Objectives Information on the recently COVID‐19‐associated pulmonary aspergillosis (CAPA) entity is scarce. We describe eight CAPA patients, compare them to colonised ICU patients with coronavirus disease 2019 (COVID‐19), and review the published literature from Western countries. Methods Prospective study (March to May, 2020) that included all COVID‐19 patients admitted to a tertiary hospital. Modified AspICU and European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria were used. Results COVID‐19‐associated pulmonary aspergillosis was diagnosed in eight patients (3.3% of 239 ICU patients), mostly affected non‐immunocompromised patients (75%) with severe acute respiratory distress syndrome (ARDS) receiving corticosteroids. Diagnosis was established after a median of 15 days under mechanical ventilation. Bronchoalveolar lavage was performed in two patients with positive Aspergillus fumigatus cultures and galactomannan (GM) index. Serum GM was positive in 4/8 (50%). Thoracic CT scan findings fulfilled EORTC/MSG criteria in one case. Isavuconazole was used in 4/8 cases. CAPA‐related mortality was 100% (8/8). Compared with colonised patients, CAPA subjects were administered tocilizumab more often (100% vs. 40%, p = .04), underwent longer courses of antibacterial therapy (13 vs. 5 days, p = .008), and had a higher all‐cause mortality (100% vs. 40%, p = .04). We reviewed 96 similar cases from recent publications: 59 probable CAPA (also putative according modified AspICU), 56 putative cases and 13 colonisations according AspICU algorithm; according EORTC/MSG six proven and two probable. Overall, mortality in the reviewed series was 56.3%. Conclusions COVID‐19‐associated pulmonary aspergillosis must be considered a serious and potentially life‐threatening complication in patients with severe COVID‐19 receiving immunosuppressive treatment.

Background There is a paucity of knowledge on the long-term outcome in patients diagnosed with COVID-19. We describe a cohort of patients with a constellation of symptoms occurring four weeks after diagnosis causing different degrees of reduced functional capacity. Although different hypothesis have been proposed to explain this condition like persistent immune activation or immunological dysfunction, to date, no physiopathological mechanism has been identified. Consequently, there are no therapeutic options besides symptomatic treatment and rehabilitation. Methods We evaluated patients with symptoms that persisted for at least 4 weeks after COVID-19. Epidemiological and clinical data were collected. Blood tests, including inflammatory markers, were conducted, and imaging studies made if deemed necessary. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction (RT-PCR) in plasma, stool, and urine were performed. Patients were offered antiviral treatment (compassionate use). Results We evaluated 29 patients who reported fatigue, muscle pain, dyspnea, inappropriate tachycardia, and low-grade fever. Median number of days from COVID-19 to positive RT-PCR in extra-respiratory samples was 55 (39–67). Previous COVID-19 was mild in 55% of the cases. Thirteen patients (45%) had positive plasma RT-PCR results and 51% were positive in at least one RT-PCR sample (plasma, urine, or stool). Functional status was severely reduced in 48% of the subjects. Eighteen patients (62%) received antiviral treatment. Improvement was seen in most patients (p = 0.000) and patients in the treatment group achieved better outcomes with significant differences (p = 0.01). Conclusions In a cohort of COVID-19 patients with persistent symptoms, 45% of them have detectable plasma SARS-CoV-2 RNA. Our results indicate possible systemic viral persistence in these patients, who may benefit of antiviral treatment strategies.

Objectives: The purpose of this study was to detect COVID-19 cases with persistent positive RT-PCR results for SARS-CoV-2, for which viable virus can be inferred, due to the presence of subgenomic (SG) viral RNA, which is expressed only in replicating viruses. Methods: RNA remnants, purified from diagnostic nasopharyngeal specimens, were used as templates for RT-PCR specific detection of SG E gene RNA. As controls, we also detected viral genomic RNA for the E gene and/or a human housekeeping gene (RNase P). Results: We assessed the samples of 60 RT-PCR-positive cases with a prolonged viral SARS-CoV-2 shedding (24-101 days) since the first diagnostic RT-PCR. SG viral RNA was detected in 12/60 (20%) of the persistent cases, 28-79 days after the onset of symptoms. The age range of the cases with prolonged viral shedding and presence of SG RNA was quite wide (40-100 years), and they were equally distributed between males (42%) and females (58%). None was HIV positive, although seven were immunosuppressed. According to the severity of the COVID-19 episodes they were mild (40%), intermediate (20%), and severe (40%) Conclusion: In a percentage of persistent positive SARS-CoV-2 PCR positive cases the presence of actively replicating virus may be inferred, far beyond diagnosis. We should not assume a universal lack of infectiousness for COVID-19 cases with prolonged viral shedding.

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There is scarce information on the actual incidence of candidemia in COVID-19 patients. In addition, comparative studies of candidemia episodes in COVID-19 and non-COVID-19 patients are heterogeneous. Here, we assessed the real incidence, epidemiology, and etiology of candidemia in COVID-19 patients, and compared them with those without COVID-19 (2020 vs. 2019 and 2020, respectively). We also genotyped all C. albicans, C. parapsilosis, and C. tropicalis isolates (n = 88), causing candidemia in both groups, providing for the first time a genotypic characterization of isolates gathered in patients with either COVID-19 or non-COVID-19. Incidence of candidemia was higher in patients with COVID-19 than non-COVID-19 (4.73 vs. 0.85 per 1000 admissions; 3.22 vs. 1.14 per 10,000 days of stay). No substantial intergroup differences were found, including mortality. Genotyping proved the presence of a low number of patients involved in clusters, allowing us to rule out rampant patient-to-patient Candida transmission. The four patients, involved in two clusters, had catheter-related candidemia diagnosed in the first COVID-19 wave, which demonstrates breaches in catheter management policies occurring in such an overwhelming situation. In conclusion, the incidence of candidemia in patients with COVID-19 is significantly higher than in those without COVID-19. However, genotyping shows that this increase is not due to uncontrolled intrahospital transmission.

Estimates of the burden of severe acute respiratory syndrome coronavirus 2 reinfections are limited by the scarcity of population-level studies incorporating genomic support. We conducted a systematic study of reinfections in Madrid, Spain, supported by genomic viral analysis and host genetic analysis, to cleanse laboratory errors and to discriminate between reinfections and recurrences involving the same strain. Among the 41,195 cases diagnosed (March 2020–March 2021), 93 (0.23%) had 2 positive reverse transcription PCR tests (55–346 days apart). After eliminating cases with specimens not stored, of suboptimal sequence quality, or belonging to different persons, we obtained valid data from 22 cases. Of those, 4 (0.01%) cases were recurrences involving the same strain; case-patients were 39–93 years of age, and 3 were immunosuppressed. Eighteen (0.04%) cases were reinfections; patients were 19–84 years of age, and most had no relevant clinical history. The second episode was more severe in 8 cases.

Aims Concerns about the prognostic value of NYHA functional class (FC) in heart failure (HF) patients carrying a prophylactic implantable cardioverter defibrillator (ICD) are still present. We aimed to compare whether mortality and arrhythmic risk were different, in a cohort of HF patients undergoing ICD‐only implant, according to their FC. Methods and results HF patients with left ventricle ejection fraction (LVEF) ≤35%, undergoing first prophylactic ICD‐only implant were collected from a multicentre nationwide registry (2006–2015). Six hundred and twenty‐one patients were identified (101 patients in NYHA I; 411 in NYHA II; 109 in NYHA III). After a mean follow‐up of 4.4 years (±2.1), 126 patients died (20.3%). All‐cause mortality risk was higher in symptomatic patients: 13.9% in NYHA I patients, 18.3% in NYHA II patients (HR: 1.8, 95% CI 1.1–3.2), and 32.9% in NYHA III patients (HR: 3.9, 95% CI 2.1–7.3). Seventy‐eight out of all deaths were due to cardiovascular causes (12.6%). Cardiovascular mortality risk was also higher in symptomatic patients: 6.9% in NYHA I patients, 11% in NYHA II patients (HR: 2.2, 95% CI 1.1–4.9), and 23.9% in NYHA III (HR: 5.5, 95% CI 2.4–12.7). One hundred and seventeen patients received a first appropriate ICD therapy (19.4%). Arrhythmia free survival did not differ among study groups [20.8% in NYHA I patients, 18.7% in NYHA II (HR: 1.1, 95% CI 0.6–1.7) and 20.8% in NYHA III patients (HR: 1.3, 95% CI 0.7–2.5)]. NYHA class independently predicted cardiovascular mortality (NYHA III vs. NYHA I: HR, 4.7; 95% CI, 1.7–12.8, P = 0.002; NYHA II vs. NYHA I: HR, 2.1, 95% CI, 1.0–5.6, P = 0.05) but not all‐cause death (NYHA III vs. NYHA I: HR: 1.8, 95% CI 0.8–3.9, P = 0.11; NYHA II vs. NYHA I: HR, 1.1, 95% CI 0.6–2.2, P = 0.71;). Atrial fibrillation, chronic kidney disease, and diabetes emerged as predictors of both all‐cause death [(HR: 1.8, 95% CI 1.2–2.8, P = 0.005), (HR: 2.2, 95% CI 1.4–3.4, P < 0.001), (HR: 2.0, 95% CI 1.3–3.1, P = 0.001), respectively] and cardiovascular mortality [(HR: 1.8, 95% CI 1.1–3.1, P = 0.02), (HR: 3.1, 95% CI 1.8–5.4, P < 0.001), (HR: 1.7, 95% CI 1.1–3, P = 0.032), respectively]. Conclusions Mortality in HF patients undergoing prophylactic ICD implantation was higher in symptomatic patients. NYHA functional class along with other comorbidities might be helpful to identify a subgroup of ICD carriers with poorer prognosis and higher risk of cardiovascular death.

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