• Coronavirus Disease 2019-Associated Invasive Fungal Infection.

      Baddley, John W; Thompson, George R; Chen, Sharon C-A; White, P Lewis; Johnson, Melissa D; Nguyen, M Hong; Schwartz, Ilan S; Spec, Andrej; Ostrosky-Zeichner, Luis; Jackson, Brendan R; et al. (Oxford University Press, 2021-11-16)
      Coronavirus disease 2019 (COVID-19) can become complicated by secondary invasive fungal infections (IFIs), stemming primarily from severe lung damage and immunologic deficits associated with the virus or immunomodulatory therapy. Other risk factors include poorly controlled diabetes, structural lung disease and/or other comorbidities, and fungal colonization. Opportunistic IFI following severe respiratory viral illness has been increasingly recognized, most notably with severe influenza. There have been many reports of fungal infections associated with COVID-19, initially predominated by pulmonary aspergillosis, but with recent emergence of mucormycosis, candidiasis, and endemic mycoses. These infections can be challenging to diagnose and are associated with poor outcomes. The reported incidence of IFI has varied, often related to heterogeneity in patient populations, surveillance protocols, and definitions used for classification of fungal infections. Herein, we review IFI complicating COVID-19 and address knowledge gaps related to epidemiology, diagnosis, and management of COVID-19-associated fungal infections. © 2021 The Author(s) 2021.
    • Coronavirus Disease 2019-Associated Mucormycosis: Risk Factors and Mechanisms of Disease.

      Narayanan, Shivakumar; Chua, Joel V; Baddley, John W (Oxford University Press, 2022-04-09)
      The severe surge of coronavirus disease 2019 (COVID-19) cases on the Indian subcontinent in early 2021 was marked by an unusually high number of COVID-19-associated mucormycosis (CAM) cases reported during this same period. This is significantly higher than predicted based on available data about prevalence and risk factors for this condition. This may be due to an unusual alignment of multiple risk factors for this condition. There is high background prevalence of mucormycosis in India likely from a high prevalence of risk factors, including undiagnosed or poorly controlled diabetes. COVID-19-induced immune dysregulation and immune suppression from steroid therapy increase the risk. The role of environmental exposure is unclear. System factors such as lack of access to healthcare during a pandemic may result in delayed diagnosis or suboptimal management with potentially poor outcomes. Here, we review currently identified risk factors and pathogenesis of CAM in a pandemic surge. © The Author(s) 2021.
    • Coronavirus Disease 2019–Associated Invasive Fungal Infection

      Baddley, John W; Thompson, George R; Chen, Sharon C -A; White, P Lewis; Johnson, Melissa D; Nguyen, M Hong; Schwartz, Ilan S; Spec, Andrej; Ostrosky-Zeichner, Luis; Jackson, Brendan R; et al. (Oxford University Press (OUP), 2021-11-16)
      Coronavirus disease 2019 (COVID-19) can become complicated by secondary invasive fungal infections (IFIs), stemming primarily from severe lung damage and immunologic deficits associated with the virus or immunomodulatory therapy. Other risk factors include poorly controlled diabetes, structural lung disease and/or other comorbidities, and fungal colonization. Opportunistic IFI following severe respiratory viral illness has been increasingly recognized, most notably with severe influenza. There have been many reports of fungal infections associated with COVID-19, initially predominated by pulmonary aspergillosis, but with recent emergence of mucormycosis, candidiasis, and endemic mycoses. These infections can be challenging to diagnose and are associated with poor outcomes. The reported incidence of IFI has varied, often related to heterogeneity in patient populations, surveillance protocols, and definitions used for classification of fungal infections. Herein, we review IFI complicating COVID-19 and address knowledge gaps related to epidemiology, diagnosis, and management of COVID-19-associated fungal infections.
    • Kinetics of SARS-CoV-2 antibody responses pre-COVID-19 and post-COVID-19 convalescent plasma transfusion in patients with severe respiratory failure: an observational case-control study

      Klein, Matthew N; Wang, Elizabeth Wenqian; Zimand, Paul; Beauchamp, Heather; Donis, Caitlin; Ward, Matthew D; Martinez-Hernandez, Aidaelis; Tabatabai, Ali; Baddley, John W; Bloch, Evan M; et al. (BMJ Publishing Group, 2021-04-23)
      Aims: While the SARS-CoV-2 pandemic may be contained through vaccination, transfusion of convalescent plasma (CCP) from individuals who recovered from COVID-19 (CCP) is considered an alternative treatment. We investigate if CCP transfusion in patients with severe respiratory failure increases plasma titres of SARS-CoV-2 antibodies and improves clinical outcomes. Methods: Patients with COVID-19 (n=34) were consented for CCP transfusion and serial blood draws pretransfusion and post-transfusion. Plasma SARS-CoV-2 antireceptor binding domain (RBD) IgG and IgM titres were measured by ELISA serially, and compared with serial plasma titre levels from control patients (n=68). The primary outcome was survival at 30 days, and secondary outcomes were length of ventilator and/or extracorporeal membrane oxygenation (ECMO) support, length of stay (LOS) in the hospital and in the intensive care unit (ICU). Outcomes were compared with matched control patients (n=34). Kinetics of antibodies and clinical outcomes were compared using LOess regression and ORs, respectively. Results: Prior to CCP transfusion, 74% of patients were anti-RBD seropositive for IgG (median 1:3200), and 81% were anti-RBD IgM seropositive (median 1:320), while 16% were seronegative. The kinetics of antibody titres in CCP recipients were similar to controls. CCP recipients presented with similar survival, duration on ventilatory and/or ECMO support, as well as ICU and hospital LOS compared with controls. Conclusions: CCP transfusion did not increase the kinetics of SARS-CoV2 antibodies and did not result in improved clinical outcomes in patients with COVID-19 with severe respiratory failure, suggesting that CCP may not be indicated in this category of patients.