Marjorie Vieira Batista

Background: Although SARS-CoV-2 infection is primarily associated with respiratory symptoms, neurological complications have been increasingly recognized, even in the absence of pulmonary involvement. Case presentation: We report a case of a 67-year-old woman with a history of multiple myeloma and recent exposure to a COVID-19-positive individual who developed rapidly progressive neurological symptoms, including dysarthria, dysphagia, and hypoesthesia, without any respiratory manifestations. Her condition deteriorated to focal and dyscognitive status epilepticus, requiring mechanical ventilation. Brain MRI showed imaging features consistent with rhombencephalitis. SARS-CoV-2 infection was confirmed through positive qRT-PCR results from both nasopharyngeal swab and cerebrospinal fluid (CSF). Further analysis of the CSF using quantitative shotgun proteomics via mass spectrometry revealed a neuroinflammatory profile indicative of blood–brain barrier disruption and differential expression of several proteins relevant to brain function, including the major prion protein, superoxide dismutase 1 (SOD-1), and other aggregation-prone proteins. Conclusions: This case supports the hypothesis that SARS-CoV-2 can invade the central nervous system and cause severe neurological impairment, even in the absence of typical respiratory symptoms. The findings underscore the importance of considering SARS-CoV-2 in the differential diagnosis of rapidly progressive neurological syndromes and highlight the need for further investigation into the mechanisms of neuroinvasion and the potential neurotropism of emerging viral variants.

Introduction: Febrile neutropenia (FN) is a frequent complication following autologous hematopoietic cell transplantation (auto-HCT). Prophylactic use of fluoroquinolones (FQs) has been shown to reduce FN incidence; however, its routine use remains controversial due to increasing concerns regarding antimicrobial resistance and uncertain impact on clinically relevant outcomes. Methods: We conducted a retrospective cohort study including adult patients who underwent auto-HCT at A.C.Camargo Cancer Center between 2016 and 2021. Patients were divided into two groups according to institutional prophylaxis policy: those who received levofloxacin prophylaxis during neutropenia between 2016 and 2018 (Px group, n = 201) and those who did not receive FQ prophylaxis between 2018 and 2021 (NPx group, n = 169). The primary outcome was the incidence of FN. Secondary outcomes included microbiologically documented infections, antimicrobial resistance patterns, and 30- and 100-day all-cause mortality. Results: FN occurred more frequently in the NPx group compared with the Px group (92% vs. 81%, p = 0.002). There were no significant differences between groups in the rate of microbiologically documented infections (23% vs. 14%, p = 0.09), 30-day mortality (3% vs. 1%, p = 0.25), or 100-day mortality (3% vs. 2%, p = 0.48). Antimicrobial resistance profiles differed significantly: the Px group had a lower proportion of pan-susceptible isolates (17% vs. 61%) and higher rates of extended-spectrum β-lactamase-producing organisms (27% vs. 6%) and methicillin-resistant bacteria (36% vs. 10%) compared with the NPx group (all p < 0.001). Conclusion: Although FQ prophylaxis was associated with a lower incidence of FN after auto-HCT, it did not translate into reductions in short-term mortality and was associated with significantly higher rates of antimicrobial resistance. Based on these findings, our institution does not recommend routine FQ prophylaxis for patients undergoing auto-HCT.

Infection is increasingly recognized as a significant cause of morbidity and mortality in patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) receiving CD19 chimeric antigen receptor (CAR) T-cell therapy. The current study analyzed the natural history, risk factors, and outcomes of infection in 3350 patients with R/R LBCL receiving commercial CD19 CAR T-cell therapy (n = 2804 axicabtagene ciloleucel [axi-cel], n = 546 tisagenlecleucel) from December 2017 to June 2022. Infection developed in 834 patients (24.9%) within 100 days after infusion, resulting in an infection density of 0.43 per 100 patient days and a 100-day cumulative incidence of 22%. Bacterial, viral, and fungal infections were recorded in 527 (15.7%), 374 (11.2%), and 108 patients (3.2%), respectively, with corresponding infection densities of 0.23, 0.15, and 0.04 per 100 patient days. After a 24-month median follow-up, 1482 patients (44%) had died, with infection as the primary cause in 173 cases (12%). The 100-day infection-related mortality (IRM) was 1.6% (95% confidence interval, 1.2-2.0). Patients with a Karnofsky performance score of ≤80, infection history before CAR T-cell therapy, axi-cel therapy, severe cytokine release syndrome (grade ≥3), and severe immune effector cell–associated neurotoxicity syndrome (grade ≥3) had increased infection risk. Infections within 100 days were an independent risk factor for inferior overall survival beyond day 100 after CD19 CAR T-cell therapy. In conclusion, study results show a significant incidence of infection and IRM in patients with R/R LBCL treated with CD19 CAR T-cell therapy. Furthermore, results identify patients at a heightened risk of infection, offering insights to guide potential interventions aimed at mitigating infection and improving patient outcomes after CAR T-cell therapy.

Pediatric patients with hematologic cancers, especially those undergoing chemotherapy, are highly vulnerable to infections and febrile neutropenia (FN). Noncompliance with FN protocols often leads to excessive antibiotic use, raising the risk of multidrug-resistant bacteria and contributing to higher mortality rates. This retrospective study aimed to assess inappropriate empirical antibiotic treatment (IEAT) rates during FN episodes and identify risk factors for mortality among pediatric patients diagnosed with acute leukemia and FN at the A.C. Camargo Cancer Center between January 1, 2010, and December 31, 2020. A total of 329 FN episodes in 84 patients were analyzed, revealing an overall IEAT rate of 40%. The study identified key issues such as 2% of inadequate Gram-positive coverage, 78% of failure to de-escalate antibiotic treatment and 62% of maintenance antibiotic administration despite negative cultures Bloodstream infections were found in 77% of episodes, with age over 13 years (p 0.003), and bloodstream infection (p 0.002) being significant risk factors for mortality.

(1) Background: Invasive aspergillosis is a life-threatening fungal infection, particularly in patients with hematologic malignancies. Isavuconazole, a broad-spectrum triazole, has emerged as a key treatment option, but real-world data in high-risk populations from middle-income countries remain limited. (2) Methods: We conducted a multicenter, retrospective study to evaluate the clinical response rate and tolerability of isavuconazole in patients with hematologic malignancies and probable or proven invasive aspergillosis across four medical centers in Brazil. (3) Results: We enrolled 50 patients aged 18 to 82 years (64% male) with proven or probable invasive aspergillosis, diagnosed in the context of complex hematologic conditions. Among them, 60% had active or refractory malignancies, and 22% had a prior COVID-19 infection. Isavuconazole was used as a first-line therapy in 64% of cases. No patients discontinued treatment due to toxicity. The 6-week overall survival was 60%. Prior COVID-19 infection was associated with a lower survival rate (44% vs. 69% in patients without COVID-19, p = 0.04). (4) Conclusions: This study provides real-world evidence supporting the efficacy and tolerability of isavuconazole in a high-risk population. The findings reinforce its role as a key antifungal therapy, particularly in patients with complex underlying conditions.