Increased Severity Of Infection Research Articles

Influence of sexual hormones on Chagas disease.

Analyze sex hormone's influence during Chagas´ Disease. Male and female BALB/c mice were divided into six groups, four experimental (sham, orchiectomized, orchiectomized and supplemented with estradiol, orchiectomized supplemented with testosterone, oophorectomized, oophorectomized and supplemented with estradiol, and oophorectomized and supplemented with testosterone), and two control (healthy and intraperitoneally with T. cruzi strain NINOA infected). Clinical data were recorded daily, parasitemia was evaluated using a Neubauer chamber during the infection, and heart histopathological analysis was performed using the paraffin embedding technique. To analyze parasitemia curves and the area under the parametric curves, two-way ANOVA test was performed to correlate groups´ data. P-values <0.05 were considered statistically significant. Higher mortality rates, cardiomegaly, hepatomegaly, ascites, edema, higher parasitemia levels, more amastigote nests, and more severe inflammatory infiltrate were found in higher testosterone concentration mice, whereas in higher estradiol concentration groups, paresia, prostration, edema, and necrosis were found. Our results showed that testosterone increased infection severity, whereas estradiol had the opposite effect. This research improves the understanding of sex hormones´infuence upon this infection to contribute with the handling of Chagas´disease.

Elevated herpesvirus antibody levels linked to schizophrenia and bipolar disorder

IntroductionPrevious research has implicated herpes simplex virus 1 (HSV1) and cytomegalovirus (CMV) in severe mental illness (SMI) with conflicting results. Both pathogens have high universal seroprevalence, are neurotropic and after the primary infection typically establish a persistent latent infection with periodic reactivations. Increased immunoglobin G (IgG) concentrations are considered to be attributable to an increased infection severity with more frequent reactivations or host immune system alterations.ObjectivesWe assessed the HSV1 and CMV IgG concentrations in previously infected (seropositive) patients with SMI and healthy controls (HC). We hypothesized that seropositive patients would show higher IgG concentrations than seropositive HC.MethodsWe included 765 patients, 515 with schizophrenia (SZ) and 250 with bipolar disorder (BP), and 541 HC. HSV1 and CMV IgG seropositivity and concentrations were measured with immunoassays. 355 patients, mean age 33 years, 45% females, and 238 HC, mean age 35 years, 44% females, were HSV1 seropositive (HSV1+) while 447 patients, mean age 33 years, 50% females, and 296 HC, mean age 34 years, 47% females, were CMV seropositive (CMV+). In our main analysis among seropositive participants, we investigated the main effect of patient/control status on HSV1 and CMV IgG concentrations.ResultsThere were no significant differences in CMV or HSV1 seropositivity frequencies between patients with SZ, patients with BP and HC. Among seropositive participants, patients had higher HSV1 (p&lt;0.001) and CMV (p=0.018) IgG concentrations than HC; stratifying by diagnosis, both patients with SZ (p=0.001) and patients with BP (p=0.001) had higher HSV1 IgG concentrations than HC, while patients with SZ, but not BP, had higher CMV (p=0.045) IgG concentrations than HC (Image). For HSV1, higher IgG concentrations were associated with higher general (p=0.017), negative (p=0.041) and positive (p=0.028) psychotic symptom scores.Image:ConclusionsSeropositive patients with SMI showed higher HSV1 and CMV IgG concentrations than seropositive HC suggesting that patients suffer a more severe infection or exhibit an altered immune response when contracting the pathogens. For HSV1, higher IgG concentrations were linked to more psychotic symptoms.Disclosure of InterestD. Andreou: None Declared, N. E. Steen: None Declared, K. N. Jørgensen: None Declared, T. Ueland: None Declared, L. Wortinger: None Declared, L. Mørch-Johnsen: None Declared, R. Yolken: None Declared, O. Andreassen Consultant of: Consultant to HealthLytix, Speakers bureau of: Received speaker’s honorarium from Lundbeck and Sunovion, I. Agartz Speakers bureau of: Received speaker’s honorarium from Lundbeck

Understanding the infection severity and epidemiological characteristics of mpox in the UK

In May 2022, individuals infected with the monkeypox virus were detected in the UK without clear travel links to endemic areas. Understanding the clinical characteristics and infection severity of mpox is necessary for effective public health policy. The study period of this paper, from the 1st June 2022 to 30th September 2022, included 3,375 individuals that tested positive for the monkeypox virus. The posterior mean times from infection to hospital admission and length of hospital stay were 14.89 days (95% Credible Intervals (CrI): 13.60, 16.32) and 7.07 days (95% CrI: 6.07, 8.23), respectively. We estimated the modelled Infection Hospitalisation Risk to be 4.13% (95% CrI: 3.04, 5.02), compared to the overall sample Case Hospitalisation Risk (CHR) of 5.10% (95% CrI: 4.38, 5.86). The overall sample CHR was estimated to be 17.86% (95% CrI: 6.06, 33.11) for females and 4.99% (95% CrI: 4.27, 5.75) for males. A notable difference was observed between the CHRs that were estimated for each sex, which may be indicative of increased infection severity in females or a considerably lower infection ascertainment rate. It was estimated that 74.65% (95% CrI: 55.78, 86.85) of infections with the monkeypox virus in the UK were captured over the outbreak.

Disease burden attributable to respiratory syncytial virus outbreaks in long-term care.

Respiratory syncytial virus (RSV) disease burden is significant among children; however, RSV can also cause excess morbidity and mortality among older adults. Populations in long-term care homes (LTCHs) may be at greater risk of exposure and increased infection severity. The objectives of this article are to identify evidence regarding disease burden and outcome severity attributable to RSV outbreaks among residents and staff in LTCHs; and to highlight reported population and outbreak characteristics. All types of evidence were eligible for inclusion. Data utilized by included studies was between the end of the 2010 H1N1 influenza pandemic and the beginning of the coronavirus disease 2019 (COVID-19) pandemic. Evidence from the following countries was considered: G7, the European Union, Australia and New Zealand. A total of 167 articles were identified; 58 full texts were analyzed and four sources of evidence were eligible for inclusion. Data related to population characteristics, outbreak type and resident and staff outcomes were manually charted. There is a paucity of evidence sources pertaining to RSV outbreak burden among residents and staff in LTCHs. Outbreak duration ranged from 13 to 21 days. For each outbreak, 4-7 residents had confirmed RSV infection. Attack rates ranged from 12% to 38%. A spectrum of disease attributable to RSV outbreaks in LTCHs was identified, ranging from mild cold-like symptoms to death. Integration of RSV into existing respiratory pathogen surveillance programs is important to characterize susceptibility, transmissibility and virulence of RSV in at-risk populations. There is a need for public health organizations to publish the findings from outbreak investigations to provide evidence to inform RSV outbreak prevention and response in LTCH settings.

Factors affecting risk of recurrence with periprosthetic infection in shoulder arthroplasty

BackgroundThe goal of treating periprosthetic infection, beside its eradication, is to avoid recurrence. The purpose of this study was to evaluate the impacts of increasing Infection Severity (IS) score (based on the 2018 International Committee on Orthopedic Infection Consensus statement), single-stage revision and the pathogenicity of the infective organism have on the risks of infection recurrence. MethodsA database of 790 revisions performed by a single surgeon from 2004-2020 was reviewed for patients with minimum 2-year follow-up and at least 1 positive culture and/or pathology result from that revision surgery. One hundred fifty-seven cases performed in 144 patients met inclusion criteria. Cases were then categorized by infection probability (IS score) according to the 2018 consensus statement. Forty-six of 157 (29%) cases were classified as definite/probable, 25/157 (16%) were classified as possibly infected, and 86/157 (55%) were classified as unlikely to be infected. Additionally, patients were grouped by single-stage surgery, and pathogenicity of infective organism. ResultsA recurrence in this study was classified as any patient requiring revision surgery that grew the same organism. The 86 cases in the unlikely group had a recurrence rate of 2.3%. The 25 cases in the possibly infected group had a recurrence rate of 12%. The 46 cases in the definite/probable group had a recurrence rate of 17.4%. Patients in the definite/probable group had a higher rate of recurrence than the possible and unlikely groups (p=0.009). The IS score was higher in the recurrence group than the non-recurrence group (7.5±4.3 vs 3.9±3.4; p<0.001). Overall, one-stage revision had a 5.0% recurrence rate, but of the 34 patients with an infection classification of definite/probable who underwent a one-stage revision, the recurrence rate was 5.9%. Highly virulent methicillin-resistant Staphylococcus aureus (MRSA) also had a recurrence rate of 30.8% compared to 4.0% and 5.9% in C. acnes and Coagulase-negative staphylococci, respectively (p=0.005). ConclusionRecurrent infection after treating a periprosthetic infection is associated with increasing severity scores as defined in 2018 consensus statement and more aggressive microorganisms. However, a single-stage surgery, even in patients with a higher IS score, did not impart a significant increased risk of recurrence.

Vaccine-breakthrough SARS-CoV-2 infections in people with multiple sclerosis and related conditions: An observational study by the New York COVID-19 Neuro-Immunology Consortium (NYCNIC-2)

Background: People with MS (PwMS) and related conditions treated with anti-CD20 and S1P modulating therapies exhibit attenuated immune responses to SARS-CoV-2 vaccines. It remains unclear whether humoral/T-cell responses are valid surrogates for postvaccine immunity. Objective: To characterize COVID-19 vaccine-breakthrough infections in this population. Methods: We conducted a prospective multicenter cohort study of PwMS and related CNS autoimmune conditions with confirmed breakthrough infections. Postvaccination antibody response, disease-modifying therapies (DMTs) at the time of vaccination, and DMT at the time of infection were assessed. Results: Two hundred nine patients had 211 breakthrough infections. Use of anti-CD20 agents at time of infection was associated with increased infection severity (p = 0.0474, odds ratio (OR) = 5.923) for infections during the Omicron surge and demonstrated a trend among the total cohort (p = 0.0533). However, neither use of anti-CD20 agents at the time of vaccination nor postvaccination antibody response was associated with hospitalization risk. Anti-CD20 therapies were relatively overrepresented compared to a similar prevaccination-era COVID-19 cohort. Conclusion: Use of anti-CD20 therapies during vaccine breakthrough COVID-19 infection is associated with higher severity. However, the attenuated postvaccination humoral response associated with anti-CD20 therapy use during vaccination may not drive increased infection severity. Further studies are necessary to determine if this attenuated vaccine response may be associated with an increased likelihood of breakthrough infection.

2349. Elucidating the Pathogenesis of Staphylococcus aureus During Hyperglycemic Osteomyelitis

Abstract Background Staphylococcus aureus is a leading cause of antibiotic-resistant bacterial infections and can infect nearly every organ of the human body. One common manifestation of S. aureus disease is invasive bone infection, or osteomyelitis. Osteomyelitis is one of the most difficult to treat infections, often necessitating prolonged antibiotic treatment and surgical interventions. Hyperglycemia, or elevated blood glucose concentration, increases the risk for developing osteomyelitis. We hypothesized that S. aureus adapts specifically to the altered host environment during hyperglycemic osteomyelitis, thereby contributing to the increased infection severity. Methods To model hyperglycemic osteomyelitis, we treated mice with streptozotocin prior to infection with S. aureus in a post-traumatic osteomyelitis model. We analyzed bacterial burdens in homogenized tissues and bone parameters with microcomputed tomography. To identify changes in the spatial molecular architecture of infected, hyperglycemic femurs, we utilized imaging mass spectrometry. Finally, to obtain a comprehensive understanding of S. aureus metabolic and virulence changes and identify genes essential for staphylococcal growth in vivo in hyperglycemic mice, we performed a transposon sequencing experiment. Results We discovered that hyperglycemic mice sustained increased bacterial burdens within infected femurs and greater dissemination to other organs. We also found that hyperglycemic infected mice experienced increased rates of bone destruction and loss of trabecular bone volume, suggesting that hyperglycemia exacerbates infection-associated bone loss. Finally, we identified 71 genes as uniquely essential for S. aureus growth during hyperglycemic infection compared to euglycemic infection. Conclusion Hyperglycemia results in increased osteomyelitis infection severity. Multiple S. aureus genes involved in metabolism with roles in bacterial fitness in acidic environments were uniquely essential for bacterial fitness during comorbid infection. By identifying genes contributing to S. aureus survival during hyperglycemic osteomyelitis, we have the potential to inform targeted therapeutic development for treatment of exacerbated infections in patients with comorbid hyperglycemia. Disclosures All Authors: No reported disclosures.

Impact of white mistletoe (Viscum album ssp. abietis) infection severity on morphology, anatomy and photosynthetic pigment content of the needles of cilicican fir (Abies cilicica)

White mistletoe (Viscum album ssp. abietis, Santalaceae) is a hemi-parasitic plant and is regarded as one of the most significant biotic factors affecting fir forests. Mistletoe affects its host in many ways, including changes in leaf development. This paper studies and quantifies the effect of white mistletoe on morphological, anatomical traits and photosynthetic pigment content of cilicican fir (Abies cilicica (Antoine & Kotschy) Carrière, Pinaceae) needles growing on uninfected branches of infected and uninfected trees in relation to varying mistletoe infection severity. Morphological (needle length and width, area and weight, and specific leaf area), anatomical (needle width and thickness, epidermis and central vein thickness, needle cross sectional and mesophyll area, epidermis plus hypodermis and central vein area, xylem and phloem area, transfusion and resin duct area), stomatal (number of stomata rows, stomatal band width, stomata length and density) traits and photosynthetic pigment content (chlorophyll a and b, total chlorophyll (a+b), total carotenoid) were measured in one-year-old needles growing on uninfected branches from a total of 48 cilicican fir trees. Of the trees, 10 were uninfected, 13 lightly infected, 14 moderately infected and 11 severely infected. The results indicated that morphological dimension of needles decreased steadily with increasing infection severity. Stomatal size of needles decreased gradually while stomatal density increased gradually with increasing infection severity. Reduced anatomical dimension were only evident in needles from moderate and severe infection classes, while chlorophyll content decreased in only severely infected trees.

Essential Fitness Repertoire of Staphylococcus aureus during Co-infection with Acinetobacter baumannii In Vivo.

ABSTRACTStaphylococcus aureus represents a major human pathogen that is frequently involved in polymicrobial infections. However, the prevalence and role of co-infectious microbes on the pathogenesis and fitness essentiality of S. aureus in vivo remain largely unknown. In this study, we firstly performed a retrospective surveillance of 760 clinical samples and revealed a notable predominance of co-infection with S. aureus and Acinetobacter baumannii. The high-density S. aureus transposon mutant library coupled to transposon insertion sequencing (Tn-Seq) further identified a core set of genes enriched in metabolism of inorganic ions, amino acids, and carbohydrates, which are essential for infection and tissue colonization of S. aureus in the murine systemic infection model. Notably, we revealed a differential requirement of fitness factors for S. aureus in tissue-specific (liver and kidney) and infection-type-specific manner (mono- and co-infection). Co-infection with A. baumannii dramatically altered the fitness requirements of S. aureus in vivo; 49% of the mono-infection fitness genes in S. aureus strain Newman were converted to non-essential, and the functionality of ATP-binding cassette (ABC) transporters was significantly elicited during co-infection. Furthermore, the number of genes essential during co-infection (503) outnumbers the genes essential during mono-infection (362). In addition, the roles of 3 infection-type-specific genes in S. aureus during mono-infection or co-infection with A. baumannii were validated with competitive experiments in vivo. Our data indicated a high incidence and clinical relevance of S. aureus and A. baumannii co-infection, and provided novel insights into establishing antimicrobial regimens to control co-infections.IMPORTANCE Polymicrobial infections are widespread in clinical settings, which potentially correlate with increased infection severity and poor clinical outcomes. Staphylococcus aureus is a formidable human pathogen that causes a variety of diseases in polymicrobial nature. Co-infection and interaction of S. aureus have been described with limited pathogens, mainly including Pseudomonas aeruginosa, Candida albicans, and influenza A virus. Thus far, the prevalence and role of co-infectious microbes on the pathogenesis and fitness essentiality of S. aureus in vivo remain largely unknown. Understanding the polymicrobial composition and interaction, from a community and genome-wide perspective, is thus crucial to shed light on S. aureus pathogenesis strategy. Here, our findings demonstrated, for the first time, that a high incidence rate and clinical relevance of co-infection was caused by S. aureus and Acinetobacter baumannii, illustrating the importance of polymicrobial nature in investigating S. aureus pathogenesis. The infection-type-specific genes likely serve as potential therapeutic targets to control S. aureus infections, either in mono- or co-infection situation, providing novel insights into the development of antimicrobial regimens to control co-infections.

Assessment of mortality and hospital admissions associated with confirmed infection with SARS-CoV-2 Alpha variant: a matched cohort and time-to-event analysis, England, October to December 2020.

BackgroundThe emergence of the SARS-CoV-2 Alpha variant in England coincided with a rapid increase in the number of PCR-confirmed COVID-19 cases in areas where the variant was concentrated.AimOur aim was to assess whether infection with Alpha was associated with more severe clinical outcomes than the wild type.MethodsLaboratory-confirmed infections with genomically sequenced SARS-CoV-2 Alpha and wild type between October and December 2020 were linked to routine healthcare and surveillance datasets. We conducted two statistical analyses to compare the risk of hospital admission and death within 28 days of testing between Alpha and wild-type infections: a matched cohort study and an adjusted Cox proportional hazards model. We assessed differences in disease severity by comparing hospital admission and mortality, including length of hospitalisation and time to death.ResultsOf 63,609 COVID-19 cases sequenced in England between October and December 2020, 6,038 had the Alpha variant. In the matched cohort analysis, we matched 2,821 cases with Alpha to 2,821 to cases with wild type. In the time-to-event analysis, we observed a 34% increased risk in hospitalisation associated with Alpha compared with wild type, but no significant difference in the risk of mortality.ConclusionWe found evidence of increased risk of hospitalisation after adjusting for key confounders, suggesting increased infection severity associated with the Alpha variant. Rapid assessments of the relative morbidity in terms of clinical outcomes and mortality associated with emerging SARS-CoV-2 variants compared with dominant variants are required to assess overall impact of SARS-CoV-2 mutations.

Induced Volatile Emissions, Photosynthetic Characteristics, and Pigment Content in Juglans regia Leaves Infected with the Erineum-Forming Mite Aceria erinea

Persian walnut (Juglans regia L., Juglandaceae), one of the essential nut crops, is affected by different diseases, including mite attacks which result in gall and erineum formation. As the proportion of leaf area covered by mite galls or erineum is typically relatively low, the impact on tree photosynthetic productivity is often considered minor, and no pest control management is usually suggested. However, the effect of erineum-forming mites on walnut photosynthesis might be disproportionately larger than can be predicted from the leaf area impacted. In the present study, we studied how the foliage photosynthetic characteristics, pigment contents, and stress-induced volatile organic compounds scaled with the severity of infection varied from 0% (control trees) to 9.9%, by erineum-forming mite Aceria erinea in J. regia. Both leaf net assimilation rate (up to 75% reduction) and stomatal conductance (up to 82%) decreased disproportionately, increasing infection severity. Leaf total chlorophyll and β-carotene contents also decreased with infection severity, although the reduction was less than for photosynthetic characteristics (28% for chlorophyll and 25% for β-carotene). The infection induced significant emissions of green leaves volatiles ((Z)-3-hexenol, (E)-2-hexenal, (Z)-3-hexenyl acetate and 1-hexanol), monoterpenes and the homoterpene 3-(E)-4,8-dimethyl-1,3,7-nonatriene, and these emissions scaled positively with the percentage of leaf area infected. These results collectively indicate that erineum-forming mite infection of walnut leaves results in profound modifications in foliage physiological characteristics that can significantly impact tree photosynthetic productivity.

The Gender Disparity in COVID-19 Case Severity

SARS-CoV-2 has made the world come to a halt, causing unprecedented global protocols and rules being implemented. Many different characteristics of this virus emerged early on. A notable characteristic that was noticed was the disparity in COVID-19 severity between the two biological genders, with males having a significantly higher fatality rate in comparison to females. As studies continue to understand this disparity, this literature review intends to summarize a few of these findings. Research on these studies were found on public research engines like ScienceDirect, Biology Medcentral, and PubMed. Papers were all peer reviewed. Another tool that was used was from the Global Health 50/50 research initiative which provided sex dis-aggregated data on COVID-19 in all countries that had accessible data. Studies have indicated that genetic factors, lifestyle factors, and “other” factors are all reasons for the disparity. T-Cell and ACE2 protein amount difference in males and females have been suggested as possible reasons for the discrepancy. Studies have also suggested that increased COVID-19 viral load also increases infection severity. This is relevant as male attitudes towards COVID-19 public health guidelines are more relaxed compared to females. Other possible factors that could play into this disparity is smoking, with active smokers having increased COVID-19 infection severity. This relates to the fact that the percent of male smokers is much higher than females. These lifestyle factors are further supported by the fact that males have higher fatality rates in respiratory tract diseases including SARS and influenza.

Identification of macrophage activation-related biomarkers in obese type 2 diabetes that may be indicative of enhanced respiratory risk in COVID-19

Hyperactivation of the immune system through obesity and diabetes may enhance infection severity complicated by Acute Respiratory Distress Syndrome (ARDS). The objective was to determine the circulatory biomarkers for macrophage activation at baseline and after serum glucose normalization in obese type 2 diabetes (OT2D) subjects. A case-controlled interventional pilot study in OT2D (n = 23) and control subjects (n = 23). OT2D subjects underwent hyperinsulinemic clamp to normalize serum glucose. Plasma macrophage-related proteins were determined using Slow Off-rate Modified Aptamer-scan plasma protein measurement at baseline (control and OT2D subjects) and after 1-h of insulin clamp (OT2D subjects only). Basal M1 macrophage activation was characterized by elevated levels of M1 macrophage-specific surface proteins, CD80 and CD38, and cytokines or chemokines (CXCL1, CXCL5, RANTES) released by activated M1 macrophages. Two potent M1 macrophage activation markers, CXCL9 and CXCL10, were decreased in OT2D. Activated M2 macrophages were characterized by elevated levels of plasma CD163, TFGβ-1, MMP7 and MMP9 in OT2D. Conventional mediators of both M1 and M2 macrophage activation markers (IFN-γ, IL-4, IL-13) were not altered. No changes were observed in plasma levels of M1/M2 macrophage activation markers in OT2D in response to acute normalization of glycemia. In the basal state, macrophage activation markers are elevated, and these reflect the expression of circulatory cytokines, chemokines, growth factors and matrix metalloproteinases in obese individuals with type 2 diabetes, that were not changed by glucose normalisation. These differences could potentially predispose diabetic individuals to increased infection severity complicated by ARDS.Clinical trial reg. no: NCT03102801; registration date April 6, 2017.

Transformation of western hemlock (Tsuga heterophylla) tree crowns by dwarf mistletoe (Arceuthobium tsugense, Viscaceae)

AbstractDwarf mistletoes (Arceuthobium species) are arboreal, hemiparasitic plants of conifers that can change the structure and function of the tree crown. Hemlock dwarf mistletoe (Arceuthobium tsugense subsp. tsugense) principally parasitizes western hemlock (Tsuga heterophylla) and effects 10.8% of all western hemlock trees in Oregon, USA. In this study, we climbed 16 western hemlock trees (age 97–321 years, height 33–54.7 m) across a gradient of infection (0%–100% of branches infected) and measured occurrence of all dwarf mistletoe infections, dwarf mistletoe caused deformities, foliage, branch and crown metrics, and sapwood area. We then modelled over 25 different response variables using linear and generalized linear models with three metrics of severity as explanatory variables: total infection incidence, proportion of all live branches infected, and proportion of all live, infected branches with 33 per cent or more foliage distal to infection. A strong effect of dwarf mistletoe intensification was the reduction of branch foliage and an increase in the proportional amount of foliage distal to infections, with severely infected trees having the majority of foliage distal to infections. Increasing severity led to an apparent crown compaction as crown volumes decreased and became increasingly comprised of deformities. Sapwood area was unrelated to infection severity. Branch length and diameters were unrelated to increasing infection severity despite severely infected branches supporting 1–70 infections. The most severely infected tree had 3,615 individual plants in the crown. Our results suggested that shifts in crown structure and branch deformation, foliage amount, and foliage distal to infection, reflected a likely reduction of capacity for tree growth that coincided with a hypothesized increase in resource demand by dwarf mistletoe plants as infection severity intensified.

Direct Exposure to SARS-CoV-2 and Cigarette Smoke Increases Infection Severity and Alters the Stem Cell-Derived Airway Repair Response.

Current smoking is associated with increased risk of severe COVID-19, but it is not clear how cigarette smoke (CS) exposure affects SARS-CoV-2 airway cell infection. We directly exposed air-liquid interface (ALI) cultures derived from primary human nonsmoker airway basal stem cells (ABSCs) to short term CS and then infected them with SARS-CoV-2. We found an increase in the number of infected airway cells after CS exposure with a lack of ABSC proliferation. Single-cell profiling of the cultures showed that the normal interferon response was reduced after CS exposure with infection. Treatment of CS-exposed ALI cultures with interferon β-1 abrogated the viral infection, suggesting one potential mechanism for more severe viral infection. Our data show that acute CS exposure allows for more severe airway epithelial disease from SARS-CoV-2 by reducing the innate immune response and ABSC proliferation and has implications for disease spread and severity in people exposed to CS.

Micro-rheological properties of lung homogenates correlate with infection severity in a mouse model of Pseudomonas aeruginosa lung infection

Lung infections caused by Pseudomonas aeruginosa pose a serious threat to patients suffering from, among others, cystic fibrosis, chronic obstructive pulmonary disease, or bronchiectasis, often leading to life-threatening complications. The establishment of a chronic infection is substantially related to communication between bacteria via quorum-sensing networks. In this study, we aimed to assess the role of quorum-sensing signaling molecules of the Pseudomonas quinolone signal (PQS) and to investigate the viscoelastic properties of lung tissue homogenates of PA-infected mice in a prolonged acute murine infection model. Therefore, a murine infection model was successfully established via intra-tracheal infection with alginate-supplemented Pseudomonas aeruginosa NH57388A. Rheological properties of lung homogenates were analyzed with multiple particle tracking (MPT) and quorum-sensing molecules were quantified with LC–MS/MS. Statistical analysis of bacterial load and quorum-sensing molecules showed a strong correlation between these biomarkers in infected lungs. This was accompanied by noticeable changes in the consistency of lung homogenates with increasing infection severity. Furthermore, viscoelastic properties of the lung homogenates strongly correlated with bacterial load and quorum sensing molecules. Considering the strong correlation between the viscoelasticity of lung homogenates and the aforementioned biomarkers, the viscoelastic properties of infected lungs might serve as reliable new biomarker for the evaluation of the severity of P. aeruginosa infections in murine models.

Metatranscriptomic Analysis Reveals Active Bacterial Communities in Diabetic Foot Infections.

Despite the extended view of the composition of diabetic foot infections (DFIs), little is known about which transcriptionally active bacterial communities are pertinent to infection, and if any differences are associated with increased infection severity. We applied a RNA sequencing approach to analyze the composition, function, and pathogenicity of the active bacterial communities in DFIs. Taxonomic profiling of bacterial transcripts revealed the presence of 14 bacterial phyla in DFIs. The abundance of the Spiroplasma, Vibrio, and Mycoplasma were significantly different in different infection severities (P < 0.05). Mild and severe stages of infections were dominated by Staphylococcus aureus and Porphyromonas asaccharolytica, respectively. A total of 132 metabolic pathways were identified of which ribosome and thiamin being among the most highly transcribed pathways. Moreover, a total of 131 antibiotic resistance genes, primarily involved in the multidrug efflux pumps/exporters, were identified. Furthermore, iron acquisition systems (synthesize and regulation of siderophores) and pathways involved in the synthesis and regulation of cell-surface components associated with adhesion, colonization, and movement of bacterial cells were the most common virulence factors. These virulence factors may help bacteria compete for scares resources and survive the host wound proteases. Characterization of transcriptionally active bacterial communities can help to provide an understanding of the role of key pathogens in the development of DFIs. Such information can be clinically useful allowing replacement of DFIs empirical therapy with targeted treatment.

Infection sequence alters disease severity-Effects of the sequential exposure of two larval trematodes to Polypedates cruciger tadpoles.

Multiple pathogens coexist in nature, and hence, host species often encounter several pathogens simultaneously. The sequence in which the host encounters the parasites influences interactions between parasites and host pathology. Here, the effects of infection by two cercaria (larvae of trematodes) types, pleurolophocercous cercaria of Acanthostomum burminis and a furcocercous cercaria, on the tadpoles of common hourglass tree frog (Polypedates cruciger) were examined. Ten days posthatch, tadpoles (Gosner stage 27/28) were used for infection exposures. First, in a single infection each cercaria type was introduced to the tadpoles separately. Second, coinfection of the two cercaria was carried out by alternating the sequences of exposure. For all the experiments, appropriate controls were instituted. Tadpoles of all groups exposed to parasites had lower survival levels compared to controls. Among the four groups exposed, the highest survival was observed in the coinfection when furcocercous was introduced first (82.5%). The lowest survival was observed in the coinfection when the A. burminis cercaria was introduced first (65.0%). In the coinfections, when A. burminis was introduced prior to furcocercous, survival of the tadpoles was reduced by 17.0% compared to the exposures of furcocercous prior to A. burminis. Prior infection with A. burminis induced negative effect on the host with an increased infection severity, while prior infection with furcocercous had reduced infection severity than lone exposures. These results suggest that furcocercous infections can be beneficial for hosts challenged with A. burminis provided that A. burminis exposure occurs second. None of the treatments had an effect on the growth of the tadpoles, but lengthening of developmental period was observed in some exposures. All exposed tadpoles developed malformations which were exclusively axial—kyphosis and scoliosis. However, there was no difference in the number of malformed individuals in the single infection (19.0%–25.0%) compared to coinfection (20.0%–22.5%) or between coinfections. The results suggest that the sequence of parasite exposure affects host–parasite interactions and hence the disease outcomes. Understanding the effects of coinfection on disease outcomes for hosts provides insight into disease dynamics.

Increased infection severity in downstream cities in infectious disease transmission and tourists surveillance analysis

Infectious disease severely threatens human life. Human mobility and travel patterns influence the spread of infection between cities and countries. We find that the infection severity in downstream cities during outbreaks is related to transmission rate, recovery rate, travel rate, travel duration and the average number of person-to-person contacts per day. The peak value of the infected population in downstream cities is slightly higher than that in source cities. However, as the number of cities increases, the severity increase percentage during outbreaks between end and source cities is constant. The surveillance of important nodes connecting cities, such as airports and train stations, can help delay the occurrence time of infection outbreaks. The city-entry surveillance of hub cities is not only useful to these cities, but also to cities that are strongly connected (i.e., have a high travel rate) to them. The city-exit surveillance of hub cities contributes to other downstream cities, but only slightly to itself. Surveillance conducted in hub cities is highly efficient in controlling infection transmission. Only strengthening the individual immunity of frequent travellers is not efficient for infection control. However, reducing the number of person-to-person contacts per day effectively limits the spread of infection.

Pregnancy Induces a Steady-State Shift in Alveolar Macrophage M1/M2 Phenotype That Is Associated With a Heightened Severity of Influenza Virus Infection: Mechanistic Insight Using Mouse Models.

Influenza virus infection during pregnancy is associated with enhanced disease severity. However, the underlying mechanisms are still not fully understood. We hypothesized that normal alveolar macrophage (AM) functions, which are central to maintaining lung immune homeostasis, are altered during pregnancy and that this dysregulation contributes to the increased inflammatory response to influenza virus infection. Time-mated BALB/c mice were infected with a low dose of H1N1 influenza A virus at gestation day 9.5. Inflammatory cells in bronchoalveolar lavage (BAL) fluid were assessed by flow cytometry. Our findings confirm previous reports of increased severity of influenza virus infection in pregnant mice. The heightened inflammatory response detected in BAL fluid from infected pregnant mice was characterized by neutrophil-rich inflammation with concomitantly reduced numbers of AM, which were slower to return to baseline counts, compared with nonpregnant infected mice. The increased infection severity and inflammatory responses to influenza during pregnancy were associated with a pregnancy-induced shift in AM phenotype at homeostatic baseline, from the M1 (ie, classical activation) state toward the M2 (ie, alternative activation) state, as evidence by increased expression of CD301 and reduced levels of CCR7. These results show that pregnancy is associated with an alternatively activated phenotype of AM before infection, which may contribute to heightened disease severity.