Hepatitis E virus (HEV) is a major cause of acute viral hepatitis. Since the coronavirus disease 2019 (COVID-19) pandemic, immunocompromised individuals face an increased risk of HEV and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infection, posing a threat of liver failure and prolonged illness. A 69-year-old male, with a history of chronic lymphocytic leukemia, was co-infected with HEV and SARS-CoV-2. Given the progressive decline in liver function post-admission, steroid therapy was initiated, which led to treatment-related complications. Additionally, the patient experienced an aggravation of COVID-19 symptoms due to persistent SARS-CoV-2 infection, effectively managed through a combination of antiviral medications and corticosteroids. This case describes the intricate clinical trajectory and therapeutic approach for managing HEV and SARS-CoV-2 co-infection, underscoring the potential efficacy of short-term corticosteroid intervention alongside comprehensive antiviral treatment.

BACKGROUND: Prompt pathogen identification can have a substantial impact on the optimization of antimicrobial treatment. The objective of the study was to assess the diagnostic value of next-generation sequencing (NGS) for identifying pathogen and its clinical impact on antimicrobial intervention in immunocompromised patients with suspected infections.
METHODS: This was a retrospective study. Between January and August 2020, 47 adult immunocompromised patients underwent NGS testing under the following clinical conditions: 1) prolonged fever and negative conventional cultures; 2) new-onset fever despite empiric antimicrobial treatment; and 3) afebrile with suspected infections on imaging. Clinical data, including conventional microbial test results and antimicrobial treatment before and after NGS, were collected. Data were analyzed according to documented changes in antimicrobial treatment (escalated, no change, or de-escalated) after the NGS results.
RESULTS: The median time from hospitalization to NGS sampling was 19 d. Clinically relevant pathogens were detected via NGS in 61.7% of patients (29/47), more than half of whom suffered from fungemia (n=17), resulting in an antimicrobial escalation in 53.2% of patients (25/47) and antimicrobial de-escalation in 0.2% of patients (1/47). Antimicrobial changes were mostly due to the identification of fastidious organisms such as Legionella, Pneumocystis jirovecii, and Candida. In the remaining three cases, NGS detected clinically relevant pathogens also detected by conventional cultures a few days later. The antimicrobial treatment was subsequently adjusted according to the susceptibility test results. Overall, NGS changed antimicrobial management in 55.3% (26/47) of patientst, and conventional culture detected clinically relevant pathogens in only 14.9% of patients (7/47).
CONCLUSIONS: With its rapid identification and high sensitivity, NGS could be a promising tool for identifying relevant pathogens and enabling rapid appropriate treatment in immunocompromised patients with suspected infections.

OBJECTIVE: This study aimed to compare how immunocompromised and immunocompetent patients responded differently to enteral nutrition (EN) support in intensive care units (ICUs) during the COVID-19 pandemic, including serum nutritional biomarkers, inflammatory biomarkers, gastrointestinal (GI) intolerance symptoms, and clinical outcomes.
METHODS: An observational, retrospective study was conducted in the ICUs of a teaching hospital in southwest China. We recruited a convenience sample of 154 patients between December 2022 and February 2023. We defined immunocompromise as primary immunodeficiency diseases, active malignancy, receiving cancer chemotherapy, HIV infection, solid organ transplantation, hematopoietic stem cell transplantation, receiving corticosteroid therapy with a target dose, receiving biological immune modulators, or receiving disease-modifying antirheumatic drugs or other immunosuppressive drugs. We conducted a Mann-Whitney U test, χ2 test, or generalized estimation equation model to explore the differences between immunocompromised and immunocompetent patients.
RESULTS: Among the 154 study participants, 41 (27%) were defined as immunocompromised. The immunocompromised patients were younger than the immunocompetent patients. There were no statistically significant differences between the two groups with respect to serum nutritional biomarkers, inflammatory biomarkers, incidence of GI intolerance symptoms, and in-hospital mortality. However, the immunocompromised patients exhibited a longer hospitalization duration than the immunocompetent patients.
CONCLUSIONS: We found that the immunocompromised patients spent more time in the hospital. These findings may help us to standardize the participants before EN interventional studies better and better individualize EN supports based on patients\' immunity status.

Data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients at early stage of immune reconstitution after hematopoietic stem cell transplantation (HSCT) are limited. In the present study, we retrospectively investigated the incidence and clinical features of SARS-CoV-2 infection in patients who underwent HSCT in 2022. Patients (allo-HSCT, n = 80; auto-HSCT, n = 37) were consecutively included in the study. The SARS-CoV-2 infection rate was 59.8%, and the median interval of HSCT to coronavirus disease 2019 (COVID-19) was 4.8 (range: 0.5-12) months. Most patients were categorized as mild (41.4%) or moderate (38.6%), and 20% as severe/critical. No deaths were attributable to COVID-19. Further analysis showed that lower circulating CD8+ T-cell counts and calcineurin inhibitor administration increased the risk of SARS-CoV-2 infection. Exposure to rituximab significantly increased the probability of severe or critical COVID-19 compared with that of mild/moderate illness (P < .001). In the multivariate analysis, rituximab use was associated with severe COVID-19. Additionally, COVID-19 had no significant effect on immune reconstitution. Furthermore, it was found that Epstein-Barr virus infection and rituximab administration possibly increase the risk of developing severe illness. Our study provides preliminary insights into the effect of SARS-CoV-2 on immune reconstitution and the outcomes of allo-HSCT recipients.

Several studies have suggested that short-course antibiotic therapy was effective in Pseudomonas aeruginosa (PA) bloodstream infections (BSI) in immunocompetent patients. But similar studies in patients with hematological malignancies were rare.
This cohort study included onco-hematology patients at 2 hematology centers in China. Inverse probability of treatment weighting was used to balance the confounding factors. Multivariate regression model was used to evaluate the effect of short-course antibiotic therapy on clinical outcomes.
In total, 434 patients met eligibility criteria (short-course, 7-11 days, n = 229; prolonged, 12-21 days, n = 205). In the weighted cohort, the univariate and multivariate analysis indicated that short course antibiotic therapy had similar outcomes to the prolonged course. The recurrent PA infection at any site or mortality within 30 days of completing therapy occurred in 8 (3.9%) patients in the short-course group and in 10 (4.9%) in the prolonged-course group (P = .979). The recurrent infection within 90 days occurred in 20 (9.8%) patients in the short-course group and in 13 (6.3%) patients in the prolonged-course group (P = .139), and the recurrent fever within 7 days occurred in 17 (8.3%) patients in the short-course group and in 15 (7.4%) in the prolonged-course group (P = .957). On average, patients who received short-course antibiotic therapy spent 3.3 fewer days in the hospital (P < .001).
In the study, short-course therapy was non-inferior to prolonged-course therapy in terms of clinical outcomes. However, due to its biases and limitations, further prospective randomized controlled trials are needed to generalize our findings.

BACKGROUND: In immunocompromised populations, such as patients with AIDS and recipients of solid organ and hematopoietic stem cell transplants, BK polyomavirus (BKPyV) can reactivate and cause several diseases, which can lead to death in their severe forms. Unlike hemorrhagic cystitis and BKPyV-associated nephropathy, BKPyV-associated pneumonia is rare, with only seven known cases worldwide. However, the disease can rapidly progress with extremely high mortality.
METHODS: Herein, we report two cases of BKPyV-associated pneumonia following hematopoietic stem cell transplantation. Both patients had consistent infectious pneumonia and graft-versus-host disease after stem cell transplantation. The diagnosis of BKPyV-associated pneumonia was confirmed by metagenomic next-generation sequencing and polymerase chain reaction after the sudden worsening of the pulmonary infection signs and symptoms concomitant with renal dysfunction and systemic immune weakening. Both patients eventually died of systemic multi-organ failure caused by severe pneumonia.
CONCLUSIONS: Currently, BKPyV reactivation cannot be effectively prevented. Immunocompromised patients must actively manage their primary lung infections, pay close attention to pulmonary signs and imaging changes. Especially during and after steroid pulse therapy or immunosuppressive therapy for graft versus host diseases, BKPyV load in blood/urine needs to be regularly measured, and the immunosuppressive intensity should be adjusted properly after the BKPyV reactivation diagnosis. Clinical trials of new antiviral drugs and therapies for BKPyV are urgently needed.

With advancements in medical technology and the growth of an aging society, the number of immunocompromised patients has increased progressively. Klebsiella pneumoniae (K. pneumoniae) is one of the most common opportunistic pathogens, causing a severe disease burden. We aimed to further clarify the differences in respiratory tract K. pneumoniae infections between immunocompromised and immunocompetent populations.
We retrospectively compared cases of respiratory tract K. pneumoniae infection in immunocompromised and immunocompetent patients admitted to Ruijin Hospital in Shanghai between January 2019 and August 2020 to clarify the differences between the two groups.
We enrolled 400 immunocompromised patients and 386 immunocompetent patients. Compared to the immunocompetent group, immunocompromised patients were more likely to develop bacteremia and shock and to require mechanical ventilation support during hospitalization. Immunocompromised patients also had a greater probability of polymicrobial infection and a higher rate of antibacterial resistance to carbapenem, which resulted in a higher intensive care unit admission rate, 30-day case fatality rate (CFR), and 6-month CFR. Multivariate analysis indicated that immunocompromised patients with respiratory diseases (odds ratio [OR], 2.189; 95% confidence interval [CI], 1.103-4.344; P = 0.025) and cardiovascular diseases (OR, 2.008; 95% CI, 1.055-3.822; P = 0.034), using mechanical ventilation (OR, 3.982; 95% CI, 2.053-7.722; P = 0.000), or infected with multidrug-resistant K. pneumoniae (OR, 3.870; 95%, 1.577-9.498; P = 0.003) were more likely to have a higher 30-day CFR.
The disease burden of K. pneumoniae infection in immunocompromised patients is high. Immunocompromised patients who presented with respiratory diseases and cardiovascular diseases, used mechanical ventilation, or were infected with multidrug-resistant K. pneumoniae experienced a higher 30-day mortality rate.

UNASSIGNED: The present study aimed to evaluate the association between the cumulative dose of glucocorticoids (GCs) and case fatality in hospitalized patients who developed pneumonia while receiving glucocorticoid therapy.
UNASSIGNED: This retrospective cohort study included 625 patients receiving long-term GC treatment who were hospitalized with pneumonia (322 male and 303 female). Data were obtained from the Dryad Digital Repository and were used to perform secondary analysis. Multivariable Cox proportional hazard regression model and restricted cubic splines (RCS) were used to evaluate the association between the cumulative dose of GCs and case fatality. Sensitivity analyses and subgroup analyses were performed.
UNASSIGNED: The 30-day and 90-day death rates were 22.9 and 26.2%, respectively. After adjusting for potential confounders, compared with those in the lowest quintile (≤ 1.5 g), the Cox proportional hazard regression model analysis showed that patients with different cumulative doses of GCs (1.5 to 2.95, 2.95 to 5, 5 to 11.5, and > 11.5 g) had lower risks for 30-day death, with respective hazard ratios of 0.86 (95% CI, 0.52 to 1.42), 0.81 (0.49 to 1.33), 0.29 (0.15 to 0.55), and 0.42 (0.22 to 0.79). The multivariable-adjusted RCS analysis suggested a statistically significant N-shaped association between the cumulative dose of GCs and 30-day death. A higher cumulative dose of GC tended to first lead to an increase in 30-day death within 1.8 g, then to a statistically significant decrease until around 8 g [HR for 1 g = 0.82 (0.69 to 0.97)], and again to an increase afterward. Similar results were found in the subgroup analyses and sensitivity analyses.
UNASSIGNED: N-shaped association between the cumulative dose of GCs and case fatality was observed in patients receiving long-term GC treatment who were hospitalized with pneumonia. Our findings may help physicians manage these patients.

Nocardia species do not replicate as rapidly as other pyogenic bacteria and nocardial infections can be highly fatal, particularly in immunocompromised patients. Here, we present the first report of fatal Nocardia kroppenstedtii bacteremic pneumonia and empyema thoracis diagnosed by next-generation sequencing (NGS) using the Oxford Nanopore Technologies\' MinION device. The bacterium was not identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Due to its low equipment cost, short turn-around-time, and portable size, the Oxford Nanopore Technologies\' MinION device is a useful platform for NGS in routine clinical microbiology laboratories.

Metagenomic next-generation sequencing (mNGS) was commonly applied given its ability to identify and type all infections without depending upon culture and to retrieve all DNA with unbiasedness. In this study, we strive to compare outcomes of mNGS with conventional culture methods in adults with sepsis, investigate the differences between the immunocompromised and control group, and assess the clinical effects of mNGS.
In our study, 308 adult sepsis patients were included. We used both mNGS and conventional culture methods to analyze diagnostic results, pathogens, and sample types. The correlation between some laboratory tests and the frequency of pathogens by groups was also analyzed. Furthermore, the clinical impacts of mNGS were estimated.
308 samples were assigned to an immunocompromised group (92/308,29.9%) and a control group (216/308,70.1%). There was the sensitivity of mNGS considered greater than that of the culture method in all samples (88.0% vs 26.3%; P <​ 0.001), in the immunocompromised group (91.3% vs 26.1%; P <​ 0.001), and the control group (86.6% vs 26.4%; P <​ 0.001), particularly in all sample types of blood (P <​ 0.001), BALF (P <​ 0.001), CSF (P <​ 0.001), sputum (P <​ 0.001) and ascitic fluid (P = 0.008). When examining the mNGS results between groups, Pneumocystis jirovecii (P < 0.001), Mucoraceae (P = 0.014), and Klebsiella (P = 0.045) all showed significant differences. On the whole, mNGS detected more pathogens than culture methods (111 vs 25), found 89 organisms that were continuously overlooked in entire samples by culture methods, and showed a favorable positive clinical effect in 76.3% (235 of 308) of patients. In 185 (60.1%) patients, mNGS prompted a modification in the course of management, which included antibiotic de-escalation in 61(19.8%) patients.
The research discovered that mNGS was more sensitive than the culture method, particularly in samples of blood, BALF, CSF, sputum, and ascitic fluid. When examining the mNGS results, Pneumocystis jirovecii and Mucoraceae were the pathogens seen more commonly in immunocompromised patients with sepsis, which required more attention from clinicians. There was a substantial benefit of mNGS in enhancing the diagnosis of sepsis and advancing patient treatment.