acutely branching septate hyphae | Budding yeast cells and/or pseudohyphae | Cysts and/or trophozoites | Encapsulated yeast cells | Budding yeast cells or spherules | Hyaline, branching septate hyphae | Broad, irregular, pauci septate hyphae | ||
Culture-based | Characteristic findings on microscopy | • | • | • | • | • | • | • |
Hyaline, acutely branching septate hyphae | Budding yeast cells and/or pseudohyphae | Cysts and/or trophozoites | Encapsulated yeast cells | Budding yeast cells or spherules | Hyaline, branching septate hyphae | Broad, irregular, pauci septate hyphae | ||
Respiratory tract | • | • | • | • | • | • | ||
Sterile sites other than blood | • | • | • | |||||
Blood | • | • | • | |||||
Non-culture-based | Aspergillus Ag | • | ||||||
Cryptococcal Ag | • | |||||||
EIA for antibody detection or Ag testing for Coccidioides and/or Histoplasma | • | |||||||
Serum 1,3, β-D-glucan | • | • | • | • | ||||
Genus-specific NAAT | • | • | • ^^ | • | • | • | • | |
Panfungal PCR (ITS1/2) | • | • | • | • | • | • | • | |
RADIOLOGY (typical or more common abnormalities on chest CT) | Peripheral, bilateral GGO +/− consolidation or visible intralobular lines (i.e., crazy paving) in early stages. Multifocal GGO (round) +/− consolidation or intralobular lines at peak stage. Reverse halo sign +/− organising pneumonia at late stage ** | As directed by clinical findings; organ involvement rare | Diffuse GGO Interstitial infiltrates (predominantly upper lobes and perihilar regions) | Nodules (1 or more) Cryptococcomas, Pulmonary infiltrates | Focal or diffuse airspace disease Upper lobe cavitation thick-walled bullae, lymphadenopathy | Similar to CAM and CAPA | GGO, mass lesions +/− cavitation Consolidation, Reverse halo sign may be present. ## |
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Basile, K.; Halliday, C.; Kok, J.; Chen, S.C.-A. Fungal Infections Other Than Invasive Aspergillosis in COVID-19 Patients. J. Fungi 2022, 8, 58. https://doi.org/10.3390/jof8010058
Basile K, Halliday C, Kok J, Chen SC-A. Fungal Infections Other Than Invasive Aspergillosis in COVID-19 Patients. Journal of Fungi. 2022; 8(1):58. https://doi.org/10.3390/jof8010058
Chicago/Turabian StyleBasile, Kerri, Catriona Halliday, Jen Kok, and Sharon C-A. Chen. 2022. "Fungal Infections Other Than Invasive Aspergillosis in COVID-19 Patients" Journal of Fungi 8, no. 1: 58. https://doi.org/10.3390/jof8010058