Immunomodulators for severe coronavirus disease-2019 in transplant patients: Do they increase the risk of secondary infection?

BACKGROUND: Current guidelines recommend immunomodulators, tocilizumab or baricitinib, for the management of severe coronavirus disease-2019 (COVID-19) in patients with increasing oxygen requirements. Given their immunosuppressive effects, there is a concern for higher rates of infection among transplant recipients. METHODS: A retrospective cohort study of transplant patients with severe COVID-19 between April 2020 and January 2022 was performed at the Mayo Clinic. The primary outcome was incidence of secondary infections after COVID-19 diagnosis. Secondary outcomes were 90-day mortality, ventilatory days, and thromboembolic events. RESULTS: A total of 191 hospitalized transplant patients were studied, including 77 (40.3%) patients who received an immunomodulator. Overall, 89% were solid organ transplant recipients, with kidney as the most common transplanted organ (50.3%). The majority (89.0%) required oxygen supplementation on admission, and 39.8% of these patients required mechanical ventilation during the hospital course. There was no significant difference in the incidence of secondary infections between those who received or did not receive an immunomodulator (p = .984). Likewise, there was no difference in 90-day mortality between patients who received or did not receive an immunomodulator (p = .134). However, higher mortality was observed among patients that developed a secondary infection (p < .001). CONCLUSION: The use of immunomodulators in transplant patients with severe COVID-19 was not significantly associated with an increased risk of secondary infections. Secondary infections were associated with higher risk of all-cause mortality. Future studies of larger cohorts are needed to explore the effect of immunomodulators on survival among transplant patients with COVID-19.

A Comparison of the Effects of Dexamethasone and Methylprednisolone, Used on Level-3 Intensive Care COVID-19 Patients, on Mortality: A Multi-Center Retrospective Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is often a mild disease, usually manifesting with respiratory complaints, and is sometimes mortal due to multiple organ failure. Hyperinflammation is a known COVID-19 component and is associated with organ dysfunction, disease severity and mortality. Controlling hyperinflammatory response is crucial in determining treatment direction. An important agent in providing this control is corticosteroids. This study aimed to determine whether dexamethasone and methylprednisolone, doses, administration time and duration in COVID-19 treatment are associated with improved treatment outcomes. METHODS: This retrospective multicenter study was conducted with participation of 6 healthcare centers which collected data by retrospectively examining files of 1,340 patients admitted to intensive care unit due to COVID-19 between March 2020 and September 2021, diagnosed with polymerase chain reaction (+) and/or clinically and radiologically. RESULTS: Mortality in the pulse methylprednisolone group was statistically significantly higher than that in the other 3 groups. Mortality was higher in older patients with comorbidities such as hypertension, diabetes mellitus, chronic kidney failure, coronary artery disease, and dementia. Pulse and mini-pulse steroid doses were less effective than standard methylprednisolone and dexamethasone doses, pulse steroid doses being associated with high mortality. Standard-dose methylprednisolone and dexamethasone led to similar effects, but standard dose methylprednisolone was more effective in severe patients who required mechanical ventilation (MV). Infection development was related to steroid treatment duration, not cumulative steroid dose. CONCLUSION: Corticosteroids are shown to be beneficial in critical COVID-19, but the role of early corticosteroids in mild COVID-19 patients remains unclear. The anti-inflammatory effects of corticosteroids may have a positive effect by reducing mortality in severe COVID-19 patients. Although dexamethasone was first used for this purpose, methylprednisolone was found to be as effective at standard doses. Methylprednisolone administered at standard doses was associated with greater PaO2/FiO2 ratios than dexamethasone, especially in the severe group requiring MV. High dose pulse steroid doses are closely associated with mortality and standard methylprednisolone dose is recommended.

Secondary infections worsen the outcome of COVID-19 in patients with hematological malignancies: A report from the ITA-HEMA-COV.

The impact of secondary infections (SI) on COVID-19 outcome in patients with hematological malignancies (HM) is scarcely documented. To evaluate incidence, clinical characteristics, and outcome of SI, we analyzed the microbiologically documented SI in a large multicenter cohort of adult HM patients with COVID-19. Among 1741 HM patients with COVID-19, 134 (7.7%) had 185 SI, with a 1-month cumulative incidence of 5%. Median time between COVID-19 diagnosis and SI was 16 days (IQR: 5-36). Acute myeloid leukemia (AML) and lymphoma/plasma cell neoplasms (PCN) were more frequent diagnoses in SI patients compared to patients without SI (AML: 14.9% vs. 7.1%; lymphoma/PCN 71.7% vs. 65.3%). Patients with SI were older (median age 70 vs. 66 years, p = 0.002), with more comorbidities (median Charlson Comorbidity Index 5 vs. 4, p < 0.001), higher frequency of critical COVID-19 (19.5% vs. 11.5%, p = 0.046), and more frequently not in complete remission (75% vs. 64.7% p = 0.024). Blood and bronchoalveolar lavage were the main sites of isolation for SI. Etiology of infections was bacterial in 80% (n = 148) of cases, mycotic in 9.7% (n = 18) and viral in 10.3% (n = 19); polymicrobial infections were observed in 24 patients (18%). Escherichia coli represented most of Gram-negative isolates (18.9%), while coagulase-negative Staphylococci were the most frequent among Gram-positive (14.2%). The 30-day mortality of patients with SI was higher when compared to patients without SI (69% vs. 15%, p < 0.001). The occurrence of SI worsened COVID-19 outcome in HM patients. Timely diagnosis and adequate management should be considered to improve their prognosis.

Secondary respiratory early and late infections in mechanically ventilated patients with COVID-19.

BACKGROUND: Patients with COVID-19 receiving mechanical ventilation may become aggravated with a secondary respiratory infection. The aim of this study was to describe secondary respiratory infections, their predictive factors, and outcomes in patients with COVID-19 requiring mechanical ventilation. METHODS: A cohort study was carried out in a single tertiary hospital in Santiago, Chile, from 1st June to 31st July 2020. All patients with COVID-19 admitted to the intensive care unit that required mechanical ventilation were included. RESULTS: A total of 175 patients were enrolled, of which 71 (40.6%) developed at least one secondary respiratory infection during follow-up. Early and late secondary infections were diagnosed in 1.7% and 31.4% respectively. Within late secondary infections, 88% were bacterial, 10% were fungal, and 2% were of viral origin. One-third of isolated bacteria were multidrug-resistant. Bivariate analysis showed that the history of corticosteroids used before admission and the use of dexamethasone during hospitalization were associated with a higher risk of secondary infections (p = 0.041 and p = 0.019 respectively). Multivariate analysis showed that for each additional day of mechanical ventilation, the risk of secondary infection increases 1.1 times (adOR = 1.07; 95% CI 1.02-1.13, p = 0.008) CONCLUSIONS: Patients with COVID-19 admitted to the intensive care unit and requiring mechanical ventilation had a high rate of secondary infections during their hospital stay. The number of days on MV was a risk factor for acquiring secondary respiratory infections.

Measles Virus Infects and Programs MAIT Cells for Apoptosis.

Measles virus (MeV) binds, infects, and kills CD150+ memory T cells, leading to immune amnesia. Whether MeV targets innate, memory-like T cells is unknown. We demonstrate that human peripheral blood and hepatic mucosa-associated invariant T (MAIT) cells and invariant natural killer T cells express surprisingly high levels of CD150, more than other lymphocyte subsets. Furthermore, exposing MAIT cells to MeV results in their efficient infection and rapid apoptosis. This constitutes the first report of direct MAIT cell infection by a viral pathogen. Given MAIT cells' antimicrobial properties, their elimination by MeV may contribute to measles-induced immunosuppression and heightened vulnerability to unrelated infections.

Risk Factors and Outcomes of Hospitalized Patients With Severe Coronavirus Disease 2019 (COVID-19) and Secondary Bloodstream Infections: A Multicenter Case-Control Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global pandemic. Clinical characteristics regarding secondary infections in patients with COVID-19 have been reported, but detailed microbiology, risk factors, and outcomes of secondary bloodstream infections (sBSIs) in patients with severe COVID-19 have not been well described. METHODS: We performed a multicenter case-control study including all hospitalized patients diagnosed with severe COVID-19 and blood cultures drawn from 1 March 2020 to 7 May 2020 at 3 academic medical centers in New Jersey. Data collection included demographics, clinical and microbiologic variables, and patient outcomes. Risk factors and outcomes were compared between cases (sBSI) and controls (no sBSI). RESULTS: A total of 375 hospitalized patients were included. There were 128 sBSIs during the hospitalization. For the first set of positive blood cultures, 117 (91.4%) were bacterial and 7 (5.5%) were fungal. Those with sBSI were more likely to have altered mental status, lower mean percentage oxygen saturation on room air, have septic shock, and be admitted to the intensive care unit compared with controls. In-hospital mortality was higher in those with an sBSI versus controls (53.1% vs 32.8%, P = .0001). CONCLUSIONS: We observed that hospitalized adult patients with severe COVID-19 and sBSI had a more severe initial presentation, prolonged hospital course, and worse clinical outcomes. To maintain antimicrobial stewardship principles, further prospective studies are necessary to better characterize risk factors and prediction modeling to better understand when to suspect and empirically treat for sBSIs in severe COVID-19.

COVID-19 and risk of subsequent life-threatening secondary infections: a matched cohort study in UK Biobank.

BACKGROUND: With the increasing number of people infected with and recovered from coronavirus disease 2019 (COVID-19), the extent of major health consequences of COVID-19 is unclear, including risks of severe secondary infections. METHODS: Based on 445,845 UK Biobank participants registered in England, we conducted a matched cohort study where 5151 individuals with a positive test result or hospitalized with a diagnosis of COVID-19 were included in the exposed group. We then randomly selected up to 10 matched individuals without COVID-19 diagnosis for each exposed individual (n = 51,402). The life-threatening secondary infections were defined as diagnoses of severe secondary infections with high mortality rates (i.e., sepsis, endocarditis, and central nervous system infections) from the UK Biobank inpatient hospital data, or deaths from these infections from mortality data. The follow-up period was limited to 3 months after the initial COVID-19 diagnosis. Using a similar study design, we additionally constructed a matched cohort where exposed individuals were diagnosed with seasonal influenza from either inpatient hospital or primary care data between 2010 and 2019 (6169 exposed and 61,555 unexposed individuals). After controlling for multiple confounders, Cox models were used to estimate hazard ratios (HRs) of life-threatening secondary infections after COVID-19 or seasonal influenza. RESULTS: In the matched cohort for COVID-19, 50.22% of participants were male, and the median age at the index date was 66 years. During a median follow-up of 12.71 weeks, the incidence rate of life-threatening secondary infections was 2.23 (123/55.15) and 0.25 (151/600.55) per 1000 person-weeks for all patients with COVID-19 and their matched individuals, respectively, which corresponded to a fully adjusted HR of 8.19 (95% confidence interval [CI] 6.33-10.59). The corresponding HR of life-threatening secondary infections among all patients with seasonal influenza diagnosis was 4.50, 95% CI 3.34-6.08 (p for difference < 0.01). Also, elevated HRs were observed among hospitalized individuals for life-threatening secondary infections following hospital discharge, both in the COVID-19 (HR = 6.28 [95% CI 4.05-9.75]) and seasonal influenza (6.01 [95% CI 3.53-10.26], p for difference = 0.902) cohorts. CONCLUSION: COVID-19 patients have increased subsequent risks of life-threatening secondary infections, to an equal extent or beyond risk elevations observed for patients with seasonal influenza.

Modelling Immune Memory Development.

The cellular adaptive immune response to influenza has been analyzed through several recent mathematical models. In particular, Zarnitsyna et al. (Front Immunol 7:1-9, 2016) show how central memory CD8+ T cells reach a plateau after repeated infections, and analyze their role in the immune response to further challenges. In this paper, we further investigate the theoretical features of that model by extracting from the infection dynamics a discrete map that describes the build-up of memory cells. Furthermore, we show how the model by Zarnitsyna et al. (Front Immunol 7:1-9, 2016) can be viewed as a fast-scale approximation of a model allowing for recruitment of target epithelial cells. Finally, we analyze which components of the model are essential to understand the progressive build-up of immune memory. This is performed through the analysis of simplified versions of the model that include some components only of immune response. The analysis performed may also provide a theoretical framework for understanding the conditions under which two-dose vaccination strategies can be helpful.

RLIM: a recursive and latent infection model for the prediction of US COVID-19 infections and turning points.

Initially found in Hubei, Wuhan, and identified as a novel virus of the coronavirus family by the WHO, COVID-19 has spread worldwide at exponential speed, causing millions of deaths and public fear. Currently, the USA, India, Brazil, and other parts of the world are experiencing a secondary wave of COVID-19. However, the medical, mathematical, and pharmaceutical aspects of its transmission, incubation, and recovery processes are still unclear. The classical susceptible-infected-recovered model has limitations in describing the dynamic behavior of COVID-19. Hence, it is necessary to introduce a recursive, latent model to predict the number of future COVID-19 infection cases in the USA. In this article, a dynamic recursive and latent infection model (RLIM) based on the classical SEIR model is proposed to predict the number of COVID-19 infections. Given COVID-19 infection and recovery data for a certain period, the RLIM is able to fit current values and produce an optimal set of parameters with a minimum error rate according to actual reported numbers. With these optimal parameters assigned, the RLIM model then becomes able to produce predictions of infection numbers within a certain period. To locate the turning point of COVID-19 transmission, an initial value for the secondary infection rate is given to the RLIM algorithm for calculation. RLIM will then calculate the secondary infection rates of a continuous time series with an iterative search strategy to speed up the convergence of the prediction outcomes and minimize the maximum square errors. Compared with other forecast algorithms, RLIM is able to adapt the COVID-19 infection curve faster and more accurately and, more importantly, provides a way to identify the turning point in virus transmission by searching for the equilibrium between recoveries and new infections. Simulations of four US states show that with the secondary infection rate ω initially set to 0.5 within the selected latent period of 14 days, RLIM is able to minimize this value at 0.07 and reach an equilibrium condition. A successful forecast is generated using New York state's COVID-19 transmission, in which a turning point is predicted to emerge on January 31, 2021. Supplementary Information: The online version contains supplementary material available at 10.1007/s11071-021-06520-1.

Monocytic HLA-DR expression kinetics in septic shock patients with different pathogens, sites of infection and adverse outcomes.

BACKGROUND: Decreased monocytic (m)HLA-DR expression is the most studied biomarker of sepsis-induced immunosuppression. To date, little is known about the relationship between sepsis characteristics, such as the site of infection, causative pathogen, or severity of disease, and mHLA-DR expression kinetics. METHODS: We evaluated mHLA-DR expression kinetics in 241 septic shock patients with different primary sites of infection and pathogens. Furthermore, we used unsupervised clustering analysis to identify mHLA-DR trajectories and evaluated their association with outcome parameters. RESULTS: No differences in mHLA-DR expression kinetics were found between groups of patients with different sites of infection (abdominal vs. respiratory, p = 0.13; abdominal vs. urinary tract, p = 0.53) and between pathogen categories (Gram-positive vs. Gram-negative, p = 0.54; Gram-positive vs. negative cultures, p = 0.84). The mHLA-DR expression kinetics differed between survivors and non-survivors (p < 0.001), with an increase over time in survivors only. Furthermore, we identified three mHLA-DR trajectories ('early improvers', 'delayed or non-improvers' and 'decliners'). The probability for adverse outcome (secondary infection or death) was higher in the delayed or non-improvers and decliners vs. the early improvers (delayed or non-improvers log-rank p = 0.03, adjusted hazard ratio 2.0 [95% CI 1.0-4.0], p = 0.057 and decliners log-rank p = 0.01, adjusted hazard ratio 2.8 [95% CI 1.1-7.1], p = 0.03). CONCLUSION: Sites of primary infection or causative pathogens are not associated with mHLA-DR expression kinetics in septic shock patients. However, patients showing delayed or no improvement in or a declining mHLA-DR expression have a higher risk for adverse outcome compared with patients exhibiting a swift increase in mHLA-DR expression. Our study signifies that changes in mHLA-DR expression over time, and not absolute values or static measurements, are of clinical importance in septic shock patients.

Treatment with broadly neutralizing influenza antibodies reduces severity of secondary pneumococcal pneumonia in mice.

Secondary bacterial pneumonia is a frequent complication of influenza, associated with high morbidity and mortality. We hypothesized that treatment with neutralizing influenza A antibody AT10_002 protects against severe secondary pneumococcal infection in a mouse model of influenza A infection. Influenza A (H3N2) virus-infected male C57Bl6 mice were treated intravenously with either AT10_002 or a control 2 days postinfection. Seven days later, both groups were infected with Streptococcus pneumoniae and killed 18 hours later. Mice receiving AT10_002 showed less loss of bodyweight compared with controls (+1% vs -12%, P < .001), lower viral loads in bronchoalveolar lavage fluids (BALFs) (7 vs 194 RNA copies per µL; P < .001), and reduced bacterial outgrowth in lung homogenates (3.3 × 101 vs 2.5 × 105 colony-forming units per mg; P < .001). The treatment group showed lower pulmonary wet weights, lower cell counts, and lower protein levels in BALF compared with controls. Treatment with AT10_002 was associated with lower levels of tumor necrosis factor-α, interleukin (IL)-6, cytokine-induced neutrophil chemoattractant (KC), and interferon-γ in BALF and lower IL-6 and KC in lung homogenates. Treatment with anti-influenza antibody AT10_002 is associated with reduced weight loss, viral load, bacterial outgrowth, and lung injury in a murine model of secondary pneumococcal pneumonia following influenza infection.

Respiratory Bordetella bronchiseptica Carriage is Associated with Broad Phenotypic Alterations of Peripheral CD4⁺CD25⁺ T Cells and Differentially Affects Immune Responses to Secondary Non-Infectious and Infectious Stimuli in Mice.

The respiratory tract is constantly exposed to the environment and displays a favorable niche for colonizing microorganisms. However, the effects of respiratory bacterial carriage on the immune system and its implications for secondary responses remain largely unclear. We have employed respiratory carriage with Bordetella bronchiseptica as the underlying model to comprehensively address effects on subsequent immune responses. Carriage was associated with the stimulation of Bordetella-specific CD4⁺, CD8⁺, and CD4⁺CD25⁺Foxp3⁺ T cell responses, and broad transcriptional activation was observed in CD4⁺CD25⁺ T cells. Importantly, transfer of leukocytes from carriers to acutely B. bronchiseptica infected mice, resulted in a significantly increased bacterial burden in the recipient's upper respiratory tract. In contrast, we found that respiratory B. bronchiseptica carriage resulted in a significant benefit for the host in systemic infection with Listeria monocytogenes. Adaptive responses to vaccination and influenza A virus infection, were unaffected by B. bronchiseptica carriage. These data showed that there were significant immune modulatory processes triggered by B. bronchiseptica carriage, that differentially affect subsequent immune responses. Therefore, our results demonstrated the complexity of immune regulation induced by respiratory bacterial carriage, which can be beneficial or detrimental to the host, depending on the pathogen and the considered compartment.

Secondary Infections with Ebola Virus in Rural Communities, Liberia and Guinea, 2014-2015.

Persons who died of Ebola virus disease at home in rural communities in Liberia and Guinea resulted in more secondary infections than persons admitted to Ebola treatment units. Intensified monitoring of contacts of persons who died of this disease in the community is an evidence-based approach to reduce virus transmission in rural communities.

Secondary dengue virus infections during the 2009 outbreak in Buenos Aires.

OBJECTIVES: To evaluate the occurrence of secondary dengue virus (DENV) infections during the 2009 outbreak in a non-endemic area. Viral loads were evaluated in serum from acute-phase patients, comparing primary and secondary infection. METHODS: Serum samples from patients with clinical diagnosis of suspected dengue were referred to the Virology Laboratory at 'Ricardo Gutiérrez' Children's Hospital. Dengue-positive samples were classified as primary or secondary DENV infections through serological methods (anti-DENV IgM and IgG). Viral loads were measured by quantitative real-time PCR (qRT-PCR) in samples obtained in the first 5 days of infection. Statistical analyses were performed to evaluate factors that might correlate with differences in the viral load of primary or secondary infection. RESULTS: A total of 229 DENV cases were confirmed; among them, 22.7% were secondary infections. No significant differences were found between the viral load of primary and secondary infections. CONCLUSION: We detected a high percentage of secondary DENV infections in a non-endemic area; this finding might correspond to socio-demographic characteristics of the group under study or indicate a previous cryptic DENV circulation causing inapparent infections.

Deltamethrin increased susceptibility to Aeromonas hydrophila in crucian carp through compromising gill barrier.

Pyrethroids serve as a significant method for managing and preventing parasitic diseases in fish. Among these, deltamethrin (DEL) is used extensively in aquatic environments. Our previous work has been confirmed that DEL exposure can induce oxidative stress and immunosuppression on the gill mucosal barrier of crucian carp (Carassius auratus). However, it is not clear whether DEL affects the susceptibility of farmed fish to bacterial infection. In this study, fish was pre-exposed to different DEL concentration (0, 0.3 and 0.6 µg L-1) and then challenged by immersion with Aeromonas hydrophila (1.0 × 10^8 CFU mL-1). After immersion challenge, fish pre-exposed to DEL developed prominent lipopolysaccharides level in gill and serum and had a significantly lower survival rate compared to the control group. In DEL pre-exposure fish after immersion, the gill apoptosis levels were significantly higher and disrupted the tight junction barrier by downregulating the zo1 and claudin12. Furthermore, fish pre-exposed to DEL exhibited increased activities of superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and malonaldehyde (MDA) levels in the early stage after immersion but experiencing decreased activities of glutathione peroxidase (GPx) and lysozyme (LZM) in the later stage after immersion. And this process was regulated by the NRF2 pathway. Additionally, fish pre-exposed to DEL after immersion had significantly lower mRNA levels of immune-related genes tlr4, myd88, tnfα, and il-1ß. Overall, these findings indicate that DEL damaged the gill barrier, weakened the immune response, raised LPS levels, and heightened vulnerability to A. hydrophila infection in crucian carp, resulting in mortality. Thus, this work will help social groups and aquaculture workers to understand the potential risk of DEL exposure for bacterial secondary infection in cultured fish.

Prevalence, risk factors, and outcomes of secondary infections among hospitalized patients with COVID-19 or post-COVID-19 conditions in Victoria, 2020-2023.

OBJECTIVES: Estimates of secondary infections are variedly reported, with few studies done in Australia. We investigated the occurrence and impact of secondary infections complicating COVID-19 and post-COVID-19 admissions in Victoria, Australia, 2020-2023. METHODS: We used linked population-wide data sets and specific International Classification of Disease, 10th Revision codes to identify and estimate the occurrence of secondary infections. Using hospital/intensive care unit length of stay in negative binomial regression and mortality, we examined the impact of secondary infections. RESULTS: Secondary infections were identified in 6.9% (13,467 of 194,660) of COVID-19 and post-COVID-19 admissions: 6.0% (11,651 of 194,660) bacterial, 0.9% (1691 of 194,660) viral, and 0.2% (385 of 194,660) fungal. Prevalence was highest during the pre-Delta (10.4%) and Omicron-BA2 (8.1%) periods. Sepsis and pneumonia were the most reported syndromes; the occurrence of sepsis declined gradually over time. The odds of secondary infections were higher among the ≥70-year-olds (adjusted odds ratio (aOR) 3.76, 95% confidence interval [CI] 3.43-4.14, vs 20-29-year-olds), individuals with chronic conditions (aOR 3.15, 95% CI 2.88-3.45, vs those without), the unvaccinated (aOR 1.59, 95% CI 1.45-1.75), and the lowest socioeconomic group (aOR 1.12, 95% CI 1.05-1.19). Patients with secondary infections had 2.43 times longer hospital length of stay and 9.60 times longer intensive care unit length of stay than those without secondary infections. The mortality risk was 2.17 times higher in those with secondary infections. CONCLUSIONS: Secondary infections occurred in 69 per 1000 COVID-19-associated hospital admissions in Victoria, mostly in high-risk groups, and were associated with severe outcomes.

Secondary infections in COVID-19: Antemortem and postmortem culture study.

Background: Secondary bacterial infections during COVID-19 hospitalization have been reported in about 6-15% of patients. Aims: To study the secondary bacterial infections that affected the COVID-19 patients during their hospitalisation and to unearth the bacteriological profile of samples obtained after their demise. Settings and Design: This prospective study was carried out at a COVID-19 dedicated, apex tertiary care centre in North India from July 2020 to April 2021. Methods and Materials: Samples of 268 patients were considered for the study. Nasopharyngeal swab specimen, blood, and tissue (lung) were collected from the deceased body as early as possible and processed. Statistical Analysis: Statistical analyses were performed using STATA version 11.1 (Stata Corp., College Station, TX, USA). Results: A total of 170 samples were received from patients before their death, which included blood, urine, respiratory samples, pus, and cerebrospinal fluid. Forty-four pathogens were isolated, which consisted of Acinetobacter baumannii (43.1%), Klebsiella pneumoniae (36.3%), Escherichia coli (11.3%), and Pseudomonas aeruginosa (4.5%), Enterococcus faecium (4.5%). Two hundred fifty-eight samples were collected from the deceased bodies wherein the nasopharyngeal sample was highest, followed by tissue and blood. A total of 43 pathogens were isolated among them which included A. baumannii (44.1%), followed by K. pneumoniae (25.5%), E. coli (20.9%), P. aeruginosa (6.97%) and Enterobacter cloacae (2.3%). All these isolates were highly resistant to antimicrobials. Conclusions: In our study, bacterial profiles in antemortem and postmortem samples were found to be similar, suggesting that resistant pathogens may be the cause of mortality in COVID-19 infected hospitalised patients.

Bacterial co-infections in cancer patients with COVID-19: predictors and antimicrobial resistance trends.

INTRODUCTION: Within the context of the coronavirus disease 2019 (COVID-19) pandemic, this study investigated the multifaceted challenges of bacterial infections in cancer patients with COVID-19. It focuses on clinical predictors, resistance patterns, and microbiological characteristics. METHODOLOGY: Over 18 months, 112 adult cancer patients with coronavirus infection confirmed by reverse transcription polymerase chain reaction (RT-PCR) were enrolled. Bloodstream and respiratory samples were evaluated for bacterial infection using the Phoenix automation system for definitive species identification. In vitro susceptibility testing followed the Clinical Laboratory Standards Institute (CLSI) M100-Ed30 guidelines. RESULTS: Bacterial infections affected 25.0% of patients, encompassing bacteremia (21.4%) and respiratory tract infections (8.0%). Multivariable analysis identified hypertension, age < 60, and critical COVID-19 as significant predictors for bacterial infections (p-values = 0.024, 0.029, and 0.039, respectively). Most patients received antimicrobial therapy (93.8%), including last-resort carbapenems (52.7%) and colistin (8.9%). Thirty-three bacterial isolates were identified, with secondary infections doubling co-infection rates. Escherichia coli, Klebsiella species, and Staphylococcus aureus were the most common co-infecting species, while Klebsiella, Acinetobacter, and Pseudomonas species were more frequently associated with secondary infections. Alarmingly, 84.8% of isolates displayed high resistance patterns. All isolated S. aureus species were methicillin-resistant, and 62.5% of Gram-negative bacteria were exclusively sensitive to colistin. CONCLUSIONS: The dominance of highly transmissible hospital-acquired bacterial species, with increased resistance and extensive antibiotic use in COVID-19 patients, necessitates strict infection control and antimicrobial stewardship. Developing customized antimicrobial strategies for cancer patients with COVID-19 is crucial to managing bacterial infections effectively and improving patient outcomes.

Safety of Proton Pump Inhibitors in Pediatric Population: A Systematic Review.

Objective. Commonly recommended drugs for adults and children include proton pump inhibitors (PPIs), proven effective for treating peptic diseases like stomach ulcers, GERD, and Helicobacter pylori infections in children over 1-year-old. Yet, prolonged PPI use carries higher risks of adverse reactions, prompting this study's analysis. Methods. We have performed a systematic review of 30 articles, which include a total of 762 505 pediatric patients. Results. Adverse effects were encountered in 6.98% of the population. The 5 most common adverse effects were respiratory tract complications, gastrointestinal complications, urinary tract infections, asthma, and ENT infections. Conclusion. Hence, PPIs should be prescribed only when necessary, and physicians should prioritize patient education when considering their use.

Investigating dynamics, etiology, pathology, and therapeutic interventions of Caligus clemensi and Vibrio alginolyticus co-infection in farmed marine fish.

This study investigated a disease outbreak characterized by caligid copepod infestations and subsequent secondary bacterial infections in European seabass (Dicentrarchus labrax) and flathead grey mullet (Mugil cephalus) cultivated at a private facility in the Deeba Triangle region of Egypt. Moribund fish displayed brown spots on the skin, tongue, and gills, along with lethargy and excess mucus. The fish suffered severe infections, exhibiting external hemorrhages, ulcers, and ascites. The fish had pale, enlarged livers with hemorrhaging. Comprehensive parasitological, bacteriological, molecular, immunity and histopathological analyses were conducted to identify the etiological agents and pathological changes. Caligid copepod infestation was observed in wet mounts from the buccal and branchial cavities of all examined fish, and the caligids were identified as Caligus clemensi through COI gene sequencing and phylogenetic analysis. Vibrio alginolyticus was confirmed as a secondary bacterial infection through biochemical tests, recA gene sequencing, and phylogenetic analyses. Antibiotic susceptibility testing revealed resistance to ß-lactams, aminoglycosides, and trimethoprim-sulfamethoxazole in V. alginolyticus isolates. Upregulation of the inflammatory marker IL-1ß in gill and skin tissues indicated a robust cell-mediated immune response against the pathogens. Histopathological examination revealed severe tissue damage, hyperplasia, hemorrhage, and congestion in the gills, along with hepatocellular degeneration and steatosis in the liver, providing initial insights into this outbreak. A comprehensive therapeutic regimen was implemented, comprising prolonged hydrogen peroxide immersion baths, followed by the application of the nature-identical plant-based compound Lice-less and probiotic Sanolife Pro-W supplementation. This integrated approach effectively eliminated C. clemensi infestations, controlled secondary bacterial infections, and restored fish health, reducing morbidity and mortality rates to minimal levels.