Search Results (176)

Background: The effect of antibiotics can be severely affected by external factors. Combining the oxidative impact of photodynamic therapy with antibiotics is largely unexplored, which may result in positive results with great impact on clinical applications. In particular, that can be relevant in the case of antibiotic resistance. Objectives: In this study, we examined the effects of aPDT using the photosensitizers (PSs), methylene blue (MB) or Photodithazine (PDZ), both alone and in combination with the antibiotics ciprofloxacin (CIP), gentamicin (GEN), and ceftriaxone (CEF), against the Gram-negative bacterium Klebsiella pneumoniae. Methods: A standard suspension of K. pneumoniae was subjected to PDT with varying doses of MB and PDZ solutions, using a 75 mW/cm² LED emitting at 660 nm with an energy of 15 J/cm². The MICs of CIP, GEN, and CEF were determined using the broth dilution method. We also tested the photosensitizers MB or PDZ as potentiating agents for synergistic combinations with antibiotics CIP, GEN, and CEF against K. pneumoniae. Results: The results showed that MB was more effective in inhibiting survival and killing K. pneumoniae compared to PDZ. The tested antibiotics CIP, GEN, and CEF suppressed bacterial growth (as shown by reduced MIC values) and effectively killed K. pneumoniae (reduced Log CFU/mL). While antibiotic treatment or aPDT alone showed a moderate effect (1 Log₁₀ to 2 Log₁₀ CFU reduction) on killing K. pneumoniae, the combination therapy significantly increased bacterial death, resulting in a ≥3 Log₁₀ to 6 Log₁₀ CFU reduction. Conclusions: Our study indicates that pre-treating bacteria with PDT makes them more susceptible to antibiotics and could serve as an alternative for treating local infections caused by resistant bacteria or even reduce the required antibiotic dosage. This work explores numerous possible combinations of PDT and antibiotics, emphasizing their interdependence in controlling infections and the unique properties each PS-antibiotic combination offers. Clinical application for the combination is a promising reality since both are individually already adopted in clinical use. Full article

Adrenomedullin (AM) is a bioactive peptide that is strongly induced during severe inflammation, including pneumonia and sepsis, and serves as an organ-protective factor. The plasma concentration of AM is markedly increased in the novel coronavirus disease COVID-19 and is closely related to the severity of the disease and prognosis of patients. We performed two investigator-initiated trials to evaluate the efficacy and safety of AM in patients with moderate-to-severe COVID-19. This multicenter, double-blind, placebo-controlled phase-2a trial evaluated COVID-19 patients with severe (n = 33) and moderate (n = 31) pneumonia in Japan. Patients were randomly assigned to receive either 15 ng/kg/min AM or placebo. The primary endpoint was the duration of mechanical ventilation (MV) for severe pneumonia and oxygen support for moderate pneumonia. The main secondary endpoint was clinical status up to 30 days after the intervention. No differences in primary or secondary endpoints were observed between the AM and placebo groups in patients with severe or moderate pneumonia. In the severe pneumonia group, three patients in the placebo group died due to respiratory failure, and one patient in the AM group died due to respiratory failure. The respiratory function test at 30 days in the moderate pneumonia group tended to be better than that in the AM group and approached significance (p = 0.073). Although mild adverse events caused by the vasodilatory effects of AM were noted, the safety of AM for treating pneumonia was confirmed. In these trials, we did not observe a definitive efficacy of AM in moderate to severe pneumonia. Alternative strategies for the treatment of AM in pneumonia require further research. Full article

Background/Objectives: The long-term sequelae of COVID-19 pneumonia, particularly the persistence of imaging abnormalities and their relationship to clinical symptoms, remain unclear. While the acute radiologic patterns are well-documented, the transition to chronic pulmonary changes—and their implications for long COVID symptoms—require systematic investigation. Methods: Our study included 93 patients with moderate to severe COVID-19 pneumonia who were admitted to Istanbul Medical Faculty Hospital, each having one follow-up CT scan over a ten-month period. Two thoracic radiologists independently calculated semi-quantitative initial chest CT scores to evaluate lung involvement in pneumonia (0–5 per lobe, total score 0–25). Two radiologists and one pulmonologist retrospectively examined the persistence of follow-up imaging findings, interpreting them alongside the relevant clinical and laboratory data. Additionally, in a subcohort (n = 46), mid-term (5–7 months) and long-term (≥10 months) scans were compared to assess temporal trajectories. Results: Among the 93 patients with long-term follow-up imaging, non-fibrotic changes persisted in 34 scans (36.6%), while fibrotic-like changes were observed in 70 scans (75.3%). The most common persistent non-fibrotic changes were heterogeneous attenuation (29%, n = 27) and ground-glass opacities (17.2%, n = 16), and the persistent fibrotic-like changes were pleuroparenchymal bands or linear atelectasis (58%, n = 54), fine reticulation (52.6%, n = 49), and subpleural curvilinear lines (34.4%, n = 32). Both persistent non-fibrotic and fibrotic-like changes were statistically correlated with the initial CT score (p < 0.001), LDH (p < 0.001), and ferritin levels (p = 0.008 and p = 0.003, respectively). Fatigue (p = 0.025) and chest pain (p < 0.001) were reported more frequently in patients with persistent non-fibrotic changes, while chest pain (p = 0.033) was reported more frequently among those with persistent fibrotic-like changes. Among the 46 patients who underwent both mid- and long-term follow-up imaging, 47.2% of those with non-fibrotic changes (17 out of 36) and 10% of those with fibrotic-like changes (4 out of 40) exhibited regression over the long term. Conclusions: Initial imaging and laboratory findings may indicate persistent imaging findings related to long-term sequelae of COVID-19 pneumonia. Many of these persistent imaging abnormalities, particularly non-fibrotic changes seen in the mid-term, tend to lessen over the long term. A correlation exists between persistent imaging findings and clinical outcomes of long COVID-19, underscoring the need for further research. Full article

Background/Objectives: Background: COVID-19 pneumonia leads to alveolar collapse and parenchymal infiltration, contributing to lung volume loss and respiratory failure. Objectives: To quantify lung volume loss and recovery in moderate and severe cases, explore mechanisms of respiratory failure, and correlate imaging findings with histopathological changes. Methods: We retrospectively analyzed 43 patients with moderate/severe COVID-19. CT scans from the acute phase and at 3–12 months follow-ups were processed using 3D Slicer. Infiltrated (−650 to −200 HU) and collapsed (−200 to 0 HU) lung regions were quantified and summed to define the affected lung volume. CT severity scores and total affected percentage were compared with lung volume loss. Histopathological analysis of three autopsy cases was used to support imaging findings. Results: Median acute phase lung volume loss was 30.6%. Patients with <25%, 25–50%, and >50% affected lung had median losses of 6.5%, 35.7%, and 39.8%, respectively. Volume loss strongly correlated with affected lung percentage (r = 0.72, p < 0.000001) and moderately with CT severity score (r = 0.52, p < 0.01). Histology confirmed alveolar area reductions over 65% in infiltrated regions. Conclusions: Lung volume loss reflects both imaging severity and histopathological damage, offering insights into the mechanisms of COVID-19 respiratory failure. CT volumetry is a valuable tool for assessing parenchymal injury and monitoring recovery, and 3D Slicer provides an accessible platform for implementing this approach. Full article

Background/Objectives: The clinical forms of coronavirus disease 2019 (COVID-19) vary widely in severity, ranging from asymptomatic or moderate cases to severe pneumonia that can lead to acute respiratory failure, acute respiratory distress syndrome, multiple organ dysfunction syndrome, and death. Our main objective was to determine the prevalence of bacterial and fungal secondary infections in an intensive care unit (ICU). Secondary objectives included analyzing the impact of these infections on mortality and medical resource utilization, as well as assessing antimicrobial resistance in this context. Methods: We conducted a retrospective cohort study that included critically ill severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients treated in an ICU and analyzed the prevalence of co-infections and superinfections. Results: A multivariate analysis of mortality found that the presence of superinfections increased the odds of death by more than 15-fold, while the Sequential Organ Failure Assessment (SOFA) score and C-reactive protein (adjusted for confounders) increased the odds of mortality by 51% and 13%, respectively. The antibiotic resistance profile of microorganisms indicated a high prevalence of resistant strains. Carbapenems, glycopeptides, and oxazolidinones were the most frequently used classes of antibiotics. Among patients, 27.9% received a single antibiotic, 47.5% received two from different classes, and 24.4% were treated with three or more. Conclusions: The incidence and spectrum of bacterial and fungal superinfections are higher in critically ill ICU patients, leading to worse outcomes in COVID-19 cases. Multidrug-resistant pathogens present significant challenges for ICU and public health settings. Early screening, accurate diagnosis, and minimal use of invasive devices are essential to reduce risks and improve patient outcomes. Full article

After the transition of coronavirus disease 2019 (COVID-19) from a pandemic to an endemic phase, data on respiratory viral infections remain limited. This study compared the clinical outcomes of SARS-CoV-2, influenza virus (INFV), and respiratory syncytial virus (RSV) infections and investigated how underlying medical conditions influence disease severity. During Omicron subvariant dominant periods, we conducted a multicenter, retrospective cohort study including laboratory-confirmed cases of SARS-CoV-2, INFV, and RSV infections in hospitalized patients aged ≥ 19 years. We compared demographic characteristics and clinical outcomes and analyzed the association between underlying comorbidities and severity of infection. A total of 1850 cases with SARS-CoV-2, 98 with INFV, and 63 with RSV infections were analyzed. Notable differences in the occurrence of fever, cough, sputum, and dyspnea were observed among patients with the three different viral infections. Pneumonia was diagnosed more frequently in patients with RSV infection (65.6%) compared to those with INFV infection (42.9%) and SARS-CoV-2 (34.4%) (p < 0.01). For patients with SARS-CoV-2 infection, the risk of pneumonia increased by 47% in the moderate-risk group and 37% in the high-risk group. Among hospitalized patients, pneumonia was more frequently identified in patients with RSV infection, with statistical significance. Furthermore, the presence of medical conditions significantly increased the risk of developing pneumonia. Full article

Background/Objectives: Proinflammatory cytokines have been associated with poor prognosis in community-acquired and COVID-19 pneumonia. There is a paucity of reports on the cytokine release syndrome, also called cytokine storm in the Mexican population with pneumonia and COVID-19; therefore, our objective was to compare proinflammatory cytokine levels in Mexican patients without COVID-19 (non-COVID-19) and those with moderate, severe, and critical COVID-19 pneumonia. Methods: This study included 30 patients with non-COVID-19 pneumonia and 57 with COVID-19 pneumonia. Disease diagnosis and severity were determined using the radiographic pulmonary edema assessment (RALE) score. Quantification of IL-6, IL-10, and TNF-α was performed using multiplex immunoassays. A receiver operating characteristic curve was constructed to classify subjects with elevated cytokine levels. Logistic regression was used to find associations between elevated cytokine levels and the presence of COVID-19 pneumonia. Results: The severity classification of patients with COVID-19 pneumonia was as follows: moderate (n = 20), severe (n = 19), and critical (n = 18). The proinflammatory cytokines IL-6 and IL-10 were significantly increased in COVID-19 patients compared to non-COVID-19 patients (p < 0.005), while TNF-α levels were lower in critically ill patients with COVID-19 pneumonia. High levels of IL-6 and IL-10, adjusted for age, sex, the presence of comorbidities, and the neutrophil-to-lymphocyte ratio (NLR), showed an elevated risk (OR IL-6 = 4.02; OR IL-10 = 9.36) of presenting pneumonia and COVID-19 compared to pneumonia without COVID-19 in patients. Likewise, 61% of COVID-19 patients with elevated proinflammatory cytokines (IL-6 and IL-10) had a fatal outcome. Conclusions: Elevated levels of both IL-6 and IL-10 are a differential risk factor for developing COVID-19 pneumonia. These elevated levels were more frequently observed in Mexican COVID-19 pneumonia patients who died at the onset of the COVID-19 pandemic. It is important that they are monitored from initial diagnosis as they may be markers of a fatal outcome in severe and critical COVID-19 patients. Full article

Background/Objectives: Antimicrobial resistance (AMR) is increasingly rising due to antimicrobial overuse and misuse. In sickle cell disease (SCD) care, frequent antibiotic use drives the rapid emergence of AMR, threatening treatment options and patient lives. This systematic review synthesizes data on AMR with regard to SCD patients for the first time. Methods: A comprehensive database search for articles published in English was conducted in PubMed, Scopus, ScienceDirect, and Web of Science, with no restriction set for the year of publication. The DerSimonian–Laird method was applied to derive the pooled prevalence, while the Mantel–Haenszel method was used to calculate the pooled odds ratio. Results: A total of 18 eligible studies covering 3220 SCD patients published between 1996 and 2024 were included in this review. The common bacterial pathogens reported in the included studies were Streptococcus pneumoniae (10 studies), Staphylococcus aureus (10 studies), and Escherichia coli (4 studies). For S. aureus, the pooled resistance was highest for penicillins (ampicillin = 100%; penicillin = 93.64%; and amoxicillin = 77.82%) followed by cefuroxime (51.23%). The pooled prevalence of methicillin-resistant S. aureus (MRSA) was 19.30%. SCD patients had 2.89 and 2.47 times higher odds of being colonized or infected with penicillin-resistant and erythromycin-resistant S. aureus strains, respectively. For S. pneumoniae, resistance prevalence was highest for co-trimoxazole (81.1%), followed by penicillin (47.08%). The pooled prevalence of multidrug-resistant (MDR) S. pneumoniae isolates was 32.12%. The majority of the studies included (n = 14, 77.8%) were of moderate quality according to the modified STROBE checklist. Conclusions: This review reveals a high prevalence of AMR with regard to SCD patients. SCD patients have an increased risk of resistance to penicillin and co-trimoxazole across several bacterial pathogens. The limited geographical distribution of the included studies underscores the urgent need for expanded AMR research on the subject, especially in regions with high SCD burden. Full article

Objectives: To identify factors associated with complicated parapneumonic pleural effusion/empyema (CPPE/empyema) in inpatients with community-acquired pneumonia (CAP) and to build a mathematical model for CPPE/empyema. Methods: This is an observational case–control study nested within a retrospective cohort, based on clinical practice, and including adults hospitalized with CAP from 2009 to 2019. Cases and controls were defined according to diagnosis of CPPE/empyema during admission. For each case, two controls were randomly selected and matched for the period of admission to avoid seasonality bias. Explanatory variables included demographic, analytical, clinical, and radiological data; treatment with corticosteroids on admission; prognostic and CAP severity scales; comorbidity; and the interval between symptoms onset and admission. Results: Of 4372 pneumonias reviewed, 2015 were excluded due to pleural effusion, blunting of the costophrenic angle without thoracentesis, or heart failure. Of the remaining 2357 patients, 106 developed CPPE/empyema (cases), and 212 were selected as controls. Factors associated with CPPE/empyema were pleuritic pain (odds ratio [OR] 7.42, 95% confidence interval [CI] 3.83–14.38), multilobar radiological involvement (OR 4.48, 95% CI 2.26–8.88), and leukocytosis (OR 4.12, 95% CI 1.94–8.76). Corticosteroids showed a protective effect (OR 0.24, 95% CI 0.09–0.61). Age (OR 0.99, 95% CI 0.97–1.02; p = 0.56) and sex (OR 1.91, 95% CI 0.94–3.88; p = 0.074) were adjustment variables. The area under the receiver operating characteristic curve was 0.847 (95% CI 0.772–0.921). Conclusions: Pleuritic pain, multilobar radiological involvement, and leukocytosis are associated with CPPE/empyema in inpatients with CAP. Treatment with corticosteroids upon admission seems to be a protective factor. The discriminative capacity of the resulting multivariable model presents moderate/high accuracy. Full article

Data from post-mortem inspections conducted using official controls on the meat production of slaughtered pigs are generally considered valuable for identifying herd health issues and ensuring meat safety. However, several studies highlighted that a multi-stage assessment of lung changes would provide more useful information on animal health than the implemented binary (yes/no) recording. For this purpose, a new scheme was developed and subsequently used by trained official veterinarians at four slaughterhouses in Austria. Implementation of the multi-stage assessment was carried out in parallel with the conventional assessment, and data collected from both schemes were analyzed and compared to evaluate effectiveness. The analysis of the data (n = 20,345) showed that the most common alteration was low-grade (28.4%), followed by moderate-grade (11.3%,) and then high-grade pneumonia (5.2%). In the case of pleurisy, 88.9% of the carcasses showed no alterations of the pleura, and 11.1% had pathological changes (low-grade pleurisy = 4.7%, moderate-grade pleurisy = 2.7%, high-grade pleurisy = 3.7%). Analysis of the results showed a strong heterogeneity of the frequency of alterations between the batches reflecting various underlying animal health issues. Among the influencing factors, the origin of the pigs had the greatest influence. The project demonstrated that the new evaluation can be carried out easily with no extra time effort once staff are trained and the technological platform for reporting is adapted. The more detailed information ensures more useful feedback is provided to the farmers and supervising veterinarians, thereby ensuing animal welfare and contributing to sustainable, improved animal husbandry. Full article

Background/Objectives: The existing literature has described the common symptoms and long-term effects of coronavirus disease (COVID-19). However, there is a lack of detailed information on how different degrees of disease severity affect survivors differently. This study aims to fill that gap by evaluating the symptoms, physical activity, and functionality of COVID-19 survivors across a spectrum of severity levels, comparing them with those of healthy individuals. Methods: An observational study was carried out following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) criteria and checklist. Participants were divided into 5 groups based on COVID-19 severity according to the World Health Organization classification: healthy (COVID-19-negative), mild (symptomatic without pneumonia or dyspnoea), moderate (pneumonia and dyspnoea without hospitalisation), severe (severe pneumonia requiring hospitalisation), and critical (severe pneumonia with admission to the intensive care unit). Descriptive variables, symptoms (Fatigue Borg Scale, Fatigue Impact Scale, Fatigue Severity Scale, Dyspnoea Borg Scale, Visual Analogue Scale, Hospital Anxiety and Depression Scale, and European Quality of Life-5 Dimensions), physical activity (the International Physical Activity Questionnaire) and functionality (Patient-Specific Functional Scale, Short Physical Performance Battery, Arm Curl test, and 2 min step test) were measured. Results: A total of 304 participants were included: healthy (n = 42), mild (n = 143), moderate (n = 49), severe (n = 52), and critical (n = 18) COVID-19 patients. The impact of COVID-19 on surviving patients varies significantly with the severity of the disease. The results show that the hospitalisation time, age, and comorbidities of the patients are greater in those with a greater severity of the disease. Patients with more severe COVID-19 also experience greater frailty, dysphagia, fatigue, dyspnoea, and pain. Additionally, those with severe cases have poorer overall health, reduced physical activity, and diminished functionality. No evidence of post-COVID-19 anxiety or depression is found in the sample, even considering the timeframe between the negative test and the assessment. Conclusions: Patients with higher COVID-19 severity (severe or critical) experience more symptoms than those with lower COVID-19 severity (mild or moderate). Additionally, those with severe cases have poorer overall health, reduced physical activity and diminished functionality. Register: Clinicaltrials.gov: NCT05731817. Full article

Studies have indicated the potential importance of the human nasal and respiratory microbiomes in health and disease. However, the roles of these microbiomes in the pathogenesis of influenza and its complications are not fully understood. Therefore, the objective of this systematic review and analysis is to identify the patterns of nasal and respiratory microbiome dysbiosis and to define the unique signature bacteria associated with influenza compared with other respiratory tract infections. We compared the respiratory microbiome composition between influenza patients and healthy controls; across different influenza severities; in adult versus pediatric influenza patients; as well as influenza versus other respiratory infections. The desired outcomes include the signature bacteria in each cohort and the Shannon index to reflect the alpha diversity. Of the 2269 articles identified, 31 studies fulfilled the inclusion criteria. These studies investigated the respiratory tract microbiomes of patients with influenza, COVID-19, pneumonia, other respiratory infections, and chronic rhinosinusitis (CRS). Our review revealed that the phylum Firmicutes and Actinobacteria, genus Actinomyces, Streptococcus and Granulicatella, and species Neisseria are more prominent in severe influenza than mild to moderate influenza. Reduced microbiome alpha diversity is noted in influenza patients compared to healthy controls. There are some similarities and differences between the signature bacteria in pediatric and adult influenza patients, e.g., Streptococcus is common in both age groups, whereas Pseudomonas is associated with adults. Intriguingly, there is a common predominance of Streptococcus and Firmicutes among influenza and pneumonia patients. COVID-19 patients exhibit an increased abundance of Firmicutes as well as Pseudomonas. In CRS patients, Proteobacteria and Haemophilus are found in high abundance. This review highlights some similarities and differences in the respiratory microbiomes and their signature organisms in influenza of varying severity and in different age groups compared with other respiratory infections. The dysbiosis of the respiratory microbiomes in these respiratory infections enhances our understanding of their underlying pathogenic mechanisms. Full article

The COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has profoundly impacted global health, with pneumonia emerging as a major complication in severe cases. The pathogenesis of COVID-19 is marked by the overproduction of reactive oxygen species (ROS) and an excessive inflammatory response, resulting in oxidative stress and significant tissue damage, particularly in the respiratory system. Antioxidants have garnered considerable attention for their potential role in managing COVID-19 pneumonia by mitigating oxidative stress and modulating immune responses. This review provides a comprehensive overview of the literature on the use of antioxidants in hospitalized patients with mild-to-moderate COVID-19. Studies exploring antioxidants, including vitamins, trace elements, nitric oxide (NO), ozone (O₃), glutathione (GSH), L-carnitine, melatonin, bromelain, N-acetylcysteine (NAC), and numerous polyphenols, have yielded promising outcomes. Through their ROS-scavenging properties, these molecules support endothelial function, reduce the thrombosis risk, and may help mitigate the effects of the cytokine storm, a key contributor to COVID-19 morbidity and mortality. Clinical evidence suggests that antioxidant supplementation may improve patient outcomes by decreasing inflammation, supporting immune cell function, and potentially shortening recovery times. Furthermore, these molecules may mitigate the symptoms of COVID-19 by exerting direct antiviral effects that inhibit the infection process and genomic replication of SARS-CoV-2 in host cells. Moreover, antioxidants may work synergistically with standard antiviral treatments to reduce viral-induced oxidative damage. By integrating findings from the literature with real-world data from our clinical experience, we gain a more profound understanding of the role of antioxidants in managing COVID-19 pneumonia. Further research combining comprehensive literature reviews with real-world data analysis is crucial to validate the efficacy of antioxidants and establish evidence-based guidelines for their use in clinical practice. Full article

Background: Canakinumab, a humanized anti-IL-1β monoclonal antibody, is known for its ability to suppress IL-1β-mediated inflammation. However, continuous monitoring of its safety remains essential. Thus, we comprehensively evaluated the safety signals of canakinumab by data mining from FAERS. Methods: We used a disproportionate analysis to quantify canakinumab-related adverse events (AEs) using four algorithms. Clinical prioritization of the detected signals was assessed with a semiquantitative score method. Serious and non-serious outcomes were compared by statistical methods. Additionally, a stratification analysis of serious infections was conducted at the system organ class (SOC) level. Results: A total of 28,496 canakinumab-related AEs were collected, and 71 suspicious signals detected. Among these, 19 preferred terms (PTs) were identified as unexpected signals, including deafness, appendicitis, brain oedema, cushingoid, cellulitis, and papilledema. Of the AEs, 16 were more likely reported as serious outcomes, such as pneumonia, abdominal pain, deafness, and infection. Based on clinical priority score, 44 PTs were classified as weak, 27 as moderate, and none as strong. Furthermore, 30 PTs demonstrated a high level of evidence, primarily derived from FDA prescribing information, randomized controlled trials, and systematic reviews. Stratification analysis of infections and infestations (serious outcomes) revealed a stronger association of severe infections with canakinumab in older or heavier individuals. All positive signals followed an early failure pattern, with the incidence of canakinumab-associated AEs decreasing over time. Conclusions: We found that most of the suspicious signals were associated with infections. More attention should be paid to serious infections, particularly in males, individuals aged ≥60 years, or those weighing >100 kg, who demonstrated the highest risk of serious infections. Full article

Pneumonia caused by Pneumocystis jirovecii infection (PCP) is a potentially life-threatening illness, particularly affecting the immunocompromised. The past two decades have shown an increase in PCP incidence; however, the underlying factors that promote disease severity and fatality have yet to be fully elucidated. Recent evidence suggests that the microbiota of the respiratory tract may play a role in stimulating or repressing pulmonary inflammation, as well as the progression of both bacterial and viral pneumonia. Here, we employed 16S rRNA metataxonomic sequencing to profile the respiratory microbiota of patients with mild-moderate and severe PCP. Our results show that the upper and lower airways of PCP patients have bacterial profiles which have been associated with a pro-inflammatory response. Furthermore, we find that severe PCP is associated with lower bacterial diversity and an increase in Prevotella and a decrease in Neisseria. Functionally, severe PCP was associated with a decrease in metabolic pathways of molecules with anti-inflammatory and antimicrobial properties. To our knowledge, this is the first study showing an association of PCP severity with shifts in the respiratory microbiome and may provide some insight into which patients are more susceptible to the more severe manifestations of the disease. Full article