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BackgroundCandida parapsilosis is a frequent cause of candidemia worldwide. Its incidence is associated with the use of medical implants, such as central venous catheters or parenteral nutrition. This species has reduced susceptibility to echinocandins and is susceptible to polyenes and azoles. Multiple outbreaks caused by fluconazole non-susceptible strains have been reported recently. A similar trend has been observed among the C. parapsilosis isolates received in the last two years at the Spanish Mycology Reference Laboratory. MethodsYeast were identified by molecular biology and antifungal susceptibility testing was performed using EUCAST protocol. ERG11 gene was sequenced to identify resistance mechanisms, and typification was carried out by microsatellite analysis. ResultsWe examined the susceptibility profile of the C. parapsilosis isolates available at our Reference Laboratory since 2000 (around 1,300 strains). During the last two years, the number of isolates with acquired resistance to fluconazole and voriconazole has increased in at least eight different Spanish hospitals. Typification of the isolates revealed that some prevalent clones had spread through several hospitals of the same geographical region. One of these clones was found in hospitals from the region of Catalonia, another in hospitals from Madrid and Burgos, and two other different genotypes from Santander. ConclusionsOur data suggests that the epidemiological situation caused by the COVID-19 pandemic might have induced a selection of fluconazole-resistant C. parapsilosis isolates that were already present at the hospitals. Further measures must be taken to avoid the establishment of clinical outbreaks that could threaten the life of infected patients.
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INTRODUCTION: A growing evidence suggests that immune dysregulation and thrombotic phenomena are key features in the pathophysiology of COVID-19. Apart from antivirals and respiratory support, anticoagulants, corticoids and immunomodulators are increasingly being prescribed, especially for more severe cases. We describe the clinical outcome of a large cohort of patients preferentially treated with glucocorticoids and interleukin inhibitors. METHODS: Single center and retrospective case series. Adult patients admitted with COVID-19 related respiratory insufficiency were included. Patients who died within 2 days after admission and those testing positive but asymptomatic were excluded. We defined two study periods: from March 3rd to March 31 st, 2020 (beginning of epidemic until peak of incidence) and April 1 st to May 7 th, 2020 (second half of epidemic). The majority of patients received respiratory support, combinations of antimicrobials, anticoagulants, corticoids and interleukin inhibitors. Antivirals were preferentially given in the first period. The clinical outcome (death and ventilator dependency) of both periods was compared. RESULTS: From March 3 rd to May 7 th, 685 patients were included for analysis (58.4% males, mean age 68.9 years). Patients in the first period (n â= â408) were younger (66.6 vs 71.1 years, p â= â0.003), presented lower mean P a O 2/F i O2 ratio at admission (256.5 vs 270.4 âmm Hg,p â= â0.0563), higher ferritin (1520 vs 1221 âng/ml, p â= â0.01), higher IL-6 (679 vs 194 âpg/ml, p â< â0.0001) and similar D-dimer levels (3.59 vs 3.39 âµg/mL, p â= â0.65) compared to the second period (n â= â277). Lopinavir/ritonavir and interferon were preferentially given in the first period (23.8% and 32% vs 1.8% and 11.9%, p â< â0.0001). Use of corticoids (88.2% vs 87.4%, p â= â0,74) and tocilizumab (26.29 vs 20.22% p â= â0.06) were similarly administered in both periods. Patients in the second period needed less mechanical ventilation (4.9% vs 16.9%, p â< â0.0001), fewer ICU admission (6.1% vs 20.1%,p â< â0.0001) and showed similar mortality (17.7% vs 15.4%, p â= â0.43). Infectious and thrombotic complications were comparable in both periods (both around 8%, with no statistical difference). Patients treated with tocilizumab (n â= â163) had lower mortality rate compared to those untreated under the same indication (7.9% vs 24.2%, p â< â0.0001). CONCLUSIONS: In this large retrospective COVID-19 in-hospital cohort, lopinavir/ritonavir and interferon showed no significant impact on survival. Extensive use of corticosteroids and tocilizumab resulted in good overall outcome and showed acceptable complication rates.
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BackgroundSevere COVID-19 is characterized by clinical and biological manifestations typically observed in sepsis. SARS-CoV-2 RNA is commonly detected in nasopharyngeal swabs, however viral RNA can be found also in peripheral blood and other tissues. Whether systemic spreading of the virus or viral components plays a role in the pathogenesis of the sepsis-like disease observed in severe COVID-19 is currently unknown. MethodsWe determined the association of plasma SARS-CoV-2 RNA with the biological responses and the clinical severity of patients with COVID-19. 250 patients with confirmed COVID-19 infection were recruited (50 outpatients, 100 hospitalised ward patients, and 100 critically ill). The association between plasma SARS-CoV-2 RNA and laboratory parameters was evaluated using multivariate GLM with a gamma distribution. The association between plasma SARS-CoV-2 RNA and severity was evaluated using multivariate ordinal logistic regression analysis and Generalized Linear Model (GLM) analysis with a binomial distribution. ResultsThe presence of SARS-CoV-2-RNA viremia was independently associated with a number of features consistently identified in sepsis: 1) high levels of cytokines (including CXCL10, CCL-2, IL-10, IL-1ra, IL-15, and G-CSF); 2) higher levels of ferritin and LDH; 3) low lymphocyte and monocyte counts 4) and low platelet counts. In hospitalised patients, the presence of SARS-CoV-2-RNA viremia was independently associated with critical illness: (adjusted OR= 8.30 [CI95%=4.21 - 16.34], p < 0.001). CXCL10 was the most accurate identifier of SARS-CoV-2-RNA viremia in plasma (area under the curve (AUC), [CI95%], p) = 0.85 [0.80 - 0.89), <0.001]), suggesting its potential role as a surrogate biomarker of viremia. The cytokine IL-15 most accurately differentiated clinical ward patients from ICU patients (AUC: 0.82 [0.76 - 0.88], <0.001). Conclusionssystemic dissemination of genomic material of SARS-CoV-2 is associated with a sepsis-like biological response and critical illness in patients with COVID-19. RNA viremia could represent an important link between SARS-CoV-2 infection, host response dysfunction and the transition from moderate illness to severe, sepsis-like COVID-19 disease.
