Molecular characterization of Candida auris outbreak isolates in Qatar from patients with COVID-19 reveals the emergence of isolates resistant to three classes of antifungal drugs.

OBJECTIVES: During the COVID-19 pandemic in Qatar, many patients who were severely ill were colonized and infected by Candida auris, an invasive multidrug-resistant yeast pathogen that spreads through nosocomial transmission within healthcare facilities. Here, we investigated the molecular epidemiology of these C. auris isolates and the mechanisms associated with antifungal drug resistance. METHODS: Whole genomes of 76 clinical C. auris isolates, including 65 from patients with COVID-19 collected from March 2020 to June 2021, from nine major hospitals were sequenced on Illumina NextSeq. Single nucleotide polymorphisms were used to determine their epidemiological patterns and mechanisms for antifungal resistance. The data were compared with those published prior to the COVID-19 pandemic from 2018 to 2020 in Qatar. RESULTS: Genomic analysis revealed low genetic variability among the isolates from patients with and without COVID-19, confirming a clonal outbreak and ongoing dissemination of C. auris among various healthcare facilities. Based on antifungal susceptibility profiles, more than 70% (22/28) of isolates were resistant to both fluconazole and amphotericin B. Variant analysis revealed the presence of multi-antifungal resistant isolates with prominent amino acid substitutions: Y132F in ERG11 and V704L in CDR1 linked to reduced azole susceptibility and the emergence of echinocandin resistance samples bearing mutations in FKS1 in comparison with pre-COVID-19 pandemic samples. One sample (CAS109) was resistant to three classes of antifungal drugs with a unique premature stop codon in ERG3 and novel mutations in CDR2, which may be associated with elevated amphotericin B and azole resistance. DISCUSSION: Candida auris isolates from patients with COVID-19 and from most patient samples without COVID-19 in Qatar were highly clonal. The data demonstrated the emergence of multidrug-resistant strains that carry novel mutations linked to enhanced resistance to azoles, echinocandins, and amphotericin B. Understanding the epidemiology and drug resistance will inform the infection control strategy and drug therapy.

Molecular characterization of Candida auris outbreak isolates in Qatar from COVID-19 patients reveals the emergence of isolates resistant to three classes of antifungal drugs

Objectives During the COVID-19 pandemic in Qatar, many severely ill patients were colonized and infected by Candida auris, an invasive multidrug-resistant yeast pathogen that spreads through nosocomial transmission within healthcare facilities. Herein, we investigated the molecular epidemiology of these C. auris isolates and the mechanisms associated with antifungal drugs resistance. Methods Whole genomes of 76 clinical C. auris isolates, including 65 from COVID-19 patients collected from Mar 2020 - Jun 2021, from nine major hospitals were sequenced on Illumina NextSeq. SNPs were used to determine their epidemiological patterns and mechanisms for antifungal resistance. The data was compared to those published prior to COVID-19 pandemic from 2018-2020 in Qatar. Results Genomic analysis revealed low genetic variability among the isolates from COVID-19 and non-COVID-19 patients, confirming a clonal outbreak and ongoing dissemination of C. auris among various healthcare facilities. Based on antifungal susceptibility profiles, over 70% (22/28) of isolates were resistant to both fluconazole and amphotericin B. Variant analysis revealed the presence of multi-antifungal resistant isolates with prominent amino acid substitutions;Y132F in ERG11 and V704L in CDR1 linked to reduced azole susceptibility, and the emergence of echinocandin resistance samples bearing mutations in FKS1 in comparison to pre-COVID pandemic samples. One sample (CAS109) was resistant to three classes of antifungal drugs with a unique premature stop codon in ERG3 and novel mutations in CDR2, which may be associated with elevated amphotericin B and azole resistance. Conclusion C. auris isolates from COVID-19 patients, and from most non-covid patient samples in Qatar were highly clonal. The data demonstrated the emergence of multidrug-resistant strains that carry novel mutations linked to enhanced resistance to azoles, echinocandins and amphotericin B. Understanding the epidemiology and drug resistance will inform infection control strategy and drug therapy.

Favipiravir for the treatment of coronavirus disease 2019 pneumonia; a propensity score-matched cohort study.

We retrospectively investigated the clinical outcomes of favipiravir in patients with COVID-19 pneumonia. Patients who between 23 May 2020 and 18 July 2020 received ≥ 24 h of favipiravir were assigned to the favipiravir group, while those who did not formed the non-favipiravir group. The primary outcome was 28-day clinical improvement, defined as two-category improvement from baseline on an 8-point ordinal scale. Propensity scores (PS) for favipiravir therapy were used for 1:1 matching. The unmatched cohort included 1493 patients, of which 51.7% were in the favipiravir group, and 48.3% were not receiving supplemental oxygen at baseline. Significant baseline differences between the two unmatched groups existed, but not between the PS-matched groups (N = 774). After PS-matching, there were no significant differences between the two groups in the proportion with 28-day clinical improvement (93.3% versus 92.8%, P 0.780), or 28-day all-cause mortality (2.1% versus 3.1%, P 0.360). Favipiravir was associated with more viral clearance by day 28 (79.8% versus 64.1%, P < 0.001). Adverse events were common in both groups, but the 93.9% were Grades 1-3. Favipiravir therapy for COVID-19 pneumonia is well tolerated but is not associated with an increased likelihood of clinical improvement or reduced all-cause mortality by 28 days.

Clinical characteristics and risk factors for COVID-19-associated Candidemia.

Patients with COVID-19-associated candidemia (CAC) in an intensive care unit (ICU) were matched 1:2 with those without candidemia, based on ICU admission date and length of stay in ICU being at least equal to that before candidemia in the corresponding case. The incidence rate of CAC was 2.34 per 1000 ICU days. Eighty cases could be matched to appropriate controls. In the multivariate conditional logistic regression analysis, age (P 0.001), and sequential organ failure assessment score (P 0.046) were the only risk factors independently associated with CAC. Tocilizumab and corticosteroids therapy were not independently associated with candidemia. LAY SUMMARY: In COVID-19 patients who need medical care in an intensive care unit, the risk of developing bloodstream Candida infection is higher in older patients and in those who have a more severe critical illness. Treatment with steroids or tocilizumab does not seem to affect the risk of candida bloodstream infection in these patients.

A 23-Year-Old Man with SARS-CoV-2 Infection Who Presented with Auditory Hallucinations and Imaging Findings of Cytotoxic Lesions of the Corpus Callosum (CLOCC).

BACKGROUND Cytotoxic lesions of the corpus callosum (CLOCC) is a rare clinical and radiological syndrome that has been associated with various infectious etiologies. CLOCC are among the recently described neurological associations with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with coronavirus disease 2019 (COVID-19). We report a case of CLOCC in a man with SARS-CoV-2 infection who presented with auditory hallucinations and rapidly developed systemic inflammatory response syndrome (SIRS). CASE REPORT A 23-year-old man with no past medical and psychiatric history presented with auditory hallucinations, restlessness, and suicidal ideations. A nasopharyngeal swab specimen tested using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay was positive for SARS-CoV-2. A brain MRI revealed an isolated oval-shaped lesion in the splenium of the corpus callosum, with hyperintense signal on diffusion-weighted imaging (DWI) and hypointense on apparent diffusion coefficient (ADC) maps, suggestive of CLOCC. After a dramatic hospital course associated with multiple organ dysfunction syndrome (MODS) and severe intra-abdominal and cerebral bleeding, he developed cardiac arrest and died on hospital day 15. CONCLUSIONS This case highlights the need for increased vigilance for the atypical manifestations of SARS-CoV-2 infection. In addition, it suggests that CLOCC can be considered as a differential diagnosis by clinicians in patients with SARS-CoV-2 infection who present with unexplained neurological and neuropsychiatric symptoms, leading to poor outcome.