Non-immunocompromised Patients Research Articles

Burden of SARS-CoV-2 infection prior to vaccine eligibility among immunocompromised children aged 1-11years at a pediatric tertiary referral hospital in Toronto, Canada.

SARS-CoV-2 seroprevalence reflects the efficacy of pandemic infection prevention and control measures. We performed anti-spike IgG serological testing on residual sera of children 1-11years old at a tertiary care referral center between October and November 2021. Immunocompromised patients had the highest SARS-CoV-2 seroprevalence, at 40.5%, compared to 19.3% in non-immunocompromised patients. Targeted infection prevention and public health interventions are warranted for pediatric immunocompromised patients in future pandemics.

Large Spontaneous Subcutaneous Abscess Formation due to Finegoldia magna in a Diabetic Patient: A Case Report.

Finegoldia magna is a member of the Gram-positive anaerobic cocci group and constitutes the flora of the skin and other parts of the body. It sometimes colonizes diabetic foot and rarely infects skin or soft tissue of non-immunocompromised patients. Here, we report the case of a severe subcutaneous abscess on the back caused by F. magna involving an immunocompromised patient with poorly controlled diabetes. A 48-year-old woman with diabetes mellitus and anemia associated with uterine fibroids was referred to us with a 1-month history of a skin manifestation on her back, with a body temperature of 35.9°C and blood pressure of 115/73 mm Hg. The manifestation involved a subcutaneous mass of 36 × 45 cm with a foul odor, partly covered with necrotic tissue, which had the appearance of a tortoiseshell-like pattern. Blood examination revealed C-reactive protein of 21.4 mg/dL and hemoglobin A1c of 9.1%. Contrast-enhanced computed tomography showed a subcutaneous abscess with internal emphysema. Emergency debridement was performed, resulting in drainage of foul-smelling gray-green pus. F. magna was detected in the pus and skin tissue. Skin and soft tissue infectious disease caused by F. magna is extremely rare, but the disease tends to become severe once developing in an immunocompromised patient, such as a patient with poorly controlled diabetes. Therefore, physicians should consider F. magna as a causative agent when poorly controlled diabetic patients suffer from severe infectious cutaneous manifestations.

The Wide Spectrum of Presentations of Cytomegalovirus Infection in Immunocompetent Hosts: An Exhaustive Narrative Review.

CMV is a ubiquitous DNA virus that establishes infection and results in 40-100% seropositivity. Viral replication occurs following an acquired primary infection (or reinfection) or by the reactivation of life-long latency. In immunocompetent patients, CMV infection is mostly asymptomatic or mild and self-limited. However, an extensive review of the literature published up to April 2024 reveals that despite immunocompetence, CMV can cause a very large variety of clinical syndromes in any part of the gastrointestinal tract (the most common pattern), the central or peripheral nervous system, and the eyes, as well as hematological, pulmonary, cardiac, and cutaneous disease. Not uncommonly, more than one system is involved, and though the disease is often self-limited, treatment with intravenous ganciclovir or oral valganciclovir may be required, and in isolated cases, fatalities may occur. Thus, a potential CMV infection should be considered in the differential of myriad syndromes in non-immunocompromised patients. Associated systemic symptoms (fever, sweats, and weight loss), lymphocytosis, and hepatitis are not uncommon and can be a useful clue. Some populations, such as critically ill patients in intensive care, pregnant women, elderly patients, and those with inflammatory bowel disease, may be more susceptible. Moreover, the potential of past, latent CMV infection (i.e., CMV seropositivity) to be associated with significant cardiovascular morbidity and all-cause mortality years later is intriguing and requires further study. All these data indicate the outstanding importance of developing a vaccine against CMV, which hopefully will become available in the foreseeable future. Meanwhile, a solid diagnosis of active CMV infection can be quickly established (or ruled out) by widely available serology tests and PCR amplification, and clinicians in all disciplines need to be more aware of the diverse guises of CMV infection and remember to consider it in any host, including an immunocompetent one.

Histoplasmosis in non-immunosuppressed patients from an endemic area in Northeastern Brazil.

Differently from immunocompromised patients, very little information is available in the literature regarding the clinical presentation, epidemiology, and outcomes of histoplasmosis in non-immunosuppressed individuals living in endemic areas. This retrospective case series study was carried out by reviewing the medical records of non-immunocompromised patients with histoplasmosis, residents in a hyperendemic area in northeastern Brazil, between 2011 and 2022. Thirty HIV-negative patients were identified with histoplasmosis, and 19 cases met the inclusion criteria: three had acute, five subacute and one chronic pulmonary forms; two with mediastinal picture and eight had disseminated disease (two with severe symptoms). The median age of our sample was 32.7 years old [interquartile range: 24-45]. Most of the patients were male (male-to-female ratio=15:4) and resided in the state capital (n=9). The majority had a previous history of exposure to well-known risk factors for Histoplasma infection. Pulmonary nodules were observed in all subacute form, two patients (acute and subacute forms) were initially treated empirically for pulmonary tuberculosis; one death was registered in the subacute form. The chronic pulmonary form of histoplasmosis was diagnosed in one patient only after the symptoms persisted despite specific treatment. The primary clinical manifestations of the moderate form of DH were enlarged lymph nodes, with histopathology being the main diagnostic method. The cases were detected as isolated occurrences and not as an outbreak, suggesting that exposure to Histoplasma can be more widespread than presumed. Despite the self-limiting nature of the disease, death can occur even in previously heathy patients.

Cryptococcal meningitis in a diabetic

A 75-year-old male, a known case of hypertension and diabetes, from Bihar, India, had presented to the medicine department with a complaint of fever for the last 1 month and drowsiness for the last 5 days. In view of drowsiness, a cerebrospinal fluid study was done which was suggestive of cryptococcosis (budding yeast in India Ink Preparation). Cryptococcal meningitis is usually found in cases of immunocompromised states like HIV and it is quite less in non-HIV patients like diabetics. Liposomal amphotericin B was started as per protocol. The patient, however, developed anuria and septic shock and succumbed to his illness. Therefore, clinicians should suspect cryptococcal meningitis in nonimmunocompromised patients also because timely treatment may be given as it has a potential cure.

Intra-abdominal infection and sepsis in immunocompromised intensive care unit patients: Disease expression, microbial aetiology, and clinical outcomes

We compared epidemiology of intra-abdominal infection (IAI) between immunocompromised and non-immunocompromised ICU patients and identified risk factors for mortality.We performed a secondary analysis on the “AbSeS” database, a prospective, observational study with IAI patients from 309 ICUs in 42 countries. Immunocompromised status was defined as either neutropenia or prolonged corticosteroids use, chemotherapy or radiotherapy in the past year, bone marrow or solid organ transplantation, congenital immunodeficiency, or immunosuppressive drugs use. Mortality was defined as ICU mortality at any time or 28-day mortality for those discharged earlier. Associations with mortality were assessed by logistic regression.The cohort included 2589 patients of which 239 immunocompromised (9.2 %), most with secondary peritonitis. Among immunocompromised patients, biliary tract infections were less frequent, typhlitis more frequent, and IAIs were more frequently healthcare-associated or early-onset hospital-acquired compared with immunocompetent patients. No difference existed in grade of anatomical disruption, disease severity, organ failure, pathogens, and resistance patterns. Septic shock was significantly more frequent in the immunocompromised population. Mortality was similar in both groups (31.1% vs. 28.9 %; p = 0.468). Immunocompromise was not a risk factor for mortality (OR 0.98, 95 % CI 0.66–1.43). Independent risk factors for mortality among immunocompromised patients included septic shock at presentation (OR 6.64, 95 % CI 1.27–55.72), and unsuccessful source control with persistent inflammation (OR 5.48, 95 % CI 2.29–12.57). In immunocompromised ICU patients with IAI, short-term mortality was similar to immunocompetent patients, despite the former presented more frequently with septic shock, and septic shock and persistent inflammation after source control were independent risk factors for death.

Immunosuppression at ICU admission is not associated with a higher incidence of ICU-acquired bacterial bloodstream infections: the COCONUT study

BackgroundImmunosuppression at intensive care unit (ICU) admission has been associated with a higher incidence of ICU-acquired infections, some of them related to opportunistic pathogens. However, the association of immunosuppression with the incidence, microbiology and outcomes of ICU-acquired bacterial bloodstream infections (BSI) has not been thoroughly investigated.MethodsRetrospective single-centered cohort study in France. All adult patients hospitalized in the ICU of Lille University-affiliated hospital for > 48 h between January 1st and December 31st, 2020, were included, regardless of their immune status. Immunosuppression was defined as active cancer or hematologic malignancy, neutropenia, hematopoietic stem cell and solid organ transplants, use of steroids or immunosuppressive drugs, human immunodeficiency virus infection and genetic immune deficiency. The primary objective was to compare the 28-day cumulative incidence of ICU-acquired bacterial BSI between immunocompromised and non-immunocompromised patients. Secondary objectives were to assess the microbiology and outcomes of ICU-acquired bacterial BSI in the two groups.ResultsA total of 1313 patients (66.9% males, median age 62 years) were included. Among them, 271 (20.6%) were immunocompromised at ICU admission. Severity scores at admission, the use of invasive devices and antibiotic exposure during ICU stay were comparable between groups. Both prior to and after adjustment for pre‐specified baseline confounders, the 28-day cumulative incidence of ICU-acquired bacterial BSI was not statistically different between immunocompromised and non-immunocompromised patients. The distribution of bacteria was comparable between groups, with a majority of Gram-negative bacilli (~ 64.1%). The proportion of multidrug-resistant bacteria was also similar between groups. Occurrence of ICU-acquired bacterial BSI was associated with a longer ICU length-of-stay and a longer duration of invasive mechanical ventilation, with no significant association with mortality. Immune status did not modify the association between occurrence of ICU-acquired bacterial BSI and these outcomes.ConclusionThe 28-day cumulative incidence of ICU-acquired bacterial BSI was not statistically different between patients with and without immunosuppression at ICU admission.

Infectious Diseases and Basal Ganglia Calcifications: A Cross-Sectional Study in Patients with Fahr's Disease and Systematic Review.

Background: It is unclear whether patients with basal ganglia calcifications (BGC) should undergo infectious disease testing as part of their diagnostic work-up. We investigated the occurrence of possibly associated infections in patients with BGC diagnosed with Fahr's disease or syndrome and consecutively performed a systematic review of published infectious diseases associated with BGC. Methods: In a cross-sectional study, we evaluated infections in non-immunocompromised patients aged ≥ 18 years with BGC in the Netherlands, who were diagnosed with Fahr's disease or syndrome after an extensive multidisciplinary diagnostic work-up. Pathogens that were assessed included the following: Brucella sp., cytomegalovirus, human herpesvirus type 6/8, human immunodeficiency virus (HIV), Mycobacterium tuberculosis, rubella virus, and Toxoplasma gondii. Next, a systematic review was performed using MEDLINE and Embase (2002-2023). Results: The cross-sectional study included 54 patients (median age 65 years). We did not observe any possible related infections to the BGC in this population. Prior infection with Toxoplasma gondii occurred in 28%, and in 94%, IgG rubella antibodies were present. The positive tests were considered to be incidental findings by the multidisciplinary team since these infections are only associated with BGC when congenitally contracted and all patients presented with adult-onset symptoms. The systematic search yielded 47 articles, including 24 narrative reviews/textbooks and 23 original studies (11 case series, 6 cross-sectional and 4 cohort studies, and 2 systematic reviews). Most studies reported congenital infections associated with BGC (cytomegalovirus, HIV, rubella virus, Zika virus). Only two studies reported acquired pathogens (chronic active Epstein-Barr virus and Mycobacterium tuberculosis). The quality of evidence was low. Conclusions: In our cross-sectional study and systematic review, we found no convincing evidence that acquired infections are causing BGC in adults. Therefore, we argue against routine testing for infections in non-immunocompromised adults with BGC in Western countries.

Venoarterial extracorporeal membrane oxygenation in immunocompromised patients with cardiogenic shock: a cohort study and propensity-weighted analysis.

The outcomes of immunocompromised patients with cardiogenic shock treated with venoarterial extracorporeal membrane oxygenation (VA-ECMO) are seldom documented, making ECMO candidacy decisions challenging. This study aims (1) to report outcomes of immunocompromised patients treated with VA-ECMO, (2) to identify pre-ECMO predictors of 90-day mortality, (3) to assess the impact of immunodepression on 90-day mortality, and (4) to describe the main ECMO-related complications. This is a retrospective, propensity-weighted study conducted in two French experienced ECMO centers. From January 2006 to January 2022, 177 critically ill immunocompromised patients (median (interquartile range, IQR) age 49 (32-60) years) received VA-ECMO. The main causes of immunosuppression were long-term corticosteroids/immunosuppressant treatment (29%), hematological malignancy (26%), solid organ transplant (20%), and solid tumor (13%). Overall 90-day and 1-year mortality were 70% (95% confidence interval (CI) 63-77%) and 75% (95% CI 65-79%), respectively. Older age and higher pre-ECMO lactate were independently associated with 90-day mortality. Across immunodepression causes, 1-year mortality ranged from 58% for patients with infection by human immunodeficiency virus (HIV) or asplenia, to 89% for solid organ transplant recipients. Hemorrhagic and infectious complications affected 39% and 54% of patients, while more than half the stay in intensive care unit (ICU) was spent on antibiotics. In a propensity score-weighted model comparing the 177 patients with 942 non-immunocompromised patients experiencing cardiogenic shock on VA-ECMO, immunocompromised status was independently associated with a higher 90-day mortality (odds ratio 2.53, 95% CI 1.72-3.79). Immunocompromised patients undergoing VA-ECMO treatment face an unfavorable prognosis, with higher 90-day mortality compared to non-immunocompromised patients. This underscores the necessity for thorough evaluation and careful selection of ECMO candidates within this frail population.

Acute Invasive Pulmonary Aspergillosis: Clinical Presentation and Treatment.

Among all clinical manifestations of pulmonary aspergillosis, invasive pulmonary aspergillosis (IPA) is the most acute presentation. IPA is caused by Aspergillus hyphae invading the pulmonary tissue, causing either tracheobronchitis and/or bronchopneumonia. The degree of fungal invasion into the respiratory tissue can be seen as a spectrum, going from colonization to deep tissue penetration with angio-invasion, and largely depends on the host's immune status. Patients with prolonged, severe neutropenia and patients with graft-versus-host disease are at particularly high risk. However, IPA also occurs in other groups of immunocompromised and nonimmunocompromised patients, like solid organ transplant recipients or critically ill patients with severe viral disease. While a diagnosis of proven IPA is challenging and often warranted by safety and feasibility, physicians must rely on a combination of clinical, radiological, and mycological features to assess the likelihood for the presence of IPA. Triazoles are the first-choice regimen, and the choice of the drug should be made on an individual basis. Adjunctive therapy such as immunomodulatory treatment should also be taken into account. Despite an improving and evolving diagnostic and therapeutic armamentarium, the burden and mortality of IPA still remains high. This review aims to give a comprehensive and didactic overview of the current knowledge and best practices regarding the epidemiology, clinical presentation, diagnosis, and treatment of acute IPA.

254. Genomic diversity of Gram-negative Bacilli from Bloodstream Infections in Hospitalized Children

Abstract Background Gram-negative bloodstream infection (BSI) in hospitalized children is associated with significant morbidity and mortality. It is unclear whether bacterial clonality of isolates during BSI in a unique patient is associated with clinical characteristics such as immunocompromise. We hypothesized that genomic diversity of BSI isolates would be higher in immunocompromised patients due to mucosal barrier injury and therefore larger translocation bottleneck. Methods We prospectively enrolled patients with a central venous catheter who were hospitalized at Boston Children’s Hospital and had a positive blood culture that grew E. coli, Klebsiella spp., or Pseudomonas aeruginosa. An aliquot from the blood culture bottle was plated on agar, and at least 24 colonies were picked randomly and subjected to whole-genome sequencing (WGS). Patient-specific reference genomes were constructed using long-read sequencing of at least 1 isolate on the PacBio platform. All isolates were sequenced using Illumina (MiSeq or NextSeq). Single nucleotide variant (SNV) calls were made using the WideVariant pipeline (github). Clinical characteristics were obtained retrospectively from the electronic medical record. We defined immunocompromise as neutropenia (ANC< 500) on the day of BSI or prior solid organ or stem cell transplant. The proportion of BSI episodes with clonal blood isolates (defined as 0 SNV) was compared between immunocompromised and non-immunocompromised patients using Fisher’s exact test. Results We enrolled 34 patients (median age 2.33 years, IQR 0.8-3.8 years), 25 having BSI from Enterobacterales (11 E. coli, 14 Klebsiella spp.) and 9 from Pseudomonas aeruginosa. Immunocompromised patients had a significantly higher proportion of Enterobacterales BSI episodes with clonal isolates compared with non-immunocompromised patients [13/18 (72%) vs. 1/7 (14%) respectively, P=0.021). This was not seen with Pseudomonas BSI, which had clonal isolates in 3/5 (60%) vs. 2/4 (50%) respectively (P=1). Conclusion Contrary to our hypothesis, immunocompromised patients were more likely to have clonal Enterobacterales BSI isolates compared with non-immunocompromised patients, perhaps due to lower host pressures for bacterial population diversification in immunocompromised patients. Disclosures Arolyn Conwill, PhD, Day Zero Diagnostics: current employee|Day Zero Diagnostics: Stocks/Bonds

Prevalence of Pneumocystis jirovecii Colonization in Non-Critical Immunocompetent COVID-19 Patients: A Single-Center Prospective Study (JiroCOVID Study).

Pneumocystis jirovecii pneumonia (PJP) is an invasive fungal infection (IFI) that occurs mainly in immunocompromised hosts. After observing a high prevalence of PJP as a complication of COVID-19 in immunocompetent patients, we conducted a study to evaluate the prevalence of P. jirovecii colonization with PCR on oral washing samples (OWS) among non-immunocompromised and non-critical patients admitted with COVID-19 pneumonia at our university hospital. All patients over 18 years of age admitted to the Infectious Diseases Unit for SARS-CoV-2 pneumonia between July 2021 and December 2022 were included. Patients undergoing invasive mechanical ventilation or ECMO, those with risk factors for developing PJP, and those receiving prophylaxis for P. jirovecii were excluded. Samples were collected by gargling with 10 mL of 0.9% NaCl on day 14 of the hospital stay or at discharge. Of 290 screened patients, 59 (20%) met the inclusion criteria and were enrolled. Only 1 of 59 patients (1.7%) tested positive for P. jirovecii detection with PCR, and the same patient was the only one to develop PJP in the follow-up period. Our results are in line with the previous findings of other studies that confirmed a very low prevalence of P. jirovecii colonization on OWS in the immunocompetent population. Despite the limitations of the study, the fact that the only patient who tested positive for P. jirovecii was the only one in our cohort to develop PJP leads us to reflect on the role of this non-invasive sample in predicting the risk of PJP in patients with COVID-19.

Abdominal surgery induces long-lasting changes in expression and binding of CTCF with impact on Major Histocompatibility Complex II transcription in circulating human monocytes.

Postoperative immunosuppression has been recognized as an important driver of surgery-related morbidity and mortality. It is characterized by lymphocyte depression and impaired monocyte capability to present foreign antigens to T-cells via Major Histocompatibility Complex, Class II (MHC-II) molecules. In patients with postoperative abdominal sepsis, we previously detected a persisting differential binding of the CCCTC-Binding Factor (CTCF), a superordinate regulator of transcription, inside the MHC-II region with specific impact on human leucocyte antigen (HLA) gene expression. In this prospective exploratory study, we investigated to which extent major surgery affects the MHC-II region of circulating CD14+-monocytes. In non-immunocompromised patients undergoing elective major abdominal surgery, a postoperative loss of monocyte HLA-DR surface receptor density was accompanied by a decline in the transcription levels of the classical MHC-II genes HLA-DRA, HLA-DRB1, HLA-DPA1 and HLA-DPB1. The surgical event decreased the expression of the transcriptional MHC-II regulators CIITA and CTCF and led to a lower CTCF enrichment at an intergenic sequence within the HLA-DR subregion. During the observation period, we found a slow and only incomplete restoration of monocyte HLA-DR surface receptor density as well as a partial recovery of CIITA, HLA-DRA and HLA-DRB1 expression. In contrast, transcription of HLA-DPA1, HLA-DPB1, CTCF and binding of CTCF within the MHC-II remained altered. In circulating monocytes, major surgery does not globally affect MHC-II transcription but rather induces specific changes in the expression of selected HLA genes, followed by differential recovery patterns and accompanied by a prolonged reduction of CTCF expression and binding within the MHC-II region. Our results hint toward a long-lasting impact of a major surgical intervention on monocyte functionality, possibly mediated by epigenetic changes that endure the life span of the individual cell.

Clinical application of metagenomic next-generation sequencing in non-immunocompromised patients with severe pneumonia supported by veno-venous extracorporeal membrane oxygenation.

This study aims to explore the pathogen-detected effect of mNGS technology and its clinical application in non-immunocompromised patients with severe pneumonia supported by vv-ECMO. A retrospective analysis was conducted on a cohort of 50 non-immunocompromised patients who received vv-ECMO support for severe pneumonia between January 2016 and December 2022. These patients were divided into two groups based on their discharge outcomes: the deterioration group (Group D), which included 31 cases, and the improvement group (Group I), consisting of 19 cases. Baseline characteristics and clinical data were collected and analyzed. Among the 50 patients enrolled, Group D exhibited a higher prevalence of male patients (80.6% vs. 52.6%, p < 0.05), more smokers (54.8% vs. 21.1%, p < 0.05), and were older than those in Group I (55.16 ± 16.34 years vs. 42.32 ± 19.65 years, p < 0.05). Out of the 64 samples subjected to mNGS detection, 55 (85.9%) yielded positive results, with a positivity rate of 83.7% (36/43) in Group D and 90.5% (19/21) in Group I. By contrast, the positive rate through traditional culture stood at 64.9% (74/114). Among the 54 samples that underwent both culture and mNGS testing, 23 (42.6%) displayed consistent pathogen identification, 13 (24.1%) exhibited partial consistency, and 18 (33.3%) showed complete inconsistency. Among the last cases with complete inconsistency, 14 (77.8%) were culture-negative, while two (11.1%) were mNGS-negative, and the remaining two (11.1%) presented mismatches. Remarkably, mNGS surpassed traditional culture in pathogen identification (65 strains vs. 23 strains). Within these 65 strains, 56 were found in Group D, 26 in Group I, and 17 were overlapping strains. Interestingly, a diverse array of G+ bacteria, fungi, viruses, and special pathogens were exclusive to Group D. Furthermore, Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae were more prevalent in Group D compared to Group I. Importantly, mNGS prompted antibiotic treatment adjustments in 26 patients (52.0%). Compared with the conventional culture, mNGS demonstrated a higher positive rate, and emerges as a promising method for identifying mixed pathogens in non-immunodeficient patients with severe pneumonia supported by vv-ECMO. However, it is crucial to combine the interpretation of mNGS data with clinical information and traditional culture results for a comprehensive assessment.

A retrospective real-world study of early short-course remdesivir in non-hospitalized COVID-19 patients at high risk for progression: low rate of hospitalization or death, regardless of immunocompetence status.

Introduction: The evidence for remdesivir therapy in immunocompromised patients is scarce. To evaluate remdesivir (RDV) effectiveness and safety in COVID-19 outpatients at high risk for progression in a real-world setting, we compare the outcome in immunocompromised (IC) patients with that in non-immunocompromised patients. Methods: Two hospitals conducted a retrospective study of all adult patients with mild-to-moderate SARS-CoV-2 infection at high risk for disease progression who were treated as outpatients with a 3-day course of RDV (1st January-30th September 2022). The primary effectiveness endpoint was a composite of any cause of hospitalization or death by day 30. A multiple logistic regression model was built to explore the association between immune status and clinical outcome, estimating adjusted odds ratios [aORs (95% CI)]. Results: We have included 211 patients, of which 57% were males, with a median age of 65years (IQR 53-77), 70.1% were vaccinated (three or four doses), and 61.1% were IC. The median duration of symptoms before RDV treatment was 3days (IQR 2-5). During follow-up, 14 (6.6%) patients were hospitalized, of which 6 (2.8%) were hospitalized for COVID-19 progression. No patient required mechanical ventilation, and two patients died (non-COVID-19-related). After accounting for potential confounders, only anti-CD20 treatment was associated with the composed outcome [aOR 5.35 (1.02-27.5, 95% CI)], whereas the immunocompetence status was not [aOR 1.94 (0.49-7.81, 95% CI)]. Conclusion: Early COVID-19 outpatient treatment with a 3-day course of remdesivir in vaccinated patients at high risk for disease progression during the Omicron surge had a good safety profile. It was associated with a low rate of all-cause hospitalization or death, regardless of immunocompetence status.

Testing of worn face mask and saliva for SARS-CoV-2.

Exhaled SARS-CoV-2 can be detected on face masks. We compared tests for SARS-CoV-2 RNA on worn face masks and matched saliva samples. We conducted this prospective, observational, case-control study between December 2021 and March 2022. Cases comprised 30 in-center hemodialysis patients with recent COVID-19 diagnosis. Controls comprised 13 hemodialysis patients and 25 clinic staff without COVID-19 during the study period and the past 2 months. Disposable 3-layer masks were collected after being worn for 4 hours together with concurrent saliva samples. ThermoFisher COVID-19 Combo Kit (A47814) was used for RT-PCR testing. Mask and saliva testing specificities were 99% and 100%, respectively. Test sensitivity was 62% for masks, and 81% for saliva (p = 0.16). Median viral RNA shedding duration was 11 days and longer in immunocompromised versus non-immunocompromised patients (22 vs. 11 days, p = 0.06, log-rank test). While SARS-CoV-2 testing on worn masks appears to be less sensitive compared to saliva, it may be a preferred screening method for individuals who are mandated to wear masks yet averse to more invasive sampling. However, optimized RNA extraction methods and automated procedures are warranted to increase test sensitivity and scalability. We corroborated longer viral RNA shedding in immunocompromised patients.

The management and outcome of cryptococcosis in patients with different immune statuses and treatment protocols: A multicenter real-world study in Jiangsu Province - China.

The incidence of cryptococcosis is increasing in non-immunocompromised patients. However, the evidence on proper management is inadequate in this population. We conducted this multi-center real-world study in pulmonary cryptococcosis patients with different immune statuses, so as to provide practical evidence for optimized clinical management of cryptococcosis, especially for mild-to-moderate immunodeficient diseases patients. This is a prospective observational study. The clinical data of patients with proven cryptococcosis were collected and analyzed from 7 tertiary teaching hospitals in Jiangsu Province, China from January, 2013 to December, 2018. Proven cases include pulmonary cryptococcosis, cryptococcal meningitis, cryptococcemia and cutaneous cryptococcosis. Patients were followed up over 24 months. According to their immune status, patients with cryptococcosis were divided into three groups, namely immunocompetent group (IC), mild-to-moderate immunodeficient diseases group (MID), severe immunodeficient diseases group (SID). Meanwhile, pulmonary crypotococcosis (PC) and extrapulmonary crypotococcosis (EPC) were also classified and analyzed. 255 proven cases of cryptococcosis were enrolled. Finally, 220 cases completed the follow-up. 143 proven cases (65.0%) were immunocompetent (IC), 41 cases (18.6%) were MID, and 36 cases (16.4%) were SID. 174 cases (79.1%) were PC and 46 cases (20.9%) were EPC. The mortality was significantly higher in SID and MID patients [47.2% (SID) vs. 12.2% (MID) vs. 0.0% (IC), p<0.001]. The mortality was also significantly higher in EPC patients [45.7% vs. 0.6% (PC), p<0.001]. Patients with alternative initial antifungal treatment had higher mortality than patients with guideline recommended initial treatment [23.1% vs. 9.5%, p=0.041]. In MID group, the mortality of receiving alternative initial antifungal treatment was significantly higher than recommended initial treatment [2/3 vs. 3/34(8.8%), p=0.043]. In pulmonary cryptococcosis patients with MID, the mortality was very similar to IC group [0.0% vs. 0.0% (IC)], lower than SID group [0.0% vs. 11.1% (SID), p=0.555]. However, in extrapulmonary cryptococcosis patients with MID, the mortality was significantly higher than that in IC [62.5% vs. 0.0% (IC)], and similar to SID patients [62.5% vs. 59.3% (SID)]. The immune status exert a significant influence on the management and prognosis of cryptococcosis patients. The mortality of cryptococcosis patients with MID is higher than that of immunocompetent patients. For MID patients with pure pulmonary cryptococcosis, it is acceptable to take the treatment recommended as IC patients. For the MID patients with extrapulmonary cryptococcosis, the mortality is high and the initial treatment should follow the regimen for SID patients. Following the recommended treatment regimen in the IDSA guideline can reduce mortality in patients with cryptococcosis. Starting on alternative initial antifungal treatment may bring worse outcomes.

Cavitary lesion from pulmonary nocardiosis in non-immunocompromised patients with chronic lung disease: A report of three cases

Cavitary lesion from pulmonary nocardiosis in non-immunocompromised patients with chronic lung disease: A report of three cases

The application value of metagenomic next-generation sequencing technology in diagnosis and treatment of pulmonary infection in immunocompromised patients

Objective: To evaluate the application value of metagenomic next-generation sequencing (mNGS) in the diagnosis and treatment of pulmonary infection in immunocompromised patients. Methods: A total of 78 patients with immunocompromised pulmonary infection [55 males and 23 females, aged (50.3±16.9) years] and 61 patients with non-immunocompromised pulmonary infection [42 males and 19 females, aged (63.6±15.9) years] in the Intensive Care Unit of the First Medical Center of College of the Pulmonary & Critical Care Medicine, Chinese PLA General Hospital from November 2018 to May 2022 were retrospectively selected. Patients in both groups received bronchoalveolar lavage fluid (BALF) mNGS and conventional microbiological tests (CMTs) while clinically diagnosed with pulmonary infection. The diagnostic positive rate, pathogen detection rate and clinical coincidence rate of the two methods were compared. At the same time, the difference of adjustment rate of anti-infective treatment strategy based on the results of mNGS detection was compared between the two groups. Results: The positive rates of mNGS in patients with pulmonary infection were 94.9% (74/78) and 82.0% (50/61) in the immunocompromised group and the non-immunocompromised group, respectively. The positive rates of CMTs in patients with pulmonary infection were 64.1% (50/78) and 75.4% (46/61) in the immunocompromised group and the non-immunocompromised group, respectively. The positive rates of mNGS and CMTs in patients with pulmonary infection in immunocompromised group showed a statistically significant difference (P<0.001). The detection rates of mNGS in the immunocompromised group for pneumocystis jirovecii and cytomegalovirus were 41.0% (32/78) and 37.2% (29/78), respectively, and the detection rates of Klebsiella pneumoniae, chlamydia psittaci and Legionella pneumophila were 16.4% (10/61), 9.8% (6/61) and 8.2% (5/61) in the non-immunocompromised patients, respectively, which were higher than those of CMTs [1.3% (1/78), 7.7% (6/78), 4.9% (3/61), 0 and 0] (all P<0.05). In the immunocompromised group, the clinical coincidence rates of mNGS and CMTs and were 89.7% (70/78) and 43.6% (34/78), respectively, with a statistically significant difference (P<0.001). In the non-immunocompromised group, the clinical coincidence rates of mNGS and CMTs were 83.6% (51/61) and 62.3% (38/61), with a statistically significant difference (P=0.008). In the immunocompromised group, according to the results of the etiology of mNGS, the adjustment rate of anti-infection treatment strategy was 87.2% (68/78), while in the non-immunocompromised group, the adjustment rate of anti-infective treatment strategy was 60.7% (37/61), with a statistically significant difference (P<0.001). Conclusion: In patients with immunocompromised pulmonary infection, mNGS has more advantages than CMTs in diagnostic positive rate, diagnosis rate of mixed infection, pathogen detection rate and guidance of anti-infection treatment strategy adjustment, which is worthy of clinical promotion and application.

#3091 A STUDY FOR HOSPITALIZED PATIENTS WITH COVID-19 WITH/WITHOUT IMMUNOSUPPRESSION AND RENAL FAILURE: DOES THE SURVIVAL RATE CHANGE?

Abstract Background and Aims Introduction The purpose of our research topic was to study the survival of immunocompromised or non-immunosuppressed patients as well as patients with Chronic Kidney Disease who were hospitalized due to covid-19 infection during a two-year period (2020-2022). Method Material and Methods A total of 1270 patients (of whom 570 were women) with a mean age of 63 years (+/- 24 years) were studied. From these, 1000 patients were without immunosuppression and 270 were theoretically and practically immunosuppressed, including 30 patients with Chronic Kidney Disease and of these 10 were with end-stage Chronic Kidney Disease. It is important to mention that 87 patients had to be hospitalized in the ICU, of which 74 died. The rest were hospitalized in the Biocontainment Unit, where 92 deaths were observed. 100 patients without immunosuppression died and 66 with immunosuppression. From the patients with End-Stage Chronic Kidney Disease, 3 died, theoretically falling into the immunocompromised category. The treatment protocol included all the therapeutic measures recommended by CCD. Results There was no statistically significant difference betweem the rate of death in immunocompromised patients and those who belonged in non immunocompromised group. However, there was a simple difference in deaths (66 out of 270 immunosuppresed patients) and 100 in non-immunocompromised patients, while there was also a difference in their need for hospitalization in the ICU and the Unit for Special Infections, but not statistically significant. Conclusion In conclusion, it appears that the immunocompromised are more prone to severe diseases having poor outcome. Furthermore, it was observed that patients with End Stage Chronic Kidney Disease had a fairly low mortality rate even though they are considered immunocompromised.