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High Mortality Co-Infections of COVID-19 Patients: Mucormycosis and Other Fungal Infections

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High Mortality Co-Infections of COVID-19 Patients: Mucormycosis and Other Fungal Infections DISCOVERIES 2021, Jan-Mar, 9(1): e126 10.15190/d.2021.5 Fungal co-infections in COVID-19 patients DOI: Focused REVIEW High mortality co-infections of COVID-19 patients: mucormycosis and other fungal infections Kinal Bhatt1,*, Arjola Agolli1, Mehrie H. Patel1, Radhika Garimella1, Madhuri Devi2, Efrain Garcia3, Harshad Amin3, Carlos Domingue3, Roberto Guerra Del Castillo3, Marcos Sanchez- Gonzalez1 1Division of Clinical and Translational Research, Larkin Health System, South Miami, FL, USA 2Pakistan Ziauddin Medical College, Karachi, Pakistan 3Larkin Community Hospital, Hialeah, FL, USA *Corresponding authors: Kinal Bhatt, MD, MPH, Division of Clinical and Translational Research, Larkin Health System, South Miami, FL, USA, 7031 SW 62nd Ave, South Miami, FL; Phone: (928) 225 0273; Email: [email protected] Submitted: February 6, 2021; Revised: Martch 30, 2021; Accepted: March 31, 2021; Published: March 31, 2021; Citation: Bhatt K, Musta A, Patel MH, Garimella R, Devi M, Garcia E et al. High mortality co-infections of COVID-19 patients: mucormycosis and other fungal infections. Discoveries 2021, 9(1): e126. DOI: 10.15190/d.2021.5 ABSTRACT infections. This report is intended to raise awareness Severe COVID-19 disease is associated with an of the importance of early detection and treatment of increase in pro-inflammatory markers, such as IL-1, mucormycosis and other fungal diseases, such as IL-6, and tumor necrosis alpha, less CD4 interferon- candidiasis, SARS-CoV-2-associated pulmonary gamma expression, and fewer CD4 and CD8 cells, aspergillosis, pneumocystis pneumonia and which increase the susceptibility to bacterial and cryptococcal disease, in COVID-19 patients, to fungal infections. One such opportunistic fungal reduce the risk of mortality. infection is mucormycosis. Initially, it was debated whether a person taking immunosuppressants, such SUMMARY as corticosteroids, and monoclonal antibodies will be 1. Introduction at higher risk for COVID-19 or whether the 2. COVID-19 and immunosuppression immunosuppresive state would cause a more severe 3. Fungal co-infections in COVID19 COVID-19 disease. However, immunosuppressants 3.1 Mucormycosis are currently continued unless the patients are at 3.2 Candidiasis (Candida auris) greater risk of severe COVID-19 infection or are on 3.3 SARS-CoV-2–assoc. pulmonary aspergillosis high-dose corticosteroids therapy. As understood so 3.4 Pneumocystis pneumonia far, COVID-19 infection may induce significant and 3.5 Cryptococcal disease (C. neoformans) persistent lymphopenia, which in turn increases the 4. Current treatment options for fungal infections in risk of opportunistic infections. It is also noted that COVID-19 patients 85% of the COVID-19 patients’ laboratory findings 4.1 Mucormycosis showed lymphopenia. This means that patients with 4.2 Candidiasis (Candida auris) severe COVID-19 have markedly lower absolute 4.3 SARS-CoV-2–assoc. pulmonary aspergillosis number of T lymphocytes, CD4+T and CD8+ T cells 4.4 Pneumocystis pneumonia and, since the lymphocytes play a major role in 4.5 Cryptococcal disease (C. neoformans) maintaining the immune homeostasis, the patients 5. Discussion with COVID-19 are highly susceptible to fungal co- 6. Conclusion www.discoveriesjournals.org/discoveries 1 Fungal co-infections in COVID-19 patients Keywords various parts of the world has demonstrated that the SARS-CoV-2, COVID-19, mucormycosis, fungal SARS-CoV-2 virus follows an exponential growth, infection, candida auris, aspergillosis, pneumocystis and the mean basic reproduction number, which pneumonia, cryptococcus neoformans, coinfection. indicates the number of new infections that can arise from a single case of COVID-19 infection, is 1 Abbreviations estimated to be 1.4-4 . Angiotensin-converting enzyme 2 (ACE 2); Allergic The COVID-19 disease is associated with a range bronchopulmonary aspergillosis (ABPA); Acquired of clinical manifestations, particularly due to SARS- immune deficiency syndrome (AIDS); Acute myeloid CoV-2’s high human-to-human transmission rate via leukemia (AML); Acute respiratory distress syndrome respiratory droplets1. However, the presence of the (ARDS); Candida Auris (C. Auris); COVID-19 associated binding receptors in different tissues determines the pulmonary aspergillosis (CAPA) Cluster of differentiation range of clinical manifestations. The clinical (CD); Centers for Disease Control and Prevention (CDC); manifestations range from a self-limiting illness with Chronic obstructive pulmonary diseases (COPD); general symptoms, such as fever, cough, and Coronavirus disease of 2019 (COVID-19); Chronic headache, to more severe complications, including pulmonary aspergillosis (CPA); Cryptococcus acute respiratory distress syndrome, sudden cardiac Neoformans (C. Neoformans); Deciliter (dL); Human immunodeficiency virus (HIV); ICU (Intensive care unit); death, liver dysfunction, and multi-organ failure. An Interferon gamma (IFN-γ); Interleukin (IL); Interquartile analysis of 13 studies on laboratory-confirmed range (IQR); Milligram (mg); Pneumocystis jirovecii (P. COVID-19 cases conducted in China demonstrated jirovecii); Reverse transcription polymerase chain the prevalence of COVID-19-associated co- reaction (RT-PCR); Severe acute respiratory syndrome infections with bacteria, viruses, and fungi3. Severe coronavirus 2 (SARS-CoV-2); Sequential organ failure COVID-19 disease is associated with an increase in assessment (SOFA); World Health Organization (WHO). pro-inflammatory markers, such as IL-1, IL-6, IL-6, and tumor necrosis alpha, less CD4 interferon- 1. Introduction gamma expression, and fewer CD4 and CD8 cells; this, therefore, increases the susceptibility to Towards the end of 2019, an outbreak of a bacterial and fungal infections4. One such pneumonia-like infection occurred in Wuhan, China, opportunistic fungal infection involved is and rapidly spread across the globe. With the mucormycosis. Mucormycosis is an opportunistic utilization of genome sequencing technology, the fungal infection that belongs to the zygomycete disease was identified as coronavirus disease or family and are ubiquitous in the environment. The more commonly known as coronavirus disease 2019 major route of infection is via inhalations of spores, (COVID-19), and the etiological agent was which then spread to the paranasal sinuses and identified as severe acute respiratory syndrome lungs. Mucormycosis is non-pathologic in coronavirus 2 (SARS-CoV-2)1. As of March 2021, immunocompetent individuals as a result of the there are 93.3 million infected cases, with 2 million presence of an intact immunity via neutrophils confirmed deaths reported worldwide. This which hence permit the elimination of these spores5. respiratory illness has significantly impacted all However, in immunocompromised patients such as sectors of life, primarily healthcare and the those with uncontrolled diabetes mellitus, diabetic economy, and as a result, on March 11, 2020, the ketoacidosis, presence of an open wound, HIV/ WHO officially recognized COVID-19 disease as a AIDS, cancer, and organ transplant, mucormycosis pandemic. The coronaviruses are enveloped, can result in a severe invasive fungal infection6. positive-sense single-stranded viruses that utilize the Infection with mucormycosis is associated with human angiotensin-converting enzyme 2 (ACE2) high mortality primarily due to complications such receptors located on cells in many organs/tissues, as cavernous sinus thrombosis, disseminated including the lung, heart, kidney, bladder, eyes, infection, osteomyelitis, and death. Diagnosis is nasal and oral cavities, brain, thyroid, liver, made via routine blood work, biopsy, and gallbladder, stomach, pancreas, intestine, radiological imaging. The standard protocol for the reproductive system of males and females, and skin, management is primarily reversal of risk factors, to gain entry and trigger a range of clinical surgical debridement as well as intravenous manifestations2. Evaluating the data available from antifungal medication such as Amphotericin B6. www.discoveriesjournals.org/discoveries 2 Fungal co-infections in COVID-19 patients Infection with SARS-CoV-2 drastically impacts the 3. Fungal co-infections in COVID19 immune system via induction of an inflammatory storm, an increase in neutrophil count as well a 3.1 Mucormycosis decrease in lymphocyte count, specifically CD4+ Mucormycosis, previously known as zygomycosis, and CD8+ T cells. Neutrophils ensure the is a severe fungal infection caused by a group of immunocompetence of individuals, so one would molds called mucoromycetes. It can affect the expect an even more increased immune response sinuses, brain or lungs and therefore can be quite against mucormycosis fungi when reading that common in people suffering or recovering from neutrophil numbers are rising during SARS-CoV-2. COVID-19. The common symptoms linked to Consequently, these patients are at increased mucormycosis are swelling in one side of the face, susceptibility of developing opportunistic infections fever, headache, nasal or sinus congestion, black such as mucormycosis, due to decreasing lesions on nasal bridge or upper inside of mouth12. lymphocyte cells5. CD4+ and CD8+ T cells serve a Fungi that most commonly cause mucormycosis are: prominent role against infection with mucormycosis Rhizopus species, Mucor species, Rhizomucor via recruiting cytokines, such as IL-4, IL-10, IL-17, species, Syncephalastrum species, Cunninghamella and IFN-γ5. Bertholletia, Apophysomyces species, and Lichtheimia species.
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