Azole resistance screening in Aspergillus species isolated from patients with COVID-associated pulmonary aspergillosis from Pakistan

Background: COVID-19 associated pulmonary aspergillosis (CAPA) complicates the course of critically ill COVID-19 patients. Delay in diagnosis and reports of azole resistance in CAPA patients lead to adverse outcome. We had previously reported CAPA rates of 21.7% from our center with high mortality. To detect azole resistance in Aspergillus species isolated from CAPA patients, we performed azole resistance screening. Material(s) and Method(s): Aspergillus species isolated from tracheal aspirates of CAPA patients admitted in Aga Khan University Hospital, Karachi, Pakistan during July 2020- January 2022, were screened for azole resistance as per CDC protocol. Minimum inhibitory concentration of screening positive strains were determined using YeastOne Sensititre plate. Result(s): 92 Aspergillus isolates were screened from 73 CAPA patients for azole resistance. Only 2 (2.17%) A. flavus isolates showed growth on voriconazole well, while other 90 (97%) isolates were screened negative for resistance (Table. 1). MICs of these two strains against posaconazole, voriconazole and itraconazole were 0.5 ug/mL, 1 ug/mL and 0.25ug/mL respectively. Table. 1: Aspergillus species distribution and growth on azole resistance screen agar Conclusion(s): We also did not find any azole resistance in this study. Periodic surveillance for the emergence of azole-resistant clinical isolates using molecular approaches is essential.

Comparison of clinical features, risk factors and outcome of invasive pulmonary aspergillosis in critically ill COVID19, influenza and community acquired pneumonia patients

Objective: To determine the frequency and outcomes of invasive pulmonary aspergillosis (IPA) in patients with influenza, COVID-19 and community acquired pneumonia (CAP) admitted in critical care units of a tertiary care hospital in Pakistan. Method(s): A prospective cross sectional study was conducted at the Aga Khan University from Nov 2019-June 2020. Adult patients admitted in critical care units with CAP, influenza and COVID-19 pneumonia were included. IPA was diagnosed as per EORTC/MSG criteria. Clinical information and outcome were collected on predesigned performa. Result(s): A total of 140 patients [70 Influenza, 35 COVID-19 and 35 CAP] were included. Of total, 20(14.2%) patients were found to have invasive aspergillosis with 10/35(28.5%), 9/75(12.8%) and 1/35(2.8%) patients in COVID-19, influenza and CAP groups, respectively. Duration of symptoms was 12.5+/-12.13 days in CAPA and 7.56+/-4.0 days in IAPA patients (p=0.24). Mean APCHE II score was 17.4+/-8.42 and 16.6+/-6.27 in patients with CAPA and IAPA respectively (p=0.85). 9(90%) CAPA patients required vasopressor support compared to 3(33%) patients in IAPA (p=0.020). 7(70%) CAPA patients required invasive mechanical ventilation compared to 4(44%) IAPA patients (p=0.37). Length of stay in hospital was highest in CAPA patients (18.3+/-7.28 days) compared to IAPA patients (11.7+/-5.33 days) (p=0.036). The number of deaths in IAPA patients and CAPA patients was 3(33.3%) and 5(50%), respectively (p=0.526). Conclusion(s): A higher proportion of patients with COVID-19 developed IPA compared to influenza and CAP. CAPA patients had a significantly longer stay in hospital and mortality.

Invasive fungal infections in COVID-19 patients from Pakistan

Objective: The objective of this study is to report the frequency and clinical characteristic of IFI in COVID-19 patients. Method(s): This observational study was conducted in Karachi, Pakistan from March 2020-April 2021. Patients with COVID-19 associated aspergillosis (CAPA) were diagnosed using ECMM/ISHAM criteria modified to include tracheal aspirate culture and/or Galactomannan Index (GMI) >4.5 in the possible CAPA category. COVID-19 associated candidemia (CAC) was defined by isolation of Candida species from blood cultures. COVID-19 associated mucormycosis (CAM) was defined as updated EORTC/MSG criteria with inclusion of COVID-19 as host factor. Pneumocystis jirovecii pneumonia (PJP) was defined by consistent clinical and radiological features and PCR positivity. Result(s): During the study period a total of 123 (3.3%) IFI in 3506 hospitalized COVID-19 patients were identified. This included 78 (2.2%) CAPA patients (42 probable;36 possible), 29 (0.8%) CAC (5 C. auris;24 non-C. auris), 10 (0.3%) CAM (7 pulmonary;3 rhinocerebral), 3 (0.08%) PJP and three (0.08%) cases of rare invasive fungal infections (2 C. neoformans;1 Trichosporon asahii). Outcome data was available on 117/123 patients. Of these 117 patients, 78 expired (66.7%). These include 52/74 (70%) CAPA patients, 17/27 (63%) CAC patients, 7/10 (70%) CAM patients and 2/3 (67%) PJP patients. Conclusion(s): We report a rate of 3.3% IFI amongst hospitalized COVID-19 patients at our center. We consider this rate to be an underestimate due to less bronchoscopic procedures and inclusion of only candidemia cases. We also report higher mortality rate with IFI in our patients than global data probably due to delayed diagnosis, co-infections and limited therapeutic options.

Comparison of risk factors and outcome of patients with and without COVID-19-associated pulmonary aspergillosis from Pakistan: A case–control study

Background: Early identification of COVID-19-associated pulmonary aspergillosis (CAPA) is particularly challenging in low- middle-income countries where diagnostic capabilities are limited, and risk factors for CAPA have not been identified. It is also essential to recognise CAPA patients who are likely to have a poorer outcome to decide on aggressive management approaches. Therefore, this study aimed to identify risk factors and outcomes for CAPA among admitted moderate to critical COVID-19 patients at our centre in Pakistan. Methods: An unmatched case–control study with ratio of 1:2 was conducted on hospitalised adult patients with COVID-19 from March 2020–July 2021. Cases were defined according to European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. Controls were defined as patients hospitalised with moderate, severe or critical COVID-19 without CAPA. Results: A total of 100 CAPA cases (27 probable CAPA;73 possible CAPA) were compared with 237 controls. Critical disease at presentation (aOR 5.04;95% CI 2.18–11.63), age ≥ 60 years (aOR 2.00;95% CI 1.20–3.35) and underlying co-morbid of chronic kidney disease (CKD) (aOR 3.78;95% CI 1.57–9.08) were identified as risk factors for CAPA. Patients with CAPA had a significantly greater proportion of complications and longer length of hospital stay (p-value <.001). Mortality was higher in patients with CAPA (48%) as compared to those without CAPA (13.5%) [OR = 6.36(95% CI 3.6–11)]. Conclusions: CAPA was significantly associated with advanced age, CKD and critical illness at presentation, along with a greater frequency of complications and higher mortality. © 2022 Wiley-VCH GmbH.

Comparison of risk factors and outcome of patients with and without COVID-19 associated pulmonary aspergillosis from Pakistan: A case-control study

BACKGROUND: Early identification of COVID-19 associated pulmonary aspergillosis (CAPA) is particularly challenging in low-middle income countries where diagnostic capabilities are limited and risk factors for CAPA have not been identified. It is also essential to recognise CAPA patients who are likely to have a poorer outcome to decide on aggressive management approaches. Therefore, this study aimed to identify risk factors and outcomes for CAPA amongst admitted moderate to critical COVID-19 patients at our center in Pakistan. METHODS: An unmatched case-control study with ratio of 1:2 was conducted on hospitalized adult patients with COVID-19 from March 2020-July 2021. Cases were defined according to European Confederation of Medical Mycology (ECMM) and the International Society for Human and Animal Mycology (ISHAM) consensus criteria. Controls were defined as patients hospitalized with moderate, severe, or critical COVID-19 without CAPA. RESULTS: A total of 100 CAPA cases (27 probable CAPA;73 possible CAPA) were compared with 237 controls. Critical disease at presentation (aOR 5.04;95% CI 2.18-11.63), age greater than or equal to 60 years (aOR 2.00;95% CI 1.20-3.35), and underlying co-morbid of chronic kidney disease (CKD) (aOR 3.78;95% CI 1.57-9.08) were identified as risk factors for CAPA. Patients with CAPA had a significantly greater proportion of complications and longer length of hospital stay (p-value <0.001). Mortality was higher in patients with CAPA (48%) as compared to those without CAPA (13.5%) [OR=6.36(95%CI 3.6-11)]. CONCLUSIONS: CAPA was significantly associated with advanced age, chronic kidney disease, and critical illness at presentation, along with a greater frequency of complications and higher mortality.

The severity of covid-19 among pregnant women and the risk of adverse maternal outcome

Background and Aim: The obstetrical complications of pregnant women might elevate to a severe stage due to ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Limited study focused on association between COVID-19 and pregnant women adverse outcomes. The present study was carried out to evaluate the severity of COVID-19 among pregnant women and risk of adverse maternal outcome. Materials and Methods: This cross-sectional study was carried out on 242 pregnant women of confirmed COVID-19 cases hospitalized in Aziz Fatimah Hospital, Faisalabad and Holy Family hospital Rawalpindi for six months duration from 5th December 2020 to 5th May 2021. Pregnant women demographic details, obstetric characterizations, adverse maternal outcomes, and laboratory findings were noted. Positive tested pregnant women through RT-PCR regardless of clinical symptoms and signs were enrolled as confirmed cases while negative tested pregnant women were excluded. Hypertensive disorders, preexisting pulmonary, obesity, renal, nulliparity, and cardiovascular disease were the maternal risk factors. Different variables were assessed through fisher s test and regression logistics model. Results: Of the total 242 pregnant women, the prevalence of mild to moderate symptoms, and severe disease were 187 (77.3%) and 43 (17.7%) respectively. About 12 (5%) had a critical stage of the disease. During this study period, about 31 (12.8%) were admitted to the intensive care unit (ICU) and 9 (3.7%) died. Mode of delivery, maternal age, underlying conditions, parity, and admission to ICU were the important demographic factors in severe COVID-19 disease. Other severe maternal outcomes were fever, cough, breath shortness and anosmia. Increase ICU admission and cesarean section delivery were significantly associated with disease severity. Conclusion: Our study founds a mortality rate of 3.7% among pregnant women with COVID-19. A higher prevalence of intensive care admission and cesarean delivery were reported in acute and severe COVID-19disease. The obstetrical and neonatal outcomes significantly affected by the severity of maternal disease;neonatal prematurity, ICU admission, and cesarean sections complications.