key: cord-0875250-bfuh7v2y
authors: Agrawal, Shruti; Phulware, Ravi Hari
title: COVID-19 associated pulmonary aspergillosis (CAPA) in a pregnant woman
date: 2021-08-20
journal: Autops Case Rep
DOI: 10.4322/acr.2021.313
sha: 517246a7bfe26b8cf13168884aab468f4e6cd5d3
doc_id: 875250
cord_uid: bfuh7v2y

Viral or bacterial co-infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported in the literature. However, the knowledge on Aspergillus co-infection among patients with coronavirus disease 2019 (COVID-19) is limited. COVID‐19‐associated pulmonary aspergillosis (CAPA) has been seen in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS), which has raised concerns about the worsening disease course of COVID-19 and increasing mortality. We describe a clinical case of CAPA infection and acute respiratory distress syndrome (ARDS) with a deathly outcome in a previously well, non-immunocompromised pregnant woman with intrauterine death of the fetus. Hence, we suggest that clinicians and pathologists keep alerting the possible occurrence of pulmonary aspergillosis in severe/critical COVID-19 patients, and aggressive investigations should be done to rule out the possibility of CAPA so that early treatment can be administrated.

A 20-year-old woman presented to the emergency department with generalized tonic-clonic seizures. The patient was diagnosed with disseminated intravascular coagulation (DIC), intrauterine death of the foetus (IUD), multi-organ dysfunction syndrome (MODS) and septicaemia at the 18 th week of gestation. She was tested positive for coronavirus (COVID-19) by RT-PCR in a private nursing home. Her laboratory test showed hemoglobin 9.3 gm/dL (reference range [RR] ; 12.0-15.0 gm/dL), total leukocyte count 22.8x10 9 /L (RR; 4.0-11.0 x10 9 /L), the platelet count was 108.9 x10 9 /L (RR; 150.0-400.0 x10 9 /L). Prothrombin time (test/control) was 24. She was immediately managed symptomatically. However, the patient's condition deteriorated despite all efforts, and she died on the second day of admission. With informed consent, the patient's autopsy was performed under strict biosafety rules, and histopathological examination was performed ( Figure 1 ).

Histopathological examination from the lung revealed diffuse interstitial edema along with acute and chronic inflammation ( Figure 1A , B), hematoxylin and eosin). Numerous septate fungal hyphae [red arrow] with acute-angled branching were found invading blood vessels ( Figure 1C , 2A-C), Grocott-Gomori's Methenamine Silver), The septate hyphae morphology was consistent with Aspergillus species ( Figure 1D and 2D).

Histopathological examination from the other organs (Kidney, Liver, Spleen, and Uterus) showed fibrin thrombi in the vessels along with the variable degree of tissue necrosis. However, they did not reveal Invasive aspergillus Infection (Figure 3 A-D).

Following the recognition of coronavirus disease, 2019 (COVID-19) as a pandemic by the World Health Organisation in March 2020, COVID-19 associated-pulmonary aspergillosis (CAPA) reports are consistently being mentioned in the literature. [1] [2] [3] Until recently, it was known that patients with acute respiratory distress syndrome due to viral infections such as influenza and SARS-CoV-2 were prone to secondary complications, especially in immunocompromised patients. Detection of aspergillosis in COVID-19 cases has been a new development wherein virusinduced severe immune dysfunction and damage to airway epithelium have been postulated to be the etiopathology for homing the fungi. 4 In fact, concerns are being raised that the fungal superinfection could predispose patients with COVID-19 to a clinically worse disease contributing to the disease-associated fatality. 1, 3 We here report a case of CAPA in a young pregnant woman diagnosed with COVID-19 with no prior history of chronic immunosuppression.

Although the patient in our case had multiple contributing factors causing her mortality, it is possible that aspergillosis played a significant role in worsening the clinical scenario. The patient died despite active management with vasopressors, mechanical ventilation, and antimicrobials. A possible reason for this could be a lack of antifungal support, which would have hampered the disease progression. Furthermore, a history of IUD leading to DIC and subsequent MODS, in this case, masked the symptoms of pulmonary aspergillosis. This was compounded by normal chest X-ray findings. The possibility of nosocomial infection was excluded as the patient died the very next day of her hospitalization. Therefore, the present case emphasizes the role of autopsies for post-mortem surveillance in such a severe disease. Also, increasing availability of reports explaining the association of aspergillosis with COVID-19 mandates screening for the fungi through non-invasive procedures such as a fungal culture or molecular studies to facilitate early detection of the fatal organism and prompt management of the disease with antifungal drugs, thereby avoiding a fatality 1,2,5 . Further research is necessary to evaluate the incidence of CAPA in SARS-CoV-2 infection and determine the population at risk, prophylaxis, and precise therapy. 

Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance

COVID-19-associated pulmonary aspergillosis (CAPA) in patients admitted with severe COVID-19 pneumonia: an observational study from Pakistan

COVID-19-associated Pulmonary Aspergillosis

Dysregulation of immune response in patients with Coronavirus

A clinical algorithm to diagnose invasive pulmonary aspergillosis in critically ill patients