Outcomes Of Infected Patients Research Articles

IgG testing, immunoglobulin replacement therapy, and infection outcomes in patients with CLL or NHL: real-world evidence

AbstractPatients with chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) can develop hypogammaglobulinemia, a form of secondary immune deficiency (SID), from the disease and treatments. Patients with hypogammaglobulinemia with recurrent infections may benefit from immunoglobulin replacement therapy (IgRT). This study evaluated patterns of immunoglobulin G (IgG) testing and the effectiveness of IgRT in real-world patients with CLL or NHL. A retrospective, longitudinal study was conducted among adult patients diagnosed with CLL or NHL. Clinical data from the Massachusetts General Brigham Research Patient Data Registry were used. IgG testing, infections, and antimicrobial use were compared before vs 3, 6, and 12 months after IgRT initiation. Generalized estimating equation logistic regression models were used to estimate odds ratios, 95% confidence intervals, and P values. The study population included 17 192 patients (CLL: n = 3960; median age, 68 years; NHL: n = 13 232; median age, 64 years). In the CLL and NHL cohorts, 67% and 51.2% had IgG testing, and 6.5% and 4.7% received IgRT, respectively. After IgRT initiation, the proportion of patients with hypogammaglobulinemia, the odds of infections or severe infections, and associated antimicrobial use, decreased significantly. Increased frequency of IgG testing was associated with a significantly lower likelihood of severe infection. In conclusion, in real-world patients with CLL or NHL, IgRT was associated with significant reductions in hypogammaglobulinemia, infections, severe infections, and associated antimicrobials. Optimizing IgG testing and IgRT are warranted for the comprehensive management of SID in patients with CLL or NHL.

Characteristics and incidence of infections in patients with multiple myeloma treated by bispecific antibodies: a national retrospective study

ObjectivesBispecific antibodies (BsAbs) are an effective treatment used in relapsed or refractory multiple myeloma. Despite a well-tolerated safety profile, infectious events appear to be frequent in clinical trials. Real-world data on epidemiology, characteristics, risk factors, and outcomes of infections in patients treated with BsAb are still needed. MethodsA retrospective, multicentre study in BsAb-treated patients with multiple myeloma was performed in 14 French centres from December 2020 to February 2023. The primary objective was to describe the incidence of infections that required hospitalization, specific treatment, or adaptation in BsAb administration. ResultsAmong 229 patients with multiple myeloma treated with BsAb, 153 (67%) received teclistamab, 47 (20%) received elranatamab, and 29 (13%) talquetamab. We reported a total of 234 infections, including 123 (53%) of grade of ≥3. Predominant infections affected the respiratory tract (n = 116, 50%) followed by bacteraemias (n = 36, 15%). The hospitalization rate was 56% (n = 131), and 20 (9%) infections resulted in death. Global cumulative incidence of the first infection was 70% in all patients, 73% in patients treated with B-cell maturation antigen-targeting, and 51% with GPRC5D-targeting BsAb. In univariate analyses, corticosteroids for cytokine release syndrome (CRS)/immune effector cell-associated neurotoxicity syndrome (ICANS) were associated with a higher risk of first infection (HR = 2.13; 95% CI, 1.38–3.28), whereas GPRC5D-targeting BsAb and anti-bacterial prophylaxis were associated with a lower risk (HR = 0.53; 95% CI, 0.3–0.94 and HR = 0.65; 95% CI, 0.46–0.9). Fine and Gray multivariate model found that only corticosteroids for CRS/ICANS were correlated with a higher risk of first infection (HR = 2.01; 95% CI, 1.27–3.19). DiscussionsThe implementation of preventive measures that aim to mitigate the risk of infection under BsAb is pivotal, notably in patients who received corticosteroids for CRS/ICANS.

Infection Outcomes and Hypogammaglobulinemia in Patients with Non-Hodgkin Lymphoma Treated with Immunoglobulin Replacement Therapy

CONCLUSIONS Patients diagnosed with non-Hodgkin lymphoma (NHL) histologies often develop hypogammaglobulinemia (HGG), a secondary immunodeficiency (SID) that is associated with exposure to NHL-related treatments. Those with HGG frequently experience infections, which represent the leading cause of death in NHL (33% of cases). Patients with HGG who experience recurrent infections may benefit from immunoglobulin replacement therapy (IgRT). We aimed to assess real-world IgRT utilization and associated infection outcomes in patients with NHL. This retrospective, longitudinal, observational study evaluated HGG (immunoglobulin G [IgG] < 500 mg/dL) status and infection outcomes among adult patients diagnosed with NHL after 2010 who had ≥ 12 months of clinical data and ≥ 3 visits/year after NHL diagnosis and received immune globulin infusion (human), 10% (IG10% [ie, Gammagard Liquid]). De-identified clinical data from the Massachusetts General Brigham Research Patient Data Registry was used. IgG testing, infection outcomes, and antimicrobial use were compared 3 months before versus 3 months after initiation of IG10%. Generalized estimating-equation logistic regression models were used to obtain odds ratios (ORs), 95% confidence intervals (CIs), and P values. A total of 13,232 patients with NHL were identified. Among patients with NHL, 623 (4.7%) received ≥ 1 IgRT during the follow-up period, of whom, 563 (90.4%) received IG10%. The majority of patients with NHL treated with IG10% were male (61.3%), White (90.1%), with a median (interquartile range [IQR]) age of 62 (53-69) years, and median (IQR) follow-up of 4.8 (2.3-7.7) years. Median (IQR) administrations of IG10% across recipients were 2 (1-4) and over half of patients (55.6%) received ≥ 2 IG10% administrations. Median (IQR) time from initiation of IG10% to end of follow-up was 25.6 (6.8-55.2) months. Most patients had ≥ 1 IgG test in the follow-up period (n = 532 [94.5%]), median (IQR) number of IgG tests was 10 (4-27), and 84.2% of patients had ≥1 IgG test result available before initiation of IG10%. Of the patients treated with IG10% who had IgG test results available (n = 532), 81.6% were identified with HGG (< 500 mg/dL). Few patients had IgG testing at the time of first NHL diagnosis (13.3%), and median (IQR) time from diagnosis to first IgG test was 4.9 (0.8-17.4) months. Of the patients with ≥ 2 IG10% administrations (n = 313), median (IQR) time from the first administration of IG10% to subsequent IgG testing was 1.0 (0.3-2.8) month. Most patients (91.3%) who received ≥ 2 IG10% administrations and ≥ 1 IgG testing had an IgG test between first and second administrations of IG10%. Median (IQR) serum IgG levels were higher in the 3 months following initiation of IG10% versus 3 months before initiation of IG10% (520.0 mg/dL [413.0-670.0] vs 339.0 mg/dL [228.0-405.0]), and significantly fewer patients had HGG (34.7% vs 83.0%, P < 0.0001). In addition, significantly lower odds of infection (OR 0.60, 95% CI 0.47-0.75), severe infection (OR 0.40, 95% CI 0.32-0.50), and associated antimicrobial use were observed 3 months after IG10% initiation (Figures 1 and 2). In this real-world study of patients with NHL, treatment with IG10% was shown to be associated with significantly lower rates of HGG as well as lower odds of infection, severe infection, and antimicrobial use 3 months after IG10% initiation. Guidelines and consensus-based recommendations are needed to optimize the use of IgG testing, initiation of IgRT, and SID management in patients with NHL.

2794. Assessing the impact of inappropriate antibiotic therapy on mortality among intensive care unit patients

Abstract Background This study evaluates the potential association between inappropriate antibiotic therapy and adverse clinical outcomes in infected patients admitted to ICUs. Methods We analyzed data from infected patients admitted to a medical-surgical Intensive Care Unit (ICU) in Belo Horizonte, a city with a population of three million in Brazil. The data was collected between January 2020 and June 2021, and included patients with healthcare-associated and community-acquired infections. In order to determine the appropriateness of antibiotic therapy, cultures and susceptibility reports were utilized. Empiric antimicrobial therapy was classified as inappropriate if the isolated strain was resistant to all empirically administered antimicrobials, while it was considered adequate if the isolated strain was susceptible to at least one of the antimicrobials used empirically. Results A total of 470 patients who received antimicrobials in the ICU were included in the analysis, all of whom had a positive culture. Among them, 65 patients experienced a FAILURE of the antimicrobial regimen, resulting in an overall failure rate of 14%. The monthly rate of inappropriate antibiotic therapy showed significant heterogeneity during the study period, ranging from 100% success in March 2021 to a failure rate of 33% in June 2021 (Fig 1). The failure rate of antimicrobial regimen was found to be significantly higher in cases where the infection was caused by multidrug-resistant (MR) strains compared to multisensitive (MS) strains, as shown in Table 1. Failure of the antimicrobial regimen was a significant risk factor for patient death, regardless of whether the infection was caused by MS or MR strains (Tables 1 and Fig 2). Patients who died tended to receive more antimicrobials compared to those who were discharged, with an average of three antimicrobials prescribed for patients who progressed to death, while discharged patients received an average of two drugs. Conclusion Inappropriate antibiotic therapy in ICU patients is associated with increased mortality risk, regardless of the type of infection. Timely and appropriate antimicrobial therapy is crucial in the management of ICU infections to improve clinical outcomes. Disclosures All Authors: No reported disclosures

Infection outcomes in patients with rheumatoid arthritis treated with abatacept and other disease-modifying antirheumatic drugs: Results from a 10-year international post-marketing study

ObjectiveTo evaluate risk of infections requiring hospitalization and opportunistic infections, including tuberculosis, in patients with rheumatoid arthritis (RA) treated with abatacept versus conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) and other biologic/targeted synthetic (b/ts) DMARDs. MethodsFive international observational data sources were used: two biologic registries (Sweden, Germany), a disease registry (USA) and two healthcare claims databases (Canada, USA). Crude incidence rates (IRs) per 1000 patient-years, with 95 % CIs, were used to estimate rate ratios (RRs) comparing abatacept versus csDMARDs or other b/tsDMARDs. RRs were adjusted for demographic factors, comorbidities, and other potential confounders and then pooled across data sources using a random effects model (REM). ResultsThe data sources included 6450 abatacept users, 136,636 csDMARD users and 54,378 other b/tsDMARD users, with a mean follow-up range of 2.2–6.2 years. Across data sources, the IRs for infections requiring hospitalization ranged from 16 to 56 for abatacept, 19–46 for csDMARDs, and 18–40 for other b/tsDMARDs. IRs for opportunistic infections were 0.4–7.8, 0.3–4.3, and 0.5–3.8; IRs for tuberculosis were 0.0–8.4, 0.0–6.0, and 0.0–6.3, respectively. The pooled adjusted RR (95 % CI), only reported for infections requiring hospitalization, was 1.2 (0.6–2.2) for abatacept versus csDMARDs and 0.9 (0.6–1.3) versus other b/tsDMARDs. ConclusionsData from this international, observational study showed similar hospitalized infection risk for abatacept versus csDMARDs or other b/tsDMARDs. IRs for opportunistic infections, including tuberculosis, were low. These data are consistent with the known safety profile of abatacept.

Infection Outcomes and Hypogammaglobulinemia in Patients with Chronic Lymphocytic Leukemia Treated with Immunoglobulin Replacement Therapy

CONCLUSIONS Hypogammaglobulinemia (HGG), a secondary immunodeficiency (SID), can manifest in patients with chronic lymphocytic leukemia (CLL) due to the disease and its treatments. Up to half of all deaths from CLL are attributed to infection; however, use of immunoglobulin replacement therapy (IgRT) for the prevention of infections in selected patients varies. We aimed to assess real-world IgRT utilization and infection outcomes in patients with CLL. A retrospective, longitudinal study evaluating real-world IgRT use in adult patients with CLL diagnosed after 2010, with ≥ 3 visits/year and ≥ 12 months of clinical data, was conducted. De-identified clinical data came from the Massachusetts General Brigham Research Patient Data Registry. Immunoglobulin G (IgG) testing, infection outcomes, and antimicrobial use were compared before versus after IgRT initiation. Generalized estimating equation logistic regression models calculated odds ratios (ORs), 95% CIs, and P-values. Of 3960 patients with CLL assessed, 2652 (67.0%) patients had IgG testing (29.0% tested at CLL diagnosis); 917 (34.6%) had HGG (IgG level < 500mg/dL). Median (interquartile range [IQR]) age was 68.0 (60.0, 76.0) years, 61.2% were men, 67.8% were treatment-naïve, and median (IQR) follow-up duration was 4.8 (2.4, 7.4) years. Among recipients of IgRT (n = 259), 56.8% received ≥ 2 administrations and the median (IQR) number of IgRT administrations was 2.0 (1.0, 4.0). Median (IQR) time from CLL diagnosis to IgRT initiation was 38.0 (11.4, 64.7) months. Significantly fewer patients had HGG 3 months after IgRT versus 3 months before (33.8% vs 72.8%; P < 0.0001). Significantly lower odds of infections and antimicrobial use were observed after IgRT initiation in 3- and 6-month time periods for: all infections, sinopulmonary and skin or soft tissue infections, infections requiring antimicrobials, all severe infections, severe sinopulmonary and skin or soft tissue infections, and severe infections requiring antimicrobials ( Table). In this real-world study of patients with CLL, IgRT was associated with significant reductions in HGG, infection rates, and infections requiring antimicrobials. Guidelines are needed to optimize IgG testing, IgRT initiation, and SID management for patients with CLL.

Comparative metabolomics reveal key pathways associated with the synergistic activities of aztreonam and clavulanate combination against multidrug-resistant Escherichia coli.

Multidrug-resistant Escherichia coli is a major threat to the health care system and is associated with poor outcomes in infected patients. The combined use of antibiotics has become an important treatment method for multidrug-resistant bacteria. However, the mechanism for their synergism has yet to be explored.

THE IMPACT OF INFLAMMATORY BOWEL DISEASES ON THE OUTCOMES OF PATIENTS ADMITTED WITH ACUTE VIRAL HEPATITIS: A 2016-2019 NATIONWIDE ANALYSIS

Inflammatory bowel diseases (IBD) are thought to be caused by a dysregulated immune response in the digestive tract, amongst other factors (environmental, genetic predisposition, microbiota). Data on acute viral hepatitis (AVH) infection outcomes in patients with underlying IBD are scarce. We aimed to investigate the relationship between IBD and outcomes of patients with AVH.

THE IMPACT OF INFLAMMATORY BOWEL DISEASES ON THE OUTCOMES OF PATIENTS ADMITTED WITH ACUTE VIRAL HEPATITIS: A 2016-2019 NATIONWIDE ANALYSIS

Abstract INTRODUCTION Inflammatory bowel diseases (IBD) are thought to be caused by a dysregulated immune response in the digestive tract, amongst other factors (environmental, genetic predisposition, microbiota). Data on acute viral hepatitis (AVH) infection outcomes in patients with underlying IBD are scarce. We aimed to investigate the relationship between IBD and outcomes of patients with AVH. METHODS This is a retrospective longitudinal study of patients admitted with a primary diagnosis of AVH (A,B,C,D,E). We retrieved data from the Nationwide Inpatient Sample (NIS) databases from the years 2016 to 2019 using ICD-10 CM codes for AVH. Multivariate logistic regression analysis was performed in patients with IBD to estimate the effect of IBD on the primary outcomes of mortality, hospital utilization, and acute hepatitis complications, adjusted for patient and hospital confounders. A T-Test and Chi Square test were performed to compare baseline characteristics in patients admitted for AVH with and without a secondary diagnosis of IBD. We used STATA® Version 17.0 Software (STATACORP, TEXAS, USA) for analysis. The p-value was set at p < 0.05 for statistical significance. RESULTS A total of 47614 adult patients with a primary diagnosis of AVH were identified; four hundred twenty five (0.9%) had a secondary diagnosis of IBD. Most were middle-aged (mean age: 44 years), male (53%) white (78%), and were admitted in large sized (51%) and teaching hospitals (68%). There was no statistically significant change in the length of stay or total healthcare cost associated with the presence of IBD. Having IBD was associated with no change in the risk of fulminant hepatitis (OR = 0.55, p= 0.262, CI: 0.19 - 0.55), hypoglycemia (OR = 1.14, p= 0.904, CI: 0.13 - 9.56), thrombocytopenia (OR = 0.46, p= 0.209, CI: 0.14 - 1.53), and coagulopathy (OR = 1.22, p= 0.781, CI: 0.29 - 5.12). No case of mortality, hepatorenal syndrome or liver transplant was reported. DISCUSSION Despite the fact that IBD is associated with a dysregulated immune response in the digestive tract, our study showed that the presence of IBD in patients affected by acute viral hepatitis does not carry a significant impact on the outcomes of IBD (hospital utilization, morbidity, mortality). Broader studies are required to establish an association between IBD and AVH outcomes.

2100. Epidemiology and Risk Factors for Invasive Fungal Infections Among Patients with Hematological Malignancies In Colombia

Abstract Background Invasive fungal infection (IFI) is a potentially lethal complication in patients with hematological malignancies (HM). However, studies are scarce in this population, especially in developing countries. The aim of this study was to investigate the prevalence, epidemiology, predictive factors, and outcomes of IFI in patients with HM hospitalized in non-HEPA-filtered rooms (resource-limited settings) in a reference center in Colombia. Methods A cross-sectional, retrospective study was conducted on the clinical data of HM patients and pulmonary infection hospitalized in a tertiary university hospital in Bucaramanga, Colombia, between 2015 and 2020. The primary outcome was proven/probable IFI according to the EORTC/MSGERC criteria. A descriptive and group comparison analysis were performed between patients with IFI and patients with non-fungal infections. The main risk factors for the development of IFI were identified by multivariate stepwise logistic regression analysis. Table 1Statistically significant variables in the univariate analysis of patient characteristics compared between patients with invasive fungal infection and patients with non-fungal infection.Image 1Associated factors to develop invasive fungal infections (IFIs) in patients with HM. The graph shows the variables showed statistically significant difference in the multivariate analysis. Results In 201 patients, the prevalence of proven/probable IFI was 21.39% (43 cases). The most common IFI was caused by Aspergillus spp. (41.8%), followed by Candida spp. (34.8%), Mucor spp. (6.9%), Penicillium spp. (4.6%) and Cryptococcus neoformans (4.6%). The lung was the most commonly affected site (n=34; 81.3%); four patients (9.3%) developed fungal sinusitis and disseminated IFI, respectively. In-hospital mortality was 86% (37/43). Multivariate logistic regression analysis (area under the ROC curve=0.90) showed that antibiotic use ≥3 weeks (OR, 4.11; 95% CI, 1.26-13.31; p< .001), history of pulmonary infection (OR, 5.75; 95% CI, 1.41-23.39; p< .001) and neutropenia duration ≥21 days (OR, 5.88; 95% CI, 1.26-19.86; p < .001) were independent risk factors for the development of IFI and mould-active prophylaxis (OR: 0.20; 95% CI: 0.060–0.705; p=0.012) was significantly associated with a lower occurrence of IFI. Conclusion HM patients in resource-limited settings have a high prevalence of IFI with an elevated mortality. The use of mould-active prophylaxis is associated with a significantly lower occurrence of IFI. Cost-effective strategies for prevention and early diagnosis of IFI are required to improve survival in patients with HM. Disclosures All Authors: No reported disclosures.

Comparative features and outcomes of major neurological complications of COVID-19.

The aim of this study was to assess the neurological complications of SARS-CoV-2 infection and compare phenotypes and outcomes in infected patients with and without selected neurological manifestations. The data source was a registry established by the European Academy of Neurology during the first wave of the COVID-19 pandemic. Neurologists collected data on patients with COVID-19 seen as in- and outpatients and in emergency rooms in 23 European and seven non-European countries. Prospective and retrospective data included patient demographics, lifestyle habits, comorbidities, main COVID-19 complications, hospital and intensive care unit admissions, diagnostic tests, and outcome. Acute/subacute selected neurological manifestations in patients with COVID-19 were analysed, comparing individuals with and without each condition for several risk factors. By July 31, 2021, 1523 patients (758 men, 756 women, and nine intersex/unknown, aged 16-101 years) were registered. Neurological manifestations were diagnosed in 1213 infected patients (79.6%). At study entry, 978 patients (64.2%) had one or more chronic general or neurological comorbidities. Predominant acute/subacute neurological manifestations were cognitive dysfunction (N=449, 29.5%), stroke (N=392, 25.7%), sleep-wake disturbances (N=250, 16.4%), dysautonomia (N=224, 14.7%), peripheral neuropathy (N=145, 9.5%), movement disorders (N=142, 9.3%), ataxia (N=134, 8.8%), and seizures (N=126, 8.3%). These manifestations tended to differ with regard to age, general and neurological comorbidities, infection severity and non-neurological manifestations, extent of association with other acute/subacute neurological manifestations, and outcome. Patients with COVID-19 and neurological manifestations present with distinct phenotypes. Differences in age, general and neurological comorbidities, and infection severity characterize the various neurological manifestations of COVID-19.

Outcomes of clostridioides difficile infection in patients with hematopoietic stem cell transplant.

e19054 Background: Hematopoietic stem cell transplantation (HSCT) recipients are at an increased risk for Clostridioides difficile infections (CDI). Despite it being the main cause of nosocomial enterocolitis in this group of patients, diagnosis of CDI remains challenging and carries significant morbidity and mortality. This is usually due to multiple comorbidities, recurrent antibiotics administration, prolonged immunosuppression, and lengthy hospitalization. This study aims to look more into outcomes and predictors of CDI in HSCT patients in terms of incidence, and mortality. Methods: The United States Nationwide Inpatient Sample was used to extract hospitalization data of patients admitted between 2016 to 2019. Using ICD10 revision codes, we identified adults with a discharge diagnosis of CDI and concomitant HSCT. The control group included non-HSCT patients with CDI. The primary outcome was in-hospital mortality. Secondary outcomes were the length of stay (LOS) and hospital charges. Additionally, predictors for developing CDI and dying from CDI were calculated in HSCT patients. Multivariate logistic regression was used to adjust for relevant variables. Results: An estimated 1,235,465 patients were admitted with CDI during the study period. CDI incidence per 100 discharges was higher among HSCT patients at 4.0% vs. 1.0% in the general population. After adjusting for comorbidities and demographic variables, HSCT was independently associated with increased odds of mortality (adjusted odds ratio [AOR] 1.47 (95%CI 1.20-1.80 and P <0.01). Mean length of stay and hospital charges increased by 1.76 days (95%CI 0.90-2.62, P < 0.01) and $59,023 (95%CI $35,940-$82,105, P < 0.01), respectively, in the HSCT group. In the HSCT group, patients with severe liver disease, malnutrition, and graft vs. host disease showed a significantly higher incidence of CDI. Predictors of mortality of HSCT patients and CDI are outlined in the attached table. Conclusions: HSCT recipients are at an increased risk for CDI compared to general population. LOS, total hospital charge, and mortality rate were significantly higher. The risk of CDI was found to be significantly higher in patients with moderate to severe liver disease, graft vs host disease, and malnutrition. The odds of mortality were found to be the highest in patients older than 65 years and those with congestive heart failure, moderate to severe liver disease, graft vs host disease, or malnutrition.[Table: see text]

COVID-19 omicron variants demonstrated different virulence in infected patients with cancer: The real-world evidence from the National COVID Cohort Collaborative (N3C).

e18672 Background: Comprehensive real-world evidence of the virulence of COVID-19 Omicron, Delta, and Alpha variants as well as the effectiveness of booster vaccinations in patients with cancer are lacking. We aimed to fill in these gaps for cancer patients and provide essential insights on the management of the fast-evolving pandemic by leveraging the nationally-representative electronic medical records from the National COVID Cohort Collaborative (N3C) registry. Methods: The virulence of COVID-19 variants was examined according to severe outcomes of infected patients with cancer, compared with non-cancer patients, using the N3C data between 12/01/2020 and 02/03/2022. Variants were inferred according to the time periods of variant dominance at > 95% accuracy. The Cox proportional hazards model was employed to evaluate the effects of COVID-19 variants, adjusting for age, gender, race/ethnicity, geographic regions, vaccination status, cancer types, smoking status, cancer treatments, and adjusted Charlson Comorbidity Index (CCI). Results: Our study cohort included 114,195 COVID-19 patients with cancer and 160,493 without cancer as control. Among them, 52,539 (21%) were infected by Omicron, 82,579 (33%) by Delta, and 115,200 (46%) by Alpha variants. Prior to the COVID-19 breakthrough infection, 7%, 22%, 3%, and 69% were vaccinated with 1 dose, 2 doses, a booster, or unvaccinated respectively. The proportions of hospitalization and death among patients with vs without cancer were 40% and 7% vs 18% and 0.4%, respectively. Characteristics of the cancer subcohort are summarized in the Table. Our analysis showed dramatically lower risks of severe outcomes for patients who were infected by Omicron (HR 0.42, 95%CI: 0.38 – 0.46) and slightly lower risks for Delta (HR 0.93, 95%CI: 0.89 – 0.98) compared with those infected by Alpha, after adjusting for other demographic clinical risk factors, and vaccination status. This trend remained similar in subgroups of patients with solid tumors, hematologic malignancies, or without cancer. Similar associations were observed when virulence was evaluated in association with mortality. The effectiveness of booster vaccinations varied across sub-cohorts stratified by variants and cancer types. Booster shots reduced the risk of severe outcomes for patients with solid tumors infected by Omicron variant or hematologic malignancies infected by Delta variants. Conclusions: Our work provides up-to-date and comprehensive real-world evidence of the virulence of COVID-19 variants in patients with cancer. Omicron variant showed significantly reduced virulence for different cancer types.[Table: see text]

"Outcomes of COVID-19 infection in patients with hematological malignancies- A multicenter analysis from Pakistan".

COVID-19 infection resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began to spread across the globe in early 2020. Patients with hematologic malignancies are supposed to have an increased risk of mortality from coronavirus disease of 2019 (COVID-19) infection. From Pakistan, we report the analysis of the outcome and interaction between patient demographics and tumor subtype and COVID-19 infection and hematological malignancy. This multicenter, retrospective study included adult patients with a history of histologically proven hematological malignancies who were tested positive for COVID-19 via PCR presented at the oncology department of 5 tertiary care hospitals in Pakistan from February to August 2020. A patient with any known hematological malignancy who was positive for COVID-19 on RT-PCR, was included in the study. Chi-square test and Cox-regression hazard regression model was applied considering p ≤ 0.05 significant. A total of 107 patients with hematological malignancies were diagnosed with COVID-19, out of which 82 (76.64%) were alive, and 25 (23.36%) were dead. The significant hematological malignancy was B-cell Lymphoma in dead 4 (16.00%) and alive group 21 (25.61%), respectively. The majority of the patients in both the dead and alive group were on active treatment for hematological malignancy while they came positive for COVID-19 [21 (84.00%) & 48 (58.54%) p 0.020]. All patients in the dead group were admitted to the hospital 25 (100.00%), and among these, 14 (56.00%) were admitted in ICU with a median 11 (6-16.5) number of days. Among those who had contact exposure, the hazard of survival or death in patients with hematological malignancies and COVID-19 positive was 2.18 (CI: 1.90-4.44) times and 3.10 (CI: 2.73-4.60) times in patients with travel history compared to no exposure history (p 0.001). Taken together, this data supports the emerging consensus that patients with hematologic malignancies experience significant morbidity and mortality resulting from COVID-19 infection.

Association of Physical Activity and Lower Respiratory Tract Infection Outcomes in Patients With Cardiovascular Disease.

BackgroundTo investigate the dose‐response association between physical activity and lower respiratory tract infection (LoRI) outcomes in patients with cardiovascular disease.Methods and ResultsUsing the Korean National Health Insurance data, we identified individuals aged 18 to 99 years (mean age, 62.6±11.3 years; women, 49.6%) with cardiovascular disease who participated in health screening from January 1, 2009, to December 31, 2012 (n=1 048 502), and were followed up until 2018 for mortality and until 2019 for hospitalization. Amount of physical activity was assessed using self‐reported questionnaires and categorized into 5 groups: 0 (completely sedentary), <500, 500 to 999, 1000 to 1499, and ≥1500 metabolic equivalents of task min/wk. After controlling for various confounders, adjusted hazard ratios (95% CIs) were 1.00 (reference), 0.74 (0.70–0.78), 0.66 (0.62–0.70), 0.52 (0.47–0.57), and 0.54 (0.49–0.60) for LoRI mortality, and 1.00 (reference), 0.84 (0.83–0.85), 0.77 (0.76–0.79), 0.72 (0.70–0.73), and 0.71 (0.69–0.73) for LoRI hospitalization among those engaging in physical activity of 0, <500, 500 to 999, 1000 to 1499, and ≥1500 metabolic equivalents of task min/wk, respectively. Assuming linear association between 0 and 2000 metabolic equivalents of task min/wk, each 500–metabolic equivalents of task min/wk increase of physical activity was associated with reduced LoRI mortality and hospitalization by 22% and 13%, respectively. The negative association was stronger in the older population than in the younger population (P for interaction <0.01).ConclusionsIn patients with cardiovascular disease, engaging in even a low level of physical activity was associated with a decreased risk of mortality and hospitalization from LoRI than being completely sedentary, and incremental risk reduction was observed with increased physical activity.

Течение коронавирусной инфекции Sars-cov-2 (ковид-19) у пациентов с сахарным диабетом 2 типа и влияние сахароснижающей терапии на исходы заболевания

Underlying diabetes mellitus type 2 are considered risk factor for increased coronavirus disease (COVID-19) disease severity and worse outcomes, including higher mortality, respiratory failure, thromboembolic complications.In this regard, it is relevant to study the factors influencing the unfavorable outcomes of the course of Covid-19 in diabetes mellitus type 2. The most important task is to organize the management of diabetes mellitus during the period of coronavirus infection and the choice of safe and effective glucose-lowering therapy. This article analyzes the impact of previous and current glucose-lowering therapy on the outcomes of coronavirus infection in patients with diabetes mellitus type 2 based on published research results

Clinical characteristics and outcomes of COVID-19 in kidney transplant recipients

Introduction. The pandemic caused by the SARS-CoV-2 coronavirus is characterized by significant morbidity and mortality. Kidney transplant recipients are at high risk of a more severe course of coronavirus infection due to ongoing immunosuppression, a high comorbidity index, and elder age.Aim. To investigate the features of the clinical course, the treatment applied and also the outcomes of the new coronavirus infection in patients after kidney transplantation.Material and methods. The retrospective study included 69 adult kidney transplant recipients continuously followed-up by our transplant nephrology service and who fell ill with COVID-19 from April 2020 till February 2021. The comparison study of the clinical pattern, laboratory and instrumental test results, treatment features and outcomes was made.Results. The most common clinical symptoms were hyperthermia (85.5%, n= 59), weakness (65.2%, n=45) and cough (52.2%, n=36), other symptoms were significantly less common. In 89.5% of cases (n=60), the virus ribonucleic acid was detected at least once by polymerase chain reaction; in 10.5% of cases (n=7), the polymerase chain reaction results were negative. According to CT, the extent of lung tissue lesion was identified as CT1 stage in 28 patients (46.7%), CT2 stage in 24 (40%); and only in 8 (13%) patients the lesion was assessed as CT3. Later on the number of patients with more than 50% lung damage increased to 16 (26.7%) and in 1 case the severity of lung tissue damage was consistent with CT4. Typical features for all patients were anemia and lymphopenia of varying severity, hypoproteinemia, increased serum creatinine and urea, C-reactive protein, ferritin, procalcitonin and D-dimer in the laboratory test results. The treatment included antiviral, antibacterial, anticoagulant therapy, corticosteroids, biological anti-cytokine drugs. In 95% of cases (n=66), the maintenance immunosuppressive therapy was changed up to complete withdrawal of the certain components. The patient survival rate with a functioning graft was 76.8% (n=53), the graft loss was observed in 4.3% of cases (n=3), and the lethal outcome was reported in 18.8% (n=13). The cause of death was a severe respiratory distress syndrome with multiple organ dysfunction complicated by sepsis and septic shock in 8 patients (61.5%). Invasive ventilation and hemodialysis were associated with 17.2 (p&lt;0.00001) and 21.5 (p&lt;0.0006) times higher risk of death, respectively.Conclusions. Severe lymphopenia is associated with a clinical worsening of the COVID-19 course. Predictors of fatal outcome were identified as follows: bacterial sepsis, invasive ventilation, the need for renal replacement therapy (p&lt;0.00001). Immunosuppression adjustment should be personalized considering the severity of infection, age, comorbidities, post-transplant timeframe, and the risk of rejection.&gt;&lt;0.00001). Immunosuppression adjustment should be personalized considering the severity of infection, age, comorbidities, post-transplant timeframe, and the risk of rejection.

927. Clinical Characteristics and Outcomes of Norovirus Infection in Patients with Hematologic Malignancies: A Retrospective, Single Center Study

BackgroundNorovirus (NV) gastroenteritis has been identified as a cause of significant morbidity among hematopoietic stem cell transplant (HSCT) recipients, often with associated complications. Current guidelines recommend symptomatic relief with antimotility agents, rehydration, and reduction in immune suppression. Nitazoxanide (NTZ) is an anti-parasitic agent but some literature suggests a benefit of nitazoxanide therapy for NV. MethodsWe conducted a single center, retrospective chart review study and evaluated adult patients (age >18 years) who had NV infection and either: 1) underwent stem cell transplantation; or 2) received myeloablative chemotherapy within 4 weeks of NV diagnosis by positive test on gastrointestinal pathogen panel during the time period from January 2015 through March 2020. Results26 patients were reviewed. 14 patients (54%) had a history of HCST prior to infection. Three patients (12%) received both myeloablative chemotherapy and HSCT within four weeks of NV infection. Six patients (46%) had autologous, six (46%) had matched unrelated donor, and one (8%) had haploidentical allogeneic transplants. Nine (69%), three (23%), and one (8%) underwent myeloablative, reduced intensity and non-myeloablative conditioning, respectively. Median duration of diarrhea was 4.5 days (IQR = 2.25-7 days). Three (12%) patients received NTZ or intravenous immune globulin. The 6 month mortality was 42% (11/26), however, none of the deaths were directly attributable to NV infection.ConclusionNV infection led to severe diarrheal disease in our cohort. Overall mortality was high, and a trend toward increased mortality was seen among patients receiving NV-directed therapy; these patients likely received NV-directed therapy due to the severity of their illness. Clinicians must have a high suspicion for this illness and obtain PCR testing for timely diagnosis and management.Table 1. Characteristics of patients with hematologic malignancies and norovirus infection Disclosures All Authors: No reported disclosures

Covid-19 Infection in Hematological Malignancies: Registry Data from India

Background: The impact of COVID-19 pandemic has been highly heterogeneous across the globe and different regions within the country. The differences in the outcome of these patients is related to their demographic profile, genetics, socio-economic conditions, and government health policies. Prior to the COVID-19 pandemic, the Healthcare Access and Quality (HAQ) Index for hematological malignancies (HAQ index <30) in a low-middle socio-demographic index(SDI) country like India was less than the mean HAQ index for all other diseases (HAQ index 41) with a significant regional disparity.(1)Several national and international registries from high socio-demographic Index (SDI) countries have reported worse short-term outcomes of coronavirus disease (COVID-19) in patients with hematologic as compared to other solid cancers. The outcomes of COVID-19 in patients with hematologic malignancies from a low-middle SDI country are yet unknown. The COVID-19 Hematologic Cancer registry of India reports these outcomes from India.Methods: Ten tertiary referral hospitals across India reported the demographic, clinical, laboratory, treatment, and outcomes of COVID-19 infection in patients with hematological malignancies. The registry was retrospective from March 21, 2020, and prospective from November 1, 2020, till March 20, 2021. Risk factors associated with severity and mortality were evaluated using the penalised logistic regression and Cox proportional hazards model.Findings: Data from 565 patients was included in this study. Among these, 429 (76%) patients were hospitalized, 186 (33%) patients had moderate/severe COVID-19.There were 116 (20.5%) non-survivors at a mean follow up of 147 (95% CI : 142-153) days. Age >60 years (HR 2·55, 1·23 - 5·27), diagnosis of acute myeloid leukemia (HR 2·85, 1·58 - 5·13), interruption or alteration of anticancer therapy (HR 2·78, 1·65 - 4·68), and post hematopoietic cell transplant status (HR 3·68, 1·82 - 7·45) predicted mortality. In contrast, increasing age [20-40 years (OR 2·54, 1·32 - 4·90), 41-60 years (OR 3·51, 1·84 - 6·71), >60 years (OR 6·04, 3·01 - 12·10), comorbidities such as diabetes mellitus (OR 1·89, 1·18 - 3·04), hypertension (OR 1·94, 1·17 - 3·19), diagnosis of AML (OR 3·70, 2·06 - 6·67), indolent non-hodgkin lymphoma (OR 3·20, 1·68 - 6·09), multiple myeloma (OR 2·88, 1·64 - 5·05), malignancy not being in remission (OR 1·71, 1·12 - 2·60)were significantly associated with severe COVID-19 on univariate analysis. Of these, only increasing age [20-40 years (OR 2·60 (1·31 - 5·15), 40-60 years (OR 3·44, 1.60 - 7·41), more than 60 years (OR 5·70, 2·43 - 13·35)] , AML (OR 2·73, 1·45 - 5·12), and malignancy not being in remission (OR 1·85, 1·18 - 2·89) were significantly associated with severe COVID-19 on multivariable analysisConclusion: The overall mortality from COVID-19 infection of the entire cohort was 20.5%; the mortality was 46.2% in patients who had moderate to severe disease COVID-19 illness. Similar to previous studies, age, diagnosis of acute myeloid leukemia and a post stem cell transplant status was associated with mortality. In addition, interruption or de-escalation of anticancer therapy during Covid-19 infection was identified as an important factor associated with higher mortality on follow up in the current study.

Effect of physical activity on mortality and hospitalization for lower respiratory tract infection in patients with cardiovascular disease

Abstract Background Despite the well-validated benefit of physical activity on various health outcomes, little is known about its effect on lower respiratory tract infection. We explored the dose-response associations between physical activity and lower respiratory tract infection outcomes in patients with cardiovascular disease. Methods Using the Korean National Health Insurance data, we identified more than 1 million individuals with cardiovascular diseases who had data on self-reported physical activity (baseline 2009–2012). Participants were followed up until 2018–2019 regarding the risk of death or hospitalization due to lower respiratory tract infection according to their physical activity level. Results Age- and sex-adjusted hazard ratios (95% confidence interval) for lower respiratory tract infection mortality were 1.00 (reference), 0.70 (0.67–0.74), 0.63 (0.59–0.66), 0.48 (0.43–0.53), and 0.51 (0.45–0.56) for those engaging in physical activity of 0, &amp;lt;500, 500–999, 1000–1499, and ≥1500 MET min/week, respectively. This was similarly applied to hospitalization due to lower respiratory tract infection. Generally, the association was stronger in the elderly population than in the younger population. Restricted cubic spline curve showed a non-linear association, that is, gradual risk reduction with a steeper slope between 0 and 500 MET min/week, reaching a plateau for 1500–1800 MET/min, and the curve flattened out thereafter. Conclusions In patients with cardiovascular disease, engaging in even low level of physical activity was associated decreased risk for lower respiratory tract infection outcomes and incremental risk reduction was shown with an increasing physical activity. Funding Acknowledgement Type of funding sources: None.