The Role of Neutrophils in Host Defense Against Invasive Fungal Infections

The COVID-19 pandemic, which originated from Wuhan, China, has rapidly spread worldwide, including India. As India grappled with the second wave, COVID-triggered fungal infection has suddenly risen tremendously, raising a sense of panic in the country. The fungal infection in COVID-19 includes Mucormycosis and Aspergillosis, as common fungal infections primarily affecting rhino-orbital structures. Many research papers have published postmortem findings in autopsies conducted on COVID-19 decedents, thereby helping to understand this contagious disease's pathogenesis. But, with the arrival of COVID-triggered fungal infection, which is a crucial invasive disease responsible for fatality, very few research papers have commented on the postmortem findings of invasive fungal infections affecting the rhino-orbital and craniocerebral structures in COVID-19 deaths. Therefore, the role of invasive fungal infection due to COVID-19 illness must be established in the causation of deaths in COVID-19 patients. This review research deals with autopsy dissection techniques and possible postmortem findings of invasive fungal infections involving the nasal and paranasal sinuses and orbital structures in COVID-19 deaths. The findings of fungal infection affecting nasal and paranasal systems may not differ in live patients and in a deceased; however, it is essential that correct interpretation of the postmortem findings aided by pre-or post-autopsy investigations is necessary to establish the role of covid triggered fungal infection in such deaths.

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Isavuconazole—Animal Data and Clinical Data

Journal of Fungi ◽

10.3390/jof6040209 ◽

2020 ◽

Vol 6 (4) ◽

pp. 209

Author(s):

Livio Pagano ◽

Chiara Cattaneo ◽

Martina Quattrone ◽

Margherita Oberti ◽

Maria Mazzitelli ◽

...

Keyword(s):

Clinical Data ◽

Fungal Infections ◽

Invasive Fungal Infections ◽

Hematological Patients ◽

Animal Data

The treatment of invasive fungal infections has deeply evolved in the last years with the inclusion of new antifungals, mainly new azoles (i.e., posaconazole, isavuconazole), to the therapeutic armamentarium. This review focuses on the role of isavuconazole for treating the most important invasive fungal infections both in animals and humans (hematological and non-hematological patients).

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Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis

mBio ◽

10.1128/mbio.01753-18 ◽

2018 ◽

Vol 9 (5) ◽

Cited By ~ 224

Author(s):

Lisa E. Gralinski ◽

Timothy P. Sheahan ◽

Thomas E. Morrison ◽

Vineet D. Menachery ◽

Kara Jensen ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Host Defense ◽

Complement System ◽

Complement Activation ◽

Fungal Infections ◽

Central Component ◽

Lung Pathology ◽

Inflammatory Monocytes ◽

The Complement System

ABSTRACT Acute respiratory distress syndrome (ARDS) is immune-driven pathologies that are observed in severe cases of severe acute respiratory syndrome coronavirus (SARS-CoV) infection. SARS-CoV emerged in 2002 to 2003 and led to a global outbreak of SARS. As with the outcome of human infection, intranasal infection of C57BL/6J mice with mouse-adapted SARS-CoV results in high-titer virus replication within the lung, induction of inflammatory cytokines and chemokines, and immune cell infiltration within the lung. Using this model, we investigated the role of the complement system during SARS-CoV infection. We observed activation of the complement cascade in the lung as early as day 1 following SARS-CoV infection. To test whether this activation contributed to protective or pathologic outcomes, we utilized mice deficient in C3 (C3–/–), the central component of the complement system. Relative to C57BL/6J control mice, SARS-CoV-infected C3–/– mice exhibited significantly less weight loss and less respiratory dysfunction despite equivalent viral loads in the lung. Significantly fewer neutrophils and inflammatory monocytes were present in the lungs of C3–/– mice than in C56BL/6J controls, and subsequent studies revealed reduced lung pathology and lower cytokine and chemokine levels in both the lungs and the sera of C3–/– mice than in controls. These studies identify the complement system as an important host mediator of SARS-CoV-induced disease and suggest that complement activation regulates a systemic proinflammatory response to SARS-CoV infection. Furthermore, these data suggest that SARS-CoV-mediated disease is largely immune driven and that inhibiting complement signaling after SARS-CoV infection might function as an effective immune therapeutic. IMPORTANCE The complement system is a critical part of host defense to many bacterial, viral, and fungal infections. It works alongside pattern recognition receptors to stimulate host defense systems in advance of activation of the adaptive immune response. In this study, we directly test the role of complement in SARS-CoV pathogenesis using a mouse model and show that respiratory disease is significantly reduced in the absence of complement even though viral load is unchanged. Complement-deficient mice have reduced neutrophilia in their lungs and reduced systemic inflammation, consistent with the observation that SARS-CoV pathogenesis is an immune-driven disease. These data suggest that inhibition of complement signaling might be an effective treatment option following coronavirus infection.

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