The considerable impact of the SARS-CoV-2 pandemic and COVID-19 on the UK National Mycology Reference Laboratory activities and workload.

Starting late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a devastating global pandemic of coronavirus-19 disease (COVID-19) with ∼179 million cases and ∼3.9 million deaths to date. COVID-19 ranges from asymptomatic infection to severe illness with acute respiratory distress requiring critical care in up to 40% of hospitalized patients. Numerous reports have identified COVID-19-associated pulmonary aspergillosis (CAPA) as an important infective complication of COVID-19. In the UK, the pandemic has had unprecedented impacts on the National Health Service (NHS'): each wave of infections required hospitals to reconfigure for large surges in patients requiring intensive care, to the detriment of most aspects of non-COVID care including planned operations, outpatient appointments, general practitioner consultations and referrals. The UK National Mycology Reference Laboratory (MRL) offers a comprehensive service for the diagnosis and management of fungal disease nationwide, with a test portfolio that includes: diagnosis of allergies to fungal and other respiratory allergens; diagnosis of superficial and invasive/systemic fungal infections using traditional mycological, serological and molecular approaches; identification and susceptibility testing of the causative fungi; therapeutic drug monitoring of patients receiving antifungal therapy. Here, we describe the impact of the first 14 months of the COVID-19 pandemic on MRL activities. Changes to MRL workload closely mirrored many of the NHS-wide challenges, with marked reductions in 'elective' mycological activities unrelated to the pandemic and dramatic surges in tests that contributed to the diagnosis and management of COVID-19-related secondary fungal infections, in particular CAPA and candidemia in COVID-19 patients in intensive care. LAY SUMMARY: The COVID-19 pandemic has had an unprecedented impact on the UK National Health Service, with hospitals forced to repeatedly reconfigure to prepare for large surges in COVID-19 patients. Here we describe the impact of the first 14 months of the UK pandemic on the workload of the National Mycology Reference Laboratory.

COVID-19-Associated Invasive Aspergillosis: Data from the UK National Mycology Reference Laboratory.

COVID-19-associated pulmonary aspergillosis (CAPA) was recently reported as a potential infective complication affecting critically ill patients with acute respiratory distress syndrome following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, with incidence rates varying from 8 to 33% depending on the study. However, definitive diagnosis of CAPA is challenging. Standardized diagnostic algorithms and definitions are lacking, clinicians are reticent to perform aerosol-generating bronchoalveolar lavages for galactomannan testing and microscopic and cultural examination, and questions surround the diagnostic sensitivity of different serum biomarkers. Between 11 March and 14 July 2020, the UK National Mycology Reference Laboratory received 1,267 serum and respiratory samples from 719 critically ill UK patients with COVID-19 and suspected pulmonary aspergillosis. The laboratory also received 46 isolates of Aspergillus fumigatus from COVID-19 patients (including three that exhibited environmental triazole resistance). Diagnostic tests performed included 1,000 (1-3)-ß-d-glucan and 516 galactomannan tests on serum samples. The results of this extensive testing are presented here. For a subset of 61 patients, respiratory specimens (bronchoalveolar lavage specimens, tracheal aspirates, and sputum samples) in addition to serum samples were submitted and subjected to galactomannan testing, Aspergillus-specific PCR, and microscopy and culture. The incidence of probable/proven and possible CAPA in this subset of patients was approximately 5% and 15%, respectively. Overall, our results highlight the challenges in biomarker-driven diagnosis of CAPA, especially when only limited clinical samples are available for testing, and the importance of a multimodal diagnostic approach involving regular and repeat testing of both serum and respiratory samples.

Epidemiology, antifungal susceptibility, and pathogenicity of Candida africana isolates from the United Kingdom.

Candida africana was previously proposed as a new species within the Candida albicans species complex, together with C. albicans and C. dubliniensis, although further phylogenetic analyses better support its status as an unusual variant within C. albicans. Here we show that C. africana can be distinguished from C. albicans and C. dubliniensis by pyrosequencing of a short region of ITS2, and we have evaluated its occurrence in clinical samples by pyrosequencing all presumptive isolates of C. albicans submitted to the Mycology Reference Laboratory over a 9-month period. The C. albicans complex constituted 826/1,839 (44.9%) of yeast isolates received over the study period and included 783 isolates of C. albicans, 28 isolates of C. dubliniensis, and 15 isolates of C. africana. In agreement with previous reports, C. africana was isolated exclusively from genital specimens, in women in the 18-to-35-year age group. Indeed, C. africana constituted 15/251 (6%) of "C. albicans" isolates from female genital specimens during the study period. C. africana isolates were germ tube positive, grew significantly more slowly than C. albicans and C. dubliniensis on conventional mycological media, could be distinguished from the other members of the C. albicans complex by appearance on chromogenic agar, and were incapable of forming chlamydospores. Here we present the detailed evaluation of epidemiological, phenotypic, and clinical features and antifungal susceptibility profiles of United Kingdom isolates of C. africana. Furthermore, we demonstrate that C. africana is significantly less pathogenic than C. albicans and C. dubliniensis in the Galleria mellonella insect systemic infection model.