Rate Of Viral Infections Research Articles

Epidemiology of Infections in Lung Transplant Recipients Treated With Belatacept.

Belatacept is a costimulatory blocker that can be used to prevent and treat rejection in lung transplant recipients (LuTRs). The epidemiology of infections in belatacept-treated LuTRs has not been systematically evaluated. We performed a single-center retrospective study of all adult LuTRs who received belatacept as prevention or treatment of antibody-mediated rejection (desensitization) or as part of maintenance immunosuppression from January 1, 2011, to June 30, 2022. We assessed the epidemiology of infections that occurred within 12 months following the first belatacept dose. Fifty-two LuTRs received at least one dose of belatacept as either desensitization (n = 32) or maintenance immunosuppression (n = 20). Among 45 patients who were cytomegalovirus (CMV) donor and/or recipient seropositive, nine (20%) developed CMV infection. Seven (77%) CMV infections occurred despite valganciclovir prophylaxis and four (44%) were associated with antiviral resistance. Three (6%) LuTRs developed Epstein-Barr virus (EBV) associated post-transplant lymphoproliferative disorder (PTLD). Twenty-five (48%) LuTRs developed 43 bacterial infections and five (10%) developed proven or probable invasive fungal disease. Incidence rates of viral, bacterial, and fungal infections were similar between the desensitization and maintenance groups: incidence rate ratios (95% confidence interval) were 0.70 (0.32-1.57), 1.31 (0.70-2.46), and 2.82 (0.31-25.2), respectively. Infection/PTLD prompted belatacept discontinuation in eight (15%) patients. In the first year after belatacept initiation, LuTRs commonly developed CMV infections, EBV+ PTLD, and bacterial infections. Multicenter collaborations are needed to better understand infection risks in LuTRs treated with belatacept.

Human body resistance dynamics in the post-covid period

The issue of the state of specific and nonspecific resistance in the post-COVID period and the possible consequences of COVID-19 remains poorly understood. A clinical and laboratory examination of 124 patients was conducted at various time points after COVID-19 infection. 62 patients recovered completely and 62 had post-COVID syndrome. The leukocyte count and leukogram were evaluated in all patients. Immunogram parameters were additionally evaluated in patients with post-COVID syndrome. The results showed that, regardless of post-COVID syndrome, leukocyte count is lower in all patients within six months after COVID-19 infection than in unaffected subjects. The absolute neutrophil count is restored only 12 months later. In the presence of post-COVID syndrome, the absolute number of CD3+, CD4+and CD19+lymphocytes was lower than in healthy people. At the same time, 3 to 15 months after that, IgA titer in patients with PCS was significantly lower and that of for total IgM and IgG was higher without any clinical or laboratory signs of inflammation. The total blood IgE level was significantly higher and increased by the end of the observation period. A decreased activity of nonspecific protection, as well as indicators of cellular and humoral immunity in patients with post-COVID syndrome is accompanied by higher rate of viral and bacterial infections of various localization. Whereas during the first period an increase in total blood ID is not accompanied by clinical signs of atopy, then 6 months later the frequency of allergy increases. During the same period, cases of a joint syndrome revealed as arthralgia or progressive joint destruction become more frequent. Atopic manifestations are often combined with joint syndrome. Thus, after a COVID-19 infection, a low long-term level of nonspecific protection remains in vivo. In patients with post-COVID syndrome, low nonspecific and specific body resistance is manifested by viral and bacterial infections of the mucous membranes and skin. An imbalance in the immune system contributes to developing allergic and autoimmune processes.

Haploidentical Stem Cell Transplantation With TCR αβ+/CD19+ Depletion in Children With Nonmalignant Hematologic Disorders: Outcomes From a Referral Center in Peru

BackgroundHaploidentical hematopoietic stem cell transplantation (haplo-HSCT) with TCR αβ+/CD19+ cell depletion is a promising therapeutic alternative for children with nonmalignant hematologic disorders, especially in low-income countries where finding a compatible donor is challenging. The use of this transplantation approach for nonmalignant hematologic disorders has not been previously described in the Peruvian pediatric population. MethodsWe present the outcomes of children under 19 with nonmalignant hematologic disorders who underwent haplo-HSCT with TCR αβ+/CD19+ cell depletion between 2018-2022 at a referral center in Lima, Peru. Survival probabilities and cumulative incidence functions were calculated using the Kaplan-Meier method. ResultsA total of 17 children aged between 1 to 18.6 years (median = 9.7 years) were included. The follow-up period ranged from 10 days to 66.20 months, with a median of 4.34 months. The probability of overall survival, event-free survival, and failure-free survival was 33.70%, 31.40%, and 68.8%, respectively. The incidence rate of graft failure was 49.80%, while the mortality rate not associated with graft failure was 18.8%. The incidence rate of acute graft-versus-host disease (GvHD) was 25.60%, and the incidence rate of viral infections was 59.40%. ConclusionsThe high incidence rates of graft failure and viral infections suggest that these factors may negatively impact the survival of children with nonmalignant hematologic disorders who undergo haplo-HSCT with TCR αβ+/CD19+ cell depletion. Therefore, optimizing the current conditioning regimens and ensuring timely access to first, second, and third-line antivirals is crucial to improve the survival of these patients.

53040 Rates of Viral Non-Respiratory Infections in Patients with Moderate-to-Severe Atopic Dermatitis in the US: A Retrospective Study of Administrative Claims

53040 Rates of Viral Non-Respiratory Infections in Patients with Moderate-to-Severe Atopic Dermatitis in the US: A Retrospective Study of Administrative Claims

Comparison of Infection Risks Between Various Inhaled and Intranasal Corticosteroids: A Pharmacovigilance Analysis Based on the FAERS Database.

This study conducted a pharmacovigilance analysis based on the FDA Adverse Event Reporting System (FAERS) database to compare the infection risk of inhaled or nasal Beclomethasone, Fluticasone, Budesonide, Ciclesonide, Mometasone, and Triamcinolone Acetonide. We used proportional imbalance analysis to evaluate the correlation between ICS /INCs and infection events. The data was extracted from the FAERS database from April 2015 to September 2023. Further analysis was conducted on the clinical characteristics, site of infection, and pathogenic bacteria of ICS and INCs infection adverse events (AEs). We used bubble charts to display their top 5 infection adverse events. We analyzed 21,837 reports of infection AEs related to ICS and INCs, with an average age of 62.12 years. Among them, 61.14% of infection reports were related to females. One-third of infections reported to occur in the lower respiratory tract with Fluticasone, Budesonide, Ciclesonidec, and Mometasone; over 40% of infections reported by Triamcinolone Acetonide were eye infections; the rate of oral infections caused by Beclomethasone were 7.39%. The reported rates of fungal and viral infections caused by beclomethasone were 21.15% and 19.2%, respectively. The mycobacterial infections caused by Budesonide and Ciclesonidec account for 3.29% and 2.03%, respectively. Bubble plots showed that the ICS group had more fungal infections, oral infections, pneumonia, tracheitis, etc. The INCs group had more eye symptoms, rhinitis, sinusitis, nasopharyngitis, etc. Women who use ICS and INCs are more prone to infection events. Compared to Budesonide, Fluticasone seemed to have a higher risk of pneumonia and oral candidiasis. Mometasone might lead to more upper respiratory tract infections. The risk of oral infection was higher with Beclomethasone. Beclomethasone causes more fungal and viral infections, while Ciclesonide and Budesonide are more susceptible to mycobacterial infections.

Comparison of Infectious Complications in Patients Receiving High-Dose Cyclophosphamide as GvHD Prophylaxis After Transplantation From A 9/10 HLA-Matched Unrelated Donor with Standard GvHD Prophylaxis After Transplant From A Fully Matched Related Donor.

The aim of this study was to evaluate whether cyclophosphamide administered after allogeneic stem cell transplantation (ASCT) from 9/10 HLA-Matched Unrelated Donors (MMUD) increases the rates of bacterial, fungal, viral infections, complications (hemorrhagic cystitis (HC)), and infection-related mortality compared to allogeneic stem cell transplantation from matched related donors (MRD). This is a retrospective multicenter study. 45 MMUD ASCT patients who received posttransplant cyclophosphamide+methotrexate+calcineurin inhibitor compared with 45 MRD ASCT patients who received methotrexate+calcineurin inhibitor. Although there was a statistically significant prolongation of neutrophil engraftment time in the PTCy arm, there was no statistically significant difference in bacterial infection frequencies between the groups (PTCy; 9 (20%), control; 8 (17.8%), p=0.778). The distribution of CMV infection in the first 100 days was similar (p=0.827), but the distribution of CMV infection rate between the 100th and 365th days was observed more frequently in the control group (p=0.005). HC rates and their grades were similar in both groups (PTCy; 4 (8.8%), control; 6 (13.3%) p=0.502). The rates of VZV infection and invasive aspergillosis were similar in the PTCy and control groups (13.3% in the PTCy and 17.8% in the control group p=0.561). There is also no statistically significant difference in survival analysis (OS, LFS, GRFS, RI, IRM, NRM) between groups. However, the incidence of cGVHD was significantly higher in the control group (P=0.035). The addition of PTCy to standard GvHD prophylaxis in MMUD ASCT does not lead to an increase in CMV reactivation, bacterial infections, invasive fungal infection, viral hemorrhagic cystitis, or mortality.

Molecular identification of the common viral respiratory viruses in backyard chickens in Basrah, Southern Iraq

Many viruses can infect different types of birds, with poultry being the most susceptible. These viral diseases have a direct negative impact on the poultry industry, with significant economic losses. This study examined a group of the most important viruses that infect backyard chickens in 2 specific areas of Basrah Governorate, south of Iraq. The study analyzed avian influenza viruses (AIVs), Newcastle disease virus (NDV), and infectious bronchitis virus (IBV). Two hundred and ninety oropharyngeal swabs, 150 from Abu Al-Khasib and 140 from Shatt Al-Arab regions in the Basrah governorate, were obtained from backyard chickens with clear respiratory signs. The samples were subjected to viral RNA extraction, and the viral nucleic acids were detected using an RT-PCR technique. The overall rate of viral infections was 74.8%, which varied depending on the type of virus: 15.8%, 31.3%, and 27.5% for AIV, NDV, and IBV, respectively. The NDV and IBV had much higher infection rates than that of AIV. In addition, the prevalence of AIV in the Shatt Al Arab district was significantly higher than in the Abul Khasib district. Moreover, there were no significant differences between the NDV and the IBV distributions in either of the targeted regions in this study.

Infections in Lymphoma Patients Treated with Bispecific Therapies: A Systematic Review and Meta-Analysis

CONCLUSION BACKGROUND Bispecific antibodies (BsAb) demonstrate efficacy in newly diagnosed and relapsed/refractory lymphomas. BsAb act by forming immune synapses between an effector cell (T cell or NK cell) surface markers and target cell surface markers, typically CD19 and CD20 in B-cell lymphoma; and CD30 in T-cell lymphomas. Improved understanding of the infection risks associated with BsAbs is required to improve patient outcome. METHODS MEDLINE, EMBASE, Cochrane and Google Scholar were searched to identify relevant studies up to June 15, 2023. Phase I-III clinical trials and observational studies of BsAb monotherapy and combination therapy in adult patients were included. Study identification, data-extraction and bias-assessment were performed by two authors (Figure 1). The primary outcome was the number of bispecific-treated lymphoma patients who experienced ≥ 1 infection of any grade. Secondary outcomes included severe infections (grade ≥ 3), fatal infections and the incidence of microbiologically confirmed bacterial, viral and fungal infections. Sub-analysis by malignant target (CD19 vs CD20), and monotherapy versus combination therapy was performed. Meta-analysis of proportions estimated the pooled infection incidence using random effects model (Mantel-Haenszel). Cochran's Q test examined heterogeneity. PROSPERO registration (CRD42023433207). RESULTS Of 1796 studies, 23 studies (1423 pts) were included, with a median age of 64 years (IQR 60 - 66). Nineteen studies (1124 pts) reported the primary outcome of all-grade infections, which occurred in 37% of patients (95%CI: 30 - 45%) (Figure 2). 13% of patients experienced a grade ≥ 3 infection (12 studies, 843 pts, 95%CI: 9 - 17) and 2% (N = 35) experienced a fatal infection (18 studies, 1318 pts, 95%CI: 1 - 2%). 35 fatal infections were reported (1124 pts), with aetiology reported in 97% (N = 34). 68% of fatal infections (23/34) were microbiologically identified. Fatal infections were predominately viral (70%, 16 infections, 15 deaths from COVID-19, 1 death from EBV), followed by fungal (17%, 4 infections, 3 deaths from pneumocystis jirovecii, 1 death from candida species), bacterial (9%, 2 infections, E. coli and Klebsiella sepsis) and 1 parasitic infection (toxoplasmosis). 11 clinically defined fatal infections occurred; 3 fatal pneumonias, and 8 cases of fatal ‘septic shock’ without a causative pathogen listed. 302 patients (8 studies) with aggressive B-cell lymphoma were compared to 129 indolent lymphoma patients (2 studies). All-grade infections were significantly higher in the aggressive B-cell lymphoma subgroup (41%, 95%CI: 33 - 49%) compared to the indolent subgroup (27%, 95%CI: 10 - 44%, z = 2.77, p = 0.005). The weighted median of prior therapies in the aggressive lymphoma group was comparable to the indolent group (3 vs. 2.5 prior therapies). Grade ≥ 3 infections (14% vs 11%) and fatal infections (3% vs 0%) did not differ significantly between aggressive and indolent subtypes (p > 0.05). Patients receiving CD20/CD3 BsAb monotherapy experienced a significantly higher rate of all-grade infections (42% vs 29%, z = -3.14, p < 0.01) and grade ≥ 3 infections (17% vs 7%, z = -3.23, p < 0.01) than patients receiving CD19/CD3 monotherapy. Fatal infections were comparable between CD20/3 and CD19/3 products. Microbiological aetiology and clinical sites of infections were not commonly reported. In subanalysis of CD20/CD3 products, pooled all-grade infections did not differ significantly between monotherapy epcoritimab (34% 95%CI: 21 - 47%) and glofitamab (39% 95%CI: 21 - 56%). Analysis of all-grade and grade ≥ 3 infections related to monotherapy mosunetuzumab and odronextumab was not possible due to inconsistent reporting of these outcomes across studies. When used in combination, all-grade infections for epcoritimab were comparable to epcoritimab monotherapy (34% 95%CI: 21 - 47% vs 42% 95%CI: 31 - 52%, z = 1.13, p = 0.258). Mosunetuzumab was given with R-CHOP in a single study, but all-grade and severe infection rates were not reported. This systematic review reports a modest rate of serious infections in lymphoma patients receiving BsAb. The higher rate of fatal viral and fungal infections highlights a potential need for increased clinical vigilance for infections classically associated with T-cell depletion. Although further data is needed, CD20-targeted BsAb may confer higher infection risk than CD19-directed products.

NK Cell Dysfunction in CLL Is Mediated through SHP-1 Signaling and Is Associated with Poor Prognosis

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease, presenting with a highly variable clinical course, outcome and response to therapy. This variability has been linked to a complex tumor microenvironment and genetic/epigenetic modifications that lead to immunosuppression. Indeed, the clinical hallmark of this disease is the susceptibility to infections and secondary malignancies. While T cell dysfunction in CLL has been well described, conflicting information exists on NK cell changes in CLL and their role in CLL immunosurveillance. Here, we analyzed samples from 75 untreated (or completed treatment >2 years ago) CLL patients and 30 healthy controls. We discovered a substantial variation in NK cell function compared with healthy controls, which we further classified into hyperfunctional, normofunctional and dysfunctional based on their ability to degranulate, and produce IFN- γ in response to K562 targets ( Figure 1). NK cells from ‘dysfunctional’ CLL samples also displayed impaired cytotoxicity against K562 targets, weaker synapse formation and Syk/Zap70 signaling in response to antibody-dependent cellular cytotoxicity (ADCC) compared to those from ‘functional’ samples. The NK functional status was strongly associated with multiple prognostic markers, including cytogenetics, IgVH mutation status, ZAP-70 expression and disease stage, with patients with dysfunctional NK cells having significantly higher rates of secondary malignancies and viral infections ( Table 1). Using multispectral flow cytometry we discovered high phenotypic heterogeneity with unique NK cell clusters present in the dysfunctional samples. Those clusters express a pattern of activation-induced exhaustion, with upregulation of multiple checkpoint molecules such as PD-1, TIGIT, LAG-3, KLRG-1, TIM-3 but not evidence of terminal differentiation (CD57 negative). Those clusters also showed concomitant expression of activating molecules such as NKG2D and DNAM-1, suggesting reversibility of their dysfunctional status. We subsequently found significantly higher (p<0.0001) constitutive phosphorylation of SHP-1 protein, a phosphatase downstream of multiple inhibitory NK cell receptors, in NK cells from dysfunctional samples. Treatment with a SHP-1 inhibitor NSC-87877 (EMD Millipore) or use of siRNA targeting SHP-1 (ThermoFisher scientific), resulted in reversal of NK dysfunction with full restoration of their functional capacity. Taken together, our data suggest that NK cells functional status plays an important role in CLL disease progression and secondary complications. The novel mechanism of NK cell immune dysfunction in CLL described here has the potential to improve outcomes with novel immunotherapies such as chimeric antigen receptors, checkpoint inhibitors and bi-specific antibody therapy that have shown disappointing results in CLL to date when compared with other B cell malignancies.

Invasive Community-Onset Gram-Positive Infections From July 2018 Through December 2022 at 2 Children's Hospitals.

Invasive infections caused by Streptococcus pyogenes (invasive group A streptococcus [iGAS]) and Streptococcus pneumoniae (invasive pneumococcal disease [IPD]) decreased substantially at the beginning of the COVID-19 pandemic. Our study sought to evaluate the extent of this decrease and the trends of these infections since reversion of societal adjustments incident to the pandemic. We also wanted to compare the frequency of these infections with invasive community-onset Staphylococcus aureus (I-CO-SA) infections and common respiratory viral infections in this period. Cases of iGAS, IPD, and I-CO-SA infections were identified prospectively and retrospectively at 2 large US children's hospitals by positive cultures from July 2018 through December 2022. Admission data were used to estimate frequency. For comparison, rates of respiratory syncytial virus (RSV), influenza, and SARS-CoV-2 were estimated by the number of positive viral test results at each institution. I-CO-SA infections showed little variation in the study period. Rates of iGAS infection and IPD decreased by 46% and 44%, respectively, from 2019 to 2020, coinciding with a substantial decrease in RSV and influenza. In 2022, RSV and influenza infection rates increased to prepandemic winter season rates, coinciding with a return to prepandemic rates of IPD (225% increase from 2021 to 2022) and a surge above prepandemic rates of iGAS infections (543% increase from 2021 to 2022). The COVID-19 pandemic had an unexpected influence on IPD and iGAS infections that was temporally related to changes in rates of viral infections.

Incidence of Acute Respiratory Infections in Dental Care Professionals

Introduction: A wide spread of causative agents of acute respiratory infections and an intensive use of aerosol-generating procedures in dentistry affect the disease incidence in dental care professionals. This issue, however, remains poorly studied. Objective: To study the incidence of acute respiratory infections in dental health personnel in order to optimize appropriate preventive measures. Materials and methods: In 2021, we conducted a descriptive retrospective epidemiological study of the workplace absence due to acute respiratory diseases among 352 dental care professionals (case study group) and 782 people unrelated to the medical field (control group). To assess the statistical significance of differences in the incidence rates, the Pearson criterion (χ2) was applied. The data were analyzed in Microsoft Office Excel 2013 and Epi Info v. 1.4.3. Results: We established that the incidence rates of viral respiratory diseases in the dental health personnel were 2.2 times higher than in the control group (301.14 and 136.83 ‰, respectively; p = 0.00001). During the respiratory illness season, the cases were 3.3 times more likely to get sick (p = 0.000001). At the same time, the incidence in the cases working in therapeutic and orthopedic departments and applying aerosol-generating procedures was 2.7 times higher compared to those working in other departments (p = 0.00153). Females generally prevailed among therapists and orthopedists (83.81 %) and the rates of viral respiratory infections in them were found to be 2.73 times higher than in male surgeons (p = 0.00134). Conclusions: The high incidence of acute respiratory infections observed in the dental care professionals, especially in those using aerosol-generating procedures in their everyday practice, shows the necessity of improving measures for prevention of respiratory tract infections in dentistry.

Standardized, risk-adapted induction therapy in kidney transplantation.

The choice of induction therapy in kidney transplantation is often non-standardized and centre-specific. Clinicians can choose between depleting and non-depleting antibodies, which differ in their immunosuppressive capacity and the concomitant risk of infection. We herein present a standardized risk-stratified algorithm for induction therapy that might help to balance the risk of rejection and/or serious infection. Prior to kidney transplantation, patients were stratified into low-risk, intermediate-risk or high-risk according to our protocol based on immunologic risk factors. Depending on their individual immunologic risk, patients received basiliximab (low risk), antithymocyte globulin (intermediate risk) or low-dose alemtuzumab (high risk) for induction therapy. We analysed the results after 3years of implementation of our risk-stratified induction therapy protocol at our kidney transplant centre. Between 01/2017 and 05/2020, 126 patients were stratified in accordance with our protocol (low risk/intermediate risk/high risk: 69 vs. 42 vs. 15 patients). The median follow-up time was 1.9 [1.0-2.5] years. No significant difference was observed in rejection rate and allograft survival (low risk/intermediate risk/high risk: 90.07% vs. 80.81% vs. 100% after 3 years (p > 0.05)) among the groups. The median eGFR at follow-up was (low risk/intermediate risk/high risk) 47 [33-58] vs 58 [46-76] vs 44 [22-55] ml/min/1.73 m2. Although the rate of viral and bacterial infections did not differ significantly, we observed a higher rate of opportunistic fungal infections with alemtuzumab induction. Our strategy offers facilitated and individualized choice of induction therapy in kidney transplantation. We propose further evaluation of our algorithm in prospective trials.

Epidemiological Differences in Hajj-Acquired Airborne Infections in Pilgrims Arriving from Low and Middle-Income versus High-Income Countries: A Systematised Review.

This systematised review aims to compare the epidemiological patterns of Hajj-acquired airborne infections among pilgrims from low and middle-income countries (LMIC) versus those from high-income countries (HIC). A PubMed search was carried out for all published articles before February 2023, using a combination of MeSH terms and text words. The Newcastle-Ottawa Scale (NOS) was used to assess data quality. From a total of 453 titles identified, 58 studies were included in the review (LMIC = 32, and HIC = 26). In the pooled sample, there were 27,799 pilgrims aged 2 days to 105 years (male: female = 1.3:1) from LMIC and 70,865 pilgrims aged 2 months to 95 years (male: female = 1:1) from HIC. Pilgrims from both HIC and LMIC had viral and bacterial infections, but pilgrims from HIC tended to have higher attack rates of viral infections than their LMIC counterparts. However, the attack rates of bacterial infections were variable: for instance, pilgrims from LMIC seemed to have higher rates of meningococcal infections (0.015-82% in LMIC vs. 0.002-40% in HIC) based on the study population, but not Mycobacterium tuberculosis (0.7-20.3% in LMIC vs. 38% in HIC). Targeted measures are needed to prevent the spread of airborne infections at Hajj.

Feasibility of steroid-free tacrolimus-basiliximab immunosuppression in pediatric liver transplantation and predictors for steroid requirement.

Avoidance of steroids in pediatric liver transplantation may reduce toxicity and morbidity. The aim of this study was to analyze the feasibility of a steroid-free tacrolimus-basiliximab immunosuppression scheme, the risk factors associated with steroid requirement, and safety parameters. Patients who underwent liver transplantation for biliary atresia between 2011 and 2019 were included and followed for 6 months after transplantation. Immunosuppression consisted of tacrolimus-based treatment with basiliximab induction. Steroid-free survival was estimated, and risk factors for steroid requirement were evaluated using multivariate Cox regression analysis. A total of 76 patients were included, of whom 42 (55.3%) required steroids (>14d) due to biopsy-proven acute rejection (47.6%, n = 20), instability in liver function tests (35.7%, n = 15), tacrolimus-related adverse drug reactions (14.3%, n = 6), or other reasons (bronchospasm episode, n = 1). Steroid-free survival was 45.9% (95% CI, 35.9-58.8). Independent factors associated with steroid requirement included tortuosity in tacrolimus trough levels (≥1.76 vs. <1.76: HR 5.8, 95% CI, 2.6-12.7; p < 0.001) and mean tacrolimus trough levels (≥ 6.4ng/mL vs. < 6.4ng/mL: HR 0.4, 95% CI, 0.2-0.7; p = 0.002). The rate of bacterial and viral infections was comparable between patients with and without steroids, although in the former group, cytomegalovirus infection developed earlier ( p = 0.03). Patients receiving steroids had higher total cholesterol, LDL, and HDL levels ( p < 0.05) during follow-up, but no changes in the height Z-score were observed 1 year after transplantation. Basiliximab induction in combination with tacrolimus-based treatment avoided steroid requirements in 45% of the patients. Tacrolimus variability and trough levels below 6.4ng/mL independently increased the risk of steroid requirement. Further efforts should be focused on personalizing immunosuppressive treatment.

Preterm and Term Infants Evaluated for Sepsis: Differences in Management and Clinical Outcomes.

To describe differences in practice patterns and outcomes of young preterm versus age-matched term infants evaluated for sepsis, because evaluation and management of this group are not well defined. We conducted a retrospective single-center study at an academic, freestanding children's hospital of previously healthy preterm and term infants aged 0 to 60 days, who presented for initial evaluation of fever and/or hypothermia from 2014 to 2019. We classified infants by gestational age as preterm (32-36 6/7 weeks) and term (37-42 weeks) and compared diagnostic evaluation, management, and clinical outcomes. Out of 363 preterm infants evaluated for sepsis, 336 met inclusion criteria; within the same study period, 2331 term infants were evaluated for sepsis, of which 600 were randomly selected and 554 were included. Clinicians performed inflammatory marker testing and chest x-rays more frequently in preterm infants 31% vs 25% (P = .034) and 50% vs 32% (P < .001), respectively. Preterm infants had a higher rate of bacteremia 5.9% vs 2.5% (P = .035), were hospitalized more frequently 72% vs 63% (P = .006), and required ICU level of care more often 32% vs 5% (P < .001) than term infants. They had lower rates of viral infections 33% vs 42% (P = .015) and no significant increased return visits. Febrile preterm and term infants, and older hypothermic preterm infants had relatively higher rates of serious bacterial infections. Hypothermic preterm infants had the longest hospitalizations. Preterm infants had increased rates of bacteremia and required higher level of care compared with age-matched term infants, likely reflecting their increased risk for sepsis and other concomitant morbidities associated with preterm birth.

Immune Reconstitution Profiling Suggests Antiviral Protection after Transplantation with Omidubicel: A Phase 3 Substudy

Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment for hematological malignancies and non-malignant disorders. Rapid immune reconstitution (IR) following allogeneic HCT has been shown to be associated with improved clinical outcomes and lower infection rates. A global phase 3 trial (NCT02730299) of omidubicel, an advanced cell therapy manufactured from an appropriately human leukocyte antigen-matched single umbilical cord blood (UCB) unit, showed faster hematopoietic recovery, reduced rates of infection, and shorter hospitalizations in patients randomized to omidubicel compared with those randomized to standard UCB. This optional, prospective substudy of the phase 3 trial characterized the IR kinetics following HCT with omidubicel compared with UCB in a systematic and detailed manner. In this substudy, 37 patients from 14 global sites were included (omidubicel: n=17, UCB: n=20). Peripheral blood samples were collected over 10 predefined time points from 7 to 365 days post-HCT. Flow cytometry immunophenotyping, T cell receptor excision circle quantification, and T cell receptor sequencing were employed to evaluate the longitudinal IR kinetics post-transplant and their association with clinical outcomes. Patient characteristics in the two comparator cohorts were overall statistically similar, except for age and total body irradiation (TBI) based conditioning regimens. The median age (range) for patients who received omidubicel or UCB was 30 (13-62) years and 43 (19-55) years, respectively. The percentages of patients receiving TBI based conditioning regimens were 47% and 70% for omidubicel and UCB recipients, respectively. Graft characteristics differed in their cellular composition. Omidubicel recipients received a 33-fold higher median dose of CD34+ stem cells, while receiving one third of the median CD3+ lymphocyte dose infused to UCB transplanted patients. Compared with UCB, omidubicel recipients exhibited faster IR of all measured lymphoid and myelomonocytic subpopulations, predominantly in the first 14 days post-transplant. This effect involved circulating natural killer (NK) cells, helper T cells, monocytes, and dendritic cells, with superior long-term B cell recovery from Day 28. One-week post-HCT, omidubicel recipients exhibited 4.1 and 7.7 -fold increases in the median helper T and NK cell counts respectively, compared to their UCB transplanted counterparts. By three weeks post-HCT, omidubicel transplanted patients were 3-fold more likely to achieve clinically relevant helper T and NK cell counts of 100 cells/ µL or above. Similar to UCB, omidubicel yielded a balanced cellular subpopulation composition and diverse T cell receptor repertoire in the short to long term. Omidubicel's CD34+ cell content correlated with faster IR by Day 7 post-HCT, which in turn coincided with earlier hematopoietic recovery. Lastly, early NK and helper T cell reconstitution correlated with a decreased rate of post-HCT viral infections, suggesting a plausible explanation for this phenomenon among omidubicel recipients in the phase 3 study. Our findings suggest that omidubicel efficiently promotes IR across multiple immune cells, including CD4+ T cells, B cells, NK cells, and dendritic cell subtypes as early as 7 days post-transplant, potentially endowing recipients of omidubicel with early protective immunity.

Low dose vs high dose tocilizumab in COVID-19 patients with hypoxemic respiratory failure

PurposeTocilizumab has been shown to decrease mortality when used concomitantly with steroids in COVID-19 with 8 mg/kg (max 800 mg) being the standard dose. Our study sought to assess whether a low dose (400 mg) shows similar benefit compared to a high dose for COVID patients concurrently on the same median dose of steroids. Materials/MethodsA retrospective, multihospital observational study of COVID-19 patients who received tocilizumab in conjunction with steroids between March 2020 and August 2021 was conducted. ResultsA total of 407 patients were analyzed with low dose group being significantly more ill at baseline as a higher percentage of patients received vasopressors, were admitted to the ICU and on mechanical ventilation. In the propensity-matched analysis, both groups receiving a median dexamethasone equivalent dose of 10 mg showed no difference in 28-day mortality (p = 0.613). The high dose group had a higher rate of fungal and viral infections. ConclusionCompared to low dose tocilizumab, the high dose did not provide additional efficacy and mortality benefit but resulted in higher fungal and viral infections. This study illustrates that low dose tocilizumab can be an alternative to high dose during a drug shortage of tocilizumab without compensating for efficacy and safety, conserving resources for more patients.

Infection and co-infection patterns of community-acquired pneumonia in patients of different ages in China from 2009 to 2020: a national surveillance study

Severe community-acquired pneumonia (SCAP) is associated with a substantial number of hospitalisations and deaths worldwide. Infection or co-infection patterns, along with their age dependence and clinical effects are poorly understood. We aimed to explore the causal and epidemiological characteristics by age, to better describe patterns of community-acquired pneumonia (CAP) and their association with severe disease. National surveillance of CAP was conducted through a network of hospitals in 30 provinces in China from 2009-20 inclusive. Patients with CAP were included if they had evidence of acute respiratory tract, had evidence of pneumonia by chest radiography, diagnosis of pneumonia within 24 h of hospital admission, and resided in the study catchment area. For the enrolled patients with CAP, nasopharyngeal and oral swabs were taken and tested for eight viral pathogens; and blood, urine, or expectorated sputum was tested for six bacterial pathogens. Clinical outcomes, including SCAP, were investigated with respect to age and patterns of infections or co-infections by performing binary logistic regression and multivariate analysis. Between January, 2009, and December, 2020, 18 807 patients with CAP (3771 [20·05%] with SCAP) were enrolled. For both children (aged ≤5 years) and older adults (aged >60 years), a higher overall rate of viral and bacterial infections, as well as viral-bacterial co-infections were seen in patients with SCAP than in patients with non-SCAP. For adults (aged 18-60 years), however, only a higher rate of bacterial-bacterial co-infection was observed. The most frequent pathogens associated with SCAP were respiratory syncytial virus (RSV; 21·30%) and Streptococcus pneumoniae (12·61%) among children, and influenza virus (10·94%) and Pseudomonas aeruginosa (15·37%) among older adults. Positive rates of detection of most of the tested pathogens decreased during 2020 compared with the 2009-19 period, except for RSV, P aeruginosa, and Klebsiella pneumoniae. Multivariate analyses showed SCAP was significantly associated with infection with human adenovirus, human rhinovirus, K pneumoniae, or co-infection of RSV and Haemophilus influenzae or RSV and Staphylococcus aureus in children and adolescents (aged <18 years), and significantly associated with infection with P aeruginosa, K pneumoniae, or S pneumoniae, or co-infection with P aeruginosa and K pneumoniae in adults (aged ≥18 years). Both prevalence and infection pattern of respiratory pathogens differed between patients with SCAP and patients with non-SCAP in an age-dependent manner. These findings suggest potential advantages to age-related strategies for vaccine schedules, as well as clinical diagnosis, treatment, and therapy. China Mega-Project on Infectious Disease Prevention and The National Natural Science Funds of China. For the Chinese translation of the abstract see Supplementary Materials section.

Immediate and long-term changes in the epidemiology, infection spectrum, and clinical characteristics of viral and bacterial respiratory infections in Western China after the COVID-19 outbreak: a modeling study.

The impact of COVID-19 on the epidemiology, clinical characteristics, and infection spectrum of viral and bacterial respiratory infections in Western China is unknown. We conducted an interrupted time series analysis based on surveillance of acute respiratory infections (ARI) in Western China to supplement the available data. The positive rates of influenza virus, Streptococcus pneumoniae, and viral and bacterial coinfections decreased, but parainfluenza virus, respiratory syncytial virus, human adenovirus, human rhinovirus, human bocavirus, non-typeable Haemophilus influenzae, Mycoplasma pneumoniae, and Chlamydia pneumoniae infections increased after the onset of the COVID-19 epidemic. The positive rate for viral infection in outpatients and children aged <5 years increased, but the positive rates of bacterial infection and viral and bacterial coinfections decreased, and the proportion patients with clinical symptoms of ARI decreased after the onset of the COVID-19 epidemic. Non-pharmacological interventions reduced the positive rates of viral and bacterial infections in the short term but did not have a long-term limiting effect. Moreover, the proportion of ARI patients with severe clinical symptoms (dyspnea and pleural effusion) increased in the short term after COVID-19, but in the long-term, it decreased. The epidemiology, clinical characteristics, and infection spectrum of viral and bacterial infections in Western China have changed, and children will be a high-risk group for ARI after the COVID-19 epidemic. In addition, the reluctance of ARI patients with mild clinical symptoms to seek medical care after COVID-19 should be considered. In the post-COVID-19 era, we need to strengthen the surveillance of respiratory pathogens.

Microbial Keratitis Isolates at a Midwestern Tertiary Eye Care Center.

The aim of the study was to describe the pathogen, antimicrobial susceptibility, and trends over time of microbial keratitis (MK) at a Midwestern tertiary eye center. Patients with MK were identified in the electronic health record from August 2012 to December 2021. Diagnostic laboratory tests with an MK diagnosis were identified and classified as laboratory positive or laboratory negative. Laboratory-positive infections were categorized as bacterial (gram-positive, gram-negative, or acid-fast bacilli), fungal, viral, Acanthamoeba , or polymicrobial. Antimicrobial susceptibilities were obtained. Trends over time were assessed using linear regression. Of 3288 patients with MK identified, 1012 (30.8%) had laboratory tests performed. Laboratory-positive infections (n = 499, 49.3%) were bacterial in 73.5% (n = 367) of cases, fungal in 7.8% (n = 39), viral in 1.6% (n = 8), Acanthamoeba in 1.4% (n = 7), and polymicrobial in 15.6% (n = 78). Of bacterial infections, 70% (n = 257) were gram-positive, with coagulase-negative Staphylococcus (CoNS; 31%) and Staphylococcus aureus ( S. aureus ; 23%) as the most common pathogens. Bacteria were acid-fast bacilli in 1.9% (n = 7) of cases and gram-negative in 28.1% (n = 103), with Pseudomonas aeruginosa as the predominant pathogen (47.7%). S. aureus showed antibiotic resistance from 0% (vancomycin and gentamicin) to 50% (erythromycin); CoNS from 0% (vancomycin, gentamicin, and moxifloxacin) to 64% (erythromycin). The rate of laboratory-negative MK significantly increased over time (slope estimate = 2.1% per year, P = 0.034). Rates of bacterial, fungal, viral, Acanthamoeba , and polymicrobial infections were stable over time (all slope P > 0.05). Bacterial keratitis accounted for most MK cases. Gram-positive bacteria were the most common isolates. CoNS and S. aureus were universally susceptible to vancomycin. Rates of MK infection types were stable over time.