IL-33 regulates age-dependency of long-term immune dysfunction induced by sepsis

Sepsis survival in adults is commonly followed by immunosuppression and increased susceptibility to secondary infections. However, the long-term immune consequences of pediatric sepsis are unknown. Here, we compared the frequency of Tregs, the activation of the IL-33/ILC2s axis in M2 macrophages, and the DNA methylation of epithelial lung cells from post-septic infant and adult mice. In contrast to adults, infant mice were resistant to secondary infection and did not show impairment in tumour controls upon melanoma challenge. Mechanistically, increased IL-33 levels, Tregs expansion, and activation of ILC2s and M2-macrophages were observed in post-septic adults but not infant mice. Impaired IL-33 production in post-septic infant mice was associated with increased DNA-methylation on lung epithelial cells. Notably, IL-33 treatment boosted the expansion of Tregs and induced immunosuppression in infant mice. Clinically, adults but not pediatric post-septic patients exhibited higher counts of Tregs and sera IL-33 levels. Hence, we describe a crucial and age-dependent role for IL-33 in post-sepsis immunosuppression.

Limb Salvage through Intermediary Wound Coverage with Acellular Dermal Matrix Template after Persistent Pseudomonas Aeruginosa Infection in a Burn Patient

Secondary infections of skin grafts pose a continuous problem in burn patients, very often leading to loss of transplanted skin grafts and making multiple surgical revisions necessary. We present a case report about persisting Pseudomonas aeruginosa infection in burn patients with known diabetes. The burn wounds in lower extremities required repeated debridements, multiple skin grafting attempts and finally an application of the dermal scaffold NovoSorb BTM. With these measures, we managed to undertake a successful reconstruction of infected burn defects and pre-vent an amputation. We concluded that the NovoSorb BTM could be seen as an additional promising tool in a burn surgery armamentarium. In cases where radical surgical wound decontamination is not possible without risking the loss of the limb, the application of NovoSorb BTM over a contaminated field can win extra time for topical infection treatment and additionally provide an excellent skin grafting ground.

Effect of Caring of Critically Sick Patients with COVID-19 Pneumonia at Undesignated ICU Wards on Secondary Infections

<b><i>Introduction:</i></b> COVID-19 has caused high rates of mortality. During pandemic peak, a significant number of patients were admitted to undesignated ICU areas before transferring to designated ICU, owing to unavailability of ICU beds. We aimed to record the effect of care of critically sick patients with COVID-19 on prevalence of secondary bacterial infection. <b><i>Methods:</i></b> We retrospectively studied all critically ill patients with COVID-19 pneumonia meeting ICU admission criteria who were admitted to Dubai hospital between January 1, 2020, and June 30, 2020. All the patients who transferred to wards other than designated ICU constitute category as cases. All patients who directly admitted to the designated ICU ward from emergency department constitute controls. The demographics, clinical parameters, and treatment profile of these patients were recorded and compared. Prevalence of secondary bacterial infection was calculated. <b><i>Results:</i></b> Patients with COVID-19 had high prevalence of secondary bacterial infection. Patients who stayed at undesignated ICU wards had higher occurrence of inpatient fever, hypoxemia, and they were more likely to be sedated and paralyzed than patients who stayed in designated ICU wards. Multiple logistic regression analysis showed care outside designated ICU ward does not predict increase in secondary nonviral microbial infections. <b><i>Conclusion:</i></b> Care of patients at undesignated ICU wards prior to admission to designated ICU does not impact prevalence of secondary bacterial infection.

An Update on Secondary Bacterial and Fungal Infections and Their Antimicrobial Resistance Pattern (AMR) in COVID-19 Confirmed Patients at a Tertiary Care Hospital

Introduction Since coronavirus disease 2019 (COVID-19) has limited treatment options, concern has been raised over secondary infections and antimicrobial resistance (AMR) patterns. It has been observed that patients who were infected with COVID-19 were predisposed to develop secondary infections. The purpose of the study is to ascertain the prevalence of the bacterial and fungal coinfections in COVID-19 patients, and also to assess the AMR patterns in the obtained isolates. Methods We have studied 200 clinical samples obtained from 122 COVID-19 positive patients. Pathogens were identified using Vitek 2 system. The demographic and clinical patterns were also observed. Results A total of 122 patients developed secondary infections. Patients aged more than 40 years were majorly affected (p-value < 0.0001). Respiratory samples (n = 96) were predominant. Klebsiella pneumoniae (n = 68) was the most common pathogen isolated followed by Acinetobacter baumannii (n = 54) and an overall 6% rise in the Carbapenem resistance was observed in the isolates. Conclusion To contain the secondary infections in COVID-19 patients, it is imperative to adhere to antimicrobial stewardship program and timely revise the empirical antibiotic policy.

SARS-CoV-2 Omicron VOC Transmission in Danish Households

The Omicron variant of concern (VOC) is a rapidly spreading variant of SARS-CoV-2 that is likely to overtake the previously dominant Delta VOC in many countries by the end of 2021. We estimated the transmission dynamics following the spread of Omicron VOC within Danish households during December 2021. We used data from Danish registers to estimate the household secondary attack rate (SAR). Among 11,937 households (2,225 with the Omicron VOC), we identified 6,397 secondary infections during a 1-7 day follow-up period. The SAR was 31\% and 21\% in households with the Omicron and Delta VOC, respectively. We found an increased transmission for unvaccinated individuals, and a reduced transmission for booster-vaccinated individuals, compared to fully vaccinated individuals. Comparing households infected with the Omicron to Delta VOC, we found an 1.17 (95\%-CI: 0.99-1.38) times higher SAR for unvaccinated, 2.61 times (95\%-CI: 2.34-2.90) higher for fully vaccinated and 3.66 (95\%-CI: 2.65-5.05) times higher for booster-vaccinated individuals, demonstrating strong evidence of immune evasiveness of the Omicron VOC. Our findings confirm that the rapid spread of the Omicron VOC primarily can be ascribed to the immune evasiveness rather than an inherent increase in the basic transmissibility.

Sirtuins and Sepsis: Cross Talk between Redox and Epigenetic Pathways

Sepsis and septic shock are the leading causes of death among hospitalized patients in the US. The immune response in sepsis transitions from a pro-inflammatory and pro-oxidant hyper-inflammation to an anti-inflammatory and cytoprotective hypo-inflammatory phase. While 1/3rd sepsis-related deaths occur during hyper-, a vast majority of sepsis-mortality occurs during the hypo-inflammation. Hyper-inflammation is cytotoxic for the immune cells and cannot be sustained. As a compensatory mechanism, the immune cells transition from cytotoxic hyper-inflammation to a cytoprotective hypo-inflammation with anti-inflammatory/immunosuppressive phase. However, the hypo-inflammation is associated with an inability to clear invading pathogens, leaving the host susceptible to secondary infections. Thus, the maladaptive immune response leads to a marked departure from homeostasis during sepsis-phases. The transition from hyper- to hypo-inflammation occurs via epigenetic programming. Sirtuins, a highly conserved family of histone deacetylators and guardians of homeostasis, are integral to the epigenetic programming in sepsis. Through their anti-inflammatory and anti-oxidant properties, the sirtuins modulate the immune response in sepsis. We review the role of sirtuins in orchestrating the interplay between the oxidative stress and epigenetic programming during sepsis.

Promising Expectations for Pneumococcal Vaccination during COVID-19

The emergence of new viral infections has increased over the decades. The novel virus is one such pathogen liable for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, popularly known as coronavirus disease 2019 (COVID-19). Most fatalities during the past century’s influenza pandemics have cooperated with bacterial co/secondary infections. Unfortunately, many reports have claimed that bacterial co-infection is also predominant in COVID-19 patients (COVID-19 associated co/secondary infection prevalence is up to 45.0%). In the COVID-19 pandemic, Streptococcus pneumoniae is the most common coinfecting pathogen. Half of the COVID-19 mortality cases showed co-infection, and pneumonia-related COVID-19 mortality in patients >65 years was 23%. The weakening of immune function caused by COVID-19 remains a high-risk factor for pneumococcal disease. Pneumococcal disease and COVID-19 also have similar risk factors. For example, underlying medical conditions on COVID-19 and pneumococcal diseases increase the risk for severe illness at any age; COVID-19 is now considered a primary risk factor for pneumococcal pneumonia and invasive pneumococcal disease. Thus, pneumococcal vaccination during the COVID-19 pandemic has become more critical than ever. This review presents positive studies of pneumococcal vaccination in patients with COVID-19 and other medical conditions and the correlational effects of pneumococcal disease with COVID-19 to prevent morbidity and mortality from co/secondary infections and superinfections. It also reports the importance and role of pneumococcal vaccination during the current COVID-19 pandemic era to strengthen the global health system.

New insights on mucormycosis and its association with the COVID-19 pandemic

COVID-19 continues to cause significant fatality worldwide. Glucocorticoids prove to play essential roles in COVID-19 management; however, the extensive use of steroids together with the virus immune dysregulation may increase the danger of secondary infections with mucormycosis, an angioinvasive fungal infection. Unfortunately, a definite correlation between COVID-19 and elevated mucormycosis infection cases is now clear worldwide. In this review, we discuss the historical record and epidemiology of mucormycosis as well as pathogenesis and associated host immune response, risk factors, clinical presentation, diagnosis and treatment. Special emphasis is given to its association with the current COVID-19 pandemic, including latest updates on COVID-19-associated mucormycosis cases globally, with recommendations for efficacious management.

Mucormycosis in Post COVID-19 Patients: A Case Study

Introduction: Acute respiratory distress syndrome (ARDS) is a common complication of severe pneumonia virus, such as the flu and COVID-19, which requires critical treatment, including asthma support, corticosteroids, and other treatments to prevent acute respiratory tract inflammation. Although steroid treatment is limited to the treatment of viral pneumonia, it is usually a double-edged sword, leading to increased morbidity and mortality. Mucormycosis is a fungal emergency with a high tendency for contaguous spread and a poor prognosis if not detected and treated promptly. Mucormycosis is believed to be caused by uncontrolled diabetes mellitus (DM) and other immunosuppressive disorders, such as corticosteroid therapy. Aim: To discuss causality factor of mucormycosis in COVID-19 infection. Conclusion: COVID-19 is correlated with a high rate of secondary infections, both bacterial and fungal, most likely as a result of immune dysregulation. Furthermore, the widespread use of steroids and broad-spectrum antibiotics as part of the COVID-19 remedy can result in the production or exacerbation of pre-existing fungal diseases. Physicians should be mindful of the likelihood of invasive secondary fungal infections in patients with COVID-19 infection, especially in those that have pre-existing risk factors, and should be able to detect and treat these infections early in order to reducing mortality and morbidity.